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From the editor
WORLDPHARMACEUTICALFRONTIERS
|
www.worldpharmaceuticals.net 3
World Pharmaceutical Frontiers
2010 Vol. 1
EDITORIAL
Editor Andrew Tunnicliffe
AndrewTunnicliffe@globaltrademedia.com
Chief sub-editor Elliott Aykroyd
Sub-editor Naomi Mackay
Features editor Phin Foster
Features writers Elly Earls, Ian Duncan
Production manager Dave Stanford
Group art director Henrik Williams
Designer Michelle Kim
Editor-in-chief John Lawrence
COMMERCIAL
Client services manager Derek Deschamps
Client services executive Ilona Molnarova
Sales manager Nathan Park
Circulation executive Daniel Trigueirinho
Head of sales Richard Jamieson
Publisher William Crocker
World Pharmaceutical Frontiers is published by Global
Trade Media, a trading division of Cornhill Publications
Limited, a member of the Audit Bureau of Circulations.
John Carpenter House, John Carpenter Street,
London, EC4Y 0AN, UK
Tel: +44 207 753 4200 Fax: +44 207 724 2089
Email: info@globaltrademedia.com
Websites: www.globaltrademedia.com
www.worldpharmaceuticals.net
ISSN 1742-3791 © 2010 Global Trade Media, a trading
division of Cornhill Publications Limited. Registered in
England No. 01564127.
All rights reserved. No part of this publication may be
reproduced, stored in a retrieval system or transmitted in any
form or by any means, electronic, photocopying or otherwise,
without prior permission of the publisher and copyright owner.
While every effort has been made to ensure the accuracy of the
information in this publication, the publisher accepts no
responsibility for errors or omissions.
The products and services advertised are those of individual
authors and are not necessarily endorsed by or connected with
the publisher nor Deloitte. The opinions expressed in the articles
within this publication are those of individual authors and not
necessarily those of the publisher nor Deloitte.
The products and services advertised are those of individual
authors and are not necessarily endorsed by or connected with
the publisher. The opinions expressed in the articles within this
publication are those of individual authors and not necessarily
those of the publisher.
Copies of World Pharmaceutical Frontiers are available from
Global Trade Media at a cost of £5.95, €8.00 or $8.95 per copy.
Printed by Williams Press
Visit www.worldpharmaceuticals.net
GlobalData
WPF017_FINAL COVER.indd 1 17/3/10 11:25:59
On the web...
Keep up with the latest developments in
the pharmaceutical industry by visiting
www.worldpharmaceuticals.net
Also in this issue
Page 8: A look at some of the biggest developments to
shape the industry
Page 12: What do executives feel about their company’s
future prospects?
Page 126: Hans Lindén tells World Pharmaceutical
Frontiers about his career
R
esearch and development (R&D) is
the lifeblood of the pharmaceutical
sector. This important role is
undertaken by both industry and academia;
sometimes as a collaborative partnership and
sometimes as independent research projects.
Its importance is clear, without it there would
be no pharmaceutical pipeline.
This year’s Pharma 40 list shows just how
important it is, according to our panel of
industry experts, with no less than eight out
of the top ten spots occupied by leading
scientific figures. That is in stark contrast to
the 2009 list where pharmaceutical
executives dominated, which is perhaps
symptomatic of the climate at that time.
Phin Foster looks at an important part of
the R&D, animal testing. Speaking with
Pfizer’s Dr David Reynolds he asks what the
future holds for this necessary, if not
controversial, function on page 89. Reynolds,
a senior director of experimental biological
sciences, argues that while animal testing
has declined over the past couple of decades
it remains an essential ingredient and will
continue to do so for some time to come.
In our special supplement on supply chain
and logistics beginning on page 49, Ian
Duncan talks with Laurent Boer of UCB on
the issue of supply chain disruption and the
strategies pharma can employ to try to
secure the delivery of their products and
other essential materials. The recent
earthquakes in Haiti and Chile and ongoing
concerns of pirate attacks off the Horn of
Africa have served to highlight the difficulties
facing companies looking to transport their
products around the world.
On page 77, Sven Stegemann discusses
what he says is an uncomfortable shift for
pharma manufacturers moving from the
tradition of quality testing to quality by
design. Although, he says, it is a difficult
transition, the rewards for doing so make it
worth the effort.
And finally, as the economies of the
world tentatively emerge from recession,
the focus of the industry turns back to
more traditional issues and confidence
grows as pharma execs discuss in the
latest ICD research on page 12.
I hope you find this edition of benefit
and look forward to welcoming you to our
next one later in the year. In the meantime,
if there is anything you have seen that you
have thoughts on, then drop me a line.
And for those of you that have been
eagerly awaiting the Pharma 40, I would
welcome your comment.
Andrew Tunnicliffe, editor,
World Pharmaceutical Frontiers
People power
Andrew Tunnicliffe, editor
WORLDPHARMACEUTICALFRONTIERS
|
www.worldpharmaceuticals.net 5
Contents
How to prepare and plan for supply chain problems.
3 From the Editor
Andy Tunnicliffe, editor
World Pharmaceutical Frontiers
Market intelligence
8 News
A round-up of all the latest
business and healtcare news.
10 Vital stats
Key facts from the industry.
12 The future’s bright
Hopes for the short- to mid-term
future of pharmaceuticals.
14 Special delivery
GlobalData takes a close look
at worldwide drug delivery.
market.
Special report
18 2010 Pharma 40
The top 40 most influential
people in the industry.
Business overview
22 A spoonful of sugar
R&D costs for life sciences have
been rising for years, but the pill
could be sweetened by EHR data.
Regulatory issues
24 Non-stop action
Continuous manufacturing is the
future, but it has its own series of
challenges, writes Nic Paton.
Regional focus
28 A Latin swing
GlobalData investigates the
steadily growing Latin America
market and assesses
theinvestment
opportunities.
30 Experience today’s and
tomorrow’s metal-based APIs
Umicore
Site selection
33 Where culture meets
business innovation
Varaždin Park for Life Sciences
and Technology
34 Gothenburg – a leader in
drug development
Business Region Goteborg
Raw materials
36 Upwardly mobile
The CPA’s Marcello Fumagalli
examines the API sector’s
performance globally.
Drug discovery & development
42 The rise of the robots
As automation and robotics
becomes ever more advanced,
their importance is on the rise.
Data management / IT
47 LIMS – reducing cost
and improving efficiencies
Thermo Fisher Scientific ❯❯
50
Cover story
18
36
Our annual round-up of the most important people in Pharma.
101
Contents
WORLDPHARMACEUTICALFRONTIERS
|
www.worldpharmaceuticals.net
6
Risk management
50 A clear road to market
Laurent Boer of UCB on robust
delivery strategies.
53 The earlier the better
DHL
56 Kings of the cool chain
Envirotainer
Cold chain
59 The shipping forecast
Ensuring shipping is as efficient
and waste-free as possible.
64 A degree of control
Tinytag (Gemini Data Loggers
(UK) Ltd)
64 Moving to electronic
temperature monitoring
Sensitech
Product security
69 Border control
EFPIA’s new coding initiative
provides a model for an end-to-
end verification solution.
71 Anti-counterfeiting
solutions – protection
where it is needed
Constantia Hueck Folien
GmbH & Co.KG
72 Serialisation solution
for a counterfeit crises
Siemens IT Solutions and Services
75 The real deal
Original1
Manufacturing
76 Better by design
The industry is moving from
quality by testing towards
quality by design.
79 Protect your assets
ABB
80 Pursuing a policy of
automatic containment
Mettler Toledo
82 Save your energy
Arup
85 Test the water
GE Analytical Instruments
86 Awash with ideas
Dr John Hutcheson explains
the issues surrounding the use
of water in manufacturing.
Contract services
89 Of mice and men
Pfizer’s Dr David Reynolds
on the advances that may see
animal studies become obsolete.
92 The higher you climb,
the harder you fall
Pharmatest Services
94 The best of both worlds
Medicilon/MPI Preclinical
Research-Shanghai
97 Considering Asian
clinical trials?
INC Research
98 Rescuing clinical trials
Harrison Clinical Research
Contract manufacturing
101 Who can you trust?
Eric Langer offers some practical
advice on contracting out any
function and an insight into
the future of outsourcing.
106 Where technology
meets versatility
Alfa Wassermann SpA
108 Business expansion
in Brazil
Nycomed
111 The outsourcing code
Rechon Life Science
Drug delivery & formulation
113 When two become one
GlobalData examines the success
of drug-device convergence.
119 Developing a
cure for protein
instability
Do-Coop Technologies
120 Predictable
behaviour of drugs
TNO
122 Health in Gum
Cafosa
125 Needle free injection
Crossject
People
126 Teaching a lifestyle
Executive director
of the EUFEPS,
Hans H Lindén,
talks to Andy
Tunnicliffe about
his work.
Directory
128 Product showcase
137 Index
76
Logistics
Pharma supply chain and logistics
CONTENTS TECHNICAL PAPERS
Turn to p49 for
our special supply
chain and logistics
supplement.
59
89
113
126
www.multipharma.ch | info@multipharma.ch
C
M
Y
CM
MY
CY
CMY
K
Multipharma_Ad_03082010_Final.pdf 3/8/10 4:05:11 PM
AstraZeneca (AZ) has announced a five-year
restructuring plan that will see it cut 8,000
positions around the world, according to David
Brennan, the company’s chief executive. Refusing
to speculate on exactly where the cuts would be
made until employees had been consulted,
Brennan said the company’s research and
development unit and its sales and marketing arm
would see the largest losses. This latest round of
cuts comes off the back of an extensive exercise
since 2007, which has seen headcount fall by more
than 12,000.
The news comes at a time when AZ’s closest
British rival, GSK, also announced cost-cutting
measures, leaving industry-watchers to ponder the
level of possible staff reductions. GSK CEO
Andrew Witty told the media of plans to reduce
costs by as much as £500 million within two years,
resulting in the loss of up to 4,000 of its 99,000
global workforce. “We remain very conscious
of the impact restructuring has on our employees.
Where possible, we will continue to try to
preserve jobs.
“As before, we will not be providing targets for
job reductions and we will announce restructuring
outcomes once employees, relevant works
councils and trade unions have been consulted.”
Meanwhile, Merck has announced plans to
cut 17,500 jobs worldwide as part of a
restructuring programme following its
acquisition of Schering-Plough.
Its plans were revealed at the same time as it
announced a leap in fourth-quarter profits.
However, the company said ‘an ongoing
reevaluation of manufacturing and R&D facilities
worldwide has not yet been completed’. It said it
would continue to hire new employees ‘in
strategic growth areas’.
M&A
Abbott deal opens
up market
Abbott has completed the
purchase of Solvay
Pharmaceuticals in a €4.5 billion
deal. The sale is seen by many
analysts as key to helping
Abbott break into emerging
markets and secure sustainable
growth, as well as providing it
with branded generics, a
foothold into a market now
seen by big pharma as a
viable option.
The acquisition of the
Belgium-based company is
expected to add as much as $2.9
billion to Abbott’s 2010 sales.
“The acquisition of Solvay
Pharmaceuticals is a key part
of Abbott’s strategy to bolster
our presence in key markets
and deliver sustainable,
industry-leading growth,” said
Chairman and CEO, Miles D
White. He went on to say the
deal would also add to Abbott’s
R&D investment.
“The combination of Solvay
and Abbott’s pharmaceutical
businesses will enable Abbott to
attain leadership in key
emerging markets, where there
is significant opportunity for
branded generics,’ said Olivier
Bohuon, executive vice
president, pharmaceutical
products group at Abbott.
“The addition of Solvay
Pharmaceuticals is the catalyst
for Abbott’s growth and
leadership in this area, and
will ensure Abbott has the
infrastructure, reach and product
offerings to continue meeting
the needs of patients around
the world.”
Solvay’s products will add to
Abbott’s already established
involvement in specialist
areas such as cardiovascular
disease, neuroscience and
gastroenterology.
They include treatments for
men’s and women’s hormonal
health, and exocrine pancreatic
insufficiency (the inability
to properly digest food), which
is also associated with
several underlying conditions
including cystic fibrosis and
chronic pancreatitis.
business
AstraZeneca’s restructure will cut 8,000 jobs worldwide.
Jobs to go at british-owned firms
in brief
Israel-based generics
manufacturer Teva
Pharmaceuticals has
announced bumper profits
for the final quarter of 2009.
Sales rose by 34% to be worth
$3.8 billion from $2.85 billion
during the same period in the
previous year. The company
said much of its $379 million
profit was the result of sales
of recently-acquired Barr
products. Teva said its yearly
profits stood at $2 billion, more
than three times the $609
million of 2008.
Germans and Italians are
the most likely to purchase
medicines online, despite
knowing that such purchases
are unregulated. The findings
were part of a recent Pfizer-
funded 14,000-strong survey
across 14 European countries
into the €10.5 billion counterfeit
market. Of the prescription-only
medicines purchased, the most
popular are those for weight
loss (45%), flu (35%) and
erectile dysfunction (25%).
The global recession and
a pledge by President
Obama to “rein in” lobbyists
failed to quell the spending
on Capitol Hill, according to
a recent study. The Center
for Responsive Politics said
lobbying spend for 2009
broke all records, amounting
to $347 billion, with the
final quarter of 2009 seeing
the most activity at a time
when the Obama healthcare
reform plan gained most
attention. Healthcare and
pharmaceuticals accounted
for $267 million, described by
a Center analyst as being ‘the
biggest amount ever spent
on lobbying efforts by a single
industry for one year’.
GSK has announced plans
to open up its work on anti-
malaria compounds, as well
as pumping funds into what it
called an open lab, aimed at
independent research teams
studying malaria. The news
will mean that other
pharmaceutical companies
and academia will have access
to as many as 13,500 already-
tested molecules, raising
hopes of a collaboration that
could yield treatments or
even preventative medicines.
The announcement, made
by CEO Andrew Witty, is the
latest in a number of initiatives
to “gain the trust of society”,
he said.
Market intelligence > News
WorldPhArMAceuticAlFrontiers
|
www.worldpharmaceuticals.net 8
$2.9bn
The amount the deal will
add in sales for Abbott
in 2010.
Xxxxxxxx > xxxxxxxxxx
WorldPharmaceuticalFrontiers
|
www.worldpharmaceuticals.net 9
healthcare
British patients at risk
of drug shortage
Experts in the UK have warned
that patients are at risk of
“serious harm” if NHS hospitals
do not stop selling drugs
abroad. Healthcare providers
have been accused of sending
drugs intended for patients on
the NHS, out for export, in an
attempt to raise funds.
Of the 40-or-so medicines
affected, well-known products
such as weight pill Xenical,
erectile dysfunction drug Cialis,
contraceptive Cerazette, breast
cancer drug Arimidex (also
known as Anastrozole) and Ailect
for Parkinson’s relief are known
to be in short supply.
The Royal Pharmaceutical
Society of Great Britain called for
the practice to stop, while UK
Health Minister Mike O’Brien
said it was “unscrupulous”.
“Rather than selling drugs to
NHS patients as they should,
they are selling them abroad for
greater profit,” he added.
Manufacturers such as Roche,
AstraZeneca and Novartis are
also concerned. Neal Patel, a
Royal Pharmaceutical Society
spokesman, said: ‘Our members
are spending long hours chasing
down supplies, which are
increasingly difficult to obtain.
The Society fears that if we do
not identify a solution through
real understanding of the
problem, then patient care will
continue to suffer.’
The UK Government is
believed to be holding a summit
shortly to discuss the issue and
ways it can be resolved.
Product saFety
middle east ring
smashed by authorities
Syrian authorities believe they
may have smashed a counterfeit
drugs ring in the country. The
series of operations, believed to
have recovered millions of
dollars’ worth of medicines, has
resulted in the detention of up to
65 individuals.
The seizure included drugs for
the treatment of cancers and
anticoagulant pills that were
claimed to be for treating heart
attacks and other diseases.
Manufacturers such as Novartis,
Roche, Pfizer, Bristol-Myers
Squibb and Sanofi-Aventis have
had their products forged.
Sanofi-Aventis, Novartis,
Bristol-Myers Squibb and Pfizer
confirmed that an operation had
taken place and counterfeit
drugs had been seized. It is
believed the ring was supplying
fake medications across a large
part of the region including Iraq,
Turkey, Lebanon, Iran and Egypt.
After breaking the news, one
Syrian official said: “When we
started the investigation, we had
no idea of the scale of these
counterfeit networks.” It is
understood that in just one
seized shipment during the
operation one brand of a
leukemia drug with a street
value of more than $4 million
was uncovered.
Syria has approved new
measures to tackle the growing
problem of counterfeit medicines
on its shores. Health Minister
Reda Saed said the country’s
president had passed a law that
would carry heavy penalties. He
went on to say Chinese
counterfeiters were also involved
in the ring, although China
refused to comment.
research & develoPment
elderly miss out on
clinical trials
A European-based group of
professionals has called on the
pharmaceutical industry to start
using older patients in itsclinical
trials. The EU project, known as
PREDICT, warned that trial data
taken from a younger pool of
recipients cannot always easily
be extrapolated, and that older
people are being excluded from
trials despite the fact that they
take the most medication. “If
treatments are not evaluated for
elderly people it is difficult for
doctors to balance the risks and
benefits,” said Dr Gary Mills,
director of Medical Economics
and Research Centre, Sheffield,
one of the project co-ordinators.
The group reviewed literature
produced on treatments aimed
at the older population but
found they showed clear
evidence that the elderly were
underrepresented among the
pool of subjects in clinical trials.
As part of their research they
interviewed health professionals
in nine countries as well as more
than 50 focus groups with elderly
patients and their carers.
Dr Mills called on the industry
to take practical steps to
rebalance the clinical trials pool.
Other professionals called on
governments to regulate in an
effort to encourage the
pharmaceutical industry to open
up clinical trials to the elderly.
Stephen Jackson, Professor of
Clinical Gerontology at King’s
College, London, said the sector
saw it as “too much trouble” to
involve older people.
m&a
deal catches eye of
novartis
In a move seen by many as an
attempt to move away from
prescription drugs, Swiss giant
Novartis has agreed to take full
control of Alcon as part of a $40
billion deal. The company spent
more than $28 billion raising its
stake in the eyecare developer to
77%. It follows the purchase of
25% from Nestlé back in 2008.
The news has ended the
uncertainty over Novartis’ plans
for the company and will be
followed by a further acquisition
worth $11 billion in coming
months, securing outright
ownership. Daniel Vasella,
chairman and chief executive of
Novartis, said: “The addition of
Alcon will strategically
strengthen our healthcare
portfolio and our position
in eye care, a sector with
dynamic growth.”
It is hoped that the two
companies can merge their
research and development
operations, potentially saving
$200 million over three years.
research & develoPment
“milestone” reached in
tB vaccine search
A group of US-based scientists
are hopeful that they have
reached a “significant milestone”
in the search for a vaccine that
could help reduce the level of TB
infection among HIV sufferers in
Africa.
The group, working out of
Dartmouth Medical School,
conducted research over seven
years involving 2,000 patients in
Tanzania. They found the vaccine
could potentially cut the number
of cases of the disease – the
leading killer of HIV sufferers on
the continent – by almost two-
fifths (39%). It could herald a new,
cheaper way of protecting people
from the condition in countries
struggling to meet the cost of the
HIV epidemic.
Lead researcher, Professor
Ford von Reyn, said: “It is the
first time we are going to have a
vaccine that is influential in
preventing opportunistic
infections in HIV patients.”
The vaccine boosts the
immune response of patients that
have had the BCG vaccine. ■
Market intelligence > News
Alcon’s intraocular lens.

Vital statistics
Market intelligence > Vital statistics
WORLDPHARMACEUTICALFRONTIERS
|
www.worldpharmaceuticals.net 10
26
The number of new drugs
approved for use in the
US by the FDA in 2009.
This was just one
more than the
previous year.
R&D
30%
The amount
invested back into
R&D by the global
pharmaceutical
industry annually.
Source: ABPI
5,281
The number of drugs to treat cancers such as leukaemia,
colorectal cancer, small cell lung cancer and melanoma
currently under development or awaiting FDA approval
in the US.
Source: MedTRACK
£10m
The amount spent
each day in the UK
by pharmaceuticals
on R&D.
Source: ABPI
GENERICS
50%
The amount of pharmaceutical
products dispensed to EU
patients that are now generics.
Source: European Generic Medicines Assoc
The amount that can be saved
by individuals requiring drugs
daily if they switch to generics.
Source: The US FDA (FDA)
52%
Value of patent expiries 2001-2015 (constant US$ billion)
2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
Source: PricewaterhouseCoopers LLP
25-
20 -
15 -
10 -
5 -
0 -
Average
annual
loss US$
16.4bn
$157 billion sales exposed to generic competition by 2011
“Research on new therapies
is critical for scientific
advancement, but we
also need data that will
help doctors use existing
therapies appropriately.”
Dr Michael Hochman, of the Keck
School of Medicine at the University
of Southern California

Many more companies will
shift towards a greater
“externalisation” of their
drug portfolios, meaning
that the returns could be
three times as high from
investing in less-risky
drugs already brought to
mid-stage development by
biotech companies.
Source: Financial Times, London
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candida ad_repro_Layout 1 10/03/2010 13:59 Page 1
O
verall, across the global pharmaceutical industry, half (50%)
of respondents in the What The Global Pharmaceutical Industry
Is Planning in 2010-2011: Procurement, Investment & Industry
Trends Outlook survey said they were more optimistic about revenue
growth for their company in the coming 12 months, relative to the last
12. A further 31% were neutral about revenue growth, compared with
17% who were less optimistic. The expectations regarding revenue
growth over the next year are mixed.
Industry professionals believe the pharmaceutical industry has been
shielded somewhat against recessionary pressures, with many
believing the greatest threat to revenues is patent expiry of many
blockbuster drugs. The number of executives who were neutral about
revenues in Q2 2009 remains similar to today. In Q2 2009, it was 35%
compared with today where neutral responses stand at 31%.
The pharmaceutical sector portrayed positive signs of economic
growth as respondents are far more optimistic compared with Q2 2009
survey. The optimism of manufacturers grew by 10%, CRO and CMO
experienced a rise of 13% and industry suppliers saw a surge of 20%.
This illustrates that the industry is comparatively positive, no doubt
boosted by the fiscal stimuli by governments worldwide.
These findings reveal that the number of less-optimistic
respondents has declined relatively as they anticipate positive growth
in the global economy through increased industrial production, a
rebound in global equity market and augmentation in international
trade. When compared with buyers, suppliers seem to be more
optimistic about the global recovery. Overall in comparison to Q2 2009,
respondents are more optimistic about revenue growth.
Asia takes its place
Asia Pacific emerged as the market with the largest expectations for
growth. Emerging economies constitute about 80% of the world’s
population and more than 20% of the global economy. The trade
liberalisation and opening up of economies have played a greater role
in revenue growth and high level of optimism in the region. The
International Monetary Fund (IMF) projects that China’s GDP will
grow at 9% during 2010 and at 6.4% for India during the same period.
It also expects that economies will start recovering from 2010.
Most of the countries in the Asian region were hit by the financial
crisis. The IMF expects that exchange rate flexibility will continue to
be important in most countries to allow the region to regain
competitiveness and build confidence. Targeted government spending
The future’s bright
As the world emerges from one of the most difficult economic climates for a generation, pharmaceutical
executives tell ICD Research – as part of its research for its latest sector survey – of their hopes for
the short- to mid-term future of the sector, and share their company’s future prospects.
Market intelligence > Market research
WORLDPHARMACEUTICALFRONTIERS
|
www.worldpharmaceuticals.net 12
Key findings:
• Overall, pharmaceutical
industry respondents are
optimistic about the
company’s revenue growth
• Respondents from Asia
Pacific and the rest of the
world are relatively more
optimistic about their
companies’ revenue
growth in comparison
with respondents from
North America and
European regions due
to globalisation of
R&D operations and
M&A activity
• Asia is growing into a drug
manufacturing
powerhouse and has
emerged as a leading
source of drug discovery
and high-end innovation
over recent years
• Brazil, Russia, India
and China prominently
figure among the most
important business
development destinations
throughout the different
stakeholder segments
• Overall, executives from the
pharmaceutical industry
expect to see increased
levels of consolidation in
their industry due to
“attractive valuations and
opportunistic takeovers”,
“cost containment/
reduction on R&D” and
“thinning pipelines”.
Source: ICD Research Industry Survey 2010

Question: Are you more or less optimistic
about revenue growth for your company over
the next 12 months? (% respondents)
Colour guide
Neutral More optimistic Less optimistic Don’t know
-
2010.
-
2009.
-
50% 31% 17% 2%
37% 35% 27% 1%
15% -
10% -
5% -
0% -
-5% -
-10% -
-15% -
Next difference between 2009 and 2010
revenue expectations
Neutral More optimistic Less optimistic Don’t know
13%
-4%
-10%
1%
will help protect poor and vulnerable groups and continued efforts will
be needed to identify financial sector risks and ensure appropriate
banking supervision to reduce vulnerabilities.
Most companies are facing significant pressure to change, with
thinning pipelines, skyrocketing R&D costs, calls for lower prices and a
greater regulatory burden, these conditions, and the financial crisis,
have made the work of creating new drugs harder than ever. Big
pharmaceutical companies are being forced to globalise R&D,
especially to emerging markets. Merger and acquisition activities are
taking place, giving way to small biotech companies.
Asia is growing into a drug manufacturing powerhouse and is
emerging as a leading source of drug discovery and high-end
innovation. Big pharmaceutical companies now rank China as the best
location for R&D in Asia, followed by India, Korea and Taiwan.
The optimism level is very high in Asia Pacific and in the rest of the
world in comparison to the results showcased in Q2 2009. The IMF
believes that financial conditions returning to normal should support a
rebound of private investment, sustaining demand even as the fiscal
stimulus wanes. The result of the survey reveals that ongoing
economic growth in emerging markets will contribute more than half
of the global growth. European companies will earn benefits from the
recovery in the US as it is their most important export destination.
Developing countries are more optimistic about global economic
recovery as the effects of they were less affected by the financial crisis.
The economic crisis has affected every industry but the drug
manufacturing sector may continue to thrive through increasing
productivity and cost of goods reduction promoting efficiency.
More than half (52%) of respondents from the global pharmaceutical
industry with revenue turnover up to US$100 million and those with
runovers between US$100 million and US$500 million are more
optimistic about revenues this year. More executives from larger
pharmaceutical companies are considering where to make future
investments and are less optimistic about company revenue growth.
The net difference in optimism trends for the pharmaceutical industry
was mapped with the individual results of 19 other industries. The
pharmaceutical industry is a significant one with a relative optimism
trend of 33%. This indicates that the sector is well on the recovery path
along with other sectors that are driving the economy. ■
Market intelligence > Market research
WorldPharmaceuticalFrontiers
|
www.worldpharmaceuticals.net 13
Source: ICD Research Industry Survey 2010

Question: are you more or less optimistic
about revenue growth for your company over
the next 12 months? (% respondents by type)
colour guide
Neutral More optimistic Less optimistic Don’t know
----------
2010.
------
2009.
----------
47% 35% 18% 2%
37% 35% 27% 1%
P
h
a
r
m
a
c
e
u
t
i
c
a
l

m
a
n
u
f
a
c
t
u
r
e
r
----------
2010.
------
2009.
----------
55% 31% 10% 3%
42% 27% 29% 2%
C
o
n
t
r
a
c
t

r
e
s
e
a
r
c
h

o
r
g
a
n
i
s
a
t
i
o
n

(
C
R
O
)

/

C
o
n
t
r
a
c
t

m
a
n
u
f
a
c
t
u
r
i
n
g

o
r
g
a
n
i
s
a
t
i
o
n

(
C
M
O
)
----------
2010.
------
2009.
----------
56% 26% 17% 1%
38% 37% 27%
D
r
u
g

m
a
n
u
f
a
c
t
u
r
i
n
g

i
n
d
u
s
t
r
y

s
u
p
p
l
i
e
r
Source: ICD Research Industry Survey 2010

Question: are you more or less optimistic
about revenue growth for your company over
the next 12 months? (% respondents by region)
colour guide
Neutral More optimistic Less optimistic Don’t know
----------
2010.
------
2009.
----------
49% 30% 19% 2%
34% 36% 29% 1%
N
o
r
t
h

A
m
e
r
i
c
a
----------
2010.
------
2009.
----------
40% 36% 22% 2%
33% 35% 32% E
u
r
o
p
e
----------
2010.
------
2009.
----------
73% 23% 4%
40% 35% 23%
A
s
i
a

P
a
c
i
f
c
----------
2010.
------
2009.
----------
68% 20% 8% 4%
45% 31% 22%
R
e
s
t

o
f

t
h
e

w
o
r
l
d
1%
2%
the report is available for purchase
Please visit www.industryreview.com or email
icdreports@progressivedigitalmedia.com
Report Name: What The Global Pharmaceutical Industry Is
Planning in 2010-2011: Procurement, Investment & Industry
Trends Outlook
Report Reference Code: ICDR1049 Price: US$2,000

www.industryreview.com
WORLDPHARMACEUTICALFRONTIERS
|
www.worldpharmaceuticals.net 14
A
s the pharmaceuticals industry continues to explore
and innovate in order to maintain growth and
profitability, the use of new and innovative drug
delivery technologies is being explored for many disease areas.
The introduction of new technologies and new routes of delivery
combined with increasing research and development (R&D)
spending, an ever-expanding competitive landscape and a larger
marketplace, have resulted in the creation of new market
opportunities for drug-delivery devices.
Market to more than triple in size
The global drug delivery devices market, comprising infusion
systems, inhalation systems and needle-free injections
segments, was valued at $26 billion in 2009. The market is
expected to grow at an average annual rate of about 18% to
exceed $80 billion in 2016. Infusion systems and inhalation
systems remain the key segments, accounting for more than
96% of the overall drug delivery devices market in 2009.
However, with an expected average annual growth rate of
more than 65%, the needle-free injections market is forecast to
be the largest segment within the drug delivery devices market
by 2016.
The inhalation systems market, comprising of dry powder
inhalers (DPIs) and metered dose inhalers (MDIs), was valued at
Special delivery
The global drug delivery market is changing like never before. Driven by the introduction of new
and innovative technologies with improved product features, the drug delivery market is forecast
to attain significantly high growth in the future. GlobalData takes a close look at this market, asks
who the key players are, and provides the lowdown on market dynamics.
Market intelligence > Industry in figures
Jyoti Ranjan Padhi
Jyoti Ranjan Padhi is a senior analyst with
leading business information and analysis
company GlobalData. Jyoti has authored
several research reports on topics related to
medical equipment, pharmaceuticals and
biotechnology industries. He has also
led and managed many research
engagements on functional areas
such as market opportunity analysis
and competitive intelligence.
$21.8 billion in 2009, contributing 84% to the overall drug
delivery devices market value in 2009. The key factors driving
growth in the inhalation systems market are the increasing
incidence of pulmonary diseases and an increasing awareness of
the inherent benefits offered by the pulmonary route for
systemic drug delivery. This global inhalation systems market is
forecast to grow by an average annual growth rate of 7% during
2009-2016 to reach $35 billion in 2016. As the MDIs segment
attains a flat growth pattern, the DPIs segment is forecast to
grow by an average annual growth rate of about 11% during
2009-2016 to reach $22 billion in 2016. However, the MDIs
market segment will continue to be a value segment within the
overall inhalation systems market. MDIs remain the most widely
used inhalers, particularly for treating asthma and chronic
obstructive pulmonary disease (COPD). MDIs are small,
relatively inexpensive and user-friendly, and are suitable for a
variety of drugs. On the other hand, DPIs are relatively
expensive and rely on inhalation strength and duration for
efficient and effective drug delivery. However, the fact that DPIs
are well-suited for systemic drug delivery and are perceived as
more environmentally-friendly than MDIs are some of the factors
driving demand for these devices.
Overall, while the inhalation systems market will continue to
be a significant revenue contributor in spite of its moderate
growth expectations, the infusion systems market is expected to
grow faster to reach $7 billion in 2016. The global infusion
systems market, comprising of infusion pumps, syringe pumps
and infusion disposable sets, was valued at $3 billion in 2009.
While the market has suffered over the past two to three years
due to negative publicity following product recalls initiated
by the FDA and also by leading companies such as Baxter,
Cardinal Health and Hospira, the underlying demand drivers
seem to be in place.
Infusion systems can administer an amount as small as 0.1mL
per injection, every minute. Infusion systems deliver medication
and fluids into a patient’s circulatory system in way that, if
performed manually by a healthcare professional, would not only
be very expensive, but impractical and unpredictable in a good
number of cases. This makes a strong case for infusion systems
as one of the most ideal and cost-effective devices intended for
use in home healthcare settings. Most importantly, the speed
with which infusion systems have undergone technological
evolution is another factor driving demand. Infusion systems
have been continuously evolving from simple microprocessor
driven devices to software-controlled sophisticated drug
libraries. Improvements have also been made in standardising
concentrations and delivery limits. One of the most recent and
advanced features available with infusion systems is the
integration with hospital information systems. The end
result is improved efficiency and a reduction in medication
dosage errors, realised through the timely transmission of
patient information.
Needle-free injectors
The global needle-free injections market, valued at $1.2 billion
in 2009, is forecast to be worth $39 billion in 2016. Factors
such as precise dosing, reduced risks of cross-contamination,
and pain-free drug delivery have helped to propel market
growth. Valued at only $2.3 million in 2000, the market has
grown at an average annual rate of more than 99% in the past
nine years.
While the initial adoption of these systems was slow due to
the high start-up and maintenance costs, needle-free injections
are now being widely used for the intradermal administration of
drugs, vaccines, hormones and anaesthetics. They are also being
used in preparing hazardous injections such as cytotoxic
chemotherapy injections, thereby reducing the risks of
accidental operator injury and environmental hazards. ❯❯
Market intelligence > Industry in figures
WORLDPHARMACEUTICALFRONTIERS
|
www.worldpharmaceuticals.net 15

Figure 1: Global drug delivery devices market,
revenues ($bn), 2009 – 2016
2009 2010F 2011F 2012F 2013F 2014F 2015F 2016F
90 -
80 -
70 -
60 -
50 -
40 -
30 -
20 -
10 -
0 -
Source: GlobalData
R
e
v
e
n
u
e

(
$
b
n
)
26
29
33
39
47
57
67
81
Source: GlobalData

Figure 2: Global inhalation systems market,
revenues ($bn), 2009 – 2016
2009 2010F 2011F 2012F 2013F 2014F 2015F 2016F
40 -
35 -
30 -
25 -
20 -
15 -
10 -
5 -
0 -
R
e
v
e
n
u
e

(
$
b
n
)
28
30
33
35
22
23
25
26
Colour guide
Dry powder inhaler devices Metered dose inhaler devices
Valued at only $2.3 million in
2000, the global needle-free
injections market has grown at an
average annual rate of 99%.
Market intelligence > Industry in figures
WORLDPHARMACEUTICALFRONTIERS
|
www.worldpharmaceuticals.net 16
Another factor contributing to the acceptance and market
penetration of these products is the fact that needle-free
injections have been successful in addressing a range of
challenges posed by traditional devices. While these systems are
easy to use and eliminate the risk of infection, from a patient’s
standpoint these devices result in the painless delivery of drugs
and have been successful in overcoming patients’ aversion
towards needles. From a technology standpoint, new
formulations are being designed to gradually release the injected
drug, thereby reducing the frequency of injections.
More than anything else, the fact that the needle-free injection
technique is also being used for insulin delivery is motivating
the leading companies to continue to pump in funds for
advancing research and strategic collaboration efforts. It is
important to note that the insulin delivery devices market is one
of the highest growth areas within the medical devices industry.
The global insulin delivery devices market, valued at $4.1 billion
in 2009, is forecast to grow at an average annual growth rate of
about 8% to reach $7 billion in 2016.
Strong pipeline and emerging technologies
With about 235 products in different stages of development, the
global drug delivery devices market landscape could undergo
significant changes in the coming years. Transdermal Drug
Delivery is clearly emerging as the technology of the future.
Transdermal drug delivery systems can be based on both
passive and active transport mechanisms. Passive transdermal
patches are meant for delivery of drugs that are stable and
which have a small molecular weight. The drug is preloaded into
the adhesive on the patch and these systems do not require
customised delivery. The active transdermal patches, on the
other hand, are meant for the delivery of drugs with a large
molecular weight and require various modalities such as heat,
microporation and iontophoresis to deliver the drug. While being
a pain-free alternative to injections, transdermal drug delivery
systems are also convenient and have minimum systemic side
effects. Also, the fact that these devices have led to increased
patient compliance resulting in subsequent increase in demand
is one of the key driving factors behind the continued research
and innovation efforts in this area.
While a host of transdermal drug delivery systems are already
in the market, many are being developed that are not just
innovative but which are also expected to address previously
unmet need. More than 40 transdermal drug delivery systems
by both small and large companies were in different stages of
development in 2009.
GSK, for instance, is working on developing and
commercialising innovative needle-free patch-based vaccines,
in collaboration with the Austria-based Intercell AG. Early in
December, 2009, the companies announced an agreement to
form a strategic alliance to accelerate the development and
commercialisation of needle-free, patch-based vaccines. The
agreement includes Intercell’s candidate vaccine for travellers’
diarrhoea (TD) and an investigational single-application
pandemic influenza vaccine, as well as the use of the patch
technology for other vaccines in GSK’s portfolio.
Interestingly, Intercell is not the only company working on
needle-free patch-based vaccines. The Denmark-based Nordic
Vaccine A/S and the Australia-based Apollo Life Sciences are
also pursuing R&D efforts in this area. Once approved and
launched, the needle-free patch-based vaccine delivery
technology is expected to revolutionise the way vaccines are
delivered by offering benefits such as simplified administration,
faster delivery and increased compliance. This technology is also
expected to enhance the effect of injected vaccines and result in
the development of new vaccines, which require transcutaneous
administration in cases where the antigen can not be delivered
safely through other routes.
Increasing realisation of the market opportunity that the
transdermal drug-delivery technology can address has also
resulted in heightened deal activity in the recent past. The

Figure 3: Global infusion systems market,
revenues ($bn), 2009 – 2016
2009 2010F 2011F 2012F 2013F 2014F 2015F 2016F
8 -
7 -
6 -
5 -
4 -
3 -
2 -
1 -
0 -
R
e
v
e
n
u
e

(
$
b
n
)
4.8
5.4
6.1
6.8
3.0
3.4
3.8
4.3
Colour guide
Infusion pumps Infusion disposable sets Syringe pumps
Source: GlobalData

Figure 4: Global drug deliverydevices market,
revenues ($bn), 2009 – 2016
2009 2010F 2011F 2012F 2013F 2014F 2015F 2016F
45 -
40 -
35 -
30 -
25 -
20 -
15 -
10 -
5 -
0 -
Source: GlobalData
R
e
v
e
n
u
e

(
$
b
n
)
1 2
5
8
14
23
29
39
Needle-free injections have
been successful in addressing a
range of challenges posed by
traditional devices.
WORLDPHARMACEUTICALFRONTIERS
|
www.worldpharmaceuticals.net 17
Market intelligence > Industry in figures
US-based Altea Therapeutics Corporation (Altea) seems to
be at the forefront in making strategic partnership agreements.
In January 2010, the company announced that it had entered
into a partnership with KAI Pharmaceuticals, for the preclinical
and clinical development of some of the KAI proprietary
peptides, using Altea’s PassPort Transdermal Delivery System. In
April 2009, Altea announced an agreement with Eli Lilly and
Amylin Pharmaceuticals for the development and
commercialisation of a novel daily transdermal patch delivering
sustained levels of exenatide, also using Altea’s PassPort
Transdermal Delivery System. In July 2008, Altea announced a
partnership with Hospira, for the development and
commercialisation of an undisclosed product using the same
delivery system.
Apart from the acquisition of Iomai Corp by Intercell AG in
May 2008, the other notable deal announced in this area in the
past two years includes the licensing and development
agreement between Eli Lilly and TransPharma Medical. In June
2008, the two companies entered into a licensing and
development agreement related to TransPharma’s ViaDerm-
hPTH (1-34) product, which is administered transdermally using
TransPharma’s proprietary technology. The product is being
developed for the treatment of osteoporosis.
Fragmented competitive landscape
While market opportunities remain immense, the global drug
delivery devices competitive landscape continues to be
fragmented, with the top five players not even accounting for
one-third of the market. GlaxoSmithKline (GSK) was the global
leader in the market with a 13% market share, followed by
AstraZeneca with a little less than 9% in 2008. GSK and
AstraZeneca’s leadership position in this market is attributed to
their strong presence in the inhalation systems market.
Interestingly, the inhalation systems and infusion systems
segments remain the only ones with clear market leadership
visibility. On the other hand, the needle-free injections segment
remains the most fragmented, with many small and medium-
sized companies such as Glide Pharma, Bioject, Antares Pharma,
Zogenix, BioValve Technologies, Crossject Medical Technology
and PenJet Corporation.
Considering the fact that the needle-free injections segment is
projected to achieve significantly high growth in future, the
global drug delivery devices competitive landscape is heading
towards obvious dynamism in the market positions of the
leading manufacturers. ■
The inhalation systems and
infusion systems segments remain
the only ones with clear market
leadership visibility.
I
t could be argued that now is the time to sit back and take
stock after what has been a financially turbulent year. If you
were looking for the defining issue of the past 12 months you
would not fail to notice the return of the so-called “mega-merger”.
Pfizer’s $68 billion acquisition of Wyeth, the $47 billion merger
between Roche and Genetech, and Merck’s $41 billion deal with
Schering-Plough may have grabbed the headlines but other deals
went through too.
With all the change since our last Pharma 40, it was perhaps
inevitable that there would be some dramatic movements in the list.
But most notable is that of President Barack Obama down from the
top spot into 31st place. While it was recognised he has a key role to
play within the pharmaceutical sector and wider healthcare reform,
our panellists felt he still had more to do. “He needs to achieve much
more in order to move up the list,” commented one.
The fact that this year the top ten is dominated by scientists and
innovators tells the story of the industry at the moment. There is a
need for pharma to refocus on its R&D in the face of the demise of
patents and the challenge of the generics market. The product pipeline
is key to any future success and now that the worst of the financial
crisis is over it is time to get back to the real business.
This year we have highlighted four areas that our panellists feel will
be key over the coming year. Legislators and regulators feature heavily
this year – perhaps because of the Healthcare Reform Bill currently
going through Congress in the US. And charitable concerns also get
fair representation. Then there are the usual contenders from business
and science. Do you agree with our panel’s conclusions? What are
your thoughts on this year’s list? Email me at: andrewtunnicliffe@
progressivedigitalmedia.com and let me know.
World Pharmaceutical Frontiers presents
2010’s top 40 most influential people in the
industry, as judged by our panel of industry
experts. Editor Andrew Tunnicliffe takes
stock of the ups and downs in what has
been a turbulent year for everyone.
WORLDPHARMACEUTICALFRONTIERS
|
www.worldpharmaceuticals.net 18
1 N Ada Yonath, director
of the Helen and Milton
A Kimmelman Center for
Biomolecular Structure and
Assembly
2 N Sir Martin J Evans, Cardiff
University, UK
3 39 Jeffrey Kindler, CEO, Pfizer
4 6 Bill and Melinda Gates,
co-chairs of the Gates
Foundation
5 N Craig Venter, president of
the J Craig Venter Institute
6 23 James Alexander
Thomson, director of
regenerative biology,
Morgridge Institute
for Research
7 N Professor Rolf Krebs
chairman of the supervisory
board of Epigenomics AG
8 N Geoffrey Ginsburg,
founding director of the
Center for Genomic Medicine
in the Duke Institute for
Genome Sciences & Policy
9 N Gregory J Hannon PhD
The Hannon Laboratory, Cold
Spring Harbour
10 10 Professor Robert Langer,
Langer Labs
11 N Eric Green, MD, PhD,
director of the National
Human Genome Research
Institute
12 N Professor Shinya
Yamanaka Institute for
Frontier Medical Sciences,
Kyoto University
13 13 Dr Margaret Chan, World
Health Organization (WHO)
director general
14 35 Ronald D Luff director of
anatomic clinical trials, Quest
Diagnostics
15 27 President Bill Clinton,
founder of the William J
Clinton Foundation
16 N Professor Marvin
Caruthers University of
Colorado
17
4
Dr Janet Woodcock,
director of the Center for Drug
Evaluation and Research, FDA
18
10
Arthur Levinson, former
chairman and CEO, Genentech
19 N Dietmar Hopp, German
billionaire
20 N Margaret Hamburg,
commissioner of the US Food
& Drug Administration
21 26 Chris Viehbacher, CEO,
Sanofi Aventis
22
5
Shlomo Yanai, president and
CEO, Teva Pharmaceuticals
23 N Marijn Dekkers, CEO at
Thermo Fisher Scientific
24 N DW Laske and Ed Oldfield
National Institutes of Health
and University of Virginia
School of Medicine
25 N Lonnel Coats, COO of Eisai
Inc and head of Human
Health Care
26 25 James M Cornelius,
chairman and CEO, Bristol
Myers Squibb
27 N Haruo Naito, president
of IfPMA
28
2
Sir Michael Rawlins,
chairman of the National
Institute of Health & Clinical
Excellence (NICE)
29 31 Frances M Visco, president
of the National Breast Cancer
Coalition
30 N Michael J Fox, founder of
Michael J Fox Foundation
31
1
President Barack Obama,
President of the United States
32
9
Daniel Vasella, chairman
and CEO, Novartis
33 N Dr Thomas Tuschl, group
leader at Tuschl Lab
34
8
Dr Surinder Singh, Drugs
Controller General of India
35 N Dr John Sampalis, founder
and president of JSS Medical
Research
36 N Katherine Sebelius, US
secretary of health and
human services
37 N Ranjit Shahani, president,
of the OPPI (Organisation of
Pharmaceutical Producers
of India)
38
29
Billy Tauzin, PhRMA
president and CEO
39
14
Sir Mark Walport, director
of the Wellcome Trust
40 N Bono, spearheaded
The Red Campaign
The final list
Position in 2009 New entrant
KEY
N
Science & Innovation Business
Philanthropists & Legislation &
Charitable causes regulation
39
Special report > Pharma 40
WORLDPHARMACEUTICALFRONTIERS
|
www.worldpharmaceuticals.net
19
SCIENCE & INNOVATION
Innovation in this field is the bedrock of the sector. That is perhaps
why this year’s list can boast so many renowned individuals; the likes
of Ada Yonath, Craig Venter and Dr Thomas Tuschl. In the 2009 list
there was not a single scientist within the top 10. Then, it was
business leaders that were seen to be the people influencing the sector
whereas now it seems normal service has resumed. Our panellists
celebrated our winner, Ada Yoneth, on her “enduring leadership and
mentoring in research” as well as for being one of very few women to
win the Nobel Prize for Science.
Big pharma need to innovate to stay
ahead of their competition. Apart
from the usual commercial rivals,
there is a growing threat from
generics further squeezing
competition. Add to that the
ongoing advances in
technology that mean even
the unimaginable just a few
years ago is now a distinct
possibility. The next 12
months could be big for
science and innovation.
Top 5
1 Ada Yonath
2 Sir Martin J Evans
3 Craig Venter
4 James Alexander Thomson
5 Professor Rolf Krebs
BUSINESS
Although the pharmaceutical sector fared better than many others,
it has seen its share of difficulties. While innovation will continue to
be key, the work of C-level executives to steady their ships has been
obvious. However, this year they have slipped down the list. In 2009
there were six C-level executives in the top 20 whereas this year
there are just two, including Arthur Levinson, former chairman and
CEO of Genentech. Perhaps the reason for this is the improving
economic climate, which has thrown the focus back on science.
Of Jeffrey Kindler our panel had mixed views. Agreeing he is a
“big player” and that despite its difficulties
Pfizer “continues to move forward and
innovate under his leadership”, one
panellist wanted to see more from him.
One of the biggest surprises is the
omission of Andrew Witty, CEO at GSK and
president of the European Federation of
Pharmaceutical Industries and Associations
(EFPIA). Despite not making it
beyond the shortlist, the panel
branded him “forward thinking”
in his efforts to raise the issue of
access to healthcare.
PHILANTHROPISTS &
CHARITABLE CAUSES
Many would see the donation of money as he main gift of a
philanthropist but it could also be said that the personality of the
donor can offer something more: a high profile and access to the
decision-makers that otherwise might not have been available.
President Bill Clinton, is one of those personalities. He was in
particular applauded by our panel for his work on trying to bring
HIV/AIDS treatments to the world’s most impoverished nations.
One panellist remarked that he was “getting the job done” and
said it was an “impressive second act”.
Proof of the importance of charitable work is that Bill and
Melinda Gates are still in the
top 10. “The foundation is
respected around the world
for its work in a number of
fields. They continue to set
an example in ‘charitable’
work through
innovation,”
said our
judges.
Top 5
1 Jeffrey Kindler
2 Arthur Levinson
3 Chris Viehbacher
4 Shlomo Yanai
5 Marijn Dekkers
Top 5
1 Bill and Melinda Gates
2 President Bill Clinton
3 Dietmar Hopp
4 Frances M Visco
5 Michael J Fox
LEGISLATION &
REGULATION
2010 is a big year for regulators, particularly in the US. With President
Obama’s Healthcare Reform Bill still going through, US lawmakers
will play a pivotal role in shaping the industry.
The major story of this year’s top 40 is that President Obama, last
year’s winner, finds himself in 31st place. There has been criticism of
his tactics in trying to get the Reform Bill passed. Our judges felt the
President needed to achieve more but one felt he would
succeed in his effort while another said he
was a “future prospect”.
India has also slipped down the list
with Dr Surinder Singh, drugs controller
general of India, at 34th place. New
to the list in 2009 Singh, then in eighth
place, was only just beaten by his Chinese
counterpart Shao Mingli. But perhaps
even more telling is the failure of
Mingli to make it onto the list at
all this year. Our panel felt he
had not risen to the
challenges the Chinese
industry is facing.
Top 5
1 Dr Margaret Chan
2 Dr Janet Woodcock
3 Margaret Hamburg
4 Haruo Naito
5 Sir Michael Rawlins
Dr Margaret Chan. Bill and Melinda Gates.
Jeffrey Kindler. Ada Yonath.
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2. sir martin J. evans
One of the 2007 winners of the
Nobel Prize for Medicine, Sir
Evans continues to conduct
research and gain the respect
of his peers. He was awarded
the Gold Medal from the Royal
Society for Medicine, the Copley
Medal from the Royal Society, and
appointed to the Advisory Board
of the Faraday Institute in 2009.
A Cambridge University graduate,
Evans continued to research
genetics including his work on the
“knockout mouse” throughout his
career. He went on to prove new
genes could be introduced into
cultured embryonic stem cells and
used to produce chimeric embryos.
3. Jeffrey Kindler
Appointed CEO of one of the
biggest pharma companies in
the world back in 2006, Kindler
has presided over the company
during a year when it was fined
$1.8 billion by the US government
for “misleading” sales advice, and
swallowed up one of its rivals,
Wyeth, in a $68 billion deal. In
recent months Kindler has become
more vocal on a number of issues
including stepping up support
for US healthcare reform, which
he hopes will help address the
inequalities in the US healthcare
system, and bringing in new laws
that will help regulate generics
whilst fostering a culture
of innovation.
4. Bill and melinda Gates
While their Foundation continues
to support work in public health
both inside the US and around
the world there has been a little
more emphasis put on other social
projects in teaching, housing,
technology and an array of other
areas. The foundation recently
committed itself to working with
the Obama Administration on its
six-year, $63 billion Global Health
Initiative which, among other
things, aims to combat AIDS, TB
and malaria, as well as increasing
access to care for women and
children. In one of its latest
commitments, Bill and Melinda told
the Davos summit the foundation
was pledging $10 billion over the
coming decade to help fund R&D
into vaccines.
5. craig Venter
Founder of the J Craig Venter
Institute, Venter continues to make
a substantial contribution to the
genetics arena. In 2009 he was
awarded the National Medal of
Science by President Obama. “Dr
Venter is being recognised for his
dedication to the advancement
of the science of genomics, his
contributions to the understanding
of its implications for society,
and his commitment to the clear
communication of information
to the scientific community, the
public, and policymakers,” stated
the notice of the award.
6. James alexander thomson
Renowned for his pioneering
work in the isolation and culture
of non-human primate and
human embryonic stem cells and
named as one of the 100 most
influential people in the world
Thomson continues to work in this
increasingly important field. He
currently holds the post of director
of regenerative biology at the
Morgridge Institute for Research
and professor in the Molecular,
Cellular, and Developmental Biology
at the University of California.
7. Professor rolf Krebs
In a career spanning more
than 35 years, Krebs has been
responsible for the development of
a large number of pharmaceutical
products, served on many advisory
boards and committees, and
contributed to more than 30
books. He has held a number of
distinguished positions culminating
in his role as chairman of the
supervisory board of Epigenomics
AG. Stating that he has had an
incredible career our judges
said he has made an “important
contribution to research and the
wider pharmaceutical community”.
8. Geoffrey Ginsburg
Having won a number of awards
for his research accomplishments
including the Innovator in Medicine
Award from Millennium in 2004 and
the Basic Research Achievement
Award in Cardiovascular Medicine
from Duke in 2005, Ginsburg was
recently appointed to the FDA’s
Clinical Pharmacology Advisory
Council. Our panel applauded his
achievements this year. What will
the next herald?
9. Gregory J hannon, Ph.d
Hannon was singled out for his
work in an important new area of
cancer. His ongoing research into
molecular imaging and exploring
the mechanisms and regulation
of RNA interference, as well as its
applications to cancer research
stands out and has won him
numerous awards. A key figure in
cancer research and treatments, he
hopes to apply the RNAi pathway
as a tool to unravel oncogene and
tumour suppressor pathways and
to identify new anticancer targets.
Research into this field is at an
exciting stage – will the next 12
months provide the breakthrough
we have been waiting for?
10. Professor robert langer
Robert Langer has spent much
of his life working in medicine,
holding esteemed positions such as
chairman of the United States Food
and Drug Administration’s Science
Board. One of his latest projects
could, one day, provide an effective
treatment for diseased arteries.
11. eric Green, md, Phd
Green’s research looks at the
application of large-scale DNA
sequencing and problems in
human genomics, genetics and
biology. Human genomics will
be a big part of the future of
pharmaceuticals as research
continues with the possibility of
medication being targeted for
individuals with specific genetic
make-ups. Our panel said they had
big hopes for things to come.
12. Professor shinya
Yamanaka
Known for his work on induced
pluripotent stem cells, and
having received the Robert Koch
Prize and Shaw Prize, Professor
Yamanka is a leading figure in the
pharmaceutical world.
13. dr margaret chan
Chan was appointed to her position
in 2006 and since then has faced
a number of issues. None have
been as big as this past year; the
first pandemic of the 21st century.
The WHO coordinated the global
response, collated statistics and
managed the public, commercial
and NGO response.
14. ronald d luff
Luff found himself in the top 40
because of his contributions in
cytology and cytopathology,
most notably for his work as
the former Chairman of the
Editorial Committee for The
Bethesda System.
15. President Bill clinton
Said to be “impressive” by
our judging panel, the Clinton
Foundation continues to support
01
ada Yonath
Yonath’s most notable success came in 2009 when
she was awarded the Nobel Prize in Chemistry
along with Venkatraman Ramakrishnan and Thomas
A. Steitz for discovering the structure of ribosomes, a potential target
for drug discovery and metabolism. The Israeli-born crystallographer
became the first woman in 45 years to win the prize for sciences and
the first-ever female Israeli to be awarded a Nobel Prize.
Having endured a difficult childhood and the untimely loss of her father,
Yonath returned to Jerusalem, where she was born, to study, achieving a
bachelor’s degree in chemistry in 1962. She received a master’s degree in
biochemistry n in 1964 and PhD in x-ray crystallography in 1968.
Her professional career includes a number of distinguished positions
and remarkable achievements including setting up the very first protein
crystallography lab in Israel in 1970. She went on to work in Europe
and the US but remains at the Weizmann Institute where she leads the
Helen and Milton A Kimmelman Center for Biomolecular Structure and
Assembly. Her pioneering research into ribosomal crystallography – the
study of the mechanisms underlying protein biosynthesis – will, it is
hoped, lead to the discovery of new medicines such as antibiotics.
Announcing her award, the Nobel Committee said: “These models are
now used by scientists in order to develop new antibiotics, directly
assisting the saving of lives and decreasing humanity’s suffering.”
Special report > Pharma 40
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JUDGING
PANEL
We would like to thank
the panel, without whom
we would not be able
to bring you what is the
definitive list of the 40
most influential people in
the pharmaceutical sector.
ANDREW JACK is
the pharmaceutical
correspondent with the
Financial Times in London.
Andrew is a distinguished
writer with a wealth of
industry knowledge.
AGNES S KLEIN
MD, DPH is
director of the
Centre for the
Evaluation of
Radiopharmaceuticals and
Biotherapeutic Products in
the Biologics and Genetic
Therapies Directorate.
JOHN RHODES
is global
managing
partner in life
sciences industry
practice at Deloitte. He is
also the Founder & Chair of
the Annual Pharmaceutical
Accounting & Reporting
Congress.
MICHAEL SANTORO
serves as an Associate
Professor with tenure at
Rutgers Business School
in New Jersey.He is a
world renowned expert on
intellectual property, ethics,
human rights, and trade.
ED SILVERMAN
is a prize-
winning
journalist who
has covered the
pharmaceutical industry for
well over a decade.
ANDREW
TUNNICLIFFE
is editor of World
Pharmaceutical
Frontiers.
work being undertaken to
promote healthier lifestyles in the
US and around the world.
16. Professor Marvin
Caruthers
Scoring highly with our judges,
Caruthers was singled out
for his work, which led to the
automation of DNA synthesis.
17. Dr Janet Woodcock
With a long and distinguished
background in pharmaceuticals
and regulation, Dr Woodcock
has been involved with the FDA
for the past 24 years. Her most-
recent initiatives have included
the “Safety First” and “Safe Use”
programmes designed to improve
drug safety management within
and outside FDA, respectively.
18. Arthur Levinson
Having worked in the industry
for many years, Levinson’s
experience is undeniable. He
oversaw the merger with Swiss
rivals Roche in 2009 and remains
an influential player within the
company. He is also expected to
be nominated to the Roche board
at their 2010 general meeting.
19. Dietmar Hopp
As a major shareholder in an
array of biotech companies –
having invested hundreds of
millions – Hopp has gone rather
quiet over recent months. But as
he has proved before, acquisitions
are second nature to him and can
sometimes come out of the blue.
20. Margaret Hamburg, MD
Dr Hamburg follows von
Eschenbach as the 21st
Commissioner of the US FDA.
Having been appointed by a
unanimous Senate vote in May
2009, she became the second
woman to take the role. The
judges praised her “new and
innovative” leadership.
21. Chris Viehbacher
Boasting a 20-year career in the
industry, Viehbacher has been at
the top of the French drug maker
for more than a year. He believes
in the model of big pharma and
says there will be far more of an
academic focus in coming years.
22. Shlomo Yanai
As CEO of one of the largest
generics company, this could be
the year this individual makes
waves. The judges felt Teva was
developing into a strong player.
23. Marijn Dekkers
Dekkers will replace current
CEO of Bayer Healthcare, Arthur
Higgins, when he steps down
from the role later in 2010. He
joins at a time of change as a
number of senior level executives
are moving on to pastures
new. How will he steer the
ship through what will surely
be a complex and potentially
destabilising transition?
24. DW Laske and Ed
Oldfield
As inventors of convection-
enhanced drug delivery these
two will always be in the back of
the mind of the pharmaceutical
industry watchers. They are both
continuing what the judges called
their “innovative” research, and
could well present another huge
breakthrough at any time.
25. Lonnel Coats
Human Health Care has, in the
past, said: “Human Health Care
is giving first thoughts to the
patients and their families and
contributes to increasing their
benefits.” Thanks to Coats’s
consistent lead on that mission,
the company tends to pass on
very profitable projects if they are
not benefiting patients.
26. James M Cornelius
Lauded for his drive to promote
ethical behaviour within the
industry, Cornelius remained
in his post during a year that
saw the company ride out the
financial crisis.
27. Haruo Naito
It may be somewhat tough
to have a major impact as his
position as president of IfPMA
only lasts until November 2010.
28. Sir Michael Rawlins
Now in his 11th year in the post,
Sir Michael is on the list again for
the continued role of excellence
and example set by NICE.
29. Frances M Visco
Remaining at the top of one of
America’s most powerful pressure
groups, the National Breast
Cancer Coalition, she has
used her influence to push the
issue of breast cancer up the
political agenda.
30. Michael J Fox
Fox found himself on the list
for his continuing efforts to
raise awareness and millions
of dollars for research into
Parkinson’s disease.
31. President Barack Obama
In his first year, President
Obama has taken great steps
to reforming the US healthcare
system, although there is work
still to be done.
32. Daniel Vasella
Having been chairman and CEO
of Novartis since1996, Vasella has
a wealth of experience.
33. Dr Thomas Tuschl
He is continuing his research
into regulatory mechanisms of
RNA interference, RNA-mediated
translational control, and nuclear
pre-mRNA splicing.
34. Dr Surinder Singh
As Drugs Controller General of
India, our panel felt he was doing
a good job in a difficult setting.
35. Dr John Sampalis
Remaining one of Canada’s
leading epidemiologists;
involved in academic and
pharmaceutical research.
36. Katherine Sebelius
If and when the US Healthcare
Reform Bill passes into
law this leading politician
will be responsible for its
implementation,
37. Ranjit Shahani
India is on the threshold of
becoming a major player in
pharmaceuticals but as director of
the OPPI, Shahini still faces some
big challenges.
38. Billy Tauzin
In his time as PhRMA president
and CEO, Tauzin has been
renowned for his efforts to drive
down the cost of healthcare.
39. Sir Mark Walport
Responsible for the day-to-
day running and strategic
management of the Wellcome
Trust, he received solid and
consistent marks from our judges.
40. Bono
The Red Campaign aims to help
fight HIV/AIDS in Africa. Under
Bono’s leadership it has raised as
much as $140 million. ■
M
ost life sciences (LS) research & development (R&D)
functions are under increasing pressure to improve
innovation, reduce development inefficiencies and
improve product safety. Patient-level data, collected through
electronic health record (EHR) systems, offers one promising
avenue for redefining R&D and revolutionising the LS value chain.
Globally–aggregated, patient-level data could support
identification of disease mechanisms and new discovery areas,
quick termination of unsuccessful compounds, rapid recruitment of
patients for trials, and continuous drug safety surveillance.
Although it has potential for the entire enterprise, this article
focuses specifically on how EHR data can improve research,
development and post-marketing surveillance.
R&D costs have increased sevenfold in the past 25 years without a
corresponding increase in new chemical entities (NCEs). A widely
accepted estimate for R&D cost per new compound was $802 million,
however this estimate has been re-assessed at $1.7 billion with the
expectation that it will only continue to increase in the future. As they
seek to lower costs, industry leaders must find ways to support
innovation and collaborate more effectively as the industry moves
toward personalised medicine. At the same time, regulators and payors
are demanding better safety and surveillance mechanisms.
Lengthy trials and delays raise costs
Skyrocketing development costs are partly attributable to the slow
pace of discovery and validation. Efforts to find better biomarkers
and terminate ineffective compounds more quickly are hampered by
the complex analysis required. Most LS researchers do not have
access to the large, comprehensive patient data sets necessary to
readily compare disease behaviour to associated genetic alterations.
The increasing rigour of clinical trials also drives up R&D costs:
average durations of the clinical phase have increased from 3.1 years
in the 1960s to 8.6 years in the 2000s.
Inefficient patient recruitment and subsequent delays are another
source of R&D cost increases. In 1998 only 40,000 of the 778,000
physicians in the US participated in clinical trials. Trials miss patient
enrolment deadlines almost 80% of the time because of the large
number of participants required and the inability to track patients
that meet prescreening criteria. The average delay from missing
enrolment deadlines is about 90 days; each day of delay costs an
estimated $1.3 million in lost sales.
Current methods don’t support the demand for safety
and surveillance
Increased media attention has piqued public concern over drug
safety at the same time as federal regulations have become more
stringent, mandating risk mitigation plans and improved visibility
into clinical trials. Since 1998, more than 70% of New Molecular
Entities (NMEs) were approved with post-marketing commitments.
Despite the increased focus on safety, most LS companies
currently measure safety and efficacy through the limited
information reported by physicians. Not only is this reactive
surveillance unsatisfactory for improving safety, it provides limited
insight into a drug’s overall risk/benefit profile.
To compound the problem, payors increasingly want “medical
evidence” on the safety and effectiveness of a drug as a
prerequisite for reimbursement decisions and are challenging the
cost of drugs that lack this evidence.
The EHR effect
Access to secondary EHR data could provide scientists with a large
database of patient information for quantitative polymerase chain
reaction (PCR) results in relation to a variety of treatments. Instead of
performing lengthy and expensive pre-clinical experiments to
uncover toxic compounds, within minutes they would be able to
draw correlations between gene expression, disease progression, and
treatment efficacy for similar classes of drugs.
Also, access to any disease demographic, locating the largest
target patient populations, and recruiting those patients during
routine clinic visits will cut not only reliance on investigators to
recruit patients but will also dramatically reduce the cycletime
for clinical trials.
Automated adverse event reporting through the EHR system
would also allow tracking of the safety and efficacy of a treatment
and could stop a potentially damaging treatment or trial before
exposing any more patients.
A long-term enabler for LS companies
EHR-derived data has the potential to transform the industry’s
approach to research, development, and post-market surveillance
(Figure 1). Some of the capabilities are already within reach while
others require further development. Early adopters can improve
efficiency, reduce costs and gain a competitive advantage in post-
marketing surveillance and clinical trial cycle time.
Research: As EHR integration becomes more sophisticated,
companies will be able to use patient-level data within the
discovery process. This data should facilitate biomarker discovery
and validation, earlier termination of unsuccessful or toxic
compounds, and advances toward personalised medicine.
A spoonful of sugar
R&D costs for life sciences have been on the increase for many years, but at last the pill may
be sweetened by EHR data, which can cut the time and cost of clinical trials and pretrials, as
Deloitte Life Sciences Division’s Terri Cooper and Glenn Carroll explain.
Market intelligence > Business overview
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Development: Access to longitudinal patient records should help
reduce clinical trial cycle times by enabling search capabilities that
track specific disease demographics, and by identifying investigators
and trial-ready sites. By using EHR data, patient populations that
meet the inclusion/exclusion criteria can be quickly identified, which
could help reduce patient recruitment times. Going one step further,
slightly altering the inclusion/exclusion criteria could dramatically
increase the patient population and in turn help further reduce
recruitment cycle times. In addition, prior clinical and diagnostic
data could help improve clinical trial design as a result of better
understanding disease progression and care pathways.

Post-marketing surveillance: There is an immediate opportunity to
use EHR data within post-marketing surveillance to measure drug
safety. In the near future, large, anonymised longitudinal patient data
sets will be available to help identify emerging health problems and
populations at high-risk for disease, support outcome studies on the
effectiveness of treatment(s) and evaluate the usefulness of diagnostic
tests. As EHR data becomes more widely available and accessible,
pharmaceutical companies are at risk from other healthcare
organisations who will compete to master EHR information to
measure drug effectiveness and outcome statistics. It is imperative
that LS companies adopt an EHR strategy early to overcome the
growing pains of leveraging a new technology and develop a means to
elucidate sophisticated, comprehensive data sets from EHR systems.
The limitations of a nascent field
Although there are many benefits from an EHR strategy, LS
organisations will face several challenges. Conceptually, using this
data effectively depends upon integrating multiple EHR systems in a
way that maximises query and search capabilities. The lack of a
common language for patient information may prevent effective
interoperability between EHRs and the IT systems used by LS
companies. Other hurdles include confidentiality issues, intellectual
property concerns, ownership/governance regarding EHR data, and
other legal and ethical considerations related to using patient data.
These issues will require the collaboration of relevant stakeholders to
establish standards and develop innovative solutions.
An EHR strategy requires proactive communication
and relationship building
In an environment focused on short-term success,
communicating the value of a long-term EHR strategy may be
difficult. Executives must first create believers and enable the
industry collaborations that will demystify the value of applying
EHR data. They’ll need to:
gain internal buy-in: ■ resolve varied and conflicting
perspectives on the relevance of patient-level data and
alleviate skepticism regarding how use of that data will
impact research innovation and decision-making
establish cross-functional lLinkages ■ : Promote
effective internal and external collaboration; because
EHR data resides in hospitals and health systems,
gaining access to patient-level information hinges on
the LS company’s ability to develop relationships with
provider institutions.
Building a foundation for long-term EHR success
Early adopters of an EHR strategy will focus on developing
the processes that will be positioned to accelerate their
ability to use patient-level data to drive cost reduction and
operational efficiencies. The first step is to develop a
comprehensive approach that is aligned with Corporate Strategy
and drives measurable business value.
Industry leaders are paving the way to an EHR strategy
Companies such as Pfizer have already recognised the
significant potential for integrating patient-level data across
multiple areas of drug discovery, development and
commercialisation. Life Sciences companies have dedicated
resources to health informatics and is in the process of
evaluating applications for EHR data use.
A variety of other healthcare companies are currently
assessing opportunities to apply external EHR data using
methodologies and governance models for future-state, EHR-
based operations. ■
Market intelligence > Business overview
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Figure 1: Potential benefts of integrating EHR data within drug development.
Trial design
(refning inclusion/exclusion criteria)
Patient and investigator recruitment
(patient recruitment)
Execution and analysis
(patient compliance tracking)
• EHR alerts increased enrolment rates from 2.4%
to 22% of recruited patients (prior knowledge of
health status could drive further improvement)
• Total cost savings for screening 40,000
patients with a 5% hit rate is approximately
$3.2 million
Studies show EHF data can drive:
• a 28% increase in eligible patient identifcation
• a doubling of monthly patient enrollment rate
• a near ten-fold increase in the enrolled to
referred ratio.
• Journaling compliance increased from 11% with
paper-based methods to 94% electronically
• EHR-based monitoring enables intervention
before patient must be excluded from dataset
• Use of EHR data and patient alerts reduces
attrition rate by 50%, reducing overall trial size
Savings: $3.2 million Additional revenue: $125 million Savings: $1.8 million
Assumption for calculating
savings and additional revenue
• Phase III clinical trial
• 40,000 patients screened givent 5% “hit” rate
• 2,000 patients enrolled in anticipation of 25%
attrition rate
• Recruitment expected to last 250 days
• Per patient screening cost: $100
• Cost per enrolled patient: $6,000
• Anticipated product revenue: $1m/day
Source: Deloitte
T
he pharmaceutical industry inevitably relies on
scientific and technological advances and
breakthroughs to maintain its dynamism, relevance and
– let’s not be shy about it – its profitability. But technological
change and advances can, in turn, create new challenges and
headaches. So it is with the rise of continuous manufacturing
and the industry’s gradual move away from batch
manufacturing, which in turn poses challenges to national
regulators and the industry alike when it comes to the
regulation and validation of pharmaceutical product.
Continuous manufacturing or processing allows a
pharmaceutical manufacturer to run, as its name suggests, a
continuous end-to-end manufacturing process. Although
relatively common in process manufacturing industries such as
food or chemicals, it is something still very much in its infancy
in the pharmaceutical world. Up to now, batch manufacturing –
where there might be a constant flow of product in and out (as
with continuous manufacturing) but where production is run for
a limited or defined period of time or for a fixed amount or batch
of product – has very much been the prevailing mode of
production. Other manufacturing operations, such as blending,
drying and tablet coating have also traditionally been operated
in batch mode.
While the intricacies of pharmaceutical regulation are
notoriously complex, in the US, the Food & Drug Administration
has relied on a ‘three-batch’ quality validation process. Quality
Non-stop
action
Continuous manufacturing is the future for the pharmaceutical industry, but it brings with it its own
series of challenges, as Novartis-MIT Center’s Professor Bernhardt Trout explains to Nic Paton.
Insight > Regulatory issues
WORLDPHARMACEUTICALFRONTIERS
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is assured by each batch within each unit of operation being
tested in quality control laboratories, with the processing cycle
being stopped until product quality is assured and pre-set
quality parameters are met. If, of course, the standards are not
met, the entire batch is rejected or sent back to be reprocessed.
But as Professor Bernhardt Trout, director of the Novartis-MIT
Center for Continuous Manufacturing, points out, continuous
manufacturing has the potential to change this approach
forever. The centre is a ten-year research collaboration aimed at
developing new technologies to replace the batch-based system
with a continuous manufacturing process, with Novartis
investing $65 million to get the centre up and running.
“The biggest leap in manufacturing terms when it comes to
regulation is the move to continuous manufacturing. So rather
than stop-and-start manufacturing, where you have a number of
batches, you have a continuous flow. This in turn creates
challenges for the traditional three-batch validation approach
because, of course, you do not have batches, so how do you do
validation?” asks Trout.
Of course, not every pharmaceutical manufacturing process
can, or even should, run continuously: mixing and crystallisation
are key areas where progress is only just starting to be made.
But the other side of the coin is that, with batch manufacturing,
manufacturers will often experience higher labour costs and
greater inventory costs. A drug’s active ingredients, for example,
have to be synthesised in a chemical manufacturing plant and
then shipped to a separate facility, where they are converted
into large batches of pills, liquids, or creams. With multiple
interruptions, including transport to separate locations, this can
mean the production of just one batch of drugs can take weeks.
What’s more, the manufacturing design and scale-up required to
produce a new drug can be financially unsustainable and
exceedingly time-consuming, argues Trout.
Continuous manufacturing, conversely, can be more efficient,
producing less waste and higher quality, as well as offering
better control and flexibility over the process. While there
is clearly a challenge around validation and regulation,
once you have it right and can show you are adhering
consistently to tight specifications built into the process,
you should not have to throw out any batches, thus reducing
costs significantly.
What also has to be stressed is that the FDA has made it very
clear that continuous manufacturing will not necessarily have to
mean a complete overhaul of its regulatory frameworks. In 2004,
for example, it issued Process Analytical Technology (PAT)
guidance around innovative pharmaceutical development,
manufacturing and quality assurance – www.fda.gov/
downloads/Drugs/GuidanceComplianceRegulatoryInformation/
Guidances/UCM070305.pdf.
This argued that flexibility, coordination, and communication
with manufacturers were going to be critical going forward.
“Manufacturers are encouraged to use the PAT framework to
develop and discuss approaches for establishing mechanistic-
based regulatory specifications for their products,” the
FDA recommended.
What this all means for pharmaceutical manufacturers is that
validation will need to be embedded within the continuous
manufacturing process rather than being something laid on top
of that process, suggests Trout. “The FDA has consistently
stated that certain regulatory frameworks are suitable for
continuous manufacturing, so the framework may not itself need
to change very much, but some of the processes will probably
have to evolve,” he explains.
“It will probably be more a case of tweaking or creating new
procedures within the existing framework rather than having to
create a whole new framework,” he adds.
What also needs to be recognised is that current regulations
do not distinguish between batch and continuous
Continuous manufacturing can be more efficient, producing less waste and
higher quality, as well as offering better control and flexibility.

Insight > Regulatory issues
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Benefits of continuous manufacturing
Continuous manufacturing can benefit patients,
healthcare providers, and the pharmaceutical industry, by:
• accelerating the introduction of new drugs through
efficient production processes
• allowing the use of smaller production facilities with
lower building and capital costs
• minimising waste, energy consumption, and raw
material use
• monitoring drug quality on a continuous basis rather
than through post-production, batch-based testing
• enhancing process reliability and flexibility to respond
to market needs.
Source: Novartis-MIT Center for Continuous Manufacturing
Professor Bernhardt Trout,
Novartis-MIT Center
Professor Bernhardt Trout is director of the
Novartis-MIT Center for Continuous
Manufacturing and co-chair of the Singapore-
MIT Alliance Program on Chemical and
Pharmaceutical Engineering. He received his SB
and SM degrees from MIT and his PhD from the
University of California at Berkeley. In
addition, he performed postdoctoral
research at the Max Planck
Institute. He has published
more than 80 papers and
currently has four patent
applications submitted.
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manufacturing, so in this context the definition of ‘batch’ means
the quantity of pharmaceutical product, rather than the mode
of manufacture.
“The validation has to be done in time rather than in batches.
So, for example, if you previously had a certain amount of
pharmaceutical product, now you have to look at it in terms of
its uniformity over a certain amount of time,” explains Trout.
The other big challenge when it comes to regulation for the
industry is globalisation, with pharmaceutical companies
working on an ever-more global basis and with ever-greater
standardisation, with continuous manufacturing a key element
within this shift. Yet the regulatory environment, even if it is
predominantly led by the FDA, is still very much structured at
regional or national level.
For pharmaceutical firms, this means that as the industry
gradually shifts more and more to continuous manufacturing,
there will need to be a lot of communication, cooperation and
coordination to ensure the regulatory and validation landscape
keeps pace, something that is clearly as much in the interest of
pharmaceutical companies as it is consumers, clinicians and
patients. Ultimately, continuous manufacturing is changing, and
will continue to dramatically change how the pharmaceutical
operates and is regulated.
“Every country or bloc will want to control its own regulatory
approach, so there is going to need to be a lot of communication
and harmonisation,” argues Trout.
“The whole landscape is very much being worked out now.
There are some partial continuous processes that are being
approved already, and there is work going on to look at full,
end-to-end continuous processes. Hopefully, validation will not
take any longer than normal.
“For pharmaceutical companies this is a big thing and, as
far as connecting with regulatory bodies goes, this is a big
thing too. The industry as a whole has to be communicating
on this. Pharmaceutical companies, obviously, are in competition
with each other, but when it comes to regulatory approval
this is something that is a pan-industry issue and needs pan-
industry activity.” ■
As the industry gradually shifts to
continuous manufacturing, there will
need to be a lot of communication,
cooperation and coordination.
April 11-15, 2010
PhoenixConventionCenter • Phoenix, Arizona, USA
SBS 16th Annual
Conference & Exhibition
Advancing the Science of Drug Discovery
During this five-day event, more than 2,000 scientists, innovators, researchers and
industry analysts from around the world will converge in Phoenix to learn about the
latest trends and basic and applied research that are transforming the way
new pharmaceuticals are developed.
Society for Biomolecular Sciences
36 Tamarack Avenue, #348, Danbury, CT 06811, USA
For more information, visit: www.sbsonline.org/conference
Assays and Automation:
Implementation, Integration and
Assessment of HTS Technologies
Critical Reagents: Strategies for
Library Design, Biological Tools
and Process Logistics
Epigenetics: An Emerging Target
Class for Drug Discovery
Lead Discovery in
Immunoinfammation:
Innate Immunity, Adaptive
Immunity and Infammation
Lead Discovery in
Neurosciences: Novel Strategies
for Ion Channel, Transporter and
GPCR Targets
Lead Discovery in Oncology
Research: Current Challenges,
Novel Screening Methodologies
and NewTarget Areas
2010 Technical Session Summaries
Photos: www.calebfoster.com
WPF ad:Layout 1 2/15/10 12:29 PM Page 1
WORLDPHARMACEUTICALFRONTIERS
|
www.worldpharmaceuticals.net
T
he Latin American pharmaceutical market is among the
fastest growing across the world. The top eight
pharmaceutical markets in Latin American were worth more
than $30 billion dollars in 2009. Although individual markets are
growing at different rates, the total market is expected to grow at a
compound annual growth rate of more than 10% over the next seven
years. Such high growth rates do attract the big pharmaceutical
companies to the region.
One of the major drivers of growth for the pharmaceutical markets
is the growth of population aged above 65 years, which provides
ample opportunities for the growth of drugs treating Alzheimer’s
disease, rheumatoid arthritis and osteoarthritis.
In addition, the national governments have stepped up efforts to
increase access to healthcare for its citizens. The Latin American
markets, which are already growing at double-digit rates, will receive
a huge boost from the increasing use of pharmaceuticals. The
economic growth of the Latin American countries is also a key driver
in the growth of pharmaceutical markets.
However, Latin American countries differ from each other in their
regulations, healthcare expenditure and in the composition of the
pharmaceutical industry. There are key challenges that need to be
watched for in each of these nations. In most Latin American
countries, the growth of pharmaceutical markets is highly dependent
on the growth of its Gross Domestic Product (GDP). In countries such
as Mexico, where a large proportion of the population pay out-of-
pocket for healthcare, a decrease in economic growth will affect the
growth of the pharmaceutical markets.
In most countries, private insurance covers a very low percentage of
the population, so economic instability could affect the pharmaceutical
industry. However, the Latin American markets performed admirably
during the global recession by maintaining their growth rates.
Brazil is the largest pharmaceutical market in Latin America and
accounts for more than $14 billion dollars, growing at double-digit
rates. Approximately 20% of the pharmaceutical market is accounted
for by generics. Regulations and initiatives in Brazil encourage the
development of the local pharmaceutical industry.
Although Brazil is in agreement with the TRIPS agreement on
Trade-Related Aspects of Intellectual Property Rights, the national
legislation permits the cancellation of patents during emergencies.
Such concerns over the intellectual property rights might discourage
foreign pharmaceutical manufacturers from entering the market.
However, Brazilian companies account for only 30% of the local
market, so the Brazilian government is increasing its investment to
Latin America is a potential sleeping giant, where the pharma market has been growing steadily
but quietly. In this report, GlobalData investigates the market, its drivers and assesses the
investment opportunities.
Special report > Regional focus
28
Figure 1: Gross domestic product, real annual
percentage change, Latin America
2002 2003 2004 2005 2006 2007 2008
Colour guide
Argentina
20.0 -
15.0 -
10.0 -
5.0 -
0.0 -
-5.0 -
-10.0 -
-15.0 -
G
D
P

(
r
e
a
l

a
n
n
u
a
l

%

c
h
a
n
g
e
)
Brazil Chile Colombia
Ecuador Mexico Peru Venezuela
Source: GlobalData, Latin Focus
create a strong local pharmaceutical manufacturing industry. The high
growth of the generics market, coupled with the expiry of several
blockbusters, has attracted the attention of overseas manufacturers.
Argentina’s pharmaceutical market is dominated by local players
who account for 57% of the market value. Despite the increasing
inflation and manufacturing costs, the pharmaceutical industry has
managed to keep the price of its drugs low. A discount of
approximately 30% was given on 600 drugs by the Argentinian
government to increase affordability and to maintain growth. Demand
continues to rise significantly in Argentina’s pharmaceutical market
propelled by the efforts of the government and its commitment to
increasing access to healthcare.
The Chilean market is characterised by a protectionist regulation
that aims at strengthening the local pharmaceutical industry. In 2006,
PhRMA claimed that the Government of Chile had failed to adequately
implement its obligations under the Chilean-US Free Trade Agreement
and the TRIPS agreement on the protection of certain test data and
linkage requirement. Chile has had a history of non-adherence to
intellectual property right laws, which makes it difficult for foreign
manufacturers to register product with the Chilean regulatory
authorities and market it in the country. However, the nation’s
pharmaceutical industry has shown strong growth due to
encouragement shown to the local pharmaceutical industry.
Mexico is the second-largest pharmaceutical market in Latin
America after Brazil and is growing rapidly. Signing the North
American Free Trade agreement required Mexico to assure its
members on the protection of intellectual property rights. In doing so,
Mexico has opened the door to trade with large pharmaceutical
markets. Enforcement of patent protection laws has also increased
foreign investment. It also enables foreign manufacturers to register
their patents with the Mexican regulatory authorities and manufacture
their products in Mexico. Branded products are purchased primarily
by population with higher income, while generics are bought by
population with lower income. Expiry of patents of blockbuster
products is also expected to spark an increase in the growth of
generics. Mexico is one of the most attractive destinations for foreign
manufacturers, however, the research and development sector has not
matured and so the majority of foreign investment in Mexico is
targeted at its manufacturing industry.
The pharmaceutical market in Columbia is highly fragmented, but
it is inching towards maturity. Also, the country has the third largest
population in Latin America whose demands will need to be met by
either local production or imports. Increasing demand for drugs in the
country due to its economic recovery is also expected to accelerate its
pharmaceutical market’s growth. However, recent delays in a free
trade agreement with the US might affect the possibility of the US
exporting its drugs to Colombia. Currently, US exports to Colombia
face an 11% tariff, which reduces the US pharmaceutical industry’s
access to Colombia’s pharmaceutical markets. US industries are losing
their share of Colombia’s import market due to the lack of a bi-lateral
trade agreement between the two countries.
The pharmaceutical market in Cuba is the smallest among the
top eight pharmaceutical markets in Latin America. However, it does
have a strong domestic pharmaceutical industry, which accounts for
more than three-quarters of the nation’s pharmaceutical market. The
government provides strong incentives that help the domestic industry.
Also, the economy has been growing at a steady rate and in turn helps
the growth of its pharmaceutical industry. The free trade embargo
placed on Cuba by the US, however, greatly affects Cuba’s ability to
trade with the world’s largest pharmaceutical industry in the US.
Peru’s pharmaceutical market is expected to grow rapidly, owing to
the introduction of universal healthcare coverage. Peru has signed a
Free Trade Agreement with the US that will help enforce intellectual
property (IP) laws in the country. Enforcement of IP laws will result in
encouragement of the use of legitimate generic drugs and in the
increase of healthcare expenditures. The domestic pharmaceutical
industry will capitalise on the increase in demand due to the
implementation of universal healthcare coverage. There is plenty of
opportunity for foreign manufacturers to capitalise on the fast-growing
pharmaceutical market and use the increase in demand.
Venezuela’s pharmaceutical market does not provide attractive
options for investments in its pharmaceutical industry. Although the
new Barrio Adentro mission will increase the healthcare coverage
provided, the country’s economic stability is in question as recession
in the country is expected to deepen in 2010. Venezuela is also against
patent protection of costly drugs and has moved to invalidate the
patents for Bayer’s antibiotic Avelox. Non-adherence to IP protection
proves to be a barrier for foreign pharmaceutical companies.
Latin American markets are hotspots for conducting clinical trials due
to the availability of large patient pools. A large percentage of the
population does not have access to high-quality healthcare and
medicines, so will be more willing to participate. Also improvement and
enforcement of healthcare regulations, intellectual property regulations
increase the attractiveness of the region for conducting clinical trials.
The majority of the Latin American pharmaceutical markets are
dominated by generic consumption. Overseas manufacturers are
presented with opportunities to capitalise on the growing economies’,
increased access to healthcare and the consequent increase in
demand from cheap drugs. The region offers numerous opportunities
for setting up manufacturing facilities and acquisitions of local drug
manufacturers. Entering the Latin American market during its current
state of economic recovery and continuous implementation of
healthcare reforms is ideal for pharmaceutical companies targeting the
attractive and rapidly pharmaceutical markets. ■
Special report > Regional focus
WorldPharmaceuticalFrontiers
|
www.worldpharmaceuticals.net 29
The free trade embargo placed on
Cuba by the US greatly affects Cuba’s
ability to trade with the world’s largest
pharmaceutical industry.

GlobalData provides industry-leading decision tools, metrics
and analysis for executives in the medical industry.
Subscribers to its Premium Desktop Services receive access
to unique databases, news and opinions, and research
reports, all of which are fully integrated with innovative
desktop tools for easy search, browse and data access.
GlobalData’s Report Store features thousands of high-quality
research reports across a broad range of industries.
www.medicaletrack.com
Company insight > Regional focus
WorldPharmaceuticalFrontiers
|
www.worldpharmaceuticals.net 30
u
micore is globally recognised with more than 40 years
of leadership in precious metals chemistry and over a
decade of platinum active pharmaceutical ingredients
(API) experience.
After obtaining 60% platinum API market share in Latin
America, the company invested $8 million in the construction
of a state-of-the-art greenfield API plant in Argentina. Opened
in January 2009, the plant now flexibly supplies platinum APIs
to key oncology players globally. The new plant has also
increased the company’s production capacity, and is able to
cover 50% of the worldwide demand for platinum API products.
international standards
Making optimum use of its unique
metallurgy and chemistry expertise,
Umicore today produces the most
important oncology platinum APIs:
cisplatin, carboplatin and oxaliplatin
Following ‘The Umicore Way’, APIs
are manufactured according to the
highest quality and social standards.
The GMP-approved plant produces
under the USP, EP and JP guidelines
and is compliant with ISO 9001 and
14001. Needless to say, the plant
and the product documentation
comply with the most stringent
international standards.
As the platinum API production is
fully integrated into Umicore’s closed
metal loop concept, customers are
assured of continuous platinum
availability, due to Umicore’s
recycling operations. Customers can
also count on the active support of
the company’s dedicated marketing and sales teams located in
more than 50 locations worldwide.
Product partners
Alongside platinum APIs, Umicore’s research and development
team has started developing other metal-based APIs to be
produced in the new plant. The preferred business model is a
cooperation where Umicore develops and manufactures the
API and its partner concentrates on
developing and marketing the drug.
Umicore is actively looking for new
partners interested in developing
new products.
Umicore is a leading manufacturer
of highly pure and active precious
metals catalysts and chemicals for
use in a broad array of industries,
spanning from automotive catalyst
manufacturing to the pharmaceutical
industry. Besides its expertise in
metal-based APIs, Umicore has
developed a wide range of
organometallic precious metal
catalysts and precursors, which are
used primarily for homogeneous
catalysis applications and have been
enabling the implementation of
innovative and cost-effective commercial scale processes in
the life science industries. ■
experience today’s and
tomorrow’s metal-based aPis
Committed to hassle-free co-operations, Umicore develops and manufactures frst-class
metal-based APIs, which enables its partners to concentrate on marketing the drugs.
Further information
Umicore
Website: www.chemistry.umicore.com
Email: api@umicore.com
Umicore’s new plant produces
under USP, EP and JP guidelines.
APIs are manufactured to the
highest quality and social standards.
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V
araždin Park is a new, highly sophisticated business
park being developed in northern Croatia, the heart
of so-called ‘New Europe’. The development is
dedicated to servicing the needs of new and already established
busineses from the primarily life-sciences arena and related
hi-tech industry sectors.
The park offers an attractive opportunity to all companies
looking for a geographically well-positioned destination. It
is ideal for a Europe-based headquarters; a destination that
can easily and at competitive cost service a wide market,
and at the same time ensure business growth in an
economically progressive, politically stable and secure, and
naturally beautiful environment.
Located a short distance from the city of Varaždin, the
park is approximately 100 hectares in size. Development is
planned in phases over the next five to seven years, with
construction expected to commence later this year.
A bespoke service will be accompanied by a landscaped
design with an emphasis on the natural surroundings, plus
a controlled access system, fully serviced plots capable of
accommodating large manufacturing and production buildings
as well as smaller office and/or laboratory facilities and
sufficient car parking facilities. Special emphasis is given
to security and to ensure privacy. In addition, the park is
already well-serviced by local public transport routes and
there is a good local railway network, as well as a local
international airport.
Park partnership
Although not a typical public-private partnership (PPP)
development, Varaždin Park is being developed in partnership
with the city of Varaždin, and enjoys the full support of the
Croatian government having been confirmed as project of
national importance.
Occupants of the park will be able to take advantage of
numerous benefits such as top-class facilities with extensive
business support services, an excellent location and easy
international access, an educated and diligent workforce, IP
protection, unrestricted repatriation of profits and capital, a
national biotech policy and much more.

Croatian growth
The Republic of Croatia is a European country with a steadfast
determination to promote the growth of its economy. Croatia is
at the forefront of an emerging region, putting the country in a
leading position in terms of attractiveness to foreign investors in
central- and southern-eastern Europe.
This small country of big opportunities offers a unique
lifestyle, accompanied with rewarding business environment.
It is transforming into a knowledge-based society and economy.
A high quality advanced education system has been established,
along with extensive information and communications
technology infrastructure that offers international businesses a
genuine opportunity to operate and grow in a supportive
environment. In addition, Croatia also has a long tradition of
excellence in a number of industries, including pharmaceuticals,
agriculture and textiles.
The park is situated in Varaždin County, one of the most
economically advanced areas in Croatia and only 50km from the
capital Zagreb and the country’s largest international airport.
Being the urban, economic, cultural and academic centre of
northern Croatia, the city of Varaždin has for years been one of
the country’s most successful destinations in attracting and
supporting foreign investments – which is why it was deemed
the perfect site for Varaždin Park.
The company behind the development of Varaždin Park is Swiss-
based Midia Group, which has been operating in Croatia for several
years and has 25 years experience of real-estate development and
investment in Europe. It specialises in both public- and private-
sector property development and investment. ■
Where culture meets
business innovation
Croatia’s frst life sciences and technology park is being developed at a highly accessible and
economically attractive location in the north of the country.
Company insight > Site selection
WorldPharmaCeutiCalFrontiers
|
www.worldpharmaceuticals.net 33
Further information
Varaždin Park for Life Sciences and Technology
Website: www.varazdinpark.com
Email: bpv@midiagroup.com
Croatia has a long tradition of
excellence in a number of industries,
including pharmaceuticals,
agriculture and textiles.
WorldPharmaceuticalFrontiers
|
www.worldpharmaceuticals.net 34
Company insight > Site selection
i
mportant research carried out by many prominent researchers
in Gothenburg has led to a large number of blockbusters
developed by the local pharmaceutical industry. At the
forefront is Professor Arvid Carlsson, who won a Nobel Prize in 2000
for his work regarding the dopamine system. He has also guided the
industry in developing new products that interfere with important
biological systems.
AstraZeneca (AZ) is by far the largest industrial site in the region.
Here, 2,500 people work within R&D. AZ has its corporate R&D
headquarters for cardiovascular/metabolic diseases and
gastrointestinal disease here too. And since the recent
reconstruction within the company, it is also the site for respiratory
and inflammatory disease research. A number of
blockbusters have been developed here including
Metoprolol (Seloken/Toprol), the first beta-1-
selective beta-blocker, and the calcium antagonist
felodipine. Other famous names include Losec/
Prilosec for the treatment of gastric ulcers, which
for many years was the most-sold product in the
world, along with the follow-up product Nexium.
The development of all these products was the
result of a close collaboration between the
Sahlgrenska Academy and the Sahlgrenska
University Hospital.
Other prominent researchers include Björn
Folkow, Professor Emeritus, an authority on
integrative physiology, and Professor Per Björntorp, who defined the
importance of the metabolic syndrome. Today a national centre for
cardiovascular and metabolic diseases (CVM) has been established
at the Sahlgrenska Academy. Here, internationally recognised
researchers such as Jan Borén, Martin Bergö, Lena Carlsson,
Suzanne Dickson, Sven Enerbäck, John-Olov Jansson and Anders
Lindahl carry out their work. The centre is very open to industrial
collaborations: surrounded by Sahlgrenska University Hospital, the
biggest university hospital in northern Europe, it is the perfect hub
for clinical research. The Gothia Forum, a newly established centre,
that coordinates all clinical trials at the Sahlgrenska University
Hospital, is the natural partner for clinical trials.
Professor Arvid Carlsson established Carlsson Research to develop
dopamine stabilisers for the treatment of CNS-related diseases. This
company was later bought by the Danish company Neurosearch, but
its R&D still takes place in Gothenburg. When Neurosearch bought
the company Professor Carlsson again started his own company, also
working with dopamine stabilisers for CNS-related diseases. Its first
compound has now entered phase 1.
Other companies of interest include Albireo – a
spinout from AstraZeneca. It took over from
AstraZeneca a portfolio of compounds related to
lower tract gastrointestinal diseases – mainly of
anti-inflammatory kinds. Two other emerging
companies are Pharmnovo and Pharmasurgics.
Stem cells are a well-developed arena in the
region, with a special focus on more applied
research. Cellartis, a leading European company on
stem cell research, focuses on using stem cells as screening systems
for new drug candidates as well as toxicology. It has collaborative
agreements with several of the big pharma companies. Recently, it
has restarted its work to develop stem cells as a therapeutic tool for
diseases such as diabetes, heart failure and CNS diseases.
What the Gothenburg region can offer is a very good climate for
drug development. It goes all the way from target identification and
pre-clinical development to clinical development. It offers a very
open-minded and creative environment for collaboration between
basic research, clinical development and the industry. And it rests on
a tradition of developing drugs with great international impact. ■
Gothenburg – a leader in
drug development
Gothenburg, on the west coast of Sweden, has a long tradition of breakthroughs in medicine,
including pharmaceuticals.
Further information
Business Region Goteborg
Website: www.goteborgbio.se
The city is the birthplace
of many blockbusters.
Many prominent researchers work in Gothenburg.
www.goteborgbio.se
World Leader in Biomaterials
The Göteborg region has a strong research tradition
with well above 150 PhD dissertations in biomaterials.
Göteborg is home to world leading scientists such as
Professors Albrektsson, Brånemark, Flodin, Kasemo
and Thomsen, to mention a few.
The Göteborg region has also a very strong life science
industry within areas such as dental implants, bone
anchored hearing aids, polymers for implantable prosthesis
and wound care and incontinence applications.
WPF_GoteborgBIO_Sept09_216x292[1].indd 1 6/5/09 15:24:55
A
ccording to the CPA’s recent report, overall the world
global APIs (active pharmaceutical ingredient) market
(including captive use + merchant market) has grown at
an average 7.2% yearly over the past four years. Of the global
market, the captive market (APIs produced and used from the
pharmaceutical companies for in-house production of finished
dosage forms) has grown faster than the merchant market (APIs
produced by both fine chemical companies and pharmaceutical
companies to be sold to third parties). This different growth rate
can be related to the following factors:
on one hand integration among pharmaceutical companies has ■
created free capacities within the pharmaceutical companies
themselves, to be devolved for in-house production of APIs
on the other hand, sales of finished dosage forms, with the ■
active ingredient incorporated, generally generate a greater
added value than sales of the active substance alone.
Overall, the world merchant APIs market is forecast to rise at an
average 6.5-7% per annum over the next five years, with generic
APIs outpacing overall growth.
The fastest-growing demand for generic APIs over the next five
years is expected in the BRIC countries – Brazil, Russia, India and
China – with annual growth rates of 15-20% each, spurred by
increasing living standards in these countries. The demand for
generic APIs in these four countries altogether will account for
approximately 37-38% of the world generic APIs demand by 2013,
with China at the top.
While the US will remain the largest world APIs market by 2013,
when the global APIs market is considered (branded/innovative
APIs + generic APIs), the country will rank second as a generic
APIs consumer at this date after China, the world’s largest APIs
consumer by 2013.
Among suppliers of APIs, the pharmaceutical companies,
producing active substances for in-house manufacturing of finished
dosage forms (captive use) and third parties (merchant market), are
steadily increasing their market shares on a worldwide scale at the
expense of fine chemical companies – those companies that
produce only active substances to be sold to the pharmaceutical
companies (third parties), which produce finished dosage forms.
China has become the largest APIs producing country in the
world, with sales grown at an average yearly 17.3% over the period
2004-2008, and a very strong position in the generic APIs sector.
Nearly 79% of APIs produced by Chinese companies in 2008 have
been exported.
Italy ranks second after China as an APIs manufacturer; its
market share on world APIs sales has been decreasing, both in the
global APIs market (including branded/innovative APIs and generic
APIs) and in the generic APIs market. In spite of this, Italian
companies have seen an increase in sales toward the US where the
Italian companies hold a market share of approximately 29% as
APIs suppliers.
Rise of the East
Like Italy, Spain – the second largest APIs producer in Western
Europe – is losing shares in the world market. Like Italian
manufacturers, however, Spanish manufacturers have increased
their presence in the US market during recent years.
India is the third largest generic APIs producer in the world, and
the second in Asia after China. Like Chinese manufacturers, Indian
generic APIs manufacturers are quickly increasing their penetration
into the world generic APIs market, at the expense of Western
producers. Production of APIs in India has grown at an average
12.6% a year over the past four years; more than 70% of APIs
produced in India are exported.
With an exponential increase over recent years, India accounts
for a substantial share of total DMFs filed in the world. This
suggests Indian generic APIs manufacturing companies will
drastically increase their penetration into the world generic APIs
business within the next few years. An increasing number of Indian
APIs/pharmaceutical companies are getting approvals from
international agencies for their manufacturing sites, such as USFDA
(US); TGA (Australia); MCC (South Africa); MHRA (UK); Health
Products and Food Branch (Canada).
Revenues generated by contract research organisations (CROs)
in both India and China are increasing much faster than the world
Upwardly
mobile
The CPA believes the APIs market is set to grow 7.2% a year over the next four years. The CPA’s
Marcello Fumagalli examines the sector’s performance globally, and focuses on China in particular.
Insight > Raw materials
WORLDPHARMACEUTICALFRONTIERS
|
www.worldpharmaceuticals.net 36
WORLDPHARMACEUTICALFRONTIERS
|
www.worldpharmaceuticals.net
average, taking advantage of low labour costs in the two countries.
In spite of this, the contract research related business in the two
countries still accounts for a small share of the world business,
which remains mostly concentrated in Western Europe and the US.
Among other Far Eastern countries, South Korea is of relative
importance in terms of APIs market size and trend. The main
obstacle for the South Korean APIs industry, however, still remains
competition from India and China, not only in chemical synthesis,
but also in fermentation operations, which have been the
traditional field of activity of the South Korean APIs industry, as
well as in the innovative R&D activity.
In Latin America, Brazil is the second largest (mostly generic)
APIs market after Mexico, but demand for APIs
in the country is growing faster than in any other country
in the region. The Brazilian APIs industry, however, is weak, and
most active substances used by the Brazilian pharmaceutical
companies are imported, mainly from non-regulated markets.
In Eastern Europe, Russia is the largest APIs consumer and
also the fastest-growing APIs market. However, there is a lack of
APIs production, and most active substances are imported from
China, India, Eastern Europe, Germany and Switzerland.
Eastern promise
The largest producer of generic APIs in Eastern Europe is
Hungary, which accounts for about 40-42% of total generic
APIs production in this region. Approximately 77% of
Hungarian APIs production is exported, mainly toward
CIS; Hungarian APIs companies, however, have
substantially increased their sales toward the US over
recent years. Other producers worthy of note in Eastern
Europe are Croatia, Slovenia, Poland and the Czech
Republic. Poland and the Czech Republic are
considered the most attractive countries in the region
for APIs outsourcing manufacturing activities. The
disadvantage of Poland and the Czech Republic, in
comparison with China and India, however, are higher
labour costs.
The most innovative route for APIs manufacturing
processes is the bio-catalysis, consisting of the use of
natural compounds (enzymes) instead of metal
compounds as catalysts to perform chemical
transformation of organic compounds. Bio-catalysis offers
many technical and economic advantages, the most
important of which is its high selectivity, which results in
high yield of the desired specific product.
The market for biogeneric (better known as biosimilar) APIs
The market for biogeneric APIs
has met difficulties in establishing
itself in developed countries such
as Western Europe, the US and
Japan.

Insight > Raw materials
Marcello Fumagalli, CPA
CPA is the chemical-pharmaceutical industries’
strategic consultant providing an ever-present
and up-to-date partnership in the role of
researcher, scientist, and expert. CPA
maintains a strong focus on the services
that improve the day-to-day running
of companies.
has met difficulties in establishing itself in developed countries
such as Western Europe and in particular the US and Japan. Among
developed regions, until now only the EU has recently introduced
an approval system for biosimilar products. In the US, the Obama
Administration has promised to include in its Legislative Agenda a
proposal to pave the way for biosimilar products. In Japan in
September 2008, the Japanese Ministry of Health, Labour and
Welfare (MHLW) issued draft guidance on biosimilars, setting up
the policies regarding development and regulatory approval
procedures for biosimilar products in the country.
The Chinese APIs industry
The growth of the Chinese APIs production by value over the past
four years (+ 17.3% per annum) has been lower than growth
registered over the same period by volume (+ 23- 25% per annum).
This trend is the consequence of a general compression of selling
prices affecting the APIs industry worldwide.
In spite of this, prices of APIs produced by Chinese companies
are subject to fluctuations. Prices of bulk APIs exported from China
have risen substantially in the first half of 2008, mainly due to the
increase of raw materials’ cost and the contemporaneous
appreciation of the local currency (RMB). In the second half of 2008
however, prices of APIs (especially antibiotic APIs) began dropping
drastically, along with the general trend of raw materials’ prices.
Nevertheless, the Chinese APIs industry (especially the generic
APIs industry) continues to heavily relate to its
cost advantages.
Another feature of the Chinese APIs industry is its export
orientation, coupled with the gradually improving quality of
exported APIs. Over the past four years, exports of APIs from China
have grown substantially, at an average 18-19% per annum by
value. The analysis of the historical trend shows that the main
characteristic of the Chinese APIs export over recent years has
been its focus on low-value products at high volumes. Although
this characteristic still remains a prevailing characteristic of the
Chinese APIs manufacturing, in recent years the Chinese PFCs
(pharmaceutical fine chemicals) industry has evolved from being an
overwhelming exporter of intermediates into a manufacturer of
APIs for the global pharmaceutical market, including more
advanced markets.
This is a real challenge for Western APIs manufacturers. As of
2008, Western Europe and North America accounted for
approximately 42% of total APIs export from China. In the US
generic APIs market, Chinese manufacturers have increased their
market share approximately 25% during the past three years.
In line with the export trend, imports of APIs in China are quickly
increasing at an average 18% a year; imports cover nearly 60% of
the total APIs consumption, including branded-innovative APIs
ordered through joint-venture agreements for the production of
brand drugs in the country by multinational pharmaceutical
companies. Prices of branded-innovative APIs, of course, are higher
than generic APIs’ prices, thus enhancing import by value.
Antibiotic products still account for approximately 18-19% of total
Chinese APIs output.
It should be noted, however, that whereas until five to ten years
ago the Chinese APIs industry was dominated by antibiotics,
having wrested the leadership from the Indian fermentation
industry, nowadays Chinese PFCs companies are steadily
expanding their production into all therapeutic sectors, including
the anti-cancer sector, one of the most recent segments. As of 2008
there was at least one Chinese APIs producer for the vast majority
of the world’s top-selling APIs.
The Chinese APIs industry still remains highly fragmented, with
more than 3,000 APIs manufacturers. In recent years an increasing
number of small-to-medium private Chinese APIs companies have
developed very quickly. Not only have newcomers entered the
market, but many Chinese manufacturers have also further
expanded their production capacity. Most of them, however, still
specialise in the production of low-value/large-volume
intermediates and APIs; only a minority of them are developing
higher-value APIs to be registered in the developed markets (US,
Canada, Western Europe, Australia, Japan). Often the more
advanced/higher-quality domestic manufacturers co-operate with
multinational enterprises for contract manufacturing activities.
Vertical integration
In addition, in recent years many Chinese APIs suppliers, spurred by
the increasing competition, have transformed themselves from pure
APIs manufacturers into “vertically integrated” pharmaceutical
companies. This allows them to improve their profitability. As a result,
most APIs manufacturers in China are pharmaceutical companies,
producing APIs for their own needs and selling both APIs (and
intermediates) and finished dosage forms to third parties as well.
According to local sources, however, this situation can no longer
be tolerated. Less than 15% of the myriad local APIs manufacturing
companies are likely to survive in the future or, at least, to have
future potential. According to local statistics, only about 60-70
entities involved with APIs manufacturing in the country have had
inspections from international authorities, including: USFDA (US),
TGA (Australia), MHRA (UK), and so on. It is worth noting, however,
that every year an increasing number of Western APIs and
pharmaceutical companies are setting up production facilities in
the country.
As a consequence of this muddled and sometimes over-sized
supply situation, competition among local APIs suppliers is
constantly increasing and Chinese companies claim profit margins
are progressively eroding. What’s more likely, however, is that lower
prices are largely being balanced by increasing sales volumes.
Chinese APIs companies, however, still have to fight with
their Indian counterparts with regards to new drug discovery and
APIs manufacturing under several aspects (DMFs, GMP
compliance, environmental issues, inspection systems, IPRs and
marketing strategies). ■
Insight > Raw materials
WorldPhArmACeuTICAlFronTIers
|
www.worldpharmaceuticals.net 38
In recent years an increasing
number of small-to-medium private
Chinese APIs companies have
developed very quickly.

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P
ut simplistically, high throughput screening (HTS) and
high content screening (HCS) are the workhorses of the
pharmaceutical industry, particularly when it comes to
searching for and creating new pharmaceutical compounds. In
HTS, a screening facility will typically hold a library of stock
plates, whose contents will have been catalogued and will have
been created by the laboratory or come from a commercial
source. From these stock plates separate assay plates, or copies
of the stock plate, are created by pipetting a small amount of
liquid from the wells of a stock plate to the corresponding wells
of a completely empty plate. Then, normally through an
automated, often robotic, process the assay-microplates are
transported from station to station for sample and reagent
addition, mixing, incubation, and finally readout or detection.
The beauty of an HTS system is the way it can be used to
prepare, incubate and analyse many plates simultaneously, so
speeding up the data-collection process, with HTS robots often
testing up to 100,000 compounds per day. The results of those
tests determine the Quantitative Structure-Activity
Relationships that relate the structure of a chemical compound
to its pharmacological activity.
The rise of the
robots
In the increasingly competitive, global and high-expense world of drug discovery and development,
HTS and HCS have been a vital part of the pharmaceutical company’s armoury for some time. As
the technology and science around automation and robotics becomes ever more advanced, their
importance is on the rise, discovers Nic Paton when he talks to robotics pioneer Dr Ross King.
Insight > Drug discovery & development
WORLDPHARMACEUTICALFRONTIERS
|
www.worldpharmaceuticals.net 42
HCS, by comparison, uses modern cell biology, with image
analysis being used to measure changes in properties of the
cells caused by external treatment, such as chemical inhibitors,
but also using automated high-resolution microscopy and
robotic handling. HCS is most often used as a technology to
determine whether or how a potential drug affects aspects of
cell function involved in or which describe a disease. HCS has
been used in drug discovery for more than a decade, with its use
growing and becoming more mainstream as technology and
innovations have advanced.
The key with both approaches is their use of automation,
often robotic-based automation, which is one of the reasons
why some of the technological breakthroughs being developed
by Professor Ross D King and his team in the department of
computer science at the University of Wales in Aberystwyth are
potentially so important. And it is why they have caught the
popular imagination.
Back in April last year, the BBC – not normally known for its
coverage of HTS and HCS – was moved to run an article on
King’s work, branding him ‘the robo-scientist’. Journalistic
licence apart, what King’s team have been developing are
‘intelligent’ robotic devices that can perform hundreds of
repetitive experiments and, critically, learn from them.
Ross’s work began as a research project back in 1999, with
funding from the Biotechnology and Biological Sciences
Research Council.
‘Our first model was called Adam. And we now have another
called Eve, which is in the final development stages. Adam and
Eve have the potential to make screening much more efficient
and cost effective because you will be saving money and doing
it faster,’ Ross explains.
‘If you can speed up the drug pipeline, that can be worth a lot
of money to pharmaceutical companies. Every day a
pharmaceutical company spends on the pipeline is a day losing
sales. So the quicker you can get a new compound, the quicker
you can get it out to the patient,’ he adds.
The automation of laboratory equipment, including advances
within HTS and HCS screening, has revolutionised laboratory
practice, argue King and his colleagues at the University of
Wales in Aberystwyth, which has been one of the pioneers in
this type of innovation.
Automation and the use of robotic technology remove the
time and drudgery, not to mention potential for human error,
that goes with constructing many wet lab experiments by hand,
allowing an increase in both the scope and scale of potential
experiments. Most lab robots, too, only require a simple
description of the various chemical and/or biological entities to
be used in the experiments, along with their required volumes and
where these entities are stored. Automation, therefore, can often
lead to significantly increased productivity and a concomitant
increase in the production of results and data requiring
interpretation. One challenge with this, however, is the potential for
an ‘interpretation bottleneck’, where the process of understanding
the results is lagging behind the production of results.
This, in turn, has led to the development of new research
fields, such as computational scientific discovery and
bioinformatics. Both disciplines, argues King, use computational
approaches from statistics and machine learning to provide an
‘automated understanding’ of the experimental results.
Another way ‘robot scientists’ change things is in making
use of an iterative approach to experimentation, in other
words where knowledge acquired from a previous iteration is
used to guide the next experimentation step. The robot scientist
uses the laboratory robot to execute the experiment or
experiments selected as most informative, has a plate reader to
analyse the experiments, generates data corresponding to the
scientific observations, uses abductive logic programming to
generate valid hypotheses that explain the observations, and
then uses these hypotheses to determine the next most
informative experiment.
Ultimately, what this means is that, at the beginning of any
investigation, the robot scientist has not discovered any
information, therefore all possible hypotheses are equally valid.
As the directed discovery process continues, each new
observation or experiment or interpretation cycle will invalidate
some of the hypotheses, thereby excluding incorrect discoveries.
The experiment selection process aims to choose the experiment
most likely to refute the most hypotheses. This iterative process
allows irrelevant experiments to be avoided, potentially saving
both laboratory time and the cost of using unnecessary reagents
and biological materials, suggests King.
Adam is able to carry out up to 1,000 experiments each day
and has been focused on examining the 6,000 different genes
contained in yeast cells and the function of these genes and their
role as they grow, in the process (and most importantly of all)
independently discovering new scientific knowledge. The real
breakthrough here is the ability of Adam and Eve to originate
Automation and the use of
robotic technology remove the
time and drudgery, not to mention
potential for human error.

Insight > Drug discovery & development
WORLDPHARMACEUTICALFRONTIERS
|
www.worldpharmaceuticals.net 43
Ross King, professor,
University of Wales
Ross King is professor in the
department of computer science at the
University of Wales in Aberystwyth, and
formerly a reader and lecturer within the
department. He is founder and head of
the 15-person Aberystwyth Computational
Biology research group, believed to be the
only ‘wet’ biology lab run in a computer
science department in the UK. He has
published more than 100 refereed
publications in computer science,
biology, and chemistry.
their own experiments, physically perform them, interpret the
results and then repeat the cycle again and again. And, with
assay plates needing to be tested against maybe a 1,000 or
10,000 million compound library, the potential of such ‘intelligent’
robotic automation for pharmaceutical companies quickly
becomes clear.
‘Our job is not to develop drugs per se but to develop new
technologies and new methodologies. It is about trying to
increase the automation of science, so it is not just about doing a
lot of experiments but about automating the full scientific
process,’ says Ross.
‘We look at the results and try to model the relationships
between activity, compounding and their share. Then we test the
compound and that relationship.
‘We are working on developing hypotheses and setting
hypotheses, looking at the results and then repeating the cycle.
The idea is that the computer is doing the science as well as
evaluating what we are doing. Once you get humans involved
there is a delay,’ he adds.
What Adam and Eve also represent, Ross argues, is the merging
of increasingly automated and remotely controllable laboratory
equipment with knowledge and discovery techniques from
artificial intelligence. Innovations such as this in effect remove
much of the drudgery and speed up the construction of many
vital ‘wet lab’ – or laboratories where chemicals, drugs, or other
WorldPharmaceuticalFrontiers
|
www.worldpharmaceuticals.net 44
HAMILTON Bonaduz AG • CH-7402 Bonaduz • Switzerland
contact@hamilton.ch • www.hamiltoncompany.com
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material or biological matter are tested and analysed requiring
water – experiments.
And what has been automated so far is only a small part of
science and only for a small number of experiments, meaning
there is plenty of potential to be tapped in the future, he enthuses.
What’s more, in perhaps one to two decades, Adam and Eve or
their equivalents could become relatively commonplace within
laboratories, he predicts.
Their ability to make ‘informed guesses’ about how effective
different chemical compounds are will revolutionise the
effectiveness, cost and speed of drug development, in particular
minimising the need for random testing of chemical compounds.
Interest is particularly focused on areas such as cancer
treatments and drugs and the potential for Eve, for example,
which has much more of a focus on drug screening than Adam
(with its focus on yeast functional genomics) to autonomously
design and screen drugs against malaria or schistosomiasis.
‘It is much more targeted and much less random. It is also
faster because you do not have to look at all the compounds; you
waste less compound and it is faster because you are combining
two processes into one,’ explains Ross.
‘This technology is synergistic with other technologies. If you
can test more compounds you can help in other areas. Assays, for
example, are being developed that work with nanotechnology,
meaning less compound is needed,’ he adds. ■
Insight > Drug discovery & development
WorldPharmaceuticalFrontiers
|
www.worldpharmaceuticals.net 45
Further research
Dr Ross is not the only clinician carrying out pioneering work in
this area. Dr Stephen Wong of Weill Cornell Medical College is
looking at bioinformatics and biomedical engineering, and how
image-based systems can help identify new applications for
FDA-approved drugs using HCS. For example, he has been
working to decipher targets in the pathways responsible for the
metastasis of breast cancer to the brain.
Researchers at Pfizer, too, are using HCS to study the genetic
variation and physiologic interactions that underlie hepatic
insulin resistance in type 2 diabetes and the prediabetic state.
Similarly, scientists at the Broad Institute of Harvard University
and MIT have been pioneering the use of HCS and image
analysis to quantify difficult phenotypes and differentiate
disease states such as leukaemia.
The computer is doing the
science as well as evaluating what
we are doing, Once you get humans
involved there is a delay.

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©

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.
It’s about integration.
Moving science forward
Which is why it’s about time you invested in a Thermo Scientific Laboratory
Information Management System (LIMS). The most successful businesses
are those that utilize technology to bring the full scope of the lab into the
business – by integrating people, data systems and instruments. We build the
integration capabilities you need into the core of every Thermo Scientific LIMS
so you can make faster and better informed business decisions, decrease your
time to market and improve your margins.
Now with Thermo Scientific WebAccess Suite,

all you need is a web browser
for full, secure, high performance access to any Thermo Scientific informatics
solution – from anywhere. Web deployment of any Thermo Scientific LIMS.
That’s all about integration. Isn’t it about time? Your time.
Call +44 161 942 3000 (Intl) or +1 866 463 6522 (US)
marketing.informatics@thermofisher.com
Thermo Scientific CONNECTS
- Integrating instruments,
informatics software and
enterprise systems for faster,
more informed decisions. To
learn how CONNECTS can help
bridge the gap between lab data
and enterprise knowledge, visit
www.thermo.com/connects
WPF_Connects.indd 1 1/25/10 11:16 AM
W
ith drug development times of approximately 15 years
and subsequent costs approaching $2 billion,
pharmaceutical companies are increasingly in search
of processes that can help them consistently deliver a return on
investment during the patent life of a drug. Enterprise level
laboratory information management systems (LIMS) are key
contributors in this effort. Delivering advanced functionality that is
specific to each stage of the drug development process,
sophisticated, purpose-built LIMS streamline processes and costs
and present organisations with unique integration opportunities.
These LIMS provide superior capabilities by delivering real-time
analysis and reports, facilitating regulatory compliance and product
quality, integrating with the company’s broader network and
providing secure access to key data throughout the organisation.
Thermo Fisher Scientific is in the informatics business and
has developed a portfolio of LIMS that meet the specific needs
of its customers. This is particularly true in the life sciences
market where laboratory requirements are unique in research
and development, discovery and manufacturing. There is no
single system that could answer the unique needs of these
laboratories so the company has developed, with the help of its
customers, purpose-built LIMS for each area of the
pharmaceutical value chain.
Standard systems
Historically, standard LIMS have only delivered 30-40% of specific
functionality targeted to each user’s needs, requiring extensive
customisation to make that LIMS function in that particular setting.
Such customisation is commonly only possible through the use of
proprietary programming languages that are developed and provided
by the LIMS vendor. The combination of minimal industry-specific
functionality and often outdated and/or costly proprietary languages
has been particularly troublesome in the pharmaceutical industry. In
addition, pharmaceutical laboratories normally create their own user
documentation, design documentation, validation scripts and help
files. As a consequence, the implementation of LIMS in various
laboratory settings has been, almost without exception, a long, costly
and painful process not only during installation but also in operating
and maintaining the system over the years.
A clear example of the benefits of purpose-built informatics
solutions can be found in pharmaceutical manufacturing. The
growing mandates of global regulatory compliance and long-term
data traceability, as well as the complexity of laboratory testing and
emphasis on batch versus sample management, have forced
pharmaceutical manufacturers into lengthy, expensive adaptations of
generic LIMS to meet their specific requirements. Extensive and
costly customisation, validation and implementation periods, in
many cases lasting 36 months or more, have become routine,
resulting in decreased productivity. However, with the increasingly
higher costs of bringing a new drug to market, pharmaceutical
manufacturers cannot afford delaying the implementation of next-
generation tools that will make them more productive. And the more
an organisation needs to deviate from an ‘out of the box’ LIMS
solution, the greater the investment is for custom software,
implementation and validation.
Contract manufacturing
As the cost of doing business continues to rise for pharmaceutical
companies, with increases in raw materials, more stringent R&D and
regulatory requirements and extended time to market, the pressure
to contain costs is at an all-time high. The growth in contract
manufacturing organisations (CMOs) is directly related to the need
within the pharmaceutical community to continue to find more
efficient and cost-effective methods of delivering a finished product.
CMOs provide a time- and cost-effective way for pharmaceutical
companies to outsource manufacturing, allowing for their activities
to be more focused on developing new drug therapies or discovering
new compounds. By outsourcing some of their manufacturing
requirements, pharmaceutical firms are able to have more flexibility
in their production and realise cost savings, and just as they are
required to comply with US Food and Drug Administration (FDA) and
other regulations, so too must outsourced suppliers, throughout the
entire process or production line. Despite CMOs delivering on
compliance promises, however, more and more pharmaceutical
businesses are dictating the software and data management
resources that are employed on their behalf.
Similarly, active pharmaceutical ingredient manufacturers
(APIs) have faced the same regulatory requirements in delivering
the active components used in the manufacture of drug therapies.
And since the sponsor pharmaceutical company is ultimately
responsible for the quality and safety of the drug that is
developed, it is often dictated to APIs that methods and
processes, as well as software, are in sync with the company and
with their CMO partners. In this way, a reliable audit trail of data
management can be traced from R&D to raw materials production
and through to manufacturing. ❯❯
LIMS – reducing cost
and improving effciencies
Standard LIMS often require costly customisation and maintenance, which is why Thermo Fisher
Scientifc has developed purpose-built solutions for each area of the pharmaceutical value chain,
writes Dave Champagne, the company’s vice president and general manager, Informatics.
Company insight > Data management/IT
WorLdPharMaCeutICaLFrontIerS
|
www.worldpharmaceuticals.net 47
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.

a
n
d

i
t
s

s
u
b
s
i
d
i
a
r
i
e
s
.
It’s about integration.
Moving science forward
Which is why it’s about time you invested in a Thermo Scientific Laboratory
Information Management System (LIMS). The most successful businesses
are those that utilize technology to bring the full scope of the lab into the
business – by integrating people, data systems and instruments. We build the
integration capabilities you need into the core of every Thermo Scientific LIMS
so you can make faster and better informed business decisions, decrease your
time to market and improve your margins.
Now with Thermo Scientific WebAccess Suite,

all you need is a web browser
for full, secure, high performance access to any Thermo Scientific informatics
solution – from anywhere. Web deployment of any Thermo Scientific LIMS.
That’s all about integration. Isn’t it about time? Your time.
Call +44 161 942 3000 (Intl) or +1 866 463 6522 (US)
marketing.informatics@thermofisher.com
Thermo Scientific CONNECTS
- Integrating instruments,
informatics software and
enterprise systems for faster,
more informed decisions. To
learn how CONNECTS can help
bridge the gap between lab data
and enterprise knowledge, visit
www.thermo.com/connects
WPF_Connects.indd 1 1/25/10 11:16 AM
WPF017_030 Advert.indd 1 27/1/10 15:18:09
WorldPharmaceuticalFrontiers
|
www.worldpharmaceuticals.net 48
Company insight > Data management/IT
Darwin LIMS™ provides intuitive user interfaces and workfows that are designed to be recognisable
to pharmaceutical manufacturing and QA/QC laboratory users. The Darwin Dashboard shows
real-time status of key parameters (above – the system’s entry screen is left); the Environmental
Monitoring screen shows data and trends throughout the manufacturing cycle (above left).
Further information
Thermo Fisher Scientifc
Website: www.thermo.com/informatics
Email: marketing.informatics@thermofsher.com
non-conforming product before it reaches the consumer. By linking
this data to the LIMS directly, pharmaceutical companies can have
greater confidence in the quality of their results and ultimately in the
quality of the product they bring to the consumer.
In order to meet the critical needs of the pharmaceutical
manufacturing laboratory, Darwin LIMS has been designed to be
familiar to users. By delivering an intuitive user interface and a logical
layout that includes common objects such as batches, drug products,
drug substances and market-based specifications, as well as standard
testing methods such as assays and dissolution testing, Darwin LIMS
addresses more of the critical needs of the pharmaceutical
manufacturing lab while delivering the increased functionality that
multi-site/multi-user labs are looking for. Darwin is developed on the
Microsoft .NET framework, supporting open development standards
so that in cases where specialised functionality is required, users can
easily extend the system using standard commercial development
tools and languages. For example, users can modify screens and
develop reports to meet their unique needs without custom coding or
IT involvement. Darwin LIMS is completely extensible for integration
with complex in-house systems using industry standard Microsoft
Visual Studio tools and skill sets that are readily available in the
marketplace or within an internal IT department.
conclusion
Pharmaceutical companies and their associated CMOs and APIs
employing Darwin LIMS as part of a comprehensive informatics
solution can expect to lower costs, risk and time associated with
implementation, training, validation, maintenance and upgrades
compared to generic LIMS that require costly customisation and
maintenance. Since a LIMS is one of the most important tools in
the pharmaceutical laboratory, Thermo Fisher Scientific believes
that by providing purpose-built solutions, it enables its customers
at every level of the delivery chain to be more productive in their
business, and ultimately lower the total cost of ownership for their
LIMS investment. ■
To meet the specific needs of pharmaceutical manufacturing R&D
and QA/QC labs as well as CMOs and APIs, Thermo Fisher Scientific
has built extensive functionality into its Darwin LIMS to facilitate
rapid deployment, validation and training in a fraction of the time
generic LIMS systems require. For FDA and International Conference
on Harmonisation (ICH) regulatory compliance, Darwin LIMS
includes activity and event-based system privileges that better
correspond with users’ work responsibilities. It can also be delivered
with the flexibility to be used in non-GMP mode for analytical
development, allowing researchers greater flexibility during
exploratory work, or GMP mode, to enforce adherence to company
standard operating procedures (SOPs) and regulatory guidelines.
Darwin LIMS also features a comprehensive test library that includes
complex pharmaceutical testing methods for dissolution, dosage unit
uniformity, product assays and a stability module that simplifies the
process of designing, implementing and managing stability studies.
integrating darwin
Until recently, environmental monitoring and LIMS have typically
been disparate systems, requiring users to monitor and aggregate
data from multiple environmental locations for product and batch
traceability. Darwin LIMS fully integrates environmental monitoring
data into the batch record and its built-in charting tools allow users
to visualise each location independent of the samples. This ensures
that any failure is apparent at the batch level and allows the
laboratory to quickly determine whether the source of the
contamination is in the laboratory or the production environment.
This built-in functionality enables laboratory managers to react to
WORLDPHARMACEUTICALFRONTIERS
|
www.worldpharmaceuticals.net 49
Pharma supply chain and logistics
CONTENTS
50 A clear road to market
How to develop robust delivery
strategies
59 The shipping forecast
Efficient and waste-free transport
69 Border control
A new end-to-end tracking system
for Europe
TECHNICAL PAPERS
53 DHL
The earlier the better
56 Envirotainer
Kings of the cool chain
64 Tinytag (Gemini Data
Loggers (UK) Ltd)
A degree of control
66 Sensitech
Electronic temperature monitors
71 Constantia Hueck Folien
Anti-counterfeiting solutions
72 Siemens
Serialisation solutions
75 Original1
The real deal
WORLDPHARMACEUTICALFRONTIERS
|
www.worldpharmaceuticals.net 50
T
he line between a company’s internal operations and its
external environment are becoming increasingly blurred. No
area exemplifies this better than the supply chain where
pharmaceutical manufacturers have to coordinate their own activities
with those of partner organisations, healthcare providers and patients.
Without a clear understanding of the context surrounding the process
of delivering a drug to market, the chain can become a tangled web.
Supply chain managers must have as clear an understanding of the
political, economic and social factors that have an effect on their
business as of their company’s own operations. Even within the EU,
local differences persist that must be accounted for; in emerging
markets and developing countries, the problems are multiplied. As
well as understanding the risks, distribution teams have to balance a
commitment to service and regulatory compliance with cost control.
Laurent Boer, UCB’s vice president of global supply chain, sees his
role as being the link between two spheres. “In today’s economic and
socio-political environment, it’s of paramount importance that supply
chain leaders are engaged with external trends,” he says. “We have to
keep them in mind when we’re making all kinds of business decisions.
The combination of market forecasting, supply to the market, and
providing a 100% service level, connect the internal and external
environments.”
Initially it was driving down costs that led to the construction of
more complex supply chains. But in pursuit of this end, they have
become stretched thin and are increasingly vulnerable to disruption,
while high patient expectations mean the effect of any problems on a
company’s reputation can be severe.
Despite the mounting challenge, there is no indication that
pharmaceutical companies will back down from outsourcing supply
functions. AstraZeneca is pursuing a particularly aggressive
programme and GSK already has an extensive network of more than
90,000 partners and suppliers.
A clear road
to market
Insight > Logistics > Risk management
The pharmaceutical sector faces unique challenges in supply chain management. Delays or
disruptions do not just affect profits, they can be a matter of life and death. Laurent Boer of
UCB tells Ian Duncan how companies can develop robust delivery strategies.
The supply chain also has to be aligned to the broader goals of the
enterprise and, while some considerations are all but universal,
individual manufacturers have specific objectives
that condition their approach to any given challenge.
UCB is an interesting case in this respect because it has a very
clearly defined conception of its place in the market. Since 2004
the company has been undergoing a process of transforming itself
from being a broad-based pharmaceutical manufacturer into a
specialist biopharmaceutical company. In the company’s published
strategy, 2010 is slated as a year when it will return to growth
following the sale of a large swathe of its emerging markets business
to GSK last year, and pulling out of selling primary care products in the
US in January.
The shift has seen a change in the way the company approaches its
supply chain, with the major challenge now being regulatory
compliance rather than delivery to a large number of pharmacies.
Boer believes that despite the changes, the patient still has to be the
focus. “You cannot get away with less than a 100% service level,” he
says. “We provide life-saving drugs, that is the fundamental difference
compared with non-pharmaceutical supply chain, and we need to
keep our eyes on that.”
Concentrating on the patients at the end of the chain, the task is
understanding how external factors will affect products reaching them
and how internal structures can facilitate that aim. It might be
tempting to look at internal procedures first as they can be more easily
controlled, but if processes are designed without a consideration of
context, they will meet obstacles.
The chain gang
To support its transition, UCB has been paying close attention to the
market trends for biologics. In addition, the company has demanded
chain managers dedicated to specific regions, who are responsible for
gathering detailed information and working with commercial teams to
spot emerging trends.
For some of UCB’s older products more informal methods still have
a role to play. “I read a newspaper article that said that due to the
weather this winter, doctors were bracing for a strong allergy season
in the spring,” Boer says. “For me that was a signal rather than a
formal forecast but I saw it as something that was going on externally.
It’s an impulse that you have to assess for its impact on demand.”
Occasionally, however, an event will occur that it is all but
impossible to plan for. Major natural disasters are a particularly good
example. “There are always events beyond imagination,” Boer admits.
“Our risk mitigation plan identifies them but assigns a very small
likelihood of them occurring.”
Preparing detailed plans to respond to such situations can be an
inefficient use of resources, so when they do arise decisive action is
needed. “The most impressive response to these events is the rise of
strong leaders within the organisation who bring together a team to
control the situation,” Boer says. “It’s not the risk mitigation plan itself
but part of how the company is built.”
Boer gives the example of UCB arranging a special express air
shipment of epilepsy medication to a child who was unable to obtain
it where he was living. While in this case it was only one patient who
benefited, it demonstrates the potential for flexibility at times when
normal supply chains are inadequate.
Events limited to one facility, such as a strike or a fire, might happen
only rarely but can have a significant impact on a supply chain. Unlike
natural disasters, there are more options open to companies to control
these risks because the damage or disruption is localised.
Contingency plans
The key is having a number of suppliers in place, or at least reliable
contingency plans. Single-sourcing has been a major trend across a
number of industries as it offered the promise of dramatically reduced
costs. The risk is that even a relatively minor event affecting a critical
supplier can cause a significant disruption, and its usefulness is now
being reconsidered.
While outsourcing brings significant benefits, it is the core company
that assumes most of the reputational risk. When a supply chain is
disrupted and a product is unavailable, patients direct their anger at
the brand owner, so there is considerable pressure to audit suppliers
and create a common vision.
To achieve this, it is vital that close relationships are formed
between the links in the chain. “I think the word ‘partner’ says it all,”
says Boer. “We work together in the supply chain and even though
they might have different business objectives, it’s certainly more than
a contractual relationship. Our suppliers have to understand the wider
context of UCB’s ambition.”
As the strictly internal elements of a company are stripped down,
establishing an overall strategy to manage risks and creating a clear
path to profitability have become increasingly important. For UCB this
has been a case of concentrating on two key product areas, central
nervous system and immunology, and creating high-value drugs for
sale in developed countries.
One consequence of this is that UCB has not been exposed to the
risks associated with operating in unstable regions of the world, such
as the pirate attacks that have threatened shipping in the western
Indian Ocean. But the strategy also brings with it other major benefits
from a supply perspective.
By limiting involvement in emerging economies to the relatively
safe-bet BRIC nations, UCB can concentrate on delivering new
biological products, which require more intensive supply chain
management. In 2009, over 85% of the UCB’s revenue was generated
in Europe and North America.
“New products have been the driver of growth in the past year,”
Boer says. “It’s very important to understand the
supply conditions and it requires a different type of attention
to the markets. ❯❯
WORLDPHARMACEUTICALFRONTIERS
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www.worldpharmaceuticals.net 51
Insight > Logistics > Risk management
Establishing an overall strategy to manage risks and creating a clear
path to profitability have become increasingly important.

“Our demand is generated in a different way. It’s not so
much about the GP any more, we are now talking about specialised
doctors, and that changes both the supply chain
and commercial dynamics.”
It is not necessarily a great deal more complicated to get
biopharmaceutical products to market, but there are far more
stringent regulatory requirements. Meeting these obligations in more
remote areas or less well-developed markets can be an almost
insurmountable challenge.
“There are always areas of the world that are difficult to deliver to,
but it’s not always so much the where, the what and the time,” Boer
says. “Quite often we have to deal with specific temperature and
humidity conditions and that puts constraints on areas of the world
that don’t look like Western Europe.
“Recently I was able to fly with a charity organisation to
Madagascar and deliver some vaccines to local hospitals. It was a
great learning experience to understand how difficult reaching
patients can be.”
Waiting game
Even in developed countries problems can persist. Neupro, is still
awaiting FDA approval for cold chain delivery in the US, despite
having been on the market in Europe for a number of years.
As manufacturers across the industry stake future growth on
biopharmaceuticals, cold chain management is an area of growing
importance and one that necessitates working with specialised
partners capable of providing storage units and logistics support.
Despite the reliance on external suppliers in this area, Boer believes
there also needs to be a greater emphasis on solving distribution
problems at the R&D stage of a drug’s development. If products are
better designed to withstand less-hospitable conditions, the more
basic aspects of delivering a product, such as transportation, can be
tackled in all but the most extreme circumstances,
“In the end you can always fix distribution,” he says, “but it would
be great during the design process to say we designed this for cold
chain distribution but we can ship it under different conditions.
That’s something we can do at a very early stage.”
In Europe, with its more unified regulatory structure, the challenge
arises in working with different national healthcare organisations, all
of which are trying to contain their own costs.
“Each market has its own characteristics,” Boer explains.
“To focus on service, we have to be prepared to understand that
individual markets might have specific requests and that requires a
very rapid response to make sure there is adequate supply.”
With the company committed to high-value products for the long
term, Boer believes the major ongoing challenge will be meeting
tight compliance requirements and meeting growing patient
expectations.
“In Europe and the US, when we talk about e-pedigree,
identification, barcoding and counterfeiting, those things are not only
an industry discussion,” he says. “In the end it’s about the consumer
and we will hear the voice of the patient ever more loudly.”
Growing pressure
These growing expectations will put greater pressure on
pharmaceutical companies to guard against any potential
disruption. Boer hopes that his company’s “patient-centric”
approach will be a tool to plot a course through these
treacherous waters.
Formulating an approach to growth with clear limits, as UCB
has done, makes it possible to minimise potential supply chain
problems. By concentrating on developed countries with strong
distribution infrastructure and a number of potential partners to
fulfil any given role, the effects of an unforeseen event on the
company’s ability to deliver are mitigated.
While it might never be possible to completely control the
external environment, through careful planning and the building
of a strong partnership network, businesses can manage the risks
they face. ■
WORLDPHARMACEUTICALFRONTIERS
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Insight > Logistics > Risk management
Laurent Boer
Laurent Boer has been vice president global
supply chain at UCB Pharma since 2007. He
is responsible for all production supply
management, demand chain management and
clinical supply chain. Previously he was director
global operations at Biogen Idec in Cambridge,
Massachusetts, where he was responsible for
global planning and logistics. Before
assuming the role in Cambridge he was
responsible for international operations in
The Netherlands.
He holds a Masters degree in
business econometrics as well as
professional degrees in logistics and
project management.
Key issues in emergency supply chain
management
In 2009 a team led by Professor Stephen Graves of MIT
identified a number of core areas that pharmaceutical
distribution managers need to address in the event of a disaster
or pandemic with the potential to cause major supply chain
disruption. They presented their findings at a US Department of
Homeland Security conference in November.

The researchers emphasised the need for pharmaceutical
manufacturers to improve both resilience and flexibility in their
supply chain. They suggested that pharmaceutical companies
need to conduct extensive planning and information-gathering
before making supply chain decisions. This included auditing
suppliers; strategies for locating distribution centres; and
analysing the impact of port disruptions.

In the wake of a disaster, the paper outlines a number of
steps companies should take in response. The authors
recommend modelling the impact a pandemic will have on
demand; sharing information effectively with partners; and
clamping down on counterfeiters who might be tempted to
profit out of the disruption.

Source: New Challenges to Emergency Management of Pharmaceutical/Healthcare
Supply Chain Disruptions
S
takeholders involved in controlled substance or narcotics
clinical trials will know that these studies can be the most
challenging and complex types of clinical research: from the
sponsor and the clinical research organisation (CRO) to the
packagers, logistics companies and investigators, everyone
understands that obtaining approvals and ensuring drug availability
in order to conduct the research is often problematic. Delays and
challenges in the supply chain not only slow down advances in
clinical research and impact the benefit to patients, but can also be
very costly to the sponsor. Inefficiency leads to inflated expenditure,
insufficient clinical data, and delays can result in rival products being
released to the market first.
Traditional practices
When deciding which countries to select for a clinical trial, site
feasibility, patient recruitment, key opinion leader endorsement,
clinical trial approval times and investigator site relationships are
more often than not at the forefront of the design discussions.
Once the clinical trial sponsor has agreed these with the CRO, a
list of countries and sites is produced so that work on site initiation
can begin. It is often only after this point that the interactive voice
recognition system (IVRS) provider and logistics company are
brought into the discussions and are asked to agree the lead-times
for shipping into each country. Inevitably, shipments are expected to
commence as soon as possible.
Challenges of supply
Different drugs under research can present unique challenges in
consideration of their distribution. Controlled substances are
naturally one of the more challenging due to the security
considerations associated with their frequently more dangerous or
addictive nature. These drugs are classified in five schedules
according to different levels of control.
Complexity is further increased because different countries have
different rules and regulations regarding the importation or
exportation of these substances when conducting a clinical study.
The EU has recognised in general the need to harmonise the
regulatory landscape to facilitate more clinical research taking place
in Europe within the member states. As a result the following clinical
trial legislation has been implemented over the past six years:
2001/20/EC (GCP) ■
2003/94/EC (GMP) ■
EUDRALEX Vol 4. ■
Article 13 (Manufacture and Import of IMP) ■
Annex 13 (Manufacture of IMP) ■
Annex 16 (QP Cert and Batch Release) ■
This regulatory harmonisation has made an impact. For example,
all clinical trials supplies being imported to France previously had to
be shipped to an in-country warehouse to undergo checks before
they could be moved on to the investigator site conducting the
research. This added extra time and further unnecessary handling in
the supply chain, along with the extra costs of an in-country
warehouse. With the passing of the harmonisation in member state
country regulation, drugs can be shipped from a central stock-
holding location within the EU directly to an investigator site. This
enables a 24-48-hour turn-around time, from an order being placed
on the IVRS through to delivery to site, which in turn enables supply
The earlier the better
The logistics provider is often the last partner to be consulted when setting up a clinical trial,
which can have a detrimental effect, in particular when conducting clinical research of controlled
substances. Alex Klim, product manager, Clinical Trials Logistics at DHL Supply Chain,
explains why involving the logistics partner at the design phase of a clinical trial can provide
a competitive advantage.
Company insight > Logistics > Risk management
WorldPharmaCeuTiCalFronTierS
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www.worldpharmaceuticals.net 53
Narcotics rules vary between states
chain companies to do what is logistically efficient by reducing
transit times and the number of people that handle a drug.
The issue, however, with controlled drugs is that, rather than a
health authority regulating trials and their supplies, member state
countries have separate ‘narcotics authorities’ that have not been
subject to regulatory harmonisation (see Table 1, above).
Therefore there are narcotics rules within the EU with regard to
pre-notification of a shipment, import and export permissions, ‘safe
custody’ of the product, and the destruction of unwanted
medication, which vary from country to country. All are important
factors that a logistics company has to be aware of, but that are not
always considered at the design phase of the clinical trial.
Balancing act
Despite many EU member states having different rules when
importing, exporting and storing controlled drugs during a clinical
trial, there is one regulation that is currently quite consistent – the
need for an in-country depot. This often consists of making someone
in-country responsible and accountable for all deliveries of controlled
substances to a hospital or pharmacy. Finding the right warehouse
while trying to maintain standard operating procedures across all the
depots within the clinical trial can be demanding.
Globally, one can always find a specialist clinical trials supplies
(CTS) organisation that can store, pick and distribute materials
during a clinical trial. These CTS providers are used to deliver ‘fine
pick’ operations where individually serialised medication packs must
be identified during blinded or double-blinded studies, and go
through a number of checks to ensure picking accuracy. However,
there are only a few with the expertise or infrastructure to store and
distribute controlled drugs (as well as having knowledge of the
unique demands of the clinical supply chain).
This expertise may be found among wholesalers that have all the
required licensing and comply with infrastructure and security
regulations. Their experience lies in the need to supply pharmacies
and doctors with prescribed medicines on a much larger scale than a
clinical trial, with far more standardised products (for example, not
blinded or needing the same degrees of cold chain control).
Selecting between the two within each country can be a difficult
choice, and often requires on-site training to up-skill a non-CTS
company’s capability while trying to maintain standard operating
procedures across all the countries involved in the same clinical trial,
so as to provide a service consistency that does not put the supply
chain at risk. A logistics company needs to take a lead role in the
supply chain to address any inconsistencies through training and
clearly defined responsibility matrices.
Planning and visibility
With inventory having to be stored in a warehouse in each country
involved in a clinical trial, and the often quite extensive exportation
and importation requirements that differ from country to country,
careful planning and accurate information is vital to maintaining the
network to ensure adequate availability of supply (not stocking out).
As the slightest error in the import or export documentation or
process can result in lengthy delays in customs, careful inventory
management, delivered through integrated reporting tools, is
required to plan and mitigate against the risk of the right medication
packs not being available for a patient visit.
This is never more evident than at the start of a clinical trial
when sites need to have drugs ready for first patient-in dates, and a
careful back-scheduling of applications, permits, training and
contracts must be undertaken so that site initiation dates can
be met. With so many logistical issues to be dealt with before the
drugs can move out of the central warehouse, logistics companies
must be factored into the chain of communication at the earliest
possible opportunity.
Involving the logistics provider
In conclusion, the earlier a logistics company is brought into the
planning of a clinical trial, the higher the likelihood of meeting key
planned research milestones.
One recent example involved a large EU-controlled drugs clinical
trial (under DHL’s supply chain management). Italy was under
consideration and patient recruitment had already commenced, but
with the heavy administrative burden required for each import it was
unrealistic to meet the required initiation date. It was therefore
decided not to initiate Italy and instead to recruit extra patients in
Poland. This decision, driven to alleviate a supply chain constraint,
helped the controlled substance gain marketing approval nine
months before its competitor product (trialling in Italy). ■
Company insight > Logistics > Risk management
WorldPharmaceutIcalFrontIers
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www.worldpharmaceuticals.net 54
Further information
DHL Supply Chain
Website: www.dhl-healthcare.co.uk
Table 1: Examples of the different authorities that regulate all matters pertaining to controlled narcotics
country
clinical trial
regulator
narcotics authority narcotics legislation
uK MHRA DoH (Home Office) 1971 Misuse of Drugs (Safe Custody) Act
Italy Ministero della Sanità Ministero della Sanità Decreto Presidente Repubblica (DPR) 9 Ottobre 1990, n. 309
Germany
BfArm (National
Competent Authority)
Bundesopiumstelle (Federal Opium Agency) Narcotics Act of 1981
France AFFSAPS
AFFSAPS (Narcotics and Psychotropics
Unit)
1970 Law No. 70-1320 Respecting health measures in
the fight against substance abuse and repression of the
trafficking in and use of poisonous substances.
Poland
GIF (Main
Pharmaceutical
Inspectorate)
National Bureau for Drug Prevention
(Narkomania)
Act of Law of 29 July 2005 on Counteracting Drug
Addiction
5335_DHL_Logistics_ICT_210x286_Ad_out.indd 1 24/2/10 14:19:53
Company insight > Logistics > Cold chain
WorldPharmaceuticalFrontiers
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www.worldpharmaceuticals.net 56
a
t a time when reliable cool chain services are becoming
more important to drug manufacturers, one company
in the field is putting renewed emphasis on the needs
of its pharmaceutical clients. After successfully branching out
into other areas such as luxury food and mobile phone delivery,
Sweden based Envirotainer is drawing on its long history in
the pharmaceutical industry to offer a new range of products
to the sector.
CEO Thomas Persson is digging deep for new ideas to better
serve the company’s partners. Persson has been working to get a
better picture of the cool chain from the moment a product leaves
the factory door until it arrives at its destination. That means
understanding the needs of manufacturers themselves as well as
those of the logistics providers. “We are really focussing on
pharma and developing better services, products and hardware for
the pharma industry and for our clients among the couriers and
airlines,” he says. “We have seen that we need to understand the
customer’s customer and that’s why we talk so much about
pharma focus.”
To support this focus Envirotainer convenes a bi-annual
advisory board with members from 17 pharmaceutical industry
companies. The advisory board works to supplement the
conversations the company’s sales teams have with clients every
day. By working closely with the industry, Envirotainer has been
able to better focus its R&D activities. “We understand how
important it is to have the pharmaceutical companies in the loop
in the early stage before we have spent too much money on
development,” Persson says.
The reason for this drive is the increasing value and complexity
of pharmaceutical products. As lead times become longer, losing a
batch in transit could cause a major delay and put patients’ lives at
risk. For producers, each batch of a product represents a significant
investment, so finding ways of minimising the chance of losses
during transit is important. The solution is to not only develop more
reliable containers but also to opt for containers that can both heat
and cool their contents.
The most common method of ensuring the temperature of
products is by using dry ice, but dry ice containers rely on handling
procedures and supervision to avoid low external temperature
causing damage to the shipped products. Envirotainer is investing
in the development of a fleet of containers that can both heat and
cool their contents. The company’s flagship model is the RKN e1,
which can maintain a steady internal temperature whether it’s
standing on the tarmac at an airport in Dubai or Stockholm.
Once transits to and from airports and any delays at customs
are factored in, even a journey within Europe can take more than
48 hours. The RKN e1’s battery can power the system for up to
100 hours and can be fully recharged in eight hours from a normal
plug socket. This stamina means no journey is too long and gives
clients’ cool chains a truly global reach. “The autonomy of it means,
you can more or less leave it standing outside and it works
regardless of the ambient temperature, for hours and hours and
hours,” Persson explains. “So it’s less vulnerable when you reload
or unload or offload or transit at an airport, which is usually where
the biggest problems are.”
Envirotainer still has 2,600 dry ice containers compared to 368
heating and cooling containers but Persson believes the latter will
increasingly become a more attractive prospect for his clients. In
January the company was acquired by AAC Capital Partners,
providing finance to fuel growth. The key to this growth will be
investment in more battery-powered containers. Last year 80 RKN
e1 containers were added to its fleet and this year there are plans
to introduce 100 more. “We’ll probably build another 100 when
those first 100 are on the market,” Persson adds.
These ambitious plans are especially impressive given that other
service providers and subcontractors in all industries have
struggled through the downturn. By expanding now, Envirotainer
should be well placed to increase its market share in the coming
months and position itself as a reliable partner of the
pharmaceutical industry. ■
the kings of the cool chain
Swedish cool chain container manufacturer Envirotainer is returning to its roots in pharma.
CEO Thomas Persson explains why the company’s growing line of heating and cooling
containers represents a lower risk choice for clients.
Envirotainer CEO Thomas Persson
says the company is “really
focussing on pharma”.
Further information
Envirotainer
Website: www.envirotainer.com
Email: info@envirotainer.com
With an air cargo container that actively regulates it’s own temperature and certified
handling partners, your valuable drugs will be better taken care of. In that way you secure
their functionality and your financial return. Year after year. At Envirotainer we offer unique
air transport solutions for healthcare products. Worldwide. www.envirotainer.com
First class transportation for your drugs.

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an email to VerticalAd@fedex.com or go to fedex.com/gb/supplychain/industrysolutions/healthcare.html
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AD_FedEx-Healthcare_210x286.indd 1 17/02/10 18:37
I
n spite of a global financial slowdown, the demand for quality
services continues to grow. At the same time, our resources are
likely to get tighter in the future, while an increasing world
population needs more food, more fresh water and of course, more
quality pharmaceutical products.
And while global warming might not have an immediate and direct
effect on transportation, it will, without doubt, indirectly influence our
global perspective and considerations in the future. An increase of a
couple of degrees Celsius in the planet’s average temperature would
change the world’s biodiversity, with the result that species and plant
life might change or cease to exist. For the medical world, plants have
often been an inspiration and important source for new medicaments.
For that reason alone, it is vital to maintain the natural balance and
biodiversity that created life on earth and which is vital to the
existence and survival for all living things on the only planet we have.
So we need to take good care of this planet of ours and reduce
greenhouse gases and CO
2
emissions as well as eliminate pollution.
That also means reducing or rather eliminating waste, especially in the
supply chain.
From that perspective, climate change will have a major say in how
we manage not only our resources of plants, food and fresh water, but
also future transportation, handling and distribution of our
requirements. We cannot let things go wrong, we cannot be ignorant.
New taxes on pollution and cap-and-trade costs will add to the daily
expense of our living, and thereby make transportation and distribution
more expensive. But we can limit the extra burden by being waste
The shipping
WORLDPHARMACEUTICALFRONTIERS
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Insight > Logistics > Cold chain
Transportation is vital in the pharmaceutical industry, and with more and more focus on how we use
the world’s resources, identifying ways to ensure shipping is as efficient and waste-free as possible, is
going to be essential, as Robert Arendal of Australia’s Cool Chain Association explains.
forecast
and quality conscious – meaning let’s do a better job in how
we organise our day-to-day work, in how we handle our
supply chain.
These issues are even more important in the cool chain, the
handling, transportation and distribution of perishables and
temperature-sensitive products (PTSPs). Irrespective of the type of
product – whether it is a strawberry or a high-value pharmaceutical
substance – they all need and deserve professional and careful
attention. Certainly, the PTSP logistics are more sensitive than some
other ‘hard freight’ products as they need a constant, maintained
specified temperature. These shipments need on-time performance
and constant attention from the service provider. The financial
consequences when something goes wrong are of course different for
a high-value pharmaceutical product, and yet, in order to eliminate
waste and keep a high standard of quality, products in the supply
chain need a reliable and professional service.
From my many years in the air freight industry, it became very clear
that while we had at our disposal some of the most sophisticated
machines, such as a high-tech, $250 million wide-body freighter, we
did not always have the right procedures to ensure that the products
we transported in our high-tech, high-value machines got the same
high-tech, high-value handling on the ground.
Considering that only 20% of the total transportation time is in the
air, it is obvious that professional attention and procedures on the
ground did not always match the same high quality in the air.
Needless to say, over the years, ground handling and distribution
have vastly improved and better procedures have come into the
equation. Computerised customs clearance – or at least
WORLDPHARMACEUTICALFRONTIERS
|
www.worldpharmaceuticals.net 61
These shipments need on-time
performance and constant attention
from the service provider.
HOW DOES IT WORK?
1 Plug Libero into any USB port of a PC.
2 The PDF Logger
®
independently generates a PDF/A report
including text and graphics of the monitored temperatures.
3 Libero acts like a memory stick, presenting you
the PDF/A file in a new drive.
4 Now, you can view, print or e-mail the complete
evaluation report.
To learn more about this unique product,
please call +41 81 750 03 11 or visit our website.
www.pdf-datalogger.com
Libero supports compliance
with PDA Technical Report No 39
for multiple alarm/time zones
based on product-specific
stability data.
The first PDF Logger
®
:
Cold Chain Monitoring
without any software,
PDF/A report inclusive, via USB port
anywhere in the world.
WORLDPHARMACEUTICALFRONTIERS
|
www.worldpharmaceuticals.net 62
Insight > Logistics > Cold chain
communication with customs – came into place in many countries,
cool storage facilities became available at many airports, and the
shipping industry improved its services.
Yet more can be done. Better procedures, better management and
training of staff handling the PTSP can be achieved on a broad scale. In
today’s world, PTSP shipments move across the globe as never before.
While certain – often major – airports and ports have the procedures
and equipment in place, many others do not. That is why a global
standard has to be in place; where a simple “manual” can be followed
and the necessary requirements for the logistics of PTSP are
safeguarded by implementing such guidelines. The amazing thing is
that such procedures are not necessarily more expensive or more
complicated than whatever else is or was in place; the guidelines on
how to handle PTSP shipments are common sense and straightforward
logic – bearing in mind that PTSP products are sensitive.
In the Cool Chain Association we developed a master table for how
to handle PTSP shipments; we divided it into various sections such as
trucking, handling, air or sea transport and
so on. All clear and easy to follow. It was up to each service supplier to
implement these standards and, if correctly done,
the service supplier could even be CCA certified, thereby identifying
their special adherence to correct procedures for the PTSP shipments.
We named the standards CCQI’s – Cool Chain Quality Indicator.
Having worked out such standards and promoted their
implementation worldwide, we also suggested that the
pharmaceutical industry could take advantage of the already
established standards. The CCQI could even be adjusted if special
requirements for the pharmaceutical industry were required. But the
basis and underlying issue is that PTSP shipments – whether it is a
shipment of strawberries or medicaments – all need some very basic
handling requirements and attention that should be applied
throughout the global PTSP chain and industry. The importance is to
establish a global coverage.
Many service providers have now aligned their handling and
distribution of PTSP’s along the standards of the CCQI’s, but on a global
scale there is still a long way to go. Basic service standards and criteria
for worldwide coverage are vital for the transportation industry if the
service suppliers wish to meet the service demand of their PTSP clients.
The next step is to take the PTSP industry into a sustainable energy
world in order that the PTSP industry can also contribute to combating
climate change, get the global temperature under control, and reduce
waste and pollution – but that is another story altogether. ■
Robert S Arendal
Robert S Arendal has had a long career, owning his
own company RA Associates, and acting as advisor to
the chairman of Atlas Air. He is chairman of the
Cool Chain Association and has been a
Goodwill Ambassador for Copenhagen for
many years.
www.taracell.com
Telefon +41 (0) 56 485 92 00
EURO pallets ISO pallets
COLD CHAIN CONTAINER
do_ta_inserat_210x286_0310.indd 1 12.3.2010 7:53:51 Uhr
T
he need to maintain a stable ambient temperature in the cold
chain has serious implications for the pharmaceutical industry,
which has the welfare of the consumer to consider and, in the
UK, the stringent requirements of the Medicines and Healthcare
Produces Regulatory Agency (MHRA) to fulfil. It is only in January that
the NPSA (National Patients Safety Agency) issued a Rapid Response
Report stating that all NHS departments and independent contractors
must comply with the need to have vaccines continually stored at a safe
temperature. This followed the published results of a primary care trust
(PCT) audit and NPSA’s own assessment.
The issue
The single biggest issue for those with responsibility for storing
pharmaceutical products had always been temperature increases
above +25°C, according to MHRA statistics. The situation regarding
vaccines is even more critical as their safe storage temperature in
order to retain potency is +2°C to +8°C, depending on the
manufacturer’s recommendations. It is this latter case that has the
been the subject of current debate, following an audit carried out by
the Nottinghamshire Primary Care Trust, which was subsequently
shared with the NPSA in June 2009. The two-year audit of 96 practices
revealed that 40% of vaccines had been stored outside the
recommended temperature range.
The NPSA searched its database for all clinical incidents and near
misses and found 260 reported problems with vaccine storage
between January 2005 and April 2009. During this time, 50 million
doses of childhood vaccines were distributed across Britain. Several
common themes were identified from these reports, which included
delays in the storage of vaccines especially after delivery; storage at
the wrong temperature; a fridge being switched off or broken; a power
cut or a fridge door left open; no temperature monitoring controls at
all; inadequate or missing equipment and, finally, inappropriate use of
domestic fridges.
The PCT did a further risk assessment to identify which of the
vaccines concerned had the greatest potential for harm. Vaccines
known to have been stored below -2°C were considered to be the
highest risk and resulted in recall from two practices. The first recall
involved approximately 200 children, the second included 360 adults
and children. These local findings, together with incidents reported to
the NPSA, has made it necessary to highlight the continuing problem
and to emphasise how too cold an environment can pose a worse
threat. Freezing, for example, can cause hairline cracks in the container,
leading to contamination of the contents. The Rapid Response Report
calls for immediate action by all NHS organisations whose departments
and providers, including independent contractors, hold vaccines
requiring cold storage. The deadline for action is 21 July 2010.
Requirements are re-emphasised
The alert calls for all NHS organisations and independent contractors
holding vaccines to:
Be issued with guidance relating to vaccine cold chain storage. A ■
document called ‘supporting information’ should be consulted.
Local policies should include having a designated person and
deputy or deputies responsible for receipt and storage of vaccines.
Have procedures are in place to ensure correct working practices ■
are being followed, such as reviewing refrigerator temperature
regularly to identify if vaccines have been stored outside
manufacturers’ recommended temperature ranges before they are
administered to patients.
Have procedures in place for remedial action where vaccines are ■
stored outside manufacturers’ recommended temperature ranges,
and ensure departments and providers are aware of these. Actions
may include initial reference to the UKMi fridge database (www.
ukmi.nhs.uk/applications/fridge) with subsequent advice sought
from NHS medicines information services or the vaccine
manufacturer.
There are penalties for failure to recognise your responsibility as a
handler of vaccines. The MHRA’s Orange Guide collates in one
convenient and authoritative source European and UK guidance
documents and information on legislation relating to the manufacture
and distribution of medicines for human use. It also makes it clear that
distributors must comply with the regulations or face penalties if their
storage or transportation environment contravenes the requirements
in any way. Adverse inspections will result in recommendations for
correction and if it is not taken the MHRA can take regulatory action.
This may include suspension or even loss, if the offence is serious
enough, of a manufacturer’s or wholesale distribution licence.
How data loggers can help
Many errors identified in the report can be avoided using data loggers.
Data logging will directly address that part of the Rapid Response
Report that states that procedures are “in place to ensure correct
working practices are being followed... such as reviewing refrigerator
temperature”. Data loggers are small, battery-operated, inexpensive
units that monitor the ambient temperature surrounding a vaccine or
any other pharmaceutical product. Although a thermometer may
already be used in a fridge for spot readings, data logging formalises
the procedure by being able to record temperatures over a set period
of time. A data logger encourages good habits and highlights the
importance of maintaining a stable temperature, pushing it to the
forefront of a staff’s mind at all times. It can be set to record at a
A degree of control
The UK’s National Patients Safety Agency issued a Rapid Response Report earlier this year stating
that all NHS departments and independent contractors must ensure that vaccines are continually
stored at a safe temperature. Temperature data loggers can make a signifcant contribution toward
meeting those requirements.
Company insight > Logistics > Cold chain
WoRldPHARmAceuTicAlFRonTieRs
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www.worldpharmaceuticals.net 64
suitable time interval, for example hourly, and then the information can
be easily downloaded and documented when required. Some loggers
have an alarm, such as a red flashing light, so that if, for example, a
refrigerator’s door is left open and the temperature goes out of range,
the alarm will be triggered, alerting the person responsible, who can
then download the data to see the fluctuations in temperature and to
make a decision on what should happen to the pharmaceuticals or
vaccines stored there.
When looking for the right data logger, it is important to look for
a specialist logger for use in refrigerators. It is useful to be aware of
World Health Organisation (WHO) recommendations in order to
maximise the potential of the data logger. Being aware of such
recommendations will also help comply with the latest Rapid
Response Alert on Cold Storage of Vaccines.
Care should be taken when positioning it in a refrigerator. For
example, data loggers that are positioned in the fridge door or near
the front of a shelf are more likely to show higher readings and
more variations in temperature than one placed at the back of a
shelf or at the bottom of the fridge where it is colder. A data logger
is best positioned in the middle of a shelf, in among the product
being monitored, as this more closely reflects the temperatures
they are exposed to.
Ice build-up should not be allowed as this reduces the
effectiveness of the vaccine. During defrosting, an alternative
refrigerator or approved cool box with a data logger should be used
to store vaccines. Temperatures in the refrigerator must be
monitored and recorded at least once each working day using a
data logger. For no extra effort this can be done more often, for
instance every hour, and the data automatically documented on a
chart for recording temperatures. Downloading data, in the form of
tables or a graph, requires just a few simple steps. Annual
calibration checks are recommended, too, so be sure to choose a
supplier who will re-certify or advise on a replacement if necessary.
There may be a need to package and transport vaccines to
outlying clinics. In this situation, WHO recommends the use of
validated cool boxes and ice packs from a recognised medical
company. While the vaccine is in transit, the temperature will
need to be monitored and a data logger can
be packaged close to the packages of
vaccines in order to keep a record of any
fluctuations. Vaccines must be kept in the
original packaging, wrapped in bubble wrap
or other insulation material and placed in a
cool box with cool packs as recommended by
the manufacturers’ instructions. This
prevents contact between the vaccine and
the cool packs.
In the workplace
Many companies have made it their business
to satisfy this important need in the
pharmaceutical chain. Logistics companies,
specialists in temperature-controlled storage
and transportation of pharmaceuticals, have
the temperature requirement first and
foremost in their minds. In this situation,
Tinytag data loggers are used to track
temperatures when the goods are in the
refrigerated vehicles. Data is then downloaded
at the next convenient point and used to verify the temperatures
for that period.
Tinytag data loggers have also been used by pharmaceutical
manufacturers in warehouses and large walk-in fridges, where
temperature-critical vaccines need to be stored at an even
temperature. Data loggers are positioned within the warehouse
and walk-in fridges and it is part of the staff’s responsibilities to
download the data from each logger to identify any fluctuations
and what may have contributed to this. Some companies go one
stage further and undertake temperature mapping exercises. This
is where multiple loggers are placed around a building and set to
record over a period of time. This data is then downloaded and
documented to report on the thermal characteristics of the
building or to determine temperature hotspots within the
warehouse and fridges. Such hotspots can occur at a change of
shift, for example, or when a delivery is made. Knowing the effect
of such changes helps make staff much more vigilant as the data
is visible for all to see.
Conclusion
The Rapid Response Alert has simply re-stressed existing
requirements and acts as a warning. The MHRA had previously
been concerned about temperatures creeping up. The recent
audit and subsequent Rapid Response Alert highlights the danger
of temperatures becoming too low. Automatic temperature
monitoring, using Tinytag data loggers, helps formalise a
procedure and provides physical evidence of pharmaceuticals
being monitored. ■
Company insight > Logistics > Cold chain
WorldPharmaCeutICalFrontIers
|
www.worldpharmaceuticals.net 65
Further information
Tinytag (Gemini Data Loggers (UK) Ltd)
Website: www.tinytag.info
Email: info@tinytag.info
A data logger is best
positioned in the middle
of a shelf, in among the
products being monitored,
as this more closely refects
the temperatures the
products are exposed to.
T
emperature indicators based on the thermal properties of
chemical compounds (chemical indicators) have been
commercially available for many years, providing accept/
reject information for perishable goods within the food supply
chain. While many believe chemical indicators may fall short of
compliance with global regulations and industry best practices,
these devices have, over time, migrated to last-mile cold chain
applications in the life science market.
In response to the increased demands for last-mile monitoring,
electronic temperature indicators have emerged over the past
decade as viable alternatives to chemical indicators, providing
superior performance and functionality. In addition, manufacturing
costs of electronic devices have dropped substantially, enabling
cost-effective deployments in a wide variety of applications.
Considerations for temperature indicator usage include:
Time and Temperature Accuracy. Typical temperature
accuracies for chemical indicators are ±1-2ºC, as opposed to
electronic devices providing accuracies of ±0.5-1ºC. Time accuracy
specifications for chemical indicators vary widely with
specifications such as threshold indication after ‘a minimum of 30
minutes’ or ‘within 15 minutes’ of exposure above/below set-point
temperature. For electronic indicators, typical time accuracies are of
the order of ±0.01% of elapsed time (less than a five-minute error per
month of operation). Some chemical time-temperature indicators
(TTIs) provide evidence of the accumulated effects of temperature
exposure. The dynamic temperature response of TTIs is governed by
the Arrhenius equation, more specifically the activation energy (E
A
)
of the temperature-sensitive material. TTI manufacturers strive to
emulate the dynamic temperature effects of the monitored product
via matching E
A
values within the indicator. In practice, this
matching is often sub-optimal, leading to substantial inaccuracies.
Device validation. Electronic indicators can be validated prior
to activation and deployment. The technology enables every
indicator to be tested for accurate operation during the
manufacturing process, thereby establishing the veracity of the
measurement for 100% of device production. Chemical indicators
cannot be validated in this fashion as validation or testing at
operational time/temperature thresholds would be destructive. In
addition, electronic indicators can typically be post-use validated
by the manufacturer. Chemical indicators cannot be reset and
tested after initial activation and use.
Custom threshold alarm settings. Most electronic
indicators can be customised to fit unique transport conditions
dictated by product storage requirements, packaging/pack out
parameters and transportation route variability. Chemical
indicators are generally offered in a limited number of time-
temperature threshold or activation energy variants. Furthermore,
most electronic devices can be programmed with several
independent time-temperature alarm conditions. As a result, a
single device can be deployed to monitor both high and low
temperature limits, eliminating the need to procure, stock, and
deploy multiple indicator devices for each shipment.
Interface ambiguity. Chemical-based TTIs incorporate user
interfaces that are dependent on colour-matching of the reactive
material or the determination of a ‘migration’ distance of the
reactive material relative to a graded time scale, necessitating
subjective interpretations of the results. In contrast, electronic
indicators integrate user interfaces and displays that offer clear,
unequivocal results of time-temperature alarm conditions.
Pre-deployment storage and shipment environment.
Many chemical indicators must be stored and shipped within
controlled conditions prior to deployment. In comparison,
electronic indicators offer broad storage and shipment
temperature ranges prior to deployment since they are
commonly supplied inactivated and are therefore unaffected by
temperature conditions prior to start. In addition to these
onerous storage and shipping conditions, some chemical
indicators require specific temperature pre-conditioning
protocols to ensure proper operation.
In summary, these attributes highlight many of the advantages of
electronic temperature indicator technology for ‘last-mile’ cold
chain monitoring applications. Viewed holistically, electronic
indicators offer effective, accurate, and cost-efficient temperature
monitoring in support of global regulatory requirements. ■
Moving to electronic
temperature monitoring
In response to the increased demands for ‘last-mile’ cold chain monitoring, electronic
temperature indicators have emerged over the past decade as viable alternatives to their
chemical counterparts, explains Jeff Hawkins, strategic marketing manager at Sensitech Inc.
Company insight > Logistics > Cold chain
WorlDPhArMACeuTICAlFronTIers
|
www.worldpharmaceuticals.net 66
Further information
Sensitech
Website: www.sensitech.com
Email: jhawkins@sensitech.com
Eliminate Cold
Chain Ambiguity
A Carrier Corp. Subsidiary
Sensitech’s electronic temperature indicators
don’t waste time with unclear signals
Global regulatory and standards-based guidance outline the need
to identify and minimize temperature abuse across the supply
chain—from manufacturer to patient. Even as pharmaceutical
product moves deeper into the supply chain and shipments
become smaller, more frequent, and less expensive, product
quality and patient safety continue to be critically important.
Sensitech’s expanded family of electronic temperature indicators
protect product quality and patient safety as well as enable
compliance with Good Cold Chain Management Practices
(GCCMP). These devices provide superior accuracy and reliability
and are the first cost competitive alternative to chemical indicators.
For more information, visit: http://www.sensitech.com/indicators
As the leading provider of cold chain visibility solutions, Sensitech
enables our Pharmaceutical customers to track and monitor
assets across the supply chain protecting the integrity, purity
and efficacy of temperature sensitive products. Sensitech is an
ISO 9001:2008 company.
The FreezeAlert and VaxAlert are WHO pre-qualified!
Reliable Accurate Validated
Freeze_Alert SG.indd 1 08-01-10 18:15
Eliminate Cold
Chain Ambiguity
A Carrier Corp. Subsidiary
Sensitech’s electronic temperature indicators
don’t waste time with unclear signals
Global regulatory and standards-based guidance outline the need
to identify and minimize temperature abuse across the supply
chain—from manufacturer to patient. Even as pharmaceutical
product moves deeper into the supply chain and shipments
become smaller, more frequent, and less expensive, product
quality and patient safety continue to be critically important.
Sensitech’s expanded family of electronic temperature indicators
protect product quality and patient safety as well as enable
compliance with Good Cold Chain Management Practices
(GCCMP). These devices provide superior accuracy and reliability
and are the first cost competitive alternative to chemical indicators.
For more information, visit: http://www.sensitech.com/indicators
As the leading provider of cold chain visibility solutions, Sensitech
enables our Pharmaceutical customers to track and monitor
assets across the supply chain protecting the integrity, purity
and efficacy of temperature sensitive products. Sensitech is an
ISO 9001:2008 company.
The FreezeAlert and VaxAlert are WHO pre-qualified!
Reliable Accurate Validated
Freeze_Alert SG.indd 1 08-01-10 18:15
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AZWorldPharma.fh10 12.11.2009 11:27 Uhr Seite 1
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T
ihe general public has a right to be confident that the
medicines they receive from their pharmacist are what both
the manufacturer and the prescribing healthcare professional
intended. However, even in this most highly regulated of
environments, the risk of counterfeit products infiltrating the legitimate
supply chain is a current reality and a growing threat. The fact that
gains for counterfeiters are potentially lucrative, and the deterrents
relatively light in comparison with other illicit activities, has combined
to make this an attractive target.
However, selling counterfeit medicines is not the same as hawking
fake designer goods to tourists in street markets. It requires the ability
to access a complex supply chain and insert or substitute the
counterfeit goods without the knowledge of the legitimate actors in
that chain. Yet despite this, the risk of counterfeits infiltrating the
legitimate supply chain has become greater than ever before and has
raised concerns over the capacity for current security arrangements to
cope with more sophisticated and organised criminal activities.
Potential weaknesses
The existing supply chain already deploys numerous security
measures designed to prevent counterfeiting; however, there are
potential weaknesses that need to be addressed. These include the
sheer volume of pharmaceutical products that cross and even re-cross
European borders, as pallets, batches or individual packs, to exploit
arbitrage opportunities between member states. This is further
complicated by the fact that such trade demands the unpacking and
repacking of medicines with the consequent loss of many security
features on the packaging. With these most basic of security features
removed, counterfeiting packs becomes far less of a challenge. It is
clear that more efficient product surveillance systems are urgently
needed. Against this background, this complex and ever-more
fragmented supply has made it increasingly difficult to identify
medicines effectively across Europe. Given the substantial movement
of medicines across European borders, an inability to verify products
that have left their original country of destination would be a
serious shortcoming.
While the European Commission recognised many of these issues
when it launched its proposals on combating counterfeits in 2008, it
did not offer a preferred solution. What it did propose was a potential
role for mass serialisation as a way of improving product traceability.
Such an approach would certainly be an important component of
improving supply chain security, although not a complete solution in
itself. However, it is clearly a step in the right direction.
A pressing need
On the assumption that the counterfeit problem is a real and pressing
one, then clearly the solution needs to be one that can be applied
rapidly and effectively. In the words of General Patton, this is a
problem that would benefit from “a good plan (violently) implemented
today, rather than a perfect plan implemented next week”. Good plan
or perfect plan, there are certain prerequisites that must be met.
First, if the safe and free movement of medicines across borders is
to be made more secure, a coordinated approach to identification and
verification of medicines is essential. This requires all national coding
systems to be interoperable and based on common standards. This
will mean that any pharmacist, in any country, can verify if a pack with
the same serial number has been dispensed before, irrespective of
country of origin and final destination. Without this standardisation
and interoperability, there is the risk that a product code will only be a
valid way of verifying provenance within national borders. Currently,
national coding systems vary considerably, not just in technology but
also in the information they contain. Second, any potential solution has
to be acceptable and accessible to all actors in the supply chain. This
means it needs to be reliable, appropriate, effective and cost-effective.
WORLDPHARMACEUTICALFRONTIERS
|
www.worldpharmaceuticals.net 69
Insight > Logistics > Product security
The risk of counterfeit products infiltrating the supply chain is growing ever greater. Colin Mackay
explains how EFPIA’s new coding initiative, recently piloted in Sweden, provides a model for an
end-to-end verification solution that will offer robust protection.
It also
means
avoiding gold-plated
solutions and basing the technology
on that which is already proven and robust.
As the representatives of the research-
based industry in Europe, the EFPIA (the
European Federation of Pharmaceutical
Industries and Associations), wanted to demonstrate its
commitment to patient safety, and proactively explored ways
to address this challenge. In September 2009, the EFPIA
launched its pilot of a potential solution based on the concept of an “end-
to-end” system, technically known as ‘product verification at the point of
dispense’. This approach works on the premise that if the authenticity of
the product is ascertained at both the beginning and end of the supply
chain – that is, at the point where it leaves the manufacturer and at the
point where it is dispensed by the pharmacist – then the risk of a
counterfeit reaching the patient is minimised. The system encodes
various elements of product information onto a two-dimensional data
matrix or barcode, including product and batch code, expiry date and an
individual pack serial number. The code is scanned by the pharmacist at
the point of dispensing. The product status is automatically checked
against a database, which provides an alert if the pack has been
dispensed before, or if it is out of date or subject to a recall.
The pilot, which was carried out in the greater Stockholm area
and concluded in January of this year, set out to prove that the
approach was feasible and that the technology worked. It was carried
out with the cooperation of the Swedish pharmacy retailer Apoteket
AB, as well as Swedish wholesalers Tamro and KD Pharma. It ran for
about four months in 25 pharmacies, during which time more than
95,000 packs were scanned and verified before they were dispensed.
The packs used in the project had been supplied by 14 leading
pharmaceutical companies. On completion, the results of the project
were analysed by measuring key technical elements, such as system
availability, reliability, and performance, by collecting and reviewing
user feedback as well as by external assessment of IT system security
and protection of data. The key findings were:
the product verification at the point of dispense works in practice ■
it provides for effective identification of fake packs as well as ■
expired packs and recalled products
the observed system availability and performance allows ■
pharmacists to work at normal pace and without significant
additional effort
the system is easy to use when fully integrated into the pharmacy ■
workflow and existing pharmacy point of sale system
the speed and ease of use provide high levels of user acceptance. ■
End-to-end, ePedigree or track and trace?
The EFPIA end-to-end approach offers a solution that is both
proportionate to the threat as well as being effective and cost-effective
for all actors in the supply chain. The results from the pilot project
show that this approach works and can meet the needs of the
crucial actors in the supply chain, namely the hospital and retail
pharmacists. Perhaps most importantly, as the proposed solution is
based on proven technology, it can be deployed relatively quickly, a
major consideration given the nature of the threat.
It is not full ePedigree, nor is it an RFID-based approach with full
track-and-trace capability. However, under the circumstances, is that
important? Probably not, as it offers a serialisation solution that is
effective, affordable and can be deployed rapidly, tackling the threat
before it grows any larger. In fact, given the less-than-homogeneous
nature of pharmacy in Europe, with many one-person and small
family businesses involved, the cost of full track and trace would be
prohibitive, while offering no conspicuous benefits.
There are legitimate concerns that track and trace is not really
suited to the multiple packing unit types used in the industry. From a
patient safety perspective, such a solution would only be gold-plating,
and by waiting to get the technology right it may well delay the
introduction of any measures; as the technology is not yet ideal for use
in a pharmacy environment it probably is not appropriate for individual
packs in the retail pharmacy environment. In addition, most of the
advantages that such an approach provides are logistical, rather than
geared towards patient safety.
The EFPIA solution, based on the model of the Swedish pilot
project, is a potentially important approach in the challenge of
eliminating counterfeits from the supply chain. It cannot be the whole
solution, but must be coupled with harmonised and standardised
product codes across Europe – as would any effective solution that
would work effectively cross-border.
If the solution is adopted, there are numerous other potential
benefits likely to spring from its deployment. Although patient safety is
the primary focus, other aspects of modern healthcare provision could
be delivered by the application of this technology. These include:
allowing product expiration to be verified ■
simplification and automation of product recall ■
automatically blocking dispensing of recalled products ■
the provision of product type verification information for ■
integration with current and future electronic patient record
(EPR) systems
a data provision capable of providing product identity for ■
reimbursement can also be used by a patient EPR system to
check that the drug dispensed matches that required on the
prescription and also could be used to highlight any potential
patient/product incompatibilities.
These are potential future functions, but could be provided by an
end-to-end verification system. However, what is most important is
that the threat of counterfeiting is treated as the growing threat it
represents. This means making it easy for actors to embrace the
solution by making it affordable, accessible, reliable and easy to use. It
also means acknowledging the reality of the modern European
pharmaceutical marketplace, with its complex cross-
border movements. ■
WORLDPHARMACEUTICALFRONTIERS
|
www.worldpharmaceuticals.net 70
Insight > Logistics > Product security
Colin Mackay
Colin Mackay is the Director of Communications and
Partnerships for EFPIA, the Brussels-based European
Federation of the Pharmaceutical Industries and
Associations. He is involved in the pilot EFPIA coding
project, validating the concept of an end-to-end verification
system based on a 2D data matrix, to reduce counterfeiting.
Company insight > Logistics > Product security
WorldPharmaceuticalFrontiers
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www.worldpharmaceuticals.net 71
t
he pharmaceutical industry uses special features to
provide protection against counterfeiting in the widest
possible range of applications.
For example, using a RFID chip for the pallet packaging
satisfies both the logistics requirements in the supply chain and
allows simple validation of the authenticity of the shipment.
Anti-counterfeiting features are increasingly being applied
when it comes to the packaging of the individual item or the
retail packaging. Both overt security features, those that are
clearly visible to the end-user, and covert features are used.
Employing RFID on individual packs is extremely difficult to
implement, however, and involves expense and considerable
technical effort. So far, other approaches have usually been
sought, and adopted.
Overall, a significant increase in the amount of security
packaging is apparent on the market. There is hardly a company
that is not intensively involved in a working group in dealing
with the problem of counterfeiting. The strategies developed
within these working groups and subsequently implemented are
different: they range from a company’s own taskforce for
checking products in the marketplace through to evaluation
using electronic and optical reader systems.
It is generally accepted, however, that when counterfeit
products appear on the market the companies affected must be
able to show that they have made serious attempts to avoid
counterfeiting and simplify its recognition. From a legal point of
view, this is particularly important where the North American
market is concerned.
In order to be able to validate the authenticity of individual
packs, the secondary packaging, usually a folded box, can have
a number of overt, covert and even haptic features. A means of
providing anti-tamper-evidence should be integrated into
packaging to prevent it being reused.
There are several arguments in favour of adopting at least
additional protection for the primary packaging:
The outer packaging is often disposed of immediately, ■
but the blister pack remains with the patient until it has
been used up completely.
Blisters cannot be opened non-destructively, so they ■
cannot be reused and are thus tamper-evident.
Parallel imports are possible worldwide so repackaging ■
cannot be ruled out. Here, too, the product stays in the
original blisters.
As a further step, the preparation itself can include security
features. For example, taggants and markers that make it easier
for the drug maker to check the authenticity can be included
in a tablet.
The number of anti-counterfeiting features and tamper-
evidence solutions available is almost unmanageably large and
a multitude of different manufacturers offer the most varied
technologies. However, protection against counterfeiting often
starts with the blister design; in other words there is a big
difference between a blister printed only in black on one side
using random printing or one printed in 10 colours on both
sides. Use of a more complex print design will deter potential
counterfeiters or they will reach the limits of their capabilities
for copying the design.
conversion stages
The various conversion stages in the manufacture of packaging
materials can be used to apply security features. With aluminium
foil, a customer-specific distinguishing mark can be applied
directly during rolling. This is one of the most effective and
economical solutions for a broad range of applications. Where
smaller quantities are involved, aluminium foils with a neutral
wallpaper design are available.
Each packaging stage should be considered separately
and has different advantages and disadvantages, but if the
worst comes to the worst, having a possible means of
identification on the primary packaging would appear to be a
particularly secure and reliable approach. The whole of the
manufacturing process as well as subsequent processing
with its associated requirements have to be taken into
account here, however. The blister cover and bottom foils are
subjected to significant abrasion by the sealing tool or the
deep-drawing operations, so not every feature is suitable for
these processes. Even at an early stage of the project, close
co-operation between the supplier of the security technology,
the machine manufacturer and the packaging material producer
is essential. ■
anti-counterfeiting solutions –
protection where it is needed
A range of anti-counterfeiting features are increasingly being applied to the packaging of
pharmaceutical products as the industry moves to reduce the problem.
Further information
Constantia Hueck Folien GmbH & Co.KG
Website: www.constantia-fexibles.com
Email: pharma@constantia-fexibles.com
H
ealth is such an important asset that we must
protect it with everything we have at our disposal.
However, the market is flooded with millions of
counterfeits as criminals forge the complete product spectrum
ranging from lifestyle products such as hair restorers to critical
pharmaceuticals such as cancer medications. Of great concern,
in addition to incalculable health risks for consumers and
billion-dollar losses for the industry, is the fact the forgeries
are difficult to detect.
The IT-based serialisation of individual pharmaceutical
packages is aimed at putting an end to this situation.
As long as a counterfeit pill is the same size, shape and colour
as the original, neither the physician nor the pharmacist – not to
mention the consumer – are able to identify it as such. This can
only be accomplished with modern analytical methods where
the medication is broken down into its components and
chemically analysed at great cost. Of course, this is impossible
in everyday use.
What is more useful and efficient is to come up with methods
that tackle the problem at the beginning of the supply chain, i.e.
where the pharmaceuticals are packaged at the manufacturer or
contract packager.
Take control
The tagging of pharmaceutical products is already being carried
out today, but mostly at the pallet or container level. As a result,
it is difficult to clearly determine the source and authenticity
of individual packages. At the pharmacy or doctor’s office, all
patients, doctors and pharmacists can do is check the printed
data such as names, active ingredients and the manufacturer’s
label against the prescription – and hope that everything is
in order.
According to the latest figures published by European
customs authorities, this is a risky undertaking, however. During
the first European Union-wide coordinated customs operation,
more than 34 million counterfeit pills were confiscated over two
months in 2008 alone. In addition to antibiotics, the impounded
products included mostly cholesterol reducers, cancer and
malaria medications, erectile dysfunction pills and painkillers.
The forgeries had either no or diluted active ingredients, or even
wrong active ingredients, which means that they could even be
deadly in a worst-case scenario.
That’s why governmental and non-governmental institutions
demand binding legal guidelines for the clear labelling of
pharmaceutical packages as is already required by the United
States’ Food and Drug Administration (FDA) and recommended
by the European Federation of Pharmaceutical Industries and
Associations (EFPIA). The latter is working to design a
standardised platform to protect against counterfeit medications
by creating a uniform coding and identification solution for the
European pharmaceutical industry.
Individual identification
The solution, which is based on information and communication
technology from Siemens, has been tested since October 2009 in a
pilot project in Sweden. It requires each package of medication to
be identified via a unique ID code before being given to the
customer. This code consists of a serialised 2-D data matrix code
and a serial number. Compared with other methods such as radio
frequency identification (RFID) tags, this method is relatively
inexpensive, because adding the data matrix imprint with regular
ink costs less than one cent. The cheapest RFID tags, on the other
hand, cost at least 10 cents. In addition, the code is easy to create
and affix as long as the manufacturer has the appropriate
equipment. In practice, the solution works like this: the code is read
with a scanner and forwarded to a system, where it is checked for
authenticity. If a number appears twice, the system issues a
warning. In response, the pharmacist or other persons handling the
product can immediately withdraw it from circulation.
Identifying forgeries takes more than a code, however.
Monitoring and tracking medication packages across the entire
supply and production chain requires an effective and
transparent data management system that ranges from the
packaging process to the enterprise resource planning (ERP)
and (supply chain management) SCM systems.
Serialisation solution
for a counterfeit crises
A new serialisation system, which requires each package of medication to be identifed via a
unique ID code before being given to the customer, is to lead the fght against the problem
of medical forgeries, which cost the industry billions of dollars in lost revenue and pose
signifcant health risks for consumers.
Company insight > Logistics > Product security
WorldPHarmaceuTIcalFronTIerS
|
www.worldpharmaceuticals.net 72
During the first EU-wide
coordinated customs operation,
more than 34 million counterfeit
pills were confiscated over two
months in 2008 alone.
Company insight > Logistics > Product security
WorldPharmaceuticalFrontiers
|
www.worldpharmaceuticals.net 73
Needless to say, all of these processes are backed-up by a
great deal of technology and a lot of industry expertise. For
example, the IT service provider, Siemens IT Solutions and
Services, as one of the main suppliers of the EFPIA project
contributes not only the links to the pharmacies but is also
responsible for the project management and the information
interfaces between pharmacies and pharmaceutical companies.
Other duties include the operation maintenance of the IT
infrastructure, data integration, and system development
and security.
Global and local
What makes the serialisation solution from Siemens so special
is the fact that it is just as suitable for globally operating
pharmaceutical companies as it is for the little pharmacy on
the corner. Since the solution is highly adaptable, it meets the
needs of today’s production and packaging environments
where products for many countries are manufactured on a
single line. Different templates meet the requirements of all
country-specific regulations and configurations such as those
governing expiration dates. In England, for example, the date
must be expressed as day-month-year, while the U.S. requires
month-date-year.
In addition, different countries have different requirements
regarding the generation of serial numbers (European
requirements are stricter than those in the U.S.). The European
pharmaceutical industry, for example, often uses randomly
generated numbers instead of consecutive serial numbers. Plus,
many companies use third-party contractors in the production
and packaging of pharmaceutical products. These include
packaging specialists, who must be included in the
comprehensive process across all stations in the supply
chain. Another important consideration to be taken into
account is the fact that most companies already have a
validated system for handling their packaging lines to which
the new, separate serialisation systems must be able to link
with reasonable effort and cost.
To meet these countless requirements, a particularly
important feature of the Siemens AutoID Connector (SAC) comes
into play: as can be expected from one of the world’s largest
SAP partners, Siemens, the serialisation solution is SAP-certified
and can therefore be fully integrated into the SAP environments
of most chemical and pharmaceutical companies. The customer
ultimately benefits, because this ensures the consistent
administration and exchange of serial numbers from logistics
partners down to the retail level. The system therefore supports
the customer not only by issuing serial numbers on the
packaging line, but during subsequent steps such as in
distribution centres or when communicating with contract
packagers or contract manufacturers.
What sounds nice in theory also works in practice. Together
with an international packaging specialist, Siemens recently
introduced its serialisation solution in a packaging line and
tested the unique identification of products on the article level –
at high speed and with great success. This success benefits the
company and its customers alike, because product serialisation
protects not only the consumer, but makes manufacturers more
efficient. Forgeries are prevented from the start, which is good
for the bottom line. In addition, the system provides
unprecedented transparency across production processes,
distribution channels and life cycles, which makes it easier to
identify potential savings. And if a batch or an individual
package nevertheless turns out to be defective, a recall is
quickly and easily accomplished. The serial number makes it
easy to find out which packages were manufactured and
distributed during a specific period of time, thus limiting
potential losses and liability claims.
the best of both worlds
While the introduction of legal guidelines for the standardised
marking of pharmaceuticals creates some costs, it also provides
companies with opportunities to improve their efficiency and
customer relationship management. California is leading the
way in the serialisation of electronic pedigrees for drugs, and
from 2015 the U.S. state’s law is expected to require every single
product to carry a unique number.
Similar policies have already been implemented or are in the
process of being introduced in several European countries too.
In Turkey, for example, since October 2009 all medical products
intended for humans must be individually encoded, and France
plans to make coding of the individual packages obligatory as of
the beginning of 2011. Outside of Europe, countries such as the
U.S. or South Korea are also considering the introduction of such
regulations. Brazil is looking to introduce serialisation
regulations by January 2011. After all, health is an important
asset all over the world. ■
In Turkey, all medical products
intended for humans must be
individually coded, and France plans
to make coding of the individual
packages obligatory from 2011.
Further information
Siemens IT Solutions and Services
Website: www.it-solutions.siemens.com
Email: juergen.manz@siemens.com
Event Partner: Associate Partners: Sponsors: Exhibitors: Organized by:
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Improving Agility Of Your
Integrated Supply Chain To Reduce
Response Time In A Volatile Market
`Great conference, excellent speakers,
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the best one in Europea
Christoph Feldman, Director, Logistics Strategy & Business Solutions Europe/AFME, Pzer
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5821.indd 1 15/02/2010 16:51
F
rom brand owners to wholesalers, retailers to consumers,
product piracy is a phenomenon affecting the entire supply
chain. An all-inclusive solution is, consequently, the most
effective way to protect against the illegal activity which is
undermining the integrity of the pharmaceutical industry.
Three shareholders have collaborated to create Europe’s first
comprehensive Software as a Service (cSaaS) solution, which gives
every participant along the supply chain total confidence in the
authenticity (or otherwise) of the product in front of them. SAP
provides the supply chain management capabilities, Nokia offers
mobile authentication solutions, and Giesecke & Devrient ensures the
security of the operation through its encryption technology.
‘There has been a lot of positive feedback within the industry
regarding the service we are able to offer,’ Original1’s CEO Claudia
Alsdorf says. ‘It is a holistic package able to both track and trace, and
verify the authenticity of a product.’
Every member of the supply chain is able to check whether or not a
product is genuine via Original1’s mobile phone-based, easy-to-use
secure item level product authentication service, which supports
barcodes, RFID tags, copy detection patterns, holograms or other
machine-readable marker technologies. Combined with detailed
product information, logistics data and track-and-trace technology, an
unprecedented level of visibility is guaranteed.
Beneficiaries of the technology operate across an array of sectors –
from retailers to government bodies. ‘The customs officer is not only
able to confirm whether or not the product is real or fake, he can also
get information about the shipment,’ Alsdorf explains. ‘If a product
was shipped yesterday out of China and arrives in Germany the next
day, something is obviously wrong in the supply chain and he can
begin to investigate.’
It is crucial that as many people as possible verify the product’s
authenticity via their mobile phones. ‘With a large number of
verification points, you get a higher information density, leading to an
increased security level,’ Alsdorf notes. The manufacturer or brand
owner is the only member of the chain who must pay per item, so the
number of authentications will not increase the cost of the service.
Original1’s user management system means that the most relevant
information is available to each member of the supply chain. ‘The
consumer needs access to the product information, but it is more
important for the customs officials to receive detailed track-and-trace
information,’ Alsdorf remarks. ‘The retailer, on the other hand, is more
interested in the right package being delivered to the right location.’
While Alsdorf’s service is key to the improvement of the situation in
Europe, the pharmaceutical industry also needs to implement a
comprehensive plan to prevent the spread of product piracy. In
response to the European Commission’s draft directive, which aims to
reduce the risks of counterfeit medicines entering the legitimate
supply chain, the European Federation of Pharmaceutical Industries
and Associations (EFPIA) has piloted a mass serialisation scheme in
Sweden. It aims to improve the coding and identification of products
through the use of a 2-d data matrix.
Yet as the situation gradually begins to improve across Europe, less-
developed nations continue to suffer. ‘We aim to expand into the
Asian-Pacific and African markets,’ says Alsdorf. ‘It is important to
have a global presence and the problems are worse in those areas.
‘We have had to adapt the service for Africa because most mobile
phones there do not have cameras. In order to use the majority of our
technologies you need to scan the product with a camera, but we
have adjusted the system to solely use SMS technology.’
As Original1 extends its offering and governments increase the
hurdles for perpetrators of criminal counterfeiting, the situation looks
set to improve. Yet until mass serialisation becomes mainstream and
every pharmaceutical company is obliged to perform a verifying scan
at the distribution point, the problem will not be entirely solved. ■
The real deal
As counterfeiters’ techniques become more sophisticated, the diffculty of controlling unauthorised
activity along the supply chain is increasing. Software service provider Original1 offers its
customers a comprehensive solution, which, as CEO Claudia Alsdorf explains, combines supply
chain integrity, secure item level product authentication and Nokia’s easy-to-use mobile technology.
Company insight > Logistics > Product security
WorldPharmaceuTicalFronTiers
|
www.worldpharmaceuticals.net 75
Further information
Original1
Website: www.original1.net
Email: info@original1.net
Mobile phones are used in the fght against piracy.
Insight > Manufacturing
WORLDPHARMACEUTICALFRONTIERS
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www.worldpharmaceuticals.net 76
I
n the late 90s, ‘benchmarking’ was a pandemic infection of
the pharmaceutical industry, which bore the hype of making
our industry stronger and more resistant in an increasingly
competitive environment through the enhancement of our own
processes and innovations by learning about the processes used
by other industries.
This was also a time when pharmaceutical companies started looking
across their own boundaries, as they felt themselves being squeezed in
a regulatory environment that did not allow a lot of changes to existing
processes. Nevertheless, the aviation industry was identified as an
interesting benchmark, because it is highly regulated, complex and –
similar to drug development – a plane must fly right the first time.
The engineering industry had been accustomed to meeting these
challenges by using the Six Sigma business management strategy.
The basic concept of Six Sigma is to improve the quality of process
outputs by identifying and removing the causes of a defect, while
minimising variability in manufacturing and business processes. At
the beginning of this century, the pharmaceutical industry, academia
and regulators started to think along these same lines to see how a Six
Sigma model could be applied to pharmaceutical product
development and manufacturing, and a few years later ended up with
commonly developed guidelines known as ICH Q8, 9 and 10.
QbD– Just another word for the same thing?
Pharmaceutical development people are likely to say that Quality-by-
Design (QbD) is not a new paradigm as they have always developed
products that meet global pharmaceutical quality standards. While
this is true, they admit that their process was based on gathering a
huge amount of data during development followed by pure repetition
of the same processes several times to define the quality based on
the resulting specification. When the product and process was then
scaled up and transferred to manufacturing, limitations of the
process became visible and required further specification tightening
or even re-qualification due to modifications to the original
processes. Product losses due to out-of-specification intermediates
or end products occurred constantly, significantly contributing to the
overall manufacturing cost of pharmaceutical products.
However, pharmaceutical development people are likely to agree
that the traditional approach, also considered as Quality-by-Testing
(QbT) does not really provide the true product and process
understanding that Quality-by-Design is aiming for. While in practice
both approaches might have been based on prior knowledge, the real
difference is that QbD seeks out the product and process parameters
that are critical for product quality (risk assessment) early on in the
development process. It then investigates the variables and their
correlation to critical process parameters to achieve the desired
product quality (Design Spaces). With the identification of the critical
process parameters, and by using Process Analytical Technologies
Better
by
design
The pharmaceutical industry is starting to
move away from a tradition of quality by
testing, towards quality by design. This may be
an uncomfortable time for drug development,
but the reward will be a comfortable future, as
Sven Stegemann discovers.
Dr Sven Stegemann
Dr Sven Stegemann is director of
pharmaceutical business development
at Capsugel, a division of Pfizer. He works
closely with the pharmaceutical industry on
new product development, scaling up
and the manufacturing of challenging
compounds.
Insight > Manufacturing
WORLDPHARMACEUTICALFRONTIERS
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(PAT), on-line quality measurements can be established in commercial
manufacturing allowing continuous process monitoring and decision
making to achieve the desired product quality.
Driving quality-by-design
Pharmaceutical manufacturing and QA people are generally viewed
as those most resistant to change, as they carry the burden of the
validation and documentation that goes along with each change.
Conversely, manufacturing people were always instructed to improve
the manufacturing process efficiency throughout the lifecycle of the
product. So it was not surprising when manufacturing people were
the first to pick up the application of QbD principles, retrospectively
identifying the critical process parameter, investigating the Design
Spaces, putting in place PAT measurements and finally
implementing them into their manufacturing processes approved by
the regulatory authorities. Aside from the regulatory flexibility
gained, product quality and process efficiency went up, resulting in
considerable manufacturing enhancements.
Pharmaceutical manufacturing and QA people are now starting to
see their time to drive innovation and efficiency in manufacturing
processes, starting with the possibility of supporting continuous
improvements using Design Spaces. They have identified the
possibility of moving away from a ‘batch manufacturing concept’ to
a ‘continuous manufacturing process’ and from a ‘final product
testing’ to an ‘in time release’ of the product. But, these expectations
can only be achieved by truly moving from QbT to a QbD approach
early in the development. So it is no surprise that in many
companies, the manufacturing department is driving the QbD
process backwards to the R&D departments, which are defining
their processes to apply QbD in product and process development.
Benchmarking, opportunities and pharmaceuticals
Some years ago, through sophisticated and expensive drug delivery
system manufacturing, companies had the potential to increase their
revenue stream. Formulation patents were successfully used to keep
generic competition away from the market while product sales were
at a peak, and the additional manufacturing costs were easily
compensated for by the several months and years of additional
exclusivity. In recent years though, the formulation patent claims have
become more specific and narrow and easy to work around, while
generic companies have developed an expertise in working around
them. Therefore, the strategy of using formulation patents does not
necessarily guarantee the expected return on investment, and also
carries the risk of being stuck with highly complex manufacturing,
while generics manufactured in low-cost countries enter the market.
With global warming, environmental protection and sustainability
in the public spotlight, companies have not only established
environmental health and safety groups, but are also aiming to make
their manufacturing processes as efficient as possible. A huge threat
to this is the high amount of product loss during today’s
Insight > Manufacturing
WorldPharmaceuticalFrontiers
|
www.worldpharmaceuticals.net 78
manufacturing, which Fritz Erni from Novartis estimated at between
5 and 15%, most of which occurs in later phases of the
manufacturing process when the resources have already been used
and rendering the product a complete loss. Moreover, the lost
material needs to be destroyed, consuming additional resources.
Another manufacturing challenge will result from the increasing
numbers and life expectancy of baby boomers and the resulting
change in the average age of the medicines user groups. Today,
roughly 10% of the population is 65 years and older, consuming
30-50% of all prescription medicines. In 2050, 20% of the population
will be 65 years and older and they are expected to use 60–90% of all
prescription medicines. Declining physiological reserves,
co-morbidity and polypharmacy are all age-related issues that
require individualisation of medicines in dose strengths as well as
visual differentiation. Rather than large-scale, one-product
operations, flexibility in manufacturing will become a critical asset to
provide individualised medicines at affordable costs.
Finally, access to medicines around the world is an ethical
obligation for the developed countries as well as the pharmaceutical
industry. To achieve this objective, affordable medicines must be
made available, even in the poorest countries, without compromising
product quality. Though some companies have set up programmes
to donate HIV treatments to the poorest countries around the world,
these initiatives alone will not be able to provide access to essential
medicines for all human beings on earth.
Qbd and beyond
When pharmaceutical companies examined the product process, the
large number of individual operational steps, high quantity of input
materials, and significant resources used to manufacture a product
suddenly became visible. Moreover, when performing the risk
assessment, companies quickly realised that each component and
each unit operation adds huge complexity and potential risk of failure
to achieving the desired product quality in routine manufacturing.
Additionally, input resources such as energy, water and waste water
used for each unit operation as well as in process controls for
intermediates and inventory, GMP manufacturing space and so forth,
all of which were normally hidden in the overheads, appeared detailed
in the manufacturing cost analysis and the sustainability reports.
The paradigm starts shifting as pharmaceutical engineering
comes into the product and process development. Instead of
focusing product development on the combination of excipients
and applying standard processes, pharmaceutical engineering tries
to understand the product and its behaviour in a process, and how
that process can be driven to achieve a consistent product
attribute in the most efficient way. Instead of staying with random
processes in which the material might be more or less exposed to
an operational step, pharmaceutical engineering aims to develop
continuous processes to consistently expose the product to an
operational step. Process engineers are now exploring new ways of
manufacturing pharmaceutical products including control
strategies to monitor and secure the desired product quality.
Eventually, the paradigm will continue to shift as the industry
recognises increased manufacturing efficiency that, in parallel, will
reduce the input resources needed to manufacture a product.
Environmental protection and sustainability can not only be used to
improve the public perception of the pharmaceutical industry, but
will also be critical for increasing the manufacturing efficiency as
costs for input and output resources such as energy, water and
waste water are expected to increase continuously over time.
Finally, the availability of affordable products around the world
comes closer to reality when products are developed using QbD and
with simplicity in mind. This should be fairly simple for products
that have no real technical or biopharmaceutical challenge. For
example, powder blends in a capsule is a basic four operational unit
process: sieving, weighing, blending and filling, and capsule filling
machines are considered standard machines that exist around the
world. Good capsule formulations consist of the API and as little as
three standard excipients such as disintegrant, lubricant and diluent.
This is just one example of how the industry can manufacture
quality medicines in a simple and efficient way and has triggered a
more rational dosage form decision process, challenging the “first
intend tablet” guidance in several leading pharmaceutical companies.

Qbd: From theory to practice
To date, there have been no general proceedings on implementing
QbD in the pharmaceutical industry and hence, each company is
trying its own way. As with all paradigm shifts, it could be assumed
that the organisations will not jump on the new guidelines and start to
implement them immediately until they are required to do so,
however, many companies have started at least one smaller project
investigating how the guidelines could be brought into practice.
One example is Johnson & Johnson. It tested the cleaning process
for a fully automatic chromatographic system used for large-scale
separations, which was cleaned by a standard protocol with final
cleaning verification. This process was reviewed and a PAT
measurement was implemented to verify the time progress, which
was then compared to the standard protocol with cleaning
verification. The results showed a 40% reduction in costs and time, as
well as a large reduction in greenhouse gases since the waste solvents
are incinerated creating a substantial amount of greenhouse gases.
Moreover, they identified a potential risk for cross-contamination
which could be eliminated, and the opportunity to move to a real-time
release of the equipment for immediate further use.
In another recent paper, Aggarwal described the manufacturing
of a small molecule with a yield of about 40%. Since many factors
could impact the synthesis, they set up a sequential design of
experiments (DoE) and identified solvent volume, catalyst load and
reaction temperature as impacting the yield of the molecule.
Further experiments found that increasing temperature, increasing
solvent volume and decreasing the amount of catalyst could raise
the yield of the drug molecule to above 90%.
It is clear that the industry is moving from guidelines and
theory to practice and shifting its paradigm. Manufacturing costs
still represent about 25-35% of pharmaceutical industry costs.
Uwe Reinhardt from Princeton University estimates manufacturing
costs at an average of 27% of the industrial costs and initial
applications of QbD have confirmed that there is considerable
potential to increase the efficiency through process simplification.
At the end of the coming decade, continuous manufacturing
processes with in-time-release might be the standard for all new
pharmaceutical products reaching the market. ■
F
n the 1980s and 1990s, after years of a lack of
investment, chemical and petrochemical companies
were grappling with infrastructure that had deteriorated
and was in poor condition. Failures of over-stretched assets
such as pipe bridges, utilities and electrical distribution systems
were causing loss of production and required unplanned and
expensive remediation. As life science companies rationalise
capacity and extend timescales for manufacturing assets they
will increasingly face the same issues. This challenge is further
compounded by the variety and diversity of assets and
standards resulting from ongoing merger and acquisition
activity in the sector.
ABB Engineering Services has a tried and tested approach to
asset assessment and asset life planning and costing. ABB’s
Reliability and Integrity Management Excellence (pRIME)
programme helps clients achieve sustainability and reliability
from assets.
The pRIME programme is applicable across all industries and
can help life science companies address asset issues. It can be
applied at a strategic
level or at a detailed
level. In so doing it
can provide:
continued licence to ■
operate – technical
justification for
operating equipment beyond its design life
stakeholder confidence in continued safe and ■
reliable operation
value added from avoiding production loss, ■
unnecessary expenditure, and from improvements made
investment information to plan future CAPEX and ■
OPEX requirements for assets. ■
Protect your assets
ABB Group provides an asset management perspective on the
challenges faced by the life sciences industry.
Company insight > Manufacturing
WorldPharmaceuticalFrontiers
|
www.worldpharmaceuticals.net 79
Further information
ABB Engineering Services
Website: www.abb.com/consulting
Technical Consultancy.
Managing performance
- managing compliance
ABB Engineering Services as part of ABB Global Consulting provides technical
services to improve performance in the areas of compliance, operations and
engineering to customers in the life sciences industries worldwide. Improving
operational performance in the life science sector through world class expertise
in: asset integrity; process safety & risk management; operations improvement;
maintenance optimization; asset retirement & data archiving; compliance
services; technical training; validation & quality. www.abb.com/consulting
ABB Engineering Services
Tel: +44 (0)1925 741111
E-mail: contact@gb.abb.com
World Pharms Frontiers (178x124mm) 12-03-10.indd 1 12/03/2010 14:48:28
The pRIME programme is
applicable across all industries.
WorldPharmaceuticalFrontiers
|
www.worldpharmaceuticals.net 80
Company insight > Manufacturing
h
ow do you maintain the safety of your staff in the lab?
Weighing out powdery, often hazardous substances on
an analytical balance is an everyday task in the
laboratory. The trend in pharmaceutical development is towards
smaller particle sizes that are easily soluble, have a greater overall
surface area per mg, and reach deep into the lungs for faster effect.
While this makes drug delivery more effective, the trend towards
micronised drugs consequently puts analysts at a greater risk.
Exposure to potent compounds can occur through four main
routes: inhalation of airborne particles, digestion due to poor
hygiene control when leaving the laboratory, dermal absorption if
gloves are damaged or not worn, and touch contamination simply
by adjusting glasses or face masks. Employers have a responsibility
to minimise this risk and a first line of defence is the use of
personal protective equipment, which can range from gloves and
safety glasses to masks and even whole body suits. Additionally,
regulation requires that hazardous substances must be weighed in
a containment system. While these measures increase personnel
safety, they are often uncomfortable and restrictive, resulting in
longer process times and increased risk of substance spillage.
Quantos offers a solution to reduce the overall exposure risk,
combining accurate automated powder dosing and a process-
specific containment system.
Implementing automation instantly reduces the risk of repeated
exposure to a hazardous substance. The Quantos dosing head is
initially loaded with compound and then sample dispensing can
begin. An RFID chip embedded in the dosing head stores relevant
information such as substance ID, amount dosed and the date.
Once the dosing head is charged, the vial or bottle is stored with
the head attached, avoiding the need to re-open during the lifetime
of the dosing head. After a maximum of 250 doses the dosing head
can be safely disposed of, avoiding unnecessary cleaning
procedures and further risk of exposure.
An added benefit of automation is the controlled and reproducible
manner of processing. Quantos dispenses accurately and
reproducibly down to 1mg (10mg USP) into vials with an opening as
small as 6mm diameter. Eliminating spillage immediately increases
process safety and results in cost savings due to less waste.
An analyst manually weighing 100mg inside a safety enclosure
typically takes two to three minutes per weighing. Quantos speeds
up the weighing process itself to increase overall throughput, and
perhaps more importantly, the drug is handled quickly and
efficiently to reduce the time for airborne contamination and
exposure to occur. 1-250mg is dosed in 30-60 seconds and the
system can be operated from outside a glove box. Up to 30
automatic doses can be achieved without user intervention with an
optional Autosampler, Quantos QS30.

Keep it contained
Exposure risk can also be significantly reduced by the correct
selection of containment system for the process being carried out.
A1 Safetech, the leading supplier of containment technologies, has
worked with Mettler Toledo to develop a purpose-built safety
enclosure for the Quantos QB1 powder dosing system, ideally
suited to the process of weighing powders and designed for
ergonomic operation that is ideal for relieving the inconvenience of
manually working inside an enclosure, especially with restrictive
personal protective equipment. Together, Quantos offers the ideal
solution to address safety risks with the added benefits of higher
dosing throughput and cost savings through accurate, smaller
sample sizes and reduced substance spillage. ■
Pursuing a policy of
automatic containment
Hygienists and safety managers aim to engineer out the use of personal protective equipment
by introducing containment technologies or safer sample handling processes. Mettler Toledo
has addressed the everyday challenge of manually weighing hazardous substances and presents
Quantos, an automated powder dosing system complete with process-specifc safety enclosure.
Quantos automated powder dosing
system with optional Autosampler for
up to 30 unattended doses, inside
process-specifc safety enclosure.
Further information
Mettler Toledo
Website: www.mt.com/quantos
Email: marketing.quantos@mt.com
Automatically dose as few as 10 mg of powder to within USP specifications –
an industry first!
Step 1 „Click“ in the innovative powder dosing head
Step 2 Enter the target weight
Step 3 Touch „Start“
Watch QWCPVQU automatically dose to your target weight – reliably, repeatably
and up to 20x faster than with a spatula.
Over JCNH of the leading global Pharmaceutical companies have already
invested in QWCPVQU powder dosing solutions.
When will you?
4
www.mt.com/quantos-wp
How do you weigh in 10 mg?
Company insight > Manufacturing
WorldPharmaceuticalFrontiers
|
www.worldpharmaceuticals.net 82
t
he built assets of companies in the pharmaceutical and
biotechnology industries have a high proportion of
manufacturing facilities and laboratories; this leads to higher-
than-average energy use compared with other industries.
Opportunities for performance improvement in new and existing
facilities are financially significant and thus worthy of consideration.
Arup works with many leading global companies, such as Procter &
Gamble, Pfizer, Walmart and Disney, to improve their energy efficiency
and sustainability performance.
drivers
Improvements in energy efficiency are a current focus for cost-
conscious companies. There is an ever-present threat of rising utility
costs and of potential legislation on carbon production, and the
reduction of energy use and of carbon emissions goes a long way to
prepare for these threats.
A clear policy, combined with sound technical guidance, is highly
advantageous to the delivery of tangible benefits. This article sets out
these two fundamental components.
sustainable policy development
A firm’s sustainability policy requires leadership commitment,
grass roots buy-in, a policy implementation team, goal-setting,
benchmarking, and the selection and measurement of key performance
indicators (KPIs). Arup’s approach to developing its own corporate
sustainability policy mirrors that of many of its clients. It includes:
the recognition by the company’s global leadership of the ■
need to implement a formal policy
the creation of a formal working group, with regional ■
representatives
the appointment of a group sustainability director to ■
develop and implement the policy
the establishment and development of global KPIs ■
the implementation of internal policy ■
the external reporting of sustainability measures. ■
Corporate sustainability guidance is most effective when planned
on two levels:
1. high-level targets
High-level targets typically include reductions in energy, water, waste
and carbon usage, and the establishment of global diversity targets.
Here, corporate direction on the capital and operating costs for
sustainability decisions is extremely beneficial.
2. technical guidance to achieve high-level targets
Arup’s research shows that there are approximately 100 potential
sustainability solutions for an individual laboratory or manufacturing
facility. In order to prevent project creep, many companies provide
clear guidance on which of these solutions should, or should not,
be implemented.
For example, some companies implement a minimum LEED
TM

rating on all projects; others focus on particular sustainability
objectives that are based on selected criteria, such as financial
payback. In addition, measurement and benchmarking have been
demonstrated as essential to drive change.
Key considerations to be included in guidance for sustainable
facility construction and operational improvements are:
sources of renewable energy ■
benefits and challenges of government incentives ■
assessment of both new and existing operations ■
selection and orientation of buildings on sites ■
building envelope (roof and façade) ■
lighting and day-lighting ■
active systems (such as mechanical systems) ■
water conservation and recycling ■
benchmark setting and the reporting of energy and ■
sustainability achievements (to promote internal and/or
external competition).
summary
Key benefits of a good approach to sustainability will include reduced
lifecycle costs, improved customer and public perceptions, enhanced
morale of employees, and readiness for future legislation. ■
save your energy
Sustainability and energy effciency are increasingly at the forefront of corporate strategies.
Although external drivers for companies are similar, policy and implementation can vary widely.
However, there are many approaches that can improve a company’s energy effciency and
sustainability, explains Duncan White, a leader of the Science and Industry business at Arup.
Further information
Arup
Website: www.arup.com
typical policy objectives
• to reduce impact from existing operations
• to demonstrate environmental stewardship
• to improve investor returns by reducing lifecycle costs
• to develop company culture around sustainability
• to specify targets on energy, carbon, water, waste, and diversity
• to prepare for the future.
How sustainable are you?
· Sustainability Policy
· Resource and conservation targets
· Renewable energy
· Energy efficiency
· Carbon emissions
· Waste reduction
· Water conservation
We are an independent global firm of
designers, planners, engineers, consultants
and technical specialists offering a broad range
of professional services. Through our work we
make a positive value added difference in the
world of pharmaceuticals and biotechnology.
We shape a better world.

www.arup.com
Contact:
Duncan White
duncan.white@arup.com
+ 44 (0)20 7636 1531

Joshua Yacknowitz
joshua.yacknowitz@arup.com
+ 1 212 229 2669
CHad3.indd 1 12/3/10 10:27:21
GE Power & Water
Water & Process Technologies
imagination at work
Analytical Instruments
To improve quality and reduce costs, pharmaceutical companies are
moving from laboratory-based water quality sampling to continuous
on-line sampling and real-time water release (RTR). If you have tried to
implement an RTR program at your facility, you know the challenges:
defining the project path, gaining cross-functional engagement,
demonstrating measurement system equivalency, and more.
GE Analytical Instruments has developed a program — Implementing
On-Line TOC for Real-Time Water Release — to assist you in delivering a
science-based, efficient approach to RTR process validation using
Total Organic Carbon (TOC).
Program Components
This RTR program has four main components: a one-day introductory
workshop, validation documentation, validation services, and a
consulting package. Each component is available separately
or with the complete RTR program. The complete program
is designed to guide you through the RTR process in
less than 6 months.
Learn More
Start improving quality and saving costs today. Find
out how you can efficiently implement an RTR process
validation. Contact us at:
303-444-2009 or 800-255-6964
geai@ge.com / www.geinstruments.com
Real-time TOC Water Release Program
Delivering Improved Quality at Reduced Cost with RTR
G
E Analytical Instruments, part of GE Power & Water,
manufactures highly sensitive and robust scientific
instruments, and is the leading provider of total
organic carbon (TOC) analysers to the pharmaceutical industry.
Companies worldwide rely on its Sievers TOC analysers for
monitoring and releasing pharmaceutical waters for USP, EP, and
JP compliance, cleaning validation and quality initiatives such
as process analytical technology (PAT). The company has
established market leadership in using TOC for cleaning
validation, and now offers a new science- and risk-based
program for implementing real-time release (RTR) of
pharmaceutical water.
Production benefits
TOC is a critical water quality attribute. Historically, the
pharmaceutical industry has measured TOC in the laboratory
using grab samples. This process is more inefficient and less
reliable than using online TOC analysers critically located within
the water distribution system. Laboratory-based quality systems
rely on analysts to take samples manually from the water system
and bring them to the laboratory for testing. This process is both
labour-intensive and time-consuming, causing delays in analysis
results and water release.
Laboratory-based testing is also very costly. Based on GE
Analytical Instruments’ estimates, a typical pharmaceutical
company analyses more than 2,500 routine TOC samples annually.
Depending on sample loads, each sample costs $55 to $111, most
of which is for manual sampling. By transitioning from the
laboratory to online TOC analysis, manufacturers can reduce
sampling costs by up to 90%.
Regulatory support
The pharmaceutical industry has been slow to adopt continuous
improvement strategies for various reasons, including the
regulatory uncertainty of applying guidances such as the FDA’s
2004 PAT document (called Guidance for Industry: PAT – A
Framework for Innovative Pharmaceutical Development,
Manufacturing, and Quality Assurance). However, because
both industry and regulators are realising that continuous
in-process measurements provide inherent quality
improvements and cost advantages, pharmaceutical quality
systems are moving to real-time analyses and process control.
The PAT document provides a framework for using process
analytical tools for compliance with current good manufacturing
practices (cGMPs). It defines RTR as “the ability to evaluate and
ensure the acceptable quality of in-process and/or final product
based on process data”.
Streamlining RTR
GE Analytical Instruments has developed a program called
Implementing On-Line TOC for Real-Time Water Release, part of
GE’s Quality System Optimization (QSO)™ service offering. For
short, the RTR program is called QSO/RTR. It provides a
framework for transitioning TOC testing from the laboratory to
the production floor. Historically, RTR programs have been
reputed to be complex, often taking years to implement. GE’s
QSO/RTR is designed to be implemented in six months. The
program incorporates lean manufacturing and Six Sigma® best
practices, aligned with cGMPs and regulatory guidance. QSO/
RTR provides a practical roadmap on how to evaluate variability
and identify opportunities for improvement in TOC sample
analysis processes. Table 1 shows some of the main components
of QSO/RTR.
Before embarking on an RTR project, it is critical that
companies assemble a team of decision-makers in areas such as
quality, operations, facilities and engineering. During the ‘Defining
Future State’ phase shown in Table 1 (above), a GE facilitator will
work with this cross-functional team through several critical
process design decisions using an analysis of the water system’s
current state, risk assessments and future state mapping to arrive
at an optimised solution for RTR. ■
Test the water
The real-time release of pharmaceutical water enables TOC testing to move from the laboratory to
the production foor, improving quality and reducing costs in the process.
Company insight > Manufacturing
WoRldPhaRmaceuTicalFRonTieRS
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www.worldpharmaceuticals.net 85
Further information
GE Analytical Instruments
Website: www.geinstruments.com
Email: geai@ge.com
Table 1: QSo/RTR Program detail
Validation Documentation and services
• Method validation
• Method comparability and transfer
• Measurement system equivalency
• Historical data collection and review
• Point-of-use quality verification
Consulting (Defining future state)
• Current state assessment
• Critical point of use screening
• Failure Mode Effects Analysis (FMEA)
and risk ranking
• Future state mapping
• Sample consolidation plan
• Implementation guidance
T
he use of water in virtually every manufacturing process is of
key importance to the pharmaceutical industry; even
processes that produce ‘solid’ products or use organic
solvents still rely on water at some stage. Ensuring that a water
system consistently and reliably meets the requirements of the
pharmacopoeial specifications, the demands of the process and the
expectations of regulatory inspectors, is never simple. Combining
these demands with the commercial and financial constraints of the
current economic environment only makes the task more difficult.
At the start of 2009 two mega-mergers and a takeover were
announced. At the end of January, Pfizer announced the takeover of
Wyeth, then six weeks later Merck & Co acquired Schering-Plough
and Roche took full control of Genentech. Other deals announced
included Solvay selling its pharma business to Abbott. The fallout from
these changes began to become apparent towards the end of the year,
with announcements of job losses. However, it was not just newly
merged companies shedding jobs; Johnson & Johnson, Lilly,
AstraZeneca and GlaxoSmithKline all announced job cuts. Further
cost-cutting seems inevitable. Also, despite the pharmaceutical
industry not feeling the full wrath of the global downturn, the crisis is
bringing new pressures, which may also lead to cuts.
Another big trend for 2009 was an expansion in interest in
emerging markets – particularly pharmaceutical companies setting up
research sites in China. Novartis, Pfizer, Bayer Schering Pharma and
Merck Serono are all setting up R&D facilities. The recession is also
opening up a big gap in output performance between the chemical
industries of the developed and developing worlds, which will
continue to widen over the next few years. There is also a significant
increase in the number of new facilities being built in countries such
as India.
A further trend that will continue for the foreseeable future is an
increasing focus on the carbon footprint of a product, process or entire
facility. Linked with this is the concept of ‘embedded water’, that is,
how much water is used in the complete manufacturing process of a
product. This may not sound important but much of the growth in
new manufacturing facilities is taking place in locations where there
are also already considerable constraints on the availability of suitable
water supplies.
Do these trends have any impact on pharmaceutical water
systems? The answer to that question is, typically, ‘no and yes’.
Pharmaceutical water standards
Apart from the introduction of Highly Purified Water in the European
Pharmacopoeia, the quality requirements for pharmaceutical grades of
water have not really changed in more than 150 years. The way the
standards are described and measured may have changed but the
basic water quality that the standards define has not. For example, the
USP Purified Water conductivity specification of 1.3 µS/cm at 25 °C
was established based on rigorous calculations that showed that at
this level of conductivity the limits of all the ‘old wet chemistry’ would
be complied with. These old test limits had effectively remained
unchanged since they were established in the 1800s. With the
introduction of instrumental monitoring methods, the various
pharmacopoeial standards are coming closer to harmonisation, and
with modern system designs, achieving the required standard has
become increasingly reliable.
Long before PAT became an acronym, and before the water
quality standards were changed, process analytical technologies
such as pressure, conductivity and flow measurement were used to
monitor and control the operation of pharmaceutical water systems.
For example, the specialist instrument supplier, Hach, supplies
monitoring instrumentation from well-known brands such as
Orbisphere and Anatel for monitoring and controlling pharmaceutical
water systems.
Awash
with ideas
The use of water in the manufacturing process is vital to the industry, yet its importance is rarely
acknowledged. Ensuring water quality is essential to the quality of the final product and to making
sure manufacturing processes are in line with regulations. Dr John Hutcheson explains the
issues surrounding the use of water within pharmaceuticals, and offers some practical advice.
Insight > Manufacturing
WORLDPHARMACEUTICALFRONTIERS
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Insight > Manufacturing
WORLDPHARMACEUTICALFRONTIERS
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www.worldpharmaceuticals.net 87
WFI production
There have been no significant changes to the design of Water for
Injection (WFI) systems. Multi effect and Vapour Compression (or
Thermo-compression) distillation equipment has continued to be
developed and improved, but the basic design principles have not
changed. In Europe, multiple-effect stills have been the preferred
choice for WFI generation for perhaps 20 or more years, but there is an
increasing use of vapour compression technology. This may be due to
technical advances but if you consider the cost per litre of generated
WFI in isolation, then thermo-compression may often be the lower-
cost option, particularly in high-volume applications or when the WFI
water is required to be cold. Depending on the various site-specific
factors, you can get quite different costs per litre for the different
generation methods. One interesting point to consider is the
requirement for services and utilities; multi-effect distillations require
higher pressure plant steam and typically a higher grade of feed water.
Skid-mounted PW systems
Over the same period there has been a significant change in the
design of Purified Water (PW) systems, both in generation and storage
and distribution systems. Many PW systems being installed now are
almost indistinguishable from WFI in respect of construction materials,
the control and monitoring systems and the use of ‘standard’ factory-
assembled skid systems. Almost every major, and many minor,
equipment supplier has developed integrated, skid-mounted, PW
generation systems. Because each design is not a one-off, the systems
have become more reliable and the use of standard systems has
reduced the design activities on each project and standardised
validation packages. This has resulted in reduced costs and project
timescales. It has also made it possible to make Factory Acceptance
Testing (FAT) more extensive and effective. Most of the Installation
Qualification (IQ) and Operational Qualification (OQ) protocols can be
carried out in the factory prior to the equipment being shipped to site.
With the development of new Reverse Osmosis (RO) membranes
and Continuous Electrodeionisation (CEDI) modules, the almost
universally used combination of technologies is Pre-treatment, RO and
CEDI. Sometimes a UV light is included, either before or after the CEDI
unit and to produce Highly Purified Water either a second RO stage, or
an Ultrafiltration (UF) stage is added after the CEDI unit. This second
membrane stage is required to ensure that the endotoxin limit of 0.25
EU/ml can be guaranteed irrespective of levels in the potable water.
CEDI developments
An interesting development described by Christ Water Technology is
the Septron Bio-Safe unit. This combines the spiral wound SeptronCEDI
module with an integrated membrane stage. The company claims that
this bio-safe unit, combined with an upstream RO stage, will enable the
production of Highly Purified water with no additional pipework, pump
or energy requirement for the membrane stage.
Arguably, the market-leading CEDI unit is the Ionpure range
manufactured and supplied by Siemens Water Technologies, with
more than 1,000 units installed in validated pharmaceutical water
systems. The first Ionpure CEDI unit was installed in a commercial
system in 1989 and since then the technology has been extensively
developed by Siemens and other water treatment companies. Initially,
RO and CEDI systems had to be chemically sanitised, but product
developments meant that both technologies could be hot-water
sanitised. However, there were process restrictions, even following the
development of hot water sanitisable units because it was important
that the rate of temperature increases and decreases was controlled to
within relatively strict limits because of the different rates of expansion
and contraction of the materials used.
A recent development in the Ionpure product range is the new
LX-HI module. With a guaranteed performance for 150 cycles, this unit
does not need any temperature ramp up or down and can be sanitised
at 85°C +/- 5°C.
PW system operation
Despite the good water conversion performance of the RO/CEDI
combination of technologies, every supplier is seeking ways of
improving the efficiency of the complete system. A characteristic of
modern pharmaceutical water systems is that the generation system
is operated continuously to minimise the possibility of bacterial
growth, but this can waste water and energy. Different companies
take different approaches to reduce this.
If a purification system were operated in a ‘stop-start’ manner, water
and energy would only be used when Purified Water was being
produced however, that could increase the risk of microbiological
excursions. Siemens Water Technologies has reported a process based
on using the capabilities of the LX-Hi CEDI module described above.
Its S3 system technology operates by shutting down the make-up
water system during periods of non-use. When there is a call for water
the system undergoes a rapid, 20- 30 minute heat sanitisation before
resuming normal operation. During long periods of non-use the system
can automatically sanitise, then return to a dormant state.
A published example of the savings that this design approach can
achieve was based on a system installed at a major healthcare products
manufacturer. Table 1, below, shows the data published by Siemens for
this system. The savings amounted to 16.4 million gallons a year.
Storage and distribution
Possibly the next step in integration is to integrate the generation
and distribution systems into one unit. For example, Elga Process
Water offers the Triton packaged integrated system, which can supply
up to 350 litres/hour of Purified or Highly Purified Water for
The generation system is
operated continuously to minimise
the possibility of bacterial growth
but can waste water and energy.
Table 1: Description of cost savings from S3 system
■Annual savings ■10-year savings projection
Rain water & filters $77,105 $1,177,989
Electricity $28,789 $417,062
Water softener $2,469 $35,799
53 operational cost $(13,838) $(200,473)
Total savings $94,525 $1,370,377
Source: Siemens Water Technologies
Insight > Manufacturing
WORLDPHARMACEUTICALFRONTIERS
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applications such as the production of clinical trial material and for
scale-up studies. However, this approach is still not common for
production scale systems.
Standardising the control and reporting system for pharmaceutical
water systems using a software package, which also meets the
requirements of 21 CFR Part 11, has been considered, with Christ
Water Technology Group offering the Aqu@View system. This system
allows remote data acquisition and evaluation, remote plant operation
and data export to packages such as MS Excel. However, despite all
the developments in the monitoring and control systems and the
generation systems, there have been no significant developments of
the basic designs of distribution loop systems.
That has recently been changed by the introduction of the
HydroGienic system by the Honeyman Group. All water distribution
systems have been based on the points of use being connected in
series, either using one loop or sometimes two or three conventional
loops operating in parallel. While this design works well, there are a
number of potential limitations. The HydroGienic system is the world’s
first parallel distribution system. The system features small-bore PTFE
hoses and a unique reverse-flow principle for hydraulic balancing.
A HydroGienic system has been installed at Dales Pharmaceuticals
in the UK. Managing director Mike Annice said: “The nature of our
business is such that we need to be able to alter production schedules
quickly and efficiently to meet changing client requirements.
Fundamental to this are facilities that can be easily adapted, and with
its ease of modification HydroGienic allows us to do exactly that.”
Reclaim/reuse
A final area where savings may be possible is water reclaim. This can
be defined as the treatment of a waste stream to produce high-quality
water that can be fed to another operation within the pharmaceutical
site. Although reclaiming water can reduce or even eliminate waste
disposal costs, unfortunately, the water can only be reused as a feed
water supply if the waste stream is of better quality than the original.
Final thoughts
Some suppliers describe themselves as ‘vertically integrated’
manufacturers so that they can integrate various aspects of their
complete range of products and services to meet the requirements of
pharmaceutical manufacturers. For example, GE Infrastructure offers a
range of water and process technologies for the pharmaceutical
industry, including Betz treatment chemistries, Osmonics membrane
systems and pre-engineered RO and deionization systems.
It will be interesting to see developments in new technologies and
the business models adopted by suppliers over the next decade to
meet requirements of pharmaceutical R&D and production operations.
Regulatory focus on water systems remains high and users now better
understand the importance of routine monitoring, maintenance and
pro-active intervention when operating parameters change.
However, possibly the largest change has been the development of
standard, skid-mounted PW generation systems, which can operate
consistently and reliably while allowing the user to implement the
control and sanitisation procedures they prefer. Suppliers are now also
working hard to further improve these systems to minimise their
environmental impact and reduce operating costs. O
Note: For full list of acknowledgements please contact the editor.
WPF017_052_Awash.indd 88 17/3/10 09:16:10
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A
s perhaps the most contentious issue in drug
development, animal testing is never far from the news.
An EU ban on the use of animals in cosmetics may have
been welcomed with almost universal endorsement in 2009, but
there are no such quick fixes for addressing the issue within the
pharmaceutical industry. Virtually every medical advancement of the
20th century has relied upon in vivo procedures somewhere along
the line and, despite the efforts of an extremely vocal minority, there
remains a general public consensus around the necessity of ongoing
in vivo studies when it comes to bringing new drugs to market.
But this does not detract from an acknowledgment within and
outside the industry of the need to minimise such tests. As such,
developers, governments and regulators have embarked upon a
number of initiatives to address the challenge.
The UK government’s formation of a National Centre for the
Replacement, Refinement and Reduction of Animals in Research
(NC3Rs) is a case in point. Launched in 2004, the centre works
alongside an array of scientific partners looking to develop robust non-
animal alternatives. Where this is not possible, efforts are made to
minimise the numbers of animals used and to improve their welfare.
Its work has generally been well received, but figures published in
the summer of last year did not make for easy reading. The Home
Office announcement that 3.7 million procedures using animals were
performed in 2008, an increase of 14% on the previous 12 months,
followed a trend of rising numbers going back several years and
begged the question: are drug developers doing enough?
At first glance, these results certainly contradict industry and
governmental assertions, and an additional 454,000 procedures
provide campaign groups with ample ammunition in their
longstanding feud with the pharmaceutical industry. But for those on
the receiving end of such criticism, the figures only tell half the story.
“A major factor is the increased amount of research overall,’ says Dr
David Reynolds, senior director of experimental biological sciences at
Of
mice
and
men
Insight > Contract services
Despite a commitment to the “Three Rs”
– reduce, replace, refine – the number
of procedures involving animal testing is
increasing year-on-year across the EU.
Pfizer’s Dr David Reynolds tells Phin
Foster why such figures can be misleading,
and highlights the advancements being
made that may some day see animal studies
become obsolete.
Pfizer. “Look at the amount of money invested in biosciences within
the UK and the EU over the past 15 years and that provides some
context. It all depends on what you’re taking as your baseline: we use
far fewer animals now than in the 80s, for example. The rise in
numbers does not equate to a lack of emphasis upon the ‘Three Rs’.”
According to the Department for Business, Innovation and Skills,
government investment through the UK science budget more than
doubled in real terms from £1.3 billion in 1997/98 to £3.6 billion in
2008/09. This certainly accounts for a significant hike in the number of
studies being conducted and another development over that time
distorts the picture further.
Small fry
Reading beyond the headline figures, one sees that 2008 saw an 85%
increase in procedures using fish, some 278,000 more cases, which
Reynolds believes is indicative of a major advancement in the mission
to refine and reduce, if not necessarily replace.
“The proportion of smaller animals now being used has increased
markedly,” he explains. “Transgenic mice have been a big driver, as
has the use of fish, but in moving down to smaller animals you will
sometimes see a rise in the numbers used because of where those
models are at. The percentage of primates or dogs used is extremely
small when compared with the total number.”
This is certainly true – dogs, cats and non-human primates
accounted for less than 1% of all procedures in 2008 – but a 16%
increase in the use of the latter still raises some eyebrows.
“Over the past ten years we’ve seen a significant advancement in
biologics,” Reynolds explains. “Unlike the development of ‘small
molecules’ that allow us to do a lot of work with smaller creatures,
these anti-bodies or proteins are much more like those that occur in
the body naturally and so a lot more specific. An anti-body raised
against a human immune receptor is unlikely to cross-react and have
any affect upon the equivalent receptor in a rat. Unfortunately, that
means an increase in the number of Old World primates being used.”
While it will be difficult to move beyond these requirements in the
immediate future, the rising level of studies in the field is continually
amassing data that should allow the numbers of such studies to come
down over time. “The more information we glean the better our
computer models become,” Reynolds agrees. “But the whole idea of
drug research is to push the boundaries of knowledge. We are
constantly moving into areas we’ve never been before and it’s
therefore very difficult to entrust a computer model with the ability to
accurately predict what will happen.”
Such an assertion should provide some perspective for those
pushing the ability of new IT platforms to immediately replace the
need for animals. Reynolds admits to keeping an eye on what external
providers are offering, but is clearly sceptical about the existence of
any such silver bullet. “Of course we take on various types of
modelling in-house,” he begins, “but what we don’t necessarily have is
the bespoke package that a small bio-tech company might offer. In
order for us to proceed with such a platform, however, it’s essential
that we understand the basis upon which the model was built and
how reliable any such predictions will be.”
Cell and tissue use
The development of increasingly complex computer models certainly
has a part to play in reducing the proportion of animal tests, but
Reynolds is clearly as excited by advances being made in cell and
tissue use, particularly when it comes to the field of pharmacokinetics.
“Pfizer, alongside a number of other industry leaders, has put a lot of
work into using tissues and cells such as human hypatocytes for
predicting absorption, distribution and so on,” he explains. “It requires
far fewer animals to support your data, sometimes none whatsoever.
This is not only beneficial ethically, but also provides major cost and
speed advantages.
‘The use of such cells or tissue to predict efficacy may be a more
trustworthy forecaster, but until you’ve done the studies to prove that,
you can’t say that human cells within a dish are a naturally better
Insight > Contract services
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Figure 1: Experiments or procedures commenced each year in the UK, 1945-2008(1)
Colour guide
Experiments(1) Procedures (2)
1945 1950 1955 1960 1965 1970 1975 1980 1985 1990 1995 2000 2005 2008
Source: UK Home Office
6 -
5 -
4 -
3 -
2 -
1 -
0 -
(1) Experiments under the 1876 Act or scientific procedures under the 1986 Act
(2) The experiments included in the 1987’s figures also counted as procedures under the 1986 Act
M
i
l
l
i
o
n
s

o
f

p
r
o
c
e
d
u
r
e
s
source of information than the whole system you can model within an
animal. We have to follow the science.”
While such work in the pharmacokinetics arena is allowing for the
gradual replacement of some animal tests, there are also
advancements being made when it comes to reducing and refining
the studies being performed. Reynolds highlights telemetry as a major
area of innovation that has come on in leaps and bounds in recent
years, enabling Pfizer and its competitors to garner better results while
directly addressing the “Three Rs” challenge.
“Through implanting devices that can take a number of readings
you’re getting data of a much higher quality than you might do
sticking electrodes on the surface of the body or anaesthetising an
animal,” he says. “It also allows us to use far fewer animals over time.
“Of course there are very stringent regulatory and ethical controls as
to how we do that, but it has been a growing trend over the past few
years and we’re always looking at ways of improving the quality,
reducing numbers and so on. You can pack a lot more into a telemetry
device than was possible five years ago and the equipment
manufacturers have regular user meetings where companies and
academic labs share their experiences and learn from one another.”
This collaborative approach to tackling the “Three Rs” is something
Reynolds returns to time and again. Animal welfare is not an area for
seeking competitive advantage and the Pfizer director is clearly a great
believer in the need for cross-industry communication.
It’s good to share
“We share in multiple ways,” he begins. “Pfizer works very closely
alongside NC3Rs and runs a series of workshops where people can
showcase the work they’ve done so far and also ask for advice from
their peers on improving existing models.
“Working alongside other companies and academic groups around
improving and replacing animal models is fundamental. An old
colleague of mine who’s now at GSK came down just the other week
to look at techniques our surgeons have developed. There are a lot of
areas that do not demand competitive secrecy.”
Despite all the best efforts of industry leaders, regulators and
government bodies, however it remains unrealistic to predict a time
when the need for animal testing will become obsolete.
“At some undefined point in the future I would hope we’ll be
able to stop using these studies altogether,” Reynolds acknowledges,
“but I don’t know when that will be and it will require a significant
increase in our understanding of human and animal biology – nobody
wants to see headlines about tests in humans going horribly wrong.
As science advances the picture will become clearer, but it will be a
slow march.” ■
Animal welfare is not an area for
seeking competitive advantage, and
the Pfizer director is a great believer
in cross-industry communication.

Insight > Contract services
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Company insight > Contract services
WorldPharmaceuticalFrontiers
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www.worldpharmaceuticals.net 92
i
f you trip and fall when jumping off a rock, you will probably
only get bruised. However, if you fall down a mountainside,
you are much more likely to crash and burn. The same
principle applies to drug discovery; preclinical attrition is less
painful than clinical. If your lead candidate is bound to fail, the
sooner it happens, the better.
All of us who are working in the field of pharmaceutical research
probably agree that reducing attrition is one of the key challenges
that drug discovery is facing these days. At the very least we need
to find ways to shift whatever attrition is inevitable towards the
early stages of drug discovery. The past years have also seen
tremendous streamlining and rightsizing of R&D operations
throughout the entire pharmaceutical industry. Unfortunately,
pharmaceutical research does not work on homeopathic principles.
You cannot keep cutting the research resources and expect higher
throughput and higher quality of results. You can stretch for a
while, but if you keep stretching long enough or hard enough you
will wear your resources so thin that sooner or later something has
got to give. In the long run you can expect a dramatic drop in both
quality and quantity of research.
Taken separately, these two issues – the need to cut attrition and
the constant pressure to cut costs separately – can easily appear as
problems or threats. However, there is a way to turn these threats
into an opportunity. Choosing the right preclinical partner will both
increase the predictiveness of your research and help you manage
and reduce your strategic costs.
never fear, help is near
This last decade has witnessed the rise of a new type of contract
research organisation, the preclinical CRO. These companies are
often small, flexible and highly specialised, which enables them to
keep abreast of the latest developments in their area of expertise,
and apply this knowledge in their service selection. This allows
them to invest significant resources in a narrow niche of research
and in turn develop specialised services and disease models whose
commercial availability is, at best, limited. In an outsourcing market
dominated by a few large service providers, these small specialised
CROs step in to fill the gaps left by the big players who mainly
focus on providing bulk services.
These preclinical CROs are a welcome solution to the discovery
and R&D departments of many pharmaceutical and biotech
companies. By outsourcing their preclinical efficacy research and
lead validation they can control and reduce fixed research costs
without sacrificing performance. That, if anything, is called killing
two birds with one stone. Validating and maintaining the speciality
methods and models these small CROs offer would often be
impractical and cost-prohibitive for a pharmaceutical company.
Pack the right gear
Everyone knows not to go hiking in high heels. In this sense, life in
the lab is not that far from life in the outdoors. Proper equipment
guarantees best results. In the lab this means the latest translational
methods. However, it is extremely hard – if not impossible – to
maintain the latest models for your preclinical research if your R&D
department is constantly under pressure to keep fixed costs at a
minimum. Yet predictive methods are an absolute must before any
drug candidate can make its way to the shelves of a local pharmacy.
Cancer drug discovery is an excellent example of this. Cancer and
its progression is a complex process of physiological events and their
consequences. Nevertheless, the preclinical efficacy of many new
cancer drug candidates is still being tested with less-than-optimal
methods, such as primary tumour models alone. Could this perhaps
be one reason why so many of these candidates fail in clinical trials?
Medical professionals worldwide are beginning to accept that
in many cases cancer should be categorised as a chronic disease
that cannot be cured, but which can be controlled. Almost invariably
this includes inhibiting the ability of malignant cancerous cells
to develop metastasis to distant sites. The only reliable and
predictive way to achieve this is to equip your drug discovery
with preclinical models that provide adequate clinical resemblance
to the clinical setting.
If we wish to reduce attrition in clinical trials, we need to pay
more attention to the tools used for preclinical research. This is
where the preclinical niche CROs, such as Pharmatest Services
can help. They often focus on a narrow field of expertise and provide
highly specialised services and disease models that are designed
specifically for diseases with unmet clinical needs. Pharmatest,
for instance, specialises in preclinical lead validation services in
disease areas with unmet clinical needs. Its services include
such speciality models as cancer metastasis models and orthotopic
cancer models, as well as models for musculoskeletal diseases,
urology and inflammation. ■
the higher you climb,
the harder you fall
Getting pharmaceutical research right at the preclinical stage saves time and money by highlighting
problems early in the process. Pharmatest believes that choosing the right preclinical partner can
help make your preclinical tests more predictive, and ultimately cut down on attrition.
Further information
Pharmatest Services
Website: www.pharmatest.f
Company insight > Contract services
WorldPharmaceuticalFrontiers
|
www.worldpharmaceuticals.net 94
i
n December 2007 two businesses came together for one
mission – to meet the growing needs of the multinational
pharmaceutical and biotech industries. MPI Research
from the US and China’s Shanghai Medicilon joined forces
to create Medicilon/MPI Preclinical Research-Shanghai, a
company that provides global pharmaceutical and biotechnology
companies with high-quality preclinical drug discovery and
development studies in an Asian facility that meets worldwide
regulatory standards.
Medicilon/MPI Preclinical Research-Shanghai is meeting the
needs of Sponsors around the globe while conducting studies
that comply with US FDA Good Laboratory Practices (GLP)
regulations. In addition to conducting GLP studies, the company
has been recognised as an accredited International Association
for Assessment and Accreditation of Laboratory Animal Care
(AAALAC) facility.
These recent advancements further underscore the company’s
commitment to providing Sponsors with quality research. A full
AAALAC accreditation is a reflection of high standards,
accountability and a commitment to animal welfare. This
achievement is recognised as a milestone and benchmark for
responsible and ethical laboratory animal care, and also sets
standards for veterinary medical care, occupational health and
safety, and physical plant or HVAC standards that rival or
exceed those of many non-accredited Western institutions.
Medicilon/MPI Preclinical Research-Shanghai recognises that
the implementation of these standards did not come without
challenges. It was a top priority to find quality suppliers of
animals and animal feed, and the company decided to adjust its
launch date for GLP offerings in order to guarantee its Sponsors
the topmost quality. The process of finding the right team to
bring the company to the highest standards required nearly two
years of close collaboration between parent companies Shanghai
Medicilon and MPI Research
high-class personnel
A team of five people from the corporate headquarters of
MPI Research in Mattawan, Michigan accepted long-term
assignments in China and trained local employees on GLP and
AAALAC standards for animal care and use. At times, this team
was supplemented with more than a dozen people based on
scientific focus areas, and also had help from three key players:
Dr. Jintao Zhang, CEO, Dr. Mingli Chen, VP of Toxicology, and Dr.
Lijie Fu, executive VP of Operations. Dr. Zhang is founder of
Shanghai Medicilon Inc. and has extensive experience of both
US- and China-based CROs. Originally from China, Dr. Chen,
MD, MS, DABT, a board-certified toxicologist with significant
pharma and CRO experience in the US, returned to the country
to apply her expertise. Dr. Fu, PhD, another national returnee,
brings substantial scientific experience, along with experience
from other China-based CROs.
With more than 62,000ft² of preclinical research capacity, and
a staff of more than 120 dedicated employees, the company
takes pride in its state-of-the-art facility that is optimally
designed for GLP toxicology, safety and efficacy studies. In
addition to these capabilities, the company also offers Sponsors
ADME, PK/TK, analytical and bioanalytical services.
Medicilon/MPI Preclinical Research-Shanghai is continually
looking for ways to meet the needs of the industry. The company
has a dedicated team that provides high quality, timely service
to its Sponsors. This team ensures top quality research by
modelling their parent companies’ use of superior systems,
proper standard operating procedures (SOPs) and extensive
training programmes, and by employing an active QA staff and
recruiting the best talent in the industry. ■
the best of both worlds
Medicilon/MPI Preclinical Research-Shanghai, a joint venture between US-based
MPI Research and Chinese company Shanghai Medicilon, is committed to providing Sponsors
quality research in an Asian facility that meets worldwide regulatory standards.
The company has more than 62,000 square feet of preclinical research capacity plus 120 staff
Further information
Medicilon/MPI Preclinical Research-Shanghai
Website: www.medicilon-mpi.com
Email: info@medicilon-mpi.com
We’ve opened more than a new research
facility. Medicilon/MPI Preclinical Research –
Shanghai has opened a new world of preclinical
discovery and development opportunities.
This new jewel brings together the best of
its parent companies, MPI Research and
Shanghai Medicilon including a skilled
scientific staff, western certification standards
for GLP and non-GLP research, and a
responsive, problem-solving culture of quality.
When research is your oyster,
we make the world your pearl.
Global reach. Quality research.
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W
ith every aspect of drug development moving east,
there are only two kinds of clinical trial sponsors:
those running sites in Asia, and those thinking
about running sites in Asia.
For the latter, Asia appears from afar an impenetrable black
box. While that box is rumoured to hold significant cost savings
and access to the fastest-growing healthcare market in the world,
tapping into it means navigating regulatory and operational
challenges compounded by language barriers.
Even for drug developers with established clinical trial sites
in Asia, expanding from one country to the next can pose
challenges. Each country has its own distinct cost structure,
population base, medical practice standards, infrastructure,
government policies and cultural differences.
Before delving into or expanding an Asian clinical programme,
trial sponsors and their CRO partners should discuss several
strategic issues.
Cost considerations
Running trial sites in China, Thailand, the Philippines or
Malaysia can save a sponsor 60% compared to running
equivalent sites in the U.S. Most countries in Asia are at least
20-30% more cost-efficient than their western counterparts.
But there are exceptions to every rule: for instance, investigator
salaries and other trial costs in South Korea can be just as high
as in the western world.
The numbers game
With more than four billion people, Asia offers sponsors a
deep pool from which to draw clinical trial participants. Yet
sponsors of late-stage trials in indications such as diabetes
or cardiovascular disease must balance population benefits
with increasing competition for enrollment in countries such
as China, Indonesia, Japan, the Philippines, Thailand and
Malaysia. A country such as South Korea is less populous,
but may also offer less competition.
Evaluating medical practice
There are certain diseases for which the standard of care in
Asia is similar to that in the West, including breast cancer, lung
cancer and diabetes. But for many indications, medical practice
standards differ both from east to west and between the different
Asian regions. Sponsors seeking to mirror Western standards may
want to consider limiting their trial sites to countries such as
Singapore, Taiwan, Hong Kong and South Korea.
Getting the job done
Sponsors should be prepared that Asian trial sites may need more
assistance when it comes to following protocol and differentiating
between medical practice and clinical research. Similarly, sponsors
should not assume that all potential Asian trial sites will have the
infrastructure – even fax machines or freezers – needed for a
clinical trial.
Political factors
Each Asian country’s policies on protocol approvals, insurance
regulations, import licences and other factors can affect a sponsor’s
success. The regulatory bodies in South Korea, Taiwan and
Singapore have adopted an FDA flavour to their practices. Yet each
Asian country has its own regulatory idiosyncrasies – in China, for
example, a sponsor should never assume that what worked in one
application will be directly applicable to another. The cookie-cutter
approach simply isn’t feasible.
Cultural considerations
Once language barriers are overcome, sponsors are often pleased to
learn that investigators in most Asian countries are eager to
participate in clinical research. Regulatory reviewers, too, are often
eager to help, if a sponsor knows what questions to ask and how to
ask them. Yet there are certain cultural considerations sponsors
need to address upfront with their investigators, such as
procedures for publicising findings from the trial.
A question of ethics
As the fastest-growing pharmaceutical market in the world, China
is a major consideration in the marketing plans of most drug
developers. Yet if a sponsor has no plans to launch a drug in certain
Asian countries, then conducting clinical research in those
countries may present ethical challenges.
The right CRO partner is aware of such ethical considerations
and can guide sponsors through these and other issues. While
challenging at first, Asia’s rewards in terms of rapid enrollment,
cost-savings and market access are not just upside – they are
essential to remaining competitive in the drug development world
of today and tomorrow. ■
Considering Asian clinical trials?
Signifcant cost savings and access to the fastest-growing healthcare market in the world is
making Asia a desirable location for clinical trial sponsors. However, before they and their CRO
partners rush into starting or expanding an Asian clinical programme, both parties should frst
address several strategic issues.
Company insight > Contract services
WorldPhArmACEuTiCAlFronTiErs
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www.worldpharmaceuticals.net 97
Further information
INC Research
Website: www.incresearch.com
Email: njain@incresearch.com
Source: Thomson Center
Watch 2006 European
Site Survey
Factors most often causing study delays
Contract & budget negotiation
& approval
Patient recruitment
and enrollment
Availability of study drug
EC review & approval
Investigator selection
Correction of CRF inquiries
Protocol design & refinement
Legal review
47%
43%
41%
40%
39%
38%
37%
36%
C
linical trials are complex and must be well performed under
GCP to ensure a successful outcome. GCP demands
satisfactory standards for design, conduct, performance,
monitoring, auditing, recording, analysis and reporting, providing
assurance that the final data are credible and accurate, and that the
rights, safety and well-being of trial subjects are protected.
Poor performance can kill a clinical trial. Typical deficiencies include
unsatisfactory trial-site placement, site management, monitoring, data
management and contractual requirements. Successful trials also need
realistic timelines, adequate resources, and maintaining trust between
sponsor, contract research organisation (CRO) and trial investigators.
To save a trial, a sponsor may be forced to appoint another CRO, such
as Harrison Clinical Research (HCR). Trial rescue proceeds with:
a) Review and analysis. Sponsor and former CRO provide
guidance to what did and did not previously work. Critical
areas must be identified, analysed and potential solutions
offered. HCR must respond rapidly and sensitively, and be
flexible in preparing an action plan.
b) Planning. Trial documentation from former CRO is
transferred to HCR project manager; project management,
recruitment, risk management and training plans may need to
be adapted. Recruitment barriers have to be resolved with a
detailed transition plan. A standard operating procedure (SOP)
outlining these steps ensures that procedures are consistent
during the take-over process. An accurate cost proposal to the
sponsor is key to further success; costs will be impacted by
trial stage, notably: status IRB/EC/regulatory authority
submissions; regulatory authority requirements delaying trial
start; status investigator contracts; subject recruitment rate;
status monitoring; proportion data already entered on
database and status data cleaning.
c) Execution and controlling. Sponsor communicates change
of CRO to investigational sites. Execution is facilitated by the
project manager who links each site with the sponsor and
CRO, assists in decision making, and ensures the agreed
deliverables are met in terms of scope, cost and quality. HCR
has identified critical success factors in rescuing clinical trials:
Cooperation with investigational sites specialised in ■
relevant indication means faster recruitment.
Long-standing relationship with IRB/EC/regulatory ■
authority plus intimate knowledge of contractual
requirements at trial site means quicker study set-up.
Experience in managing large trials in relevant indication ■
means efficient use of time and resources.
Highly experienced CRAs means positive audits and ■
database lock to agreed timelines.
d) Closure and completion. The ability of a target-oriented
team to meet the transition challenges and execute the action
plan enables successful completion and closure of trial sites.
When rescuing a clinical trial HCR adopts a strategy that begins
with meeting the sponsor, sharing and understanding the expected
deliverables and outputs, and building a basis for trust and effective
teamwork. Rescuing trials successfully offers learning experiences for
both the sponsor and CRO and a sound basis for performing clinical
trials well in the future. A trusting collaboration is better prepared to
deliver ‘right first time’. ■
Rescuing clinical trials
By following a procedure of analysis, planning, execution and closure, a newly appointed contract
research organisation can turn around a failing clinical trial.
Company insight > Contract services
WORLDPHARMACEUTICALFRONTIERS
|
www.worldpharmaceuticals.net 98
Further information
Harrison Clinical Research
Website: www.harrisonclinical.com
Telephone: +49 89 126 6800
H
a
r
r
i
s
o
n
Outsourcing
Dedication
Harrison
Clinical
Research
Munich, Germany Tel.: +49-89-126680-0
Vienna, Austria Tel. +43-1-504 6591-0
Brussels, Belgium Tel.: +32-2-4643 900
Ely, United Kingdom Tel.: +44-1353-668 339
Barcelona, Spain Tel.: +34-93-226 6964
Levallois-Perret, France Tel. +33-1-55 90 5710
Rome, Italy Tel. +39-06 79 31 2131
Rehovot, Israel Tel.: +972-8-931 6330
Kiev, Ukraine Tel. +380-44 431 9836
Moscow, Russia Tel. +7-495-514 1392
Warsaw, Poland Tel. +48-22 434 2660
HCRAmerica Tel. +1-609-987 1700
A full-service CRO with dedication
to your project as key to your success
At Harrison Clinical Research we understand that your project needs dedication and experienced staff to accomplish your goals on
time and within budget. A collaborative attitude, which characterizes HCR staff, has created a strong bond between our Sponsors
and our company for more than two decades. Client satisfaction and repeat business are the best proof of this achievement.
HCR activities include: Phase I -I Ia Clinical Pharmacology Unit, Clinical Operations (Phase I -IV), Trial Application Services, Data
Management / CDI SC, Statistical Evaluation, Medical Writing, Auditing, Training, Scientific Consulting. www.harrisonclinical.com
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WORLDPHARMACEUTICALFRONTIERS
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B
usiness guru Dr James Brian Quinn once described
outsourcing as “one of the greatest organisational and
industry structure shifts of the century”, and his statement
only continues to gain relevance as the pharmaceutical industry
matures. With companies increasingly working to reduce their capital
outlay by cutting costs on new facilities and specialist staff,
subcontracting has become the norm.
According to the Department of Justice, one third of sales of US
pharmaceutical companies (an estimated $100 billion) is now being
generated outside the US, while a Business Monitor International
report forecasts that the market for contract manufacturing
organisations (CMOs) will be worth $33.7 billion by 2014.
But if pharmaceutical companies are going to prosper in 2010, they
need to know how to select reliable partners. According to Eric
Langer, managing partner of BioPlan Associates, a life sciences
and biopharmaceutical marketing research firm, the number one
factor that comes up year after year when organisations are
looking to form strategic partnerships is “establishing a good
working relationship”.
“Many of the companies that are acting as outsourcers are not
service-oriented,” he says. “But the majority of companies that are
requesting outsourcing services are looking for a service provider,
not merely a technology. CMOs in particular have difficulties
addressing customer orientation and, while their technology may be
successful, the relationship can still fail if they cannot manage their
customers’ expectations.”
On top of ensuring that their chosen partner organisation
understands the demands of supplying a service, pharmaceutical
companies must take quality standards into account. According to
Langer, however, outsourcers who have even the most stringent
quality assurance measures in place will be overlooked if they are
incapable of demonstrating ‘soft skills’ such as time management.
“Last year over half of the companies surveyed in our annual report
said that relationships were suffering because vendors find it difficult
to stick to a schedule,” he remarks.
Moreover, companies are increasingly looking to partner with
subcontractors who can effectively handle cross-contamination issues
and demonstrate regulatory compliance expertise. “As the industry
matures, outsourcers do find themselves more capable of handling the
soft skills, which means that some of the more challenging factors are
Who can
you trust?
Pharmaceutical companies are doing everything they can to cut capital expenditure, and
this increasingly involves outsourcing operations. But contracting out any function – whether it
is clinical trials, research and development or manufacturing – is fraught with difficult decisions.
Eric Langer offers some practical advice on choosing partners, and gives Elly Earls an insight
into the future of the industry.
Insight > Contract manufacturing
Eric Langer
Eric Langer has more than 20 years’ experience
in biotechnology and life sciences international
marketing, management, market assessment,
and publishing. He has held senior management
and marketing positions at biopharmaceutical
supply companies. He is also an experienced
biotechnology strategist, marketing
practitioner, publisher, and researcher. He
has published, edited and authored
books, reports, and major studies.

starting to rise to the surface,” notes Langer, who has held senior
management positions at biopharmaceutical supply companies.
The main rationale behind the continuous increase in outsourcing
operations is cost-cutting. Capital expenditure was the most
significant budget cut last year, leading to a decline in new facility
construction and a decrease in the number of scientific and operations
staff hired. Efficiency is becoming a primary focus, and this is
particularly relevant when choosing subcontractors.
Value for money
“Value for money can be measured by whether or not you return to
that vendor again if you have a similar project,” Langer believes. “The
key word here is ‘expectations’. You need to establish and define your
expectations on both sides before you launch the relationship. If, when
the project is completed, the outsourcing company met all your
expectations, you’ll come back again.”
Setting expectations and defining projects and outcomes in such a
nebulous environment, however, is difficult. “Many companies do it in
an ad hoc manner because when you’re providing a service it’s
difficult to define the value of what you’re offering,” Langer explains.
“Companies need to spend the time up-front ensuring that the
outsourcer you’re about to be ‘engaged’ to will be a good one for the
long haul. If it isn’t a good fit, it won’t be good value at any price.”
In a technical environment such as pharmaceutical manufacturing,
every service supplier knows that, at some point, things will go wrong,
and companies need to ensure that they are working with outsourcers
who can cope.
“Dealing with problems after the fact is reactionary and risky,”
Langer emphasises. “A better approach is for the subcontractor to
understand that they are a service provider and that their problem-
handling procedures should be modelled after those demonstrated
across other more-established service industries.
“Outsourcers must have a customer service plan in place, and
implementing emergency procedures needs to be a natural response
at all levels of the organisation.”
Proper procedures
Many companies acting as subcontractors are just not up to scratch.
But their reluctance to invest in the procedures and training to handle
potential problems, because it may add, say, 10% to the cost of a
contract, makes them a poor choice for pharmaceutical companies.
“They need to spend the time evaluating their suppliers’ change
control procedures and whether they have a rational communications
process,” Langer confirms. “Vendors that seem to handle problems as
they arise are not going to be effective in the long term.”
In Langer’s opinion, when complications do present themselves, the
liability lies wholly with the service supplier, so pharmaceutical
companies must choose their outsourcers wisely.
Neither clinical research nor contract manufacturing is a
revolutionary new industry, yet each year modern technology and
innovative processes are introduced. And just like the pharmaceutical
companies, CMOs must be in the position to adopt these new
procedures in a streamlined manner, keeping their costs down but
their productivity up.
“Outsourcers must sometimes eliminate one staff position or ask
people to complete one less quality-management step,” Langer
Insight > Contract manufacturing
WorldPharmaceuticalFrontiers
|
www.worldpharmaceuticals.net 103
Source: ICD Research Industry Survey 2010
Figure 1: outsourcing issues: Biomanufacturing
by contract manufacturing organisations
colour guide
Important Very important
62.5% 30.8%
Establish a
good working
relationship
Comply with my
company’s quality
standards
Protect intellectual
property
Have enough
capacity to meet my
sales demand
Stick to
a schedule
Effectively handle
cross-contamination
issues
Offer a secure
supply (control
of capacity)
Have regulatory
compliance
expertise
Have production
platforms that are
relevant to my product
Provide lead times
suffcient to cover
technology transfer
Reduce my time and
regulatory requirements
for product licensure
Provide superior
technology transfer
services
Demonstrate a track
record with products
simliar to mine
Provide lead times
suffcient to cover
development processes
Provide standard
performance metrics
Provide superior
process development
services
Help me determine
the value of capital
avoidance
Be local to me

Critical issues when considering outsourcing biopharmaceutical
manufacturing to a contract manufacturing organisation (CMO), 2008
% responding “very important” & “important”
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
58.7% 35.6%
55.8% 31.7%
52.9% 28.8%
52.9% 41.3%
51.9% 37.5%
47.1% 43.3%
47.1% 40.4%
34.6% 44.2%
33.7% 50.0%
32.7% 48.1%
31.7% 55.8%
28.8% 50.0%
26.0% 51.9%
19.2% 44.2%
11.5% 42.3%
8.7% 18.3%
19.2% 51.9%
acknowledges. “But what they’re saying is that they’re not cutting
corners – rather they are eliminating redundancy in order to deliver
the same quality to their customers at the costs dictated by the
economic environment.”
Regulatory compliance is one area, however, in which service
suppliers cannot streamline their procedures. Regulatory bodies will
not disappear, and the industry is swiftly realising that the vast costs
associated with quality management are here to stay. At Johns
Hopkins University in Baltimore, Maryland, the fastest-growing
programme in the biotechnology graduate programme is regulatory
affairs, as students recognise that the need for regulatory and
validation expertise is not going away.
With the escalating growth of the pharmaceutical industry in
India and China, this issue becomes ever more pertinent. In terms
of company count, India is currently 11th in the world and third in
the Asia-Pacific region with 300 biotechnology-related firms across
the nation. Alongside this, the pharmaceutical market in China is
growing annually at a rate of 20% and is currently estimated at
more than $37 billion. Asia as a whole is a recognised growth
region in terms of CMOs, with the 10% increase seen in 2009 set to
increase to 20% by 2013.
Yet with pharmaceutical companies increasingly interested in
partnering with outsourcers who can demonstrate comprehensive
regulatory expertise, the plethora of potential subcontractors in the
Asia-Pacific are falling short. “Companies in India and China are
getting there,” Langer, who authored the study Advances in
Biopharmaceutical Technology in China, insists. “They need to
either bring people from Western nations back in-house or educate
the people within their countries to ensure that the level of
expertise and quality orientation across the board is ensured.”
The number of universities that are training people in India and
China with PhDs in biotechnology and quality management is
increasing exponentially. “They now have
a very unusual situation where graduates
are having difficulty finding work, so it
becomes a question of increasing the
quality of these people. That will definitely
be an issue in the short term,” Langer says.
As the outsourcing industry continues
to grow, Langer has no doubt that it
will mature still further. “The
situation that was there five
years ago doesn’t exist any
more,” he concludes. “And in five
to ten years’ time we’re going to
see further maturation on the side of
both the outsourcing organisations and
the clients. Outsourcers that are able to
adapt to the need for flexibility, streamlined
operations and customer-orientation will thrive, while clients’
expectations will become much more ingrained within the
organisation.”
Surviving the tough transition period is the key for organisations
on both sides of the equation. And, given the benefits of
outsourcing for both parties in the current environment, great
expectations are attached to the future of strategic partnerships. ■
Insight > Contract manufacturing
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G U A R A N T E E
G U A R A N T E E
March World Pharmaceutical Frontiers
Live: 210mm x 286mm Bleed: 216mm x 292mm
WorldPharmaceuticalFrontiers
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Company insight > Contract manufacturing
G
reat versatility is what makes Alfa Wassermann a unique
partner. Nearly all pharmaceutical forms are manufactured
in its production plant from tablets to capsules, from
creams to ointments. The plant is located in central Italy and since
1985 – when it was established – constant investment in new
technologies has led Alfa Wassermann to reach high quality and
reliability levels for pharmaceutical product processing. The plant’s
flagship, however, is the sterile department.
An important project to enlarge the department – called “Stelyo 1” –
to a total of 1,800sqm, was completed in 2010. Here, sterile products
are manufactured – from nose sprays to injectable liquids and
lyophilised products. The department was designed to ensure the
greatest versatility of organisational flows and of the whole
manufacturing process, while always maintaining the highest safety
standards where products are concerned.
The manufacturing activities of this department will triple during
the first months of 2010, thanks to the start-up in 2009 of a cutting-
edge, high-productivity line for filling ampoules and bottles. In
addition, two new, cutting-edge twin lyophilisers from Ima Edwards
started to operate in the department. Each of them has a capacity of
37sqm, and allows manufacturing batches up to 100,000 bottles and
more than 200,000 ampoules. Flexibility was a major consideration
during the upgrade of the plant. The department can also manufacture
small and medium-sized batches, as well as different format products,
such as bottles and ampoules with different types of sealing.
Lyophilisers were installed in dedicated premises, so that it is
possible to lyophilise different products at the same time.
Lyophilisation is a critical process; various factors contribute to
obtaining a product with the qualities required, and for this reason
installations – which are completely automated – enable management
and supervision of all critical parameters thanks to a control system
that is able to manage the progress of the process in real time. It can
also signal any abnormalities of the installation that may affect product
quality. The working environment around the lyophiliser meets all
regulatory requirements for manufacturing sterile products, thereby
ensuring a suitable environment for processing lyophilised products.
There are no particular limits for the type of active principles
contained in manufactured products; indeed, Alfa Wassermann’s
historic know-how is based on its experience working on many
molecules, including hormones and long-chain peptides.
Another strength of the new sterile department is its innovative
preparation room. Two independent solution preparation lines were
installed in the new sterile products department. Each line is
composed of a preparation tank and two tanks for storing solutions.
The two lines are identical and can work batch sizes ranging from 30l
to 1,000l of solution. The fillers installed in the sterile environment can
be fed directly from the two storing tanks, thanks to a piping system.
It is also possible to fill two fillers at the same time.
The installations are automated and controlled by a supervision
system that controls all the manufacturing phases, as well as
installation management. Both installations can be washed and
sterilised on the spot, to ensure the best conditions before starting the
preparation phase.
The choices made during the expansion phase have enabled Alfa
Wasserman to present to the market contract manufacturing products
that comply with the highest qualitative standards, while remaining
competitive in terms of costs. The quality is also testified by the positive
results of the audit carried out by the inspectors of Alfa Wassermann
customers, important national and multinational pharmaceutical
companies that commercialise the drugs manufactured in Alanno in the
Italian market and in major European markets, such as Germany, France,
the UK and Austria, as well as in South American markets. ■
Where technology
meets versatility
Since it was established in 1948, Alfa Wassermann SpA has been deeply rooted in the
Italian pharmaceutical market through the research, production and marketing of prescription
and over-the-counter drugs.
Further information
Alfa Wassermann SpA
Website: www.alfawassermann.it
www.alfawassermannmanufacturing.it
The fagship sterile department.
For our customers we are the strategic business partner. With our specialist know-
how and many years of experience we anticipate developments and trends relevant
for our customers. And we offer you individual solutions.
Your benet: We make our customers successful, providing maximum exibility,
a short time-to-market and reliable availability of goods.
Your partner – hameln pharma:
t specialist for contract manufacturing of parenteral solutions
t more than 50 years of experience
t facilities and services in accordance with cGMP and FDA
t producing for healthcare markets worldwide
t new sterile facility which received the Facility of the Year
Award 2009 in the Operational Excellence category
hameln pharmaceuticals gmbh
Langes Feld 13
31789 Hameln, Germany
Fon: +49 5151 581-0
Fax: +49 5151 581-258
Mail: welcome@hameln-pharma.com
First choice for
contract manufacturing of parenterals
www.hameln-pharma.com
B
razil makes up 37% of the Latin
American pharmaceutical market,
which was valued at $34 billion in
2008. This compares with Mexico’s 25%,
Venezuela’s 13%, Argentina’s 9%,
Colombia’s 5%, and 12% for the remaining
countries in the region. With sector growth
of 12.5% in 2008, Brazil also saw the
strongest rate of growth among the world’s
major pharmaceutical markets after China.
Nycomed is to strengthen its focus on the
Brazilian market and plans to double
business volume in the country over the
next five years.
Nycomed first arrived in Brazil in 2007 as
a result of the merger with German
company Altana Pharma. Since then,
sales growth has been driven by the launch
of new products, the acquisition
of additional licences and improvements to
the sales organisation.
Over the past five years Nycomed’s sales
have grown at an annual rate of 14.6%,
faster than the market as a whole.
Contract manufacturing
The company has invested $55 million in a 33,000m
2
pharmaceutical manufacturing facility, which is one of
the biggest and most modern plants in Latin America.
Located in Jaguariuna, 130km south-west of Sao Paulo,
there are 400 employees working at the facility, which features
state-of-the-art technology for solids, semi-solids and liquid
preparations, plus a humidity- and temperature-controlled
storage area for 5,900 pallets.
The plant can manufacture 100 million packages a year.
Currently running at around 60% of capacity, clients include
multinationals such as Bristol Mayers Squibb, Procter &
Gamble, Boehringer Ingelheim, Johnson & Johnson, Pfizer,
Mantecorp and Solvay.
Besides producing synthetic and phytotherapeutical
medicines according to the highest national and international
quality standards – the plant is certified by ANVISA (Brazilian
Sanitary Agency), INVIMA (Colombian Sanitary Agency),
Mercosul and recently EMEA – the Jaguariuna plant is
qualified to produce personal hygiene products as well as
some cosmetics. It is also Nycomed’s back-up plant for its
product Pantoprazole.
The Jaguariuna plant is an integral part of a global
contract manufacturing organisation, currently consisting
of a total of eight manufacturing sites that together offer the
whole range of pharmaceutical technologies from solid to
liquid preparations.
In total, Nycomed operates 16 manufacturing facilities in 12
countries, all of them meeting the highest international
standards for quality. Being near to clients is part of the
company’s understanding of providing a full service.
Nycomed tailors its services towards specific customers
and tasks, providing expertise not only in scientific matters
but also by supplementing its clients’ understanding of their
target markets for the supply and distribution of products.
Partnership plays a vital role in all of the company’s
operational activities, and helps to guarantee that products not
only reach exactly the right customers, but also reach them in
the most efficient manner possible. ■
Business expansion in Brazil
Nycomed is to strengthen its focus on the Brazilian market and plans to double business volume
in the country over the next fve years.
Company insight > Contract manufacturing
WorldPharmaCeutiCalFrontiers
|
www.worldpharmaceuticals.net 108
Further information
Nycomed
Website: www.nycomed.com
Nycomed is set to focus on Brazil.
You scratch my back. I’ll scratch yours.
(No kidding.)
A passion for people’s health. Rechon Life Science. PO Box 60043, SE-216 10 Limhamn, Sweden
If you have pharmaceutical production you’re considering
moving, then give me a call. You’ll find me remarkably accommo-
dating, to say the least.
That’s because right now, our plant has more capacity than
ever. Capacity that I would obviously like to see filled as soon as
possible.
Our specialty is making aseptics in various forms – vials,
ampoules and single-dose syringes. We’re also really good with
sprays – nasal and oral. Needless to say, we’re FDA-approved.
And ready to start as soon as you are.
So call me today. I’ll make you an offer that’s quite irresistible.
www.rechon.com
Anders Ulfhielm
CEO, Rechon Life Science
+46-705 947 618
I
n the shadow of the financial crisis, pharmaceutical
companies are considering outsourcing functions to
service providers that specialise in non-core functions.
Successful outsourcing allows a company to focus more on the
performance of product development and to delegate other
operations to one or more service providers who can reduce
costs and improve performance in these non-core functions.
However, the greatest challenge to get the improvements and
cost reductions is the way the outsourcing is performed.
Rechon Life Science offers services across the entire
pharmaceutical development process,
from phase II development through
validation, manufacturing, packaging
and labelling.
“There is an increasing need for
the pharmaceutical industry to
become more time and cost effective,
and we can speed up the entire
process, from the first contact and the
idea stage to contract manufacturing,”
says Anders Ulfhielm, executive vice-
president, business development for
Rechon Life Science.
To get a win-win situation for all involved parties the
following critical success factors are essential.
Communications management
An outsourcing contract can facilitate communications
management by creating procedures for exchanging information
and communicating issues first within the internal
organisational structure of the outsourcing service provider and
the customer and then between the parties.
“With the Rechon project management tools, we secure a fast
and efficient reliable communication between the parties. Being
located in the south of Sweden also gives us several advantages.
We are only 20-25 minutes away from Kastrup, Copenhagen, and
have fast entry to the rest of Europe,” says Ulfhielm.
Performance management
The greatest performance management challenge is to clarify
the scope and define the critical functions that are delivering
customers’ success with outsourced functions. After identifying
these critical functions, performance measurement must be
put in place.
Rechon Life Science has a very interesting platform for the
developing and manufacturing of pharmaceuticals. Offering
excellent conditions in terms of experienced staff and state-of-
the-art technology, the company aims to help clients speed up
their processes and reach patients faster.
Because Rechon Life Science is owned by a Chinese
company, other added values could be part of collaboration.
“Being part of a global Chinese cooperation has several
advantages; for example we can provide our customers with an
established manufacturing in China and knowledge of the
attractive Chinese market,” says Ulfhielm. “It is also an
advantage when searching for cost effective raw material.”
Change management
Both parties need to share cost reliability. The customer enters
into a contract based on the savings,
while the service provider performs its
services to create a profit margin.
An outsourcing contract needs to
include a structured change
management procedure with routines
for additional services that justify
additional fees. Procedures to address
new or additional services to
customer personnel must be clearly
approved. If not, it creates conflicts.
“To secure this we also have a
quotation and agreement procedure
including an efficient project management,” says Ulfhielm. “This
help clients to speed up their market entry at a lower cost.”
Dispute management
It’s important to put a lot of effort into creating the contract.
Procedures for managing and resolving disputes need to be
established before a dispute arises. It is very important to
have an open mindset in the communication between the
parties. An outsourcing contract needs to encourage the
parties to acknowledge and address disputes as they arise,
rather than sweep them under a carpet where they often
become more serious.
For the future, Ulfhielm hopes that Rechon Life Science
will become a well renowned and respected contract
manufacturer for the pharmaceutical industry, for both small
and large companies.
“We want to be a reliable partner to companies throughout
their entire process of drug development, not just deliver a
naked vial. With passion and professionalism we want to
improve quality of life.” ■
The outsourcing code
Passion and professionalism create the right conditions for successful outsourcing, explains
Anders Ulfhielm, executive vice-president, business development for Rechon Life Science.
Company insight > Contract manufacturing
WorlDPharmaCeuTICalFronTIers
|
www.worldpharmaceuticals.net 111
Further information
Rechon Life Science Group
Website: www.rechon.se
Rechon Life Science offers services across the
entire pharmaceutical development process.
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Haselmeier USA
517 Benheld Road, Suite 301
Severna Park, MD 21146
Contact Robert J. Kilgore
r.kilgore@haselmeier.com
T (410) 647-7300
Haselmeier GmbH
Dufourstr. 32
8008 Zürich/Switzerland
Contact Volker Wirth
v.wirth@haselmeier.com
T +41(0)44 250 52 41
For more information
please call us or visit us at
www.haselmeier.com
Tel: +1 763-488-4843 www.cimalabs.com
2 half page adverts (286x210).indd 1 15/3/10 09:47:21
A
s the global pharmaceutical and medical devices industries
continue to face a host of market challenges, such as
demanding clinical and regulatory standards, cost and
productivity pressures, pricing and reimbursement pressures, increasing
research and development (R&D) expenses, an ever-expanding
competitive landscape, a consolidating industry and increasing consumer
demand, companies are exploring avenues beyond the traditional industry
boundaries to create new and innovative healthcare solutions
characterised by improved safety and efficacy profiles, and enhanced
treatment outcomes.
The convergence or integration of two or more core technologies, such
as diagnostics and/or devices with a drug or biologic to create
combination products, has been rapidly emerging as one of the most
popular strategies to ensure innovation and
product differentiation. More than anything
else, innovation through convergence is
leading to early diagnosis and safe and
effective treatment for an array of
disease conditions. As companies
seek new and innovative ways to
maintain growth and
profitability, convergence is
rapidly emerging as a strategic
priority. Each year, the number
of combination products under
development increases
significantly as more companies
realise the inherent strategic
benefits of introducing new and
innovative combination products
into the market.
Drug-device convergence
Drug-device combination products
are a major part of the global
combination products market. Examples
of drug-device convergence include devices
coated with a drug, devices meant for the delivery
of a drug, drugs packaged with devices, and devices that monitor
patients and precisely deliver drugs. Some of these products provide
superior therapeutic benefits over the conventional approach, while
some of them are characterised by portability and user-friendliness,
resulting in comfort and convenience to patients.
One of the most prominent and successful examples of drug-device
convergence are drug eluting stents (DES). Drug eluting stents, also
known as drug coated stents or medicated stents, are coronary stents
placed into narrowed and diseased coronary arteries to prevent
re-stenosis (blocking and reclogging of the stented artery). Cordis
Corporation, a Johnson & Johnson company, was the first to receive
the FDA’s approval for a DES with its CYPHER Sirolimus-eluting
Coronary Stent in April, 2003. The company had a monopoly until
March 2004, when Boston Scientific Corporation received approval for
TAXUS Express2 Paclitaxel-Eluting Coronary Stent. The latest
entrants to the US drug eluting stents market are Medtronic
and Abbott, who received the US FDA’s
permission to market the Endeavor
Zotarolimus-Eluting Coronary Stent and
the XIENCE V Everolimus Eluting
Coronary Stent in February and July
2008.
The success of the drug
eluting stents can be easily
judged from the growth that the
US market has witnessed since
2003, notwithstanding the
decline during 2006-2007 due to
negative publicity following safety
concerns. In 2009 the US drug
eluting stents market was valued
at $1.9 billion.
The success of the drug eluting
stents was followed by intensified
R&D activity by many companies to
develop the next-generation stents.
Abbott, for instance, is working on what
would be the thinnest drug-eluting stent on
the market, the ‘Thinman’, and on a
bioabsorbable stent. Abbott has the most advanced
clinical programme as far as bioabsorbable stents are
concerned and the company, in November 2009, announced three-
year data from the first 30 patients in the first phase of the ABSORB
clinical trial, demonstrating that its fully bioabsorbable drug eluting
When two
become one
Like most businesses across the world, the pharmaceutical and medical device industry is
facing a growing demand to cut costs while producing ever-more innovative products. Creating
combination products is rapidly emerging as a key way to make an impact in a competitive market.
GlobalData examines the success of drug-device convergence.
Insight > Drug delivery & formulation
WORLDPHARMACEUTICALFRONTIERS
|
www.worldpharmaceuticals.net 113
coronary stent had successfully treated coronary artery disease and
was absorbed into the walls of treated arteries. To build upon the
promising results of the ABSORB trial, the company is initiating a
large-scale trial called ABSORB EXTEND, which will enroll about 1,000
patients from up to 100 centres in Europe, Asia-Pacific, Canada and
Latin America.
While more than 80 coronary drug eluting stents are in development
by different companies, coronary stenting is not the only area on which
companies are focusing their R&D efforts. The clinical success of
coronary stents has motivated many companies to develop drug-device
combination products for peripheral arteries that carry blood to parts of
the body other than the heart and brain. In August 2009, US-based Cook
Medical launched the Zilver PTX Drug-Eluting Peripheral Stent in
Europe. Touted as a highly effective medical treatment for peripheral
arterial disease (PAD), the device is expected to reduce the number of
leg amputations and painful bypass graft surgeries performed annually
on European patients. While the product is still an investigational device
in the US, the therapeutic potential that it offers makes it one of the
most keenly-watched stents in the pipeline in the US.
Bone graft
Another successful example of convergence-based innovation is
Medtronic’s spinal fusion solution, the Infuse Bone Graft and the
LT-Cage Device. The Infuse Bone Graft and the LT-Cage Device are
used in Anterior Lumbar Interbody Fusion (ALIF), a procedure used to
treat problems such as disc degeneration, spinal instability and
deformities in the curve of the spine. Using the Infuse Bone Graft
inside an LT-Cage Device reduces the pain and complications
associated with treating degenerative disc disease (DDD) by
eliminating a second surgery. During traditional spinal fusion
procedures, the second surgery is usually carried out to harvest bone
from a patient’s own hip for transplantation to the spine. The LT-Cage
Device is designed to restore the degenerated disc space to its original
height, thereby relieving the pressure on nerves. The Infuse Bone
Graft, consisting of a solution containing rhBMP-2 (recombinant
human Bone Morphogenetic Protein-2) and an absorbable collagen
sponge, is used to fill the LT-Cage Device. While rhBMP-2 stimulates
bone formation, the collagen sponge acts as a scaffold.
The fact that the Infuse Bone Graft has already been used to treat
more than 500,000 patients is indicative of its market acceptance. With
the incidence of spinal disorders increasing at a significant pace each
year, the Infuse Bone Graft and the LT-Cage Device clearly represent
one of the best innovations in drug-device convergence within the
orthopaedics space.
Diabetes
Interestingly, the disease area that has seen the most drug-device
convergence is diabetes. Prefilled insulin syringes, insulin pens and
insulin pumps all represent the results of innovation driven by
convergence. However, what represents a real technological
Insight > Drug delivery & formulation
WorlDPharmaceuticalFrontiers
|
www.worldpharmaceuticals.net 114
Superior new active ingredients are a pre-
requisite for successful new products. How-
ever, there is also an additional prerequisite:
the ideal delivery system.
Existing forms on the market often fail to
meet therapeutic requirements. Drug deli-
very, whether transdermal or oral, is often
the better alternative. We are among the lead-
ing worldwide manufacturers in this area
and can develop successful products for you
because we cover all areas of competency.
In transdermal and oral film drug delivery.
LTS Lohmann Therapie-Systeme AG
Lohmannstraße 2
D-56626 Andernach
P.O.B. 1525
Phone: +49 (0) 2632 99-0
Fax: +49 (0) 2632 99-2200
E-Mail: ltsgroup@ltslohmann.de
Internet: http://ltslohmann.com
LTS Lohmann Therapy Systems Corp.
21 Henderson Drive
West Caldwell, NJ 07006
USA
Phone: +1 800 587-1872 (only from USA)
Phone: +1 973 276-8921
Fax: +1 973 575-5174
Internet: http://lts-corp.com
We make products from active substances
Production and
Packaging
We offer the full range
of production scale:
from bench scale to
global market capaci-
ties. Our “full-service”
approach covers com-
plex levels of active
ingredients and high-
quality lamination
through to tailor made
packaging solutions.
Technological
Diversity
We begin by analy-
sing your problem
and your objectives
and we create a so-
lution for each medi-
cation based on spe-
cifically developed
technology. We strive
to be the ideal part-
ner of the phar-
maceutical industry.
Clinical
Trials
Within the CRS Clini-
cal Research Servic-
es GmbH, which is
linked to the LTS
group of companies,
we handle nearly all
issues related to clin-
ical pharmacology
quickly and success-
fully.
Research and
Development
We develop systems
for applications
where the existing
galenic forms cannot
be implemented, are
not optimally effec-
tive, or where they
fail to solve com-
pliance problems.
You supply the active ingredient.
We develop and manufacture the product.
LTS_AZ_US-4c_07_GB.indd 1 25.01.2008 9:59:35 Uhr
breakthrough and a significant step towards artificial pancreas technology
is Medtronic’s MiniMed Paradigm REAL-Time Insulin Pump and
Continuous Glucose Monitoring System. It is the world’s only system to
integrate an insulin pump with continuous glucose monitoring. By
integrating convenient and round-the-clock continuous glucose
monitoring with small and portable insulin pumps that can deliver fast-
acting insulin 24 hours a day, the system not only offers improved
treatment alternatives but also offers the comfort and convenience critical
for the management of diabetes.
And these are not the only examples. Some other key examples of
drug-device convergence include transdermal patches that transport
drugs locally and systematically through the skin, dental bone-grafting
material with growth factor, and antibiotic-coated orthopaedic implants,
among others. While cardiovascular, orthopaedics and diabetes represent
the key disease areas with an array of drug-device combination products
already on the market, the pace at which R&D is being carried out
indicates that the industry could see the launch of products in other areas
as well. Interestingly, the wound care management market is already
seeing a lot of activity.
Concerns and challenges
Perhaps the biggest challenge to drug-device convergence is the reality of
the unique and in most cases mutually exclusive business models of a
pharma and a device company. Developing a combination product is not
just about the convergence of different technologies. It is also about the
successful alignment of the knowledge, capabilities and business
objectives of two different companies operating in two different industries.
It is important to note that a majority of companies explore partnership
opportunities beyond their industry boundaries in a bid to develop a
combination product. Cordis Corporation has entered into an exclusive
worldwide licence with Wyeth
Pharmaceuticals, a division of Wyeth, for
the localised delivery of Sirolimus in
certain fields of use, including delivery
via vascular stenting. Boston Scientific
Corporation holds an exclusive licence
from Angiotech Pharmaceuticals, for the
use of Paclitaxel and other agents in the
coronary vascular field. In September
2004, Cook Medical restructured its
licence agreement with Angiotech
Pharmaceuticals to accommodate
Cook’s decision to focus its product
development efforts on peripheral
vascular and gastrointestinal drug-
eluting medical devices.
There are many more examples of a
device manufacturer partnering with a
drug manufacturer and vice-versa. While
every deal brings with it a multitude of
financial, commercial, regulatory and
other challenges, the problems multiply
significantly when one of the partners is
a drug company and the other one a
device manufacturer. A drug and a
device manufacturer do not just have
unique organisational and financial
structures, but also different product
development, regulatory and marketing
challenges. For instance, while drugs
take much longer to reach the market,
the time-to-market for devices is far
lower.
So in most cases, it becomes very
important to work out at what stage a
collaboration needs to be carried out.
While the drug and device industries are
regulated by the same regulatory
authority and face a lot of similar
regulatory challenges, it is imperative for
the partnering companies to carefully
Insight > Drug delivery & formulation
WorldPharmaCeutiCalFrontiers
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www.worldpharmaceuticals.net 116
Melting… is not a novelty….
the environment makes the difference!
Melting… is not a novelty….
the environment makes the difference!
Alpex Pharma is an independent Swiss drug delivery company specialized in the development
and manufacture of proprietary solid dosage forms such as Orally Disintegrating Tablets, Buccal
Effervescent Tablets. The predominant focus for Alpex is the development of solid dosage
drugs and at the same time, improve the patient compliance and convenience.
The company, established in 1985, was managed from 1992 by Elan Corporation as Elan Pharma
SA. It became independent in 2004.
Alpex has an efficient formulation development team and a manufacturing site with an excellent
cGMP track record.
Alpex products are marketed worldwide and has a consistent pipe-line of new formulations for the
European and the US market.
Its state-of-the-art facility is conveniently located in north of Lugano and houses two independent
dedicated plants for pharmaceutical and nutraceutical products.
For more information, please contact:
Alpex Pharma SA – Via Cantonale
CH-6805 Mezzovico (Lugano), Switzerland
Tel: +41 (0) 91 935 51 10
Fax: +41 (0) 91 935 51 20
Email: contact@alpex.com
Website: www.alpex.com
Tablets and
forms to deliver drugs directly into the oral cavity in order to potentially improve the bioavailability of
examine the implications of a collaborative agreement before initiating a
combination product development programme.
Unfortunately, problems do not end with a successful alliance. Getting
marketing approval from the FDA and other regulatory agencies is
another big challenge. It is important to work out how a combination
product is classified, which in most cases influences the regulatory path
and ultimately the time-to-market. Currently, the review responsibility for
combination products in the US is assigned by the FDA Office of
Combination Products (OCP), established on December 24, 2002, as
required by SEC. 204 of the Medical Device User Fee and Modernization
Act of 2002 (MDUFMA). The OCP determines a combination product’s
‘primary mode of action’ and assigns the premarket review responsibility
to one of the medical product centres – the Center for Biologics
Evaluation and Research (CBER), the Center for Drug Evaluation and
Research (CDER), and the Center for Devices and Radiological Health
(CDRH). A total of 333 combination products were submitted for review to
the US FDA in the fiscal year ended 2007, an increase of 42% over the
number in the fiscal year ended 2006.
Because combination products involve components that would, ideally,
be regulated by different regulatory authorities and in most cases by
different FDA centres, the regulation of combination products involves
many challenges. The differences in the regulatory pathways for each
component in a particular combination product can affect the regulatory
processes of all aspects of the product lifecycle.
Essentially, while drug-device convergence provides new avenues for
growth and profitability, it is important for the collaborating companies to
consider their differences in needs and expectations,. However, driven by
the fact that drug-device convergence is leading to a host of unmet
clinical needs being addressed, and also providing additional revenue
streams, the challenges associated with drug-device collaboration will be
overshadowed by predictions about the emergence of new, innovative
combination products in multiple disease areas. ■
Insight > Drug delivery & formulation
WORLDPHARMACEUTICALFRONTIERS
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www.worldpharmaceuticals.net 117
Figure 1: Combination Product Applications,
US FDA, FY 2004 – FY 2007
FY 2004 FY 2005 FY 2006 FY 2007
N
u
m
b
e
r

o
f

s
u
b
m
i
s
s
i
o
n
s
Colour guide
Center for drug
evaluation and
research
Center for devices and
radiological health
Center for biologics
evaluation and
research
Source: US Food and Drug Administration (FDA)
350 -
300 -
250 -
200 -
150 -
100 -
50 -
0 -
100
112
36
103
139
31
96
104
35
148
142
43
Presspart and Presspart Nemo.
Living and breathing drug delivery.
Two specialist metal and plastic component divisions have joined
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3980-21 Presspart 178x124 Ad.indd 1 12/03/2010 18:07
T
he development of protein-based pharmaceuticals
is plagued by the ‘bio-monsters’ of instability and reduced
activity. Too many compounds cannot retain the protein’s
therapeutic properties long enough to benefit patients.
We all know why – the protein’s structural stability is
undermined during the stringent purification required for
vaccine and protein production, while thermostability issues
make the compound vulnerable to damage from normal
shipping temperatures.
The protein’s biological clock begins ticking as soon as it debuts
in the lab. The process of developing the therapeutic compound,
sending it through the market distribution chain and preparing it
for clearance in the patient is a race against time and nature.
The industry’s response has been to ‘stop the clock’ by adding
salts, sugars and other chemicals to the protein buffer solution, and
by stabilising the protein through refrigeration/freezing.
But these solutions have led to other problems: degradation with
reduced activity, undesirable side-effects from additives, painful
injections due to a viscous solution, and the risk of tissue necrosis.
And despite the costly stabilising efforts, the short-lived efficacy of
suspensions has necessitated recalls of vaccine batches that fell
below required potency levels.
Nanotechnology
The ideal answer would be to provide proteins with the
environment that they need: an aqueous solution that mimics
in-vivo conditions.
Do-Coop Technologies has investigated the unique properties
of water together with the physical principles of in-vivo
conditions. The result is a patented water-based nanotechnology
branded as Neowater.
The unique molecular organisation of Neowater is derived
from the interaction of the water, carbon dioxide and a minute
amount of suspended insoluble nanoparticles arranged in
clusters. Neowater harnesses the resulting surface effect to
create structure within the water that is a superior environment
for biological reactions.
Various studies have demonstrated that Neowater confers
increased stability on proteins at elevated temperatures, as well
as at 4°C. β-Galactosidase (β-gal), alkaline phosphatase (AP),
restriction enzymes and Taq polymerase are just some of the
proteins that showed greater stability at elevated temperatures
in Neowater.
A Neowater environment not only induces thermostability in
proteins, but the ordered aqueous environment also maintains and
enhances protein bioactivity in pharmaceutical formulations.
Moreover, the reduced need for additives lowers the viscosity of a
Neowater-based formulation, improving vaccination procedures.
Study results
One evaluation study, conducted by Do-Coop Technologies
and a leading European pharmaceutical company, examined
the in-vitro binding activity of a commercial antibody when
solvated with Neowater. The results demonstrated better binding
affinity to an antigen, under various storage conditions and at
elevated temperatures. Not only that, but exposure of the
therapeutical agent to body temperature (37°C) showed a three-
fold increase in antigen binding capability, a result that strongly
suggests that Neowater contributes to antibody activity under
in-vivo conditions.
The revolutionary nature of Neowater in mirroring intracellular
water allows companies to accelerate and improve biological
reactions with minimal customisation, and enables in-vivo
responses closer to those of living organisms. Companies can move
from in-vitro development to in-vivo delivery, and from early
laboratory experiments to late-stage studies in humans, more
smoothly and cost-effectively, with more confidence of success.
The achievement of all these benefits simply by switching to a
Neowater solution is reality. It’s just good science, good sense, and
good news for an industry plagued by faltering R&D pipelines.
And, who knows? Perhaps the next protein rescued by Do-Coop’s
nanotechnology will be the blockbuster drug of the decade. ■
A revolutionary cure
for protein instability
An ordered aqueous solution that mimics in-vivo conditions may prove to be the cure for the
instability and reduced bioactivity that afficts many protein-based therapeutic formulations.
Company insight > Drug delivery & formulation
WorldPhArmAceuTicAlFroNTierS
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www.worldpharmaceuticals.net 119
Mirroring of intracellular water
accelerates and improve biological
reactions with minimal customisation,
and enables in-vivo responses closer
to those of living organisims.

Further information
Do-Coop Technologies
Website: www.docoop.com
Telephone: +972 3533 3804
WorldPharmaceuticalFrontiers
|
www.worldpharmaceuticals.net 120
Company insight > Drug delivery & formulation
t
he most reliable method of predicting the performance of
a drug is through a human study, but countless human
trials take their toll on pharmaceutical companies both in
terms of time spent and money paid out. TNO, a research
organisation offering innovative solutions for the pharmaceutical
industry, is now using a combination of methods to make reliable
predictions about drugs at an early stage of development.
“We will test, say, five formulations of a drug using our in vitro
and in silico methods,” explains Miriam Verwei, project leader of
Pharmacokinetics at TNO. “The pharmaceutical company will then
know which formulation is the most promising and which
formulation they need to test in a human study. If you do not have
to perform a human trial with each compound and each
formulation, it saves a lot of money.”
Newly developed drugs tend to demonstrate low solubility and
low permeability, resulting in low bioavailability. Consequentially,
more sophisticated formulations are required to keep the
bioavailability of drugs at an acceptable level.
Before reaching the stage of human trials, Verwei and her
colleagues will investigate various individual processes to work out
exactly which process is responsible for the low bioavailability of a
particular drug. This then provides the pharmaceutical company with
reliable information about which process they need to focus on to
ensure that bioavailability is at a suitably high level.
“We have an in vitro gastrointestinal model (TIM), which reliably
simulates human conditions and looks at whether the drug can be
absorbed after being released from the formulation,” Verwei, an expert
on both in vitro and in silico studies, begins. “The next step is
focussing on intestinal absorption – that is whether the compound
will go through the intestinal wall. If you combine these two
processes, you can get a good idea of which process is responsible for
low bioavailability. Companies then get more information at an earlier
stage of development, making the whole process more efficient.”
TNO’s main priority, according to Johan TeKoppele, science
manager of the Biosciences Business Unit, is the most accurate
possible translation of information.
“The translation of testing is the key issue in our whole portfolio
ranging from pre-clinical to clinical trials,” he expands. “We are
constantly focussed on how our pre-clinical research predicts what
will happen in humans.”
During and following the economic downturn, pharmaceutical
companies have been focused on saving as much money as
possible, yet TeKoppele refuses to compromise on the standard of
information TNO provides. “We are really working from the angle of
how we can get the best value – the most relevant information, that
is – for the lowest cost,” he says. “But sometimes you want to pay a
bit more and have far superior information; it pays off in the longer
run. Quality, standards and innovation levels are key for us. We want
to take fundamental knowledge and turn it into applications or, to
put it another way, we want to turn science into value.”
Nowhere is this philosophy more clearly illustrated than in the
areas of research TNO plans to undertake in the coming months
and years, particularly in the arena of systems biology.
“Systems biology is a different way of thinking about biology,”
TeKoppele explains. “It’s a very new field and, because of this, new
issues and questions keep popping up. So it is our aim to connect
systems biology to the existing methods of drug development. If
we can add this to our pre-clinical testing facilities, there is no
doubt that we can add value to our clients’ research.”
Other areas TNO will be investigating include personalised
medicine or subgroup treatment and microdosing, which allows
companies to perform studies on humans at a very early stage of
drug development. The pharmaceutical industry can certainly rest
assured that TNO is fully committed to predicting – in pre-clinical
settings – how drugs will behave when administered to humans. ■
Predictable behaviour of drugs
Pharmaceutical companies are looking to predict the behaviour of drugs earlier and earlier in the
development phase, making subsequent human trials more effcient and saving time and money.
TNO, an independent research organisation, is offering innovative solutions.
TNO’s in vitro
gastrointestinal
model TIM
Further information
TNO
Website: www.tno.nl/pharma
Email: info-pharma@tno.nl
TNO.NL/PHARMA
Unique gastrointestinal models
• Models simulate the dynamic conditions in the
upper GI tract (TIM-1) and the colon (TIM-2)
Permeability in vitro models
• Caco-2 and other GI mucosal cell lines
• Transport chambers with rat or pig GI tissues
Unique models for active transport proteins
• MDCKII cells with human transporter proteins
(e.g. Pgp, BCRP)
• HEK293 cells with human transporter proteins
(e.g. OCT, URAT)
• Isolated membranes with specific transporters
• Transportocyte
®
assays for specific uptake
transporters
In silico modelling (PBPK modelling, TIMpk)
• Combined in vitro kinetic data to reliably predict
plasma concentrations
For more information: info-pharma@tno.nl
TNO is an independent research organisation.
TNO services for bioavailability
Predicting bioavailability
KvL-Z.08-02.599 Ead World Pharmaceutical Frontiers v2.indd 1 21-1-2010 9:10:26
M
edicated chewing gum is considered a
valid drug delivery system that releases
the active ingredient by chewing.
Medicated chewing gum offers a wide range of
advantages that make it an excellent alternative.
Chewing gum has been proven as a great delivery
vehicle for nutrients and drugs. For example,
nicotine smoking cessation chewing gum is one of
the most successful controlled-release drugs.
Chewing gum also offers the possibility of rapidly
absorbing the drug through the oral mucosa
leading to fast onset of action and bioavailability.
Also, it has superior sensorial properties compared
with other dosage forms; it has a more attractive
appeal and offers the patient an active control over
the treatment.
Then there are the benefits of chewing gum in
general; the most significant one is that of oral care.
Chewing sugar-free gum after eating is clinically
proven to be an important part of good oral health.
There are many studies that demonstrate that
chewing gum stimulates saliva flow and increases
plaque pH, which prevents tooth decay. Moreover,
chewing gum increases alertness and
concentration, helps to control weight management
and reduces stress.
Added to the therapeutic effect of the drug there
is a very positive synergistic effect brought on by the action of
chewing, which has a positive effect on the patient’s compliance.
Cafosa sees a strong potential for medicated chewing gum as an
innovative and valid alternative to standard, chewable or orally
disintegrating tablet presentations.
Recently as a part of “a taste for bold ideas”, the Bill & Melinda
Gates Foundation gave grants to encourage creativity among
scientists, especially on those areas that have never been focused
on health before.
One of the winning projects was from a group of researchers
at the University of California, Los Angeles, who were planning
to develop a chewing gum that can be used as a diagnostic tool.
Called MALiVA, it will detect the presence of malaria in a
person’s saliva.
During chewing, particles in the gum will react with malaria
proteins, which can be detected and characterised when the gum
is scanned with a magnet.
In order to make the production of medicated chewing gum
easier, Cafosa has developed Health in Gum, an innovative concept
for the pharmaceutical industry. Health in Gum is an excipient, a
directly compressible powder gum containing a mix of ingredients,
to which you only need to add your own APIs.
Health in Gum is specially designed for in-house use in
pharmaceutical facilities and does not require specific chewing
gum production equipment. It performs excellently using
standard tabletting equipment.
Health in Gum offers an innovative drug delivery system
that benefits from all the advantages of chewing gum and
also contributes to improved compliance. It has been created
to simplify the manufacturing process of chewing gum in a
quick and cost-effective way. It is directly compressible and
works at room temperature, which allows the use of thermo-
sensitive APIs. ■
Health in Gum
Chewing gum is an excellent alternative to traditional drug delivery methods. Cafosa has developed Health
in Gum, to make the production of medicated chewing gum easier, says technical director Roser Amposta.
Company insight > Drug delivery & formulation
WorldPHarMaceuticalFrontiers
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www.worldpharmaceuticals.net 122
Further information
Cafosa
Website: www.healthingum.com
www.cafosa.com
Health in Gum is a directly compressible powder gum.
Innovating in oral drug delivery systems is easier than ever
Health in Gum is an oper door to innovation. It is a step further in medicated chewing
gum. Health in Gum is an excipient, a directly compressible powder gum with excellent
flow and compactibility properties.
You only have to select the Health in Gum powder that meets your requirements, add
your API and mix it in a powder blender. Then it is ready to be compressed with standard
tabletting equipment.
Health in Gum allows the use of thermo/water sensitive APIs. With Health in Gum you
can explore new bioavailability profiles for your APIs.
Innovating in oral drug delivery systems is that easy.
A POWDERFUL
WAVE OF INNOVATION
www.healthingum.com
HiG Anunci 210x286.indd 1 10/2/10 12:31:31
12, quai Henri I V - 75004 Pari s - France - Tél éphone : + 33 ( 0) 1 48 04 67 45 - Tél écopi e : + 33 ( 0) 1 48 04 67 23
www. crossj ect . com - i nf o@crossj ect . com
Finally, a needle-free injection device that does not look like a syringe.
The Crossject needle-free injection device reconciles all "needle phobics" with
injections, eliminates the risk of needle-stick injury and needle contamination and
thanks to its easy use improves patients' quality of life.
Its innovative and highly versatile technology and its modular concept allow
fast customization both for injection routes (intradermal, subcutaneous or intra-
muscular) and drug characteristics.
Based on standard components and industrial tools, its drug container can be
easily handled on a standard filling line.
Crossject is your new partner for therapeutics challenges.
The Crossject needle-free injection device: a new option to improve your patient care
I nnov at i v e ne e dl e - f r e e i nj e c t i on s y s t e ms
No need for needles
P
L
E
S
S
Annonce_210x286_02-2010 22/02/10 9:56 Page 1
C
rossject’s Zeneo is a needle-free,
pre-filled, single-use injection
device for intradermal,
subcutaneous or intramuscular injections.
It allows a fast, simple, two-step, injury-
proof injection and offers an elegant
solution for needle-phobic patients,
needle-stick injury risk prevention and
infectious waste management. Zeneo’s
ease of use makes it suitable for self-
injection therapy too.
The device uses the stored chemical
energy in a miniscule blend of ‘energetic’
materials that is released to generate
controlled pressure and activate a piston,
similar to those in traditional syringes,
which in turn generates a high-speed jet
of liquid. This liquid penetrates the skin,
the subcutaneous layers and tissues up to
the desired depth.
Development strategy
From the beginning, Crossject’s objective has been to target
several poorly met public health needs, including:
obviation of needle phobia, which affects 10% of ■
patients, often compelling them to reject any needed
injection treatment
reduction of needle-stick injury, which negatively impacts ■
medical professionals, care-givers and people directly in
contact with contaminated waste
elimination of complicated injection procedures, which ■
prevent patient self-injection and increase treatment
costs; when self-injection is proposed, it usually requires a
specific patient education programme; these injection
procedures are also largely inappropriate in the case of
emergency drug administration.
A strong demand
Half of the pharmaceutical drugs currently in early clinical
development require parenteral injection because of their
pharmacokinetic properties.
Most of them are biological drugs. This creates a potential
market of several billion US dollars for disposable needle-free
injection devices.
Several companies have tried to capture this opportunity
over the past few years. Many succeeded as far as signing
partnerships with big pharmas, but most failed when it
came to providing simple devices and/or industrialising
their production.
Best-in-class partners
From the beginning, Crossject has recognised the technical
challenges it faces.
Its strategy has been to bring together a pool of experts for
the industrial development of its unique technology. Crossject
has also attracted the best-in-class global partners in key areas
such as glass technology and pharmaceutical manufacturing,
and has succeeded where others have failed.
Crossject has developed its technology, passed the most
stringent manufacturing tests and successfully run several
clinical studies, including a 100-patient efficacy study sponsored
by its partner GSK Biologicals. ■
Needle-free injection
Using technology similar to that used in airbags, Crossject’s new injection device circumvents
needle phobia and reduces the risk of needle-stick injury.
Company insight > Drug delivery & formulation
WorlDPhArmACeutiCAlFroNtiers
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www.worldpharmaceuticals.net 125
Further information
Crossject
Website: www.crossject.com
Email: info@crossject.com
Zeneo allows a fast, simple,
two-step, injury-proof injection and
offers an elegant solution for needle-
phobic patients.
A two-step, patient-
friendly device:
remove the safety cap,
position and gently
press the device
against the skin.
Andrew Tunnicliffe. When you were young what career
path did you see yourself taking?
Hans Lindén: I saw a career in chemistry, as a researcher in a
lab, or in mathematics, as a teacher, primarily. In chemistry, it
would be biochemistry – the chemistry of life because it seemed
to me to be a fascinating field. This was in the early sixties, and I
had read the book by Watson and Crick on the discovery of the
double helix, years before.
In 1965 I was offered a job in computer programming and
systems development training by Bolinder-Munktell (a Volvo
company). They needed young people. It was tempting, but I
thought it would be too theoretical, so I declined. Shortly after, I
decided to go for pharmacy because it would be more about
chemistry and medicine and contact with people.
During your time at the University of Uppsala in
Stockholm you achieved a lot. Did your early success
shape your career?
Yes, it did, but not really the way I thought it would. We started
with chemistry and biochemistry after one year and I was
impatiently looking forward to it. Well, there I was disappointed,
although a very good professor
was teaching. I gave up
biochemistry and found
organic chemistry
and analytical
chemistry, in
particular – with
all these new
separation
techniques and
columns and
chromatographs –
more appealing,
but I did not go for
it completely. Years
later, the professor
told me that the world
was missing at least one good
analytical chemist. “Oh, who is
this?,” I responded. “You,”
he answered.
How did such a huge vote of confidence affect you?
I was totally surprised, of course. The comment made me reflect
on whether an analytical approach or a personality-based
approach would be generally applicable and useful elsewhere
than in chemistry. Obviously, it was.
The second thing that helped shape my career was that
during my studies I was drawn into the student association and
committees. This in turn took me into close contact with the
faculty, staff and the university administration. I became
swamped by administrative tasks of the faculty, which I did part-
time, in parallel with completing my studies. Obviously, there
was some organisational talent that was picked up and further
nurtured. Of course, it was also the start of building and
expanding a personal network, although it was never really
planned, or done systematically.
Thirdly, each summer I spent a number of weeks working in the
laboratory for clinical chemistry at one of the bigger hospitals in
Stockholm, having got special permission, because it was usual for
medical students to be recruited. In the first years of my studies, I
also sat by those who were waking up after surgery in a post-
operation department (seeing to the respirator and so on), to make
some money, and had even done some work in a home for old
people. All these gave me clinical insight into two issues: what are
disease, accidents, age, new life and death in reality, and how do
we help and cope with it all? This was invaluable for a young
pharmacy student. Fourthly, I had good mentors.
And how did this time contribute to your personal
development as a young adult?
The human body and tissue did not seem to be as fragile as I had
thought they would be. In other cases, you could not see if there
was life at all for a while, unless trained to. There were impressive
instruments in the hands of the doctors and nurses, and lively and
joking patients on the ward as well. Some patients did not really
understand why they were there, but the test results were clear.
Life and quality of life got a new and deeper meaning, I think. You
could feel pretty safe, I thought. If something happened to your
body and you were taken there, they’d do whatever they could to
help and to make you survive and recover.
You mention good mentors; can you name a few of them
and why were they good mentors?
I think I will refrain from doing that. I might forget someone. They
were positive and encouraging. They introduced me to colleagues
People > Hans Lindén
Boasting a career that has so far spanned five decades, executive director of
the European Federation for Pharmaceutical Sciences (EUFEPS) Hans Lindén
has seen many changes within the pharmaceutical industry. He talks to Andrew
Tunnicliffe about his work, life and combining the two during a time of great change.
Teaching a lifestyle
WorldPharmaceuticalFrontiers
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People > Hans Lindén
and leaders in the profession; those in science, those not in science
and those in between, at all levels. They engaged me or
recommended me for tasks, jobs and positions that I thought I was
too young or not sufficiently experienced for. They stayed behind,
supported and gave advice and shared experiences – some of them
spending a lot of time reorganising and correcting drafts and
manuscripts for free, for years, including in my second language.
how did you first move from academia and get into the
pharmaceutical industry?
One week or so before graduation, I was offered a job as course
director and department head at the Swedish Pharmaceutical
Society/Academy of Pharmaceutical Sciences. I accepted and never
regretted it, although it was occasionally difficult, because I had no
real experience in leading a group of people. Courses were offered for
pharmacy staff and specialists, those in industry research at many
levels and those running the regulatory operations. Upper levels in
industry research knew what would be needed, not only for the next
year, but for many years, depending on what was in the pipeline –
and my colleagues and I knew who was good in what discipline in
the university. Biopharmacy, PK/PD, clinical evaluation of drugs,
registration procedures and safety were, for example, rapidly
developing new course topics. We were also among the first in the
country to produce educational videos.
how has the pharmaceutical industry changed in the
time you have been involved in it?
I never worked in – but with – industry. Observing it from
outside, there seem to be other or additional key driving factors
today than 20-30 years ago. There is a lot more focus on the
business side for instance. Getting a product through to market
also seems to be more complicated and demanding than ever
before, not least money wise. I do not think that scientists were
brighter before, but there are fewer breakthrough drugs today –
or the concept of a breakthrough is perceived differently.
What is the biggest change facing the sector today?
I think it will have to seriously start reflecting on or mapping out
what resources it has within, what is available and what is
needed, including education and training and research not
funded or fundable within, and how to make the best use of
them in the interest of the medical needs of mankind. It is there
to serve, which will continue to take know-how, leadership and
funds. If the world can agree on how to combat terrorism and
global warming, would it be able to agree on how to combat
human disease for all humans as well. Actually, it would be good
to start applying a systems approach to medicine supply from a
global perspective.
is there one thing of which you are most proud?
I have been heavily engaged in creating national action
programmes for young people and medicine, the elderly and
medicine, and on medicine information for young parents, for the
Medicines Information Council in Sweden. The first and the last
one were pretty easy to agree on, the second was not. The next
action programme, which took a lot of time from the very beginning
ten years ago, was the New Safe Medicines Faster project (NSMF),
aimed at European money for medicine research. Obviously, this
project listed, worded and communicated needs that many felt, and
the ball started rolling. It became the forerunner of today’s
Innovative Medicines Initiative Joint Undertaking programme. It’s
too early, though, to judge the outcome of it. I always liked projects.
They have a starting point, and they should have an ending point.
and if there was anything you could change or perhaps
do again what would that be?
Perhaps I would have listened and reflected more, concentrating on
and pushing strategic considerations, moves and initiatives.
is there something that you had always wanted to
achieve, personally or professionally, but have never
been able to for one reason or another?
Better balance between work and family and friends, which in
reality would mean more time for members of the family including
myself and less time for work.
so do you feel there may have been something missing
from your personal life, or that you could have ensured
you had more time?
Looking back, it could certainly have been different for me and
my family in many ways. Priorities could have been different,
too. Less time for what we call work and more of what we do
not normally define as work might have been better. But did
people hundreds or thousands of years ago differentiate
between work and their other life as we do, or did they just have
to carry on living it with all its facets?
Were there times you wished you had another career?
Yes, an eight to five o’clock job, leaving home at a particular time
and being back home at a particular time, Monday through Friday –
especially when there were small children and reports to be
finished before 7am. But I doubt if this would ever have been me.
travel is a part of that but there must have been times
where you had an adventure?
Missing a train connection, when pressed for time, and there being
no taxi. There was a bus, though, and a driver. I asked: “Are you
going in that direction?” “Yes”, he answered. “Can I go with you,
and you drop me off?” I asked. “Yes.” The bus belonged to a
women’s handball team on its way home from a successful
tournament and they made it for my meeting.
What do you enjoy doing in your spare time?
Being with family and friends, and also silence, reading and
different activity, be it at home, among islands in the
archipelago, in the mountains, travelling or elsewhere. It was,
for example, a joy to build a wooden terrace by hand on a slope
at our small summer house about one hour’s drive from home
this summer.
What from work helps in your personal life?
Human beings are not very different, wherever you are. ■
Medicofarma is a privately owned
Polish pharmaceutical and
nutraceutical contract manufacturer.
Its core business is contract packaging,
manufacturing and developing.
The company’s production plant
was built in 2004 and is located in
Radom, in the heart of Poland, a 55
minute drive from Warsaw Airport.
This modern factory is equipped with
state-of-the-art technological lines
and meets GMP requirements.
Medicofarma’s mission is to provide
an excellent service at competitive
East European prices. Because of
its flexibility and customer-oriented
approach, many customers have
moved manufacturing of their
products to Medicofarma.
Medicofarma is entirely
dedicated to contract
manufacturing and does not
have, nor does it intend to
have, any own brands.
The company’s services
include:
packaging of solid forms: ■
PVC, PVC/PVDC, PVC/
PE/PVDC, Aclar, Alu-Alu
blisters; glass and plastic bottles,
sachets; packaging
in folding boxes and cards
manufacturing of solid forms: ■
powder blends and granulates,
tablets, film-coated tablets,
sugar-coated tablets, hard gelatin
capsules filling
complete formulation ■
development: through to scale-up
production, manufacturing of trial
batches, analytical development,
stability testing, storage of product
samples for stability testing and
release to the market. ■
Directory > Product showcase
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PDF Logger for cold chain monitoring
Further information: Elpro-Buchs AG
Website: www.pdf-datalogger.com
Made in Poland
Further information: Medicofarma SA
Website: www.medicofarma.pl
The Libero PDF Logger is the world’s first
PDF data logger for cold-chain monitoring.
It provides new benefits such as speed,
higher specifications, reductions in
validation work and faster data access,
and measures and stores temperatures
during cold chain transport. At destination,
it plugs into any PC’s USB port. It
automatically creates a PDF/A report with
text, alarm information, statistics and a line
chart. It acts as a USB memory stick and
the PC will automatically show the file as a
new-found drive. The evaluation report can
be viewed by Adobe Acrobat Reader, and
printed or emailed. Libero features include:
Automatic PDF report. No software, ■
driver, data cable or interface is needed
at destination. It speeds up the time
taken to accept or investigate the
shipment because the PDF/A file can be
emailed immediately to the sender.
Universal connection method. All ■
modern PCs are equipped with USB
ports, so the PDF Logger can be
connected to any PC, meaning no
more incompatibility issues or extra
cost for infrastructure.
Higher accuracy. A good data logger ■
for cold-chain temperature monitoring
shows a +/- 0.5º accuracy – Libero is
accurate to +/- 0.2º. The result is more
reliable temperature and humidity data.
Pre-configured profiles and five alarm ■
zones. Libero can be programmed by
SmartStart, loading any pre-defined
profile onto the device in a second,
so no complicated programming
is required and shipment-related
information can be added easily.
Elpro, a leading manufacturer of data
loggers for cold-chain temperature
monitoring, monitoring of bio repositories,
clean rooms and storage facilities, is
dedicated to supporting pharmaceutical
and biopharma companies. ■
Directory > Product showcase
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tesa scribos® GmbH, a subsidiary of tesa
SE, offers brand protection strategy advice
and security and application technologies
for counterfeit, diversion and warranty
fraud protection, and theft prevention.
Holospot® is a discreet, forgery-proof ■
information carrier that attaches to
any product. It uses laser inscription
of computer-generated lithograms into
small, polymeric data carriers, and offers
multiple overt and covert security levels,
with the possibility to identify every
product individually. Authentication is
possible with or without special devices
and can be customised.
CodeSeal is a security label with ■
integrated information. Its item-unique
security codes are integrated into
a physical verification system and
it is suited to providing counterfeit
protection, traceability and authenticity
verification for each product.
IdentSeal® is inscribed by laser with ■
visible text or high-contrast bar codes. It
offers overt protection and identification
plus effective tamper-evidence. Brand
owners can choose between specific
surface structures, non-removable
imprints or fluorescent UV features to
further enhance security.
SecuritySeal adhesive tapes and labels ■
protect against manipulation and theft
by means of an irreversible optical proof
of first opening.
SecurityPrint labels use guilloches, ■
luminescence inks, thermoreactive and
colour-shifting inks, as well as anti-
copy protection.
trust & trace uses a physically secure ■
product coding system with track and
trace systems to optimise distribution
and prevent counterfeiting and trade
on the grey market. Finally, customer-
specific labels can be combined with
several security features. ■
Brand protection solutions
Further information: tesa scribos Gmbh
Website: www.tesa-scribos.com
Haselmeier is a leading designer and
manufacturer of pens and autoinjectors
for injectable pharmaceuticals. For 40
years the company has combined
experience and innovation to produce
disposable and re-usable self-injection
delivery systems, many featuring its
hidden needle design.
The Axis Pen System is a variable
dose injection device for manual
injection. It is available in a disposable
or re-usable presentation. Providing a
new unique technical function the
product features:
dose adjustment from 0.01ml to 0.6ml ■
per injection
no or minimal priming ■
easy and safe dose correction ■
accurate dose reading with sliding ■
window
no rotating outer components ■
protected dose scale. ■
The i-Pen is a reusable variable dose
injection device for use with a 3ml
cartridge. It is available as a standard
design or can be customised. It features:
dose adjustment from 0.01ml to 0.6ml ■
per injection
compact size enables easy handling ■
and portability
large, easy-to-read dose indicator. ■
The Softpen is a reusable injection
device featuring Haselmeier’s patented
hidden needle design. On de-pressing the
pen clip, the needle automatically enters
the subcutaneous tissue followed by
delivery of the solution. Features include:
fully automatic needle insertion and ■
injection
needle is hidden prior to injection ■
multiple injection from a 3ml cartridge. ■
The Haselmeier disposable Penlet
is a fully automatic fixed-dose injection
device designed for use with a 3ml
cartridge. Features include:
ready for use by the patient, no dose ■
adjustment required
fully automatic needle insertion ■
and injection
needle is hidden prior to injection. ■ ■
Pen-size dose delivery
Further information: haselmeier
Website: www.haselmeier.com
Products can be traced
throughout the supply chain.
Directory > Product showcase
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CIMA® is a world leader in the drug
delivery partnering business,
specialising in the formulation, taste-
masking and manufacturing of
pharmaceuticals using its orally
disintegrating tablet (ODT), oral
transmucosal, tamper-deterrent,
solubilisation and oral powder drug
delivery technologies.
ODTs disintegrate in the mouth and
can be taken without water. CIMA offers
compressed (OraSolv® and DuraSolv®)
and lyophilised (Lyoc™) tablets with
customised release profile, enteric
coating, flavouring and colouring options.
Oravescent®, oral transmucosal
buccal tablet technology delivers drugs
directly through the oral mucosa rather
than in the gastrointestinal tract.
Transmucosal drug delivery can result in
a greater rate and extent of drug uptake
into the systemic circulation, which may
also reduce the dose of drug required to
produce a therapeutic effect.
OraGuard™ extended-release/
tamper-deterrent technology provides a
robust extended-release PK profile, even
during co-administration with alcohol.
It is also resistant against various
tampering methods including crushing
and ingestion, injection or snorting,
chewing, aqueous extraction for
IV dosing and alcohol extraction.
Solubilisation (MicroSolv™) is a solid
self-emulsifying drug delivery system
(S-SEDDS) that CIMA developed for
insoluble drug candidates. The drug
is emulsified and adsorbed onto
a powder that can be manufactured
as a tablet, capsule or ODT.
Granules/oral powder comprises
drug granules packaged in a sachet.
It can accommodate high doses
(>1 gram) of drug product. Customised
granule size, release profile, enteric
coating, flavouring and colouring
options are available.
CIMA has proven commercialisation
success with more than 20 products
marketed in more than 70 countries.
Its expertise includes R&D, formulation,
manufacturing and packaging.
The company puts these capabilities
to work for its partners to
commercialise their products and
bring them to doctors and patients
around the world. ■
Pharmaceutical partners
Further information: cima
Website: www.cimalabs.com
For more than 40 years, Ferro Pfanstiehl
Laboratories (FPL) Inc, a wholly owned
subsidiary of Ferro Corporation, has
manufactured clinical and commercial
quantities of active pharmaceutical
ingredients (APIs), high potency,
high containment APIs, advanced
intermediates, and other small molecule
new chemical entities.
The FPL site is FDA registered,
inspected and approved, and client
audited on a regular basis, while the
company has also received SafeBridge
Certification. Its focus on safety and
quality enables it to handle compounds in
a secure environment.
The company holds more than 15 active
US and international Drug Master Files. It
focuses on delivering value throughout the
product lifecycle, from clinical trial
materials to commercial production with
outstanding technical support. FPL’s
staff supplements its clients’ teams
with experience in scale-up, process
chemistry, methods development,
validations and regulatory affairs. It is
on this platform that the company offers
the following products and services:
fee for service and contract ■
manufacturing of APIs, cytotoxic and
potent drugs and advanced
intermediates and linkers
contract manufacturing services for ■
high purity carbohydrates and
excipients, sugar acids, esters,
alcohols, lactones and salts, and
pharmaceutical-grade salt solutions
method development, process and ■
cleaning validation for stability testing,
and clinical trial material with
supporting documentation
DMF preparation, submission and ■
maintenance.
FPL is also a leading supplier
of speciality and blocked sugars of high
purity low endotoxin (HPLE)
carbohydrates produced under API-
level cGMP, ICH-Q7A compliant
conditions. The company manufactures
HPLE sugar excipients including
versions of sucrose, trehalose, maltose,
galactose and non-animal derived
galactose for injectable products and
ingredients for use in today’s risk-
based regulatory environment. ■
the right ingredient
Further information: Ferro Pfanstiehl laboratories
Website: www.ferro.com
Directory > Product showcase
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Processes of temperature monitoring
in the healthcare field require
constant validation and must follow
strict regulations, particularly the
Federal Drug Administration (FDA)’s
21 CFR Part 11.
Tecnosoft, with its wide experience
of temperature data loggers
development, provides a full range
of solutions for sterilisation monitoring
and many other applications in the
pharmaceutical and medical markets.
Tecnosoft’s new software,
TS Manager, is compatible with
SterilDisks, which are widely
used in the food and pharmaceutical
industries to control high-temperature
processes of up to 140°C. The software
has been designed according to FDA
regulations and has been approved
as 21 CFR Part 11 compatible.
TS Manager also works with
other loggers, including SterilCyl,
for bottles monitoring and narrow
places, and TempStick, suitable for
environment, fridges, fridge cells
and transport monitoring, as well
as many others.
The TS Manager enables users
to start and download several
loggers at once and analyse acquired
data through different profiles
using formulas and parameters
such as F0 and mean kinetic
temperature, to immediately check
the monitored process.
TS Manager is a multi-user software
with login, password and permissions.
All operations are logged and data
cannot be modified, as requested
by the regulations.
The software is also designed
for validators requiring a quick
and powerful solution to validate
customers’ processes and
equipment. Tecnosoft offers
a validation kit, which includes
three temperature loggers and
a temperature and pressure logger,
at a highly competitive price.
The company can save a customer
database, and for each customer
its equipment, and have the history
of all validation. Tecnosoft can then
print detailed reports and export
data in XML and PDF, with digital
signature implementation. ■
temperature validation software
Further information: tecnosoft srl
Website: www.tecnosoft.eu
Xceleron works alongside leading
pharmaceutical and biotechnology
companies to meet the industry’s most
fundamental challenge: improving the
efficiency and cost-effectiveness of
drug development.
Xceleron uses 14C microtracers and
ultra-sensitive accelerator mass
spectrometry (AMS) in a powerful
combination to provide unique early
clinical insights into drug candidate
performance in humans.
Pharmaceutical companies have
exhibited great interest in the use of
innovative phase 1 clinical study designs
to quantify absolute bioavailability (and
other fundamental kinetic parameters)
and metabolite safety. Such studies have
been designed by Xceleron in a way that
adds a small increment to the existing
expense of a human safety study.
Using a 14C microtracer combined
with AMS allows absolute bioavailability
information to be generated from a study
design in which a sub-therapeutic
intravenous dose is administered
concomitantly with a therapeutic extra-
vascular dose. This ideal clinical study
design does not require IV toxicity data
or extensive formulation of the IV dose.
Metabolite safety has gained
prominence since the publication of FDA
and ICH guidelines in 2008 and 2009.
Xceleron has developed, in collaboration
with its clients, a unique approach that
provides a very cost-effective phase 1
metabolism screen. By pooling samples
across subjects and time-points to form
one sample for analysis, a human
metabolite profile is produced that can
be used to compare preclinical models.
Xceleron combines technical expertise
with vast drug development experience
and rigorous quality control procedures
to provide its partners with data they
can rely on. The company has developed
the most extensive and validated
quality infrastructure for the analysis
of 14C by AMS.
Pharmaceutical and biotechnology
customers have turned to Xceleron
to help them make better-informed
decisions throughout every stage of drug
development. Xceleron-generated data
has been used to support the marketing
applications of seven approved drugs,
and several others in late-stage testing. ■
Phase 1 enhancement
Further information: Xceleron
Website: www.xceleron.com
Directory > Product showcase
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Tired of manually opening and closing
screw-cap tubes? The new Hamilton
DeCapper for screw-cap tubes will take
care of this awkward and time-
consuming task while you use your time
for more interesting activities.
Available in a 96-tube rack, its
straightforward and intuitive
touchscreen interface provides a simple
operation. It is the only instrument
available that enables multiple racks to
be processed concurrently. Additionally,
single rows or a complete rack can be
opened or closed. The Decapper’s three
key advantages are:
flexibility ■
time-saving ■
safety. ■
The Decapper has a sensor that
detects and controls the movements of
the caps and provides the user with
superior process safety. ■
Simple decapping
Further information: Hamilton Bonaduz
Website: www.hamilton.ch
Whether you are designing a new water
system or retrofitting an existing system
with on-line analysers, Hach Lange
products provide the information necessary
for the highest quality assurance. The
company brings together trusted names in
the industry to offer complete analysis for
purified water (PW), water for injection
(WFI), pure steam and high purity water
(HPW) in the analysis of total organics,
dissolved gases and trace particles.
Anatel total organic carbon (TOC) and
conductivity systems were the first ever
designed for online use and specifically
created to help meet requirements of USP
<643> and <645>. As required by the USP
and EP, all Anatel analysers assure
complete oxidation of the organics with
the unique ‘dynamic end-point detection’
algorithm. Designed as a fully compliant
TOC analyser that meets the requirements
of USP, EP and JP requirements for TOC
and conductivity, the Anatel PAT700
enables process compliance in the most
demanding regulatory environments.
Polymetron conductivity analysers
ensure industry standards are met for
ultrapure water systems. The Polymetron
9126 Purecal is an easy-to-use portable
calibration system used as a certified
reference for validation in on-line ultrapure
water conductivity measuring systems
and meets USP, EP and JP standards.
For water systems that use ozone for
sanitisation, Orbisphere dissolved gas
analysers are ideal for integration into
pharmaceutical water systems. Orbisphere
controllers analyse a single channel or
multiple channels so
monitoring of the feed
tank, post-destruction and return lines
using a single point of control can be
performed easily. For measuring ozone in
ultrapure water loops, the Orbisphere
C1100 ozone sensor with the Orbisphere
510 provides operators ‘True Zero’, drift-
free accurate measurements that reduce
production line stoppages and waste.
For the most critical applications
including WFI, high accuracy particle
counters have long been considered the
industry standard for performance to meet
USP, EP, JP and KP compendia tests. ■
Ultrapure water analysis
Further information: HACH LANGE Sàrl
Website: www.hach-lange.com
Orbisphere C1100 ozone sensor
The Decapper’s touchscreen facility provides a
straightforward and controlled operation.
Directory > Product showcase
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Oncology Services (OS) is a leading,
internationally operating CRO with
unmatched expertise and extensive
experience in oncology drug development
and study management.
With operations in Europe and India,
OS provides end-to-end solutions for
drug development, including services of
Phase I to IV, regulatory affairs, consulting
for drug development, medical writing,
data management and statistics, quality
assurance and pharmacovigilance.
With oncology emerging as a
therapeutic field that demands exclusive
focus, intensive efforts and expertise for
successful drug development, Oncology
Services (OS) offers efficient clinical
study execution by bringing to bear all
of these essentials.
With a history of more than 150 clinical
trials, Oncology Services has
comprehensive expertise in all major
oncology indications, and experience in
managing all the phases of clinical trials
with more than 6,500 patients.
A vast experience in the field has
enabled OS to evolve a thorough
knowledge of patient population and
disease profile in oncology, significantly
enhancing the recruitment process.
Its well-developed network of clinical
investigators ensures swift completion of
study enrolment – a key issue in achieving
successful study management.
With extensive devotion to oncology
drug trials over the years, Oncology
Services’ performance in oncology clinical
trials has made it a trusted and preferred
partner for some of the world’s leading
oncology research companies.
Over the years, OS has been able to win
the confidence of its clients thanks to its
work ethic, which places special emphasis
on client-CRO synergy, which in turn
ensures the service provider becomes
an extension of the client’s drug
development team.
Another key aspect that results
in successful study management
is its proactive risk analysis and
contingency planning.
With these distinctive features,
Oncology Services has marked a victory
in terms of timely and efficacious
completion of projects, which is the
primary stipulation in anti-cancer
drug development. ■
a leader in oncology
Further information: oncology services
tel: +49 178 8087 262 email: wolfgang.beier@oncology-services.de Website: www.oncology-services.com
Efficient recovery of active pharmaceutical
ingredients (APIs) after spray and fluid bed
drying is still a problem for many
companies. For the recovery of these
sensible products, cyclone collectors are
frequently irreplaceable, as they can
capture the powder directly and avoid
filter hold-up. Cyclones also avoid
contamination of filter bags, product cross-
contamination and product degradation
with temperature. However, product losses
due to cyclones’ low efficiency represent a
high cost because of the high values of
APIs. Where applicable, cyclones have to
be complemented with a bag filter to
avoid emissions to the atmosphere.
Hurricane cyclones demonstrate
impressive efficiencies in capturing
inhalable powders with a median volume
diameter (MVD) of less than 3-5µm. Their
geometries maximise powder collection
for each different application while
minimising re-entrainment and keeping
pressure drop at reasonable levels. For the
same pressure drop a single Hurricane is
more efficient than any other known
cyclone available in the marketplace.
A ReCyclone comprises a Hurricane and
a particle separator (mechanical or
electrostatic re-circulator), placed
downstream of the cyclone. Recirculation
reintroduces the fine, non-captured
particles into the cyclone after those have
been driven to the outer walls of the
re-circulator by centrifugal or electrical
forces. While this tangential gas stream is
enriched in particles, the axial gas stream
exhaust to the stack is practically invisible.
Efficiency increases due to recirculation
and agglomeration of small particles with
coarser ones coming from the process. ■
effcient powder recovery
Further information: advanced cyclone systems
tel: +351 225 322 096 Website: www.advancedcyclonesystems.com
A ReCyclone
Directory > Product showcase
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Experts in the design of refrigerating
packaging, Sofrigam develops temperature
control packaging systems to enable its
clients to:

control and secure the cold chain ■
reduce logistics costs ■
optimise the volumes shipped ■
respond to international ■
regulations/norms.
The performance of refrigerating
packaging depends on the insulating
material and the cool packs. This is why
Sofrigam’s engineering staff creates
packaging solutions using high-
performance polyurethane panels from a
leading European producer as well as
exclusive cooling packs. All the company’s
solutions are tested and qualified in the
metrological laboratory.
Frizbox Pallet shipper
The Frizbox Pallet Shipper has been
designed to enable pharmaceutical
laboratories to transport large volumes of
vaccines (several millions per year) in
complete safety.
A decade after its creation, the
efficiency of the Frizbox is recognised and
now adopted by the world’s biggest
pharmaceutical laboratories.
Volume: from 300 litres to more than ■
1,000 litres
Temperature range: +2°C/+8°C, ■
+15°C/+25°C, -18°C
Conservation period: up to five days. ■
the sofribox
This is a thermally insulated box with cold
packs to preserve product temperature.
Volume: from one to 500 litres ■
Temperature range: +2°C/+8°C, ■
+15°C/+25°C, -18°C
Conservation period: up to five days. ■
sofribag
There is a range of Sofribag cooling bags
for transporting heat-sensitive products.
Volume: from four to 35 litres ■
Temperature: +2°C/+8°C, -18°C ■
Conservation period: up to 24 hours. ■
Sofrigam also develops made-to-
measure solutions for transportation. ■
Keep yours cool
Further information: sofrigam
email: helena.ezzahid@sofrigam.com Website: www.sofrigram.com
Fast melt technology allows tablets to
be taken any time, anywhere, without
water. The development and commercial
manufacture of fast melt, orodispersible
tablets (ODT), along with effervescent
technology, are at the forefront of focus
for Swiss drug delivery company
Alpex Pharma.
capabilities include:
Orodispersible tablets ■
(fast melt technology)
Effervescent technology ■
Formulation development and ■
consequent commercial
manufacturing
Contract manufacturing in GMP ■
state-of-the-art facility
Taste masking ■
advantages of alpex odt:
Convenient dosage form at any time ■
and place, can be taken without water
Easy to use for patients with ■
swallowing disorder
Potential faster onset of action than ■
conventional oral dosage forms
Increased patient compliance ■
Broad applicability to many ■
therapeutic categories
Lifecycle management, expanded ■
patent protection
High drug concentration, up to ■
500mg/tablet
Marketing advantage – greater choice ■
for patients and consumers
Alpex Pharma employs a unique patent
protected process for the manufacturing
of ODT tablets. Its tablets have a
significant advantage, as they are robust
enough to be filled into bottles and
shipped in bulk and do not have strict
restrictions for drug loading or use of taste-
masking technologies.
ODT technology can be applied across
many categories: analgesics/inflammation,
Parkinson’s, migraine, hypnotics/narcotics,
antacids/ulcer, erectile dysfunction, anti-
diarrhoeas, cough/cold/flu remedies, anti-
emetics, cardiovascular, antihistamines,
irritable bowel. ■
a quick solution
Further information: alpex Pharma
tel: +41 935 51 10 Fax: +41 91 935 51 20 email: contact@alpex.com Website: www.alpex.com
Alpex Pharma HQ
Directory > Product showcase
WorldPharmaceuticalFrontiers
|
www.worldpharmaceuticals.net 135
Lomapharm specialises in the production
of tablets and liquid pharmaceuticals and
high-quality dietary supplements.
Founded in 1878, this family-run
company is one of three affiliated
companies within the Lohmann Group,
located near Hamelin, Germany. The
Group’s core expertise is processing and
refining iron and mineral salts and their end
products, and all production at Lomapharm
complies with GMP standards.
Lomapharm delivers 3-4 billion tablets a
year to its customers. The versatile range
of machines can produce mixtures for
direct tablet compression, as well as
granulates, via dry granulation or wet
granulation with subsequent drying.
Tabletting is carried out by computer-
controlled high-capacity presses. Coating
takes place in a range of drum coaters
with up to 500kg capacity. The ‘art of
sugar coating’ is performed in up to 24
modern tablet-coating pans with
capacities of up to 120kg each. This
enables Lomapharm to process small and
large batches of high-quality film- and
sugar-coated tablets. Lomapharm is also
now in the position to handle Microtablets
and to offer contract manufacturing of
such solid dosage form.
Lomapharm has modern clean rooms
that comply with the stringent
specifications laid down for sterile
production. The filling lines fill ampoules
and eye-drops up to 10ml – usually
prepared in batches of up to 650kg.
Lomapharm produces solutions and
sophisticated suspensions in batches up
to 2.9t and also under nitrogen depending
on the specific product.
The broad range of services is rounded
off by the development and galenic
optimisation of pharmaceutical
formulations, design of dietary
supplements, up-scaling, stability testing
pursuant to ICH regulations, and support
in approval application procedures. ■
a tradition of competence
Further information: lomapharm
tel: +49 515 563 9000 Fax: + 49 515 563 9099 email: service@lomapharm.de Website: www.lomapharm.de
For the pharmaceutical industry, product
piracy is a serious issue that threatens
both patients’ health, and the profits of
the companies that invest so much in
developing effective medication. The
more sophisticated counterfeiters
become, the more important it is for
manufacturers to “raise the bar” regularly
– by introducing new technologies that
will foil the fraudsters’ efforts (at least
for a while).
Now Merck has helped to develop a
new holistic security concept that will
combat product piracy more effectively:
ESAN. This “virtual pharmaceutical
product” uses a twin-level security
strategy to make life difficult for
counterfeiters. At first glance, ESAN looks
like any other conventional folded box
sample, complete with blisters, capsules,
tablets and a package insert. Look closer,
though, and you will discover that both
the packaging and the contents have
been security-enhanced.
The packaging features numerous
hidden and forensic security features
from the Merck Securalic product line.
The security features are built into the
ivy leaf design element printed on the
folded box. Securalic products are also
used for both two-coloured blisters in
UV flexo printing.
The capsules are coated and dyed
with Candurin, Merck’s special range of
mineral-based pearl effect colours.
Candurin is based on a natural silicate,
and meets the international quality and
security standards of the pharmaceutical
industry. Its unique appearance is highly
attractive – and very difficult to reproduce.
This combination of Candurin pearl
effect colours and Securalic products
plays an important role in making ESAN
so secure. This new demonstration tool
may be bad news for counterfeiters – but
for patients and manufacturers, it is very
good news indeed. ■
esan – a new approach to anti-piracy
Further information: merck
Website: www.merck-pigments.com
Lomapharm has a versatile range of machines
ESAN – a virtual
pharmaceutical
product.
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WPF017_FINAL COVER.indd 1 17/3/10 11:25:59
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we’re busy working on the next issue analysing
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WorldPharmaceuticalFrontiers
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www.worldpharmaceuticals.net 137
Brand Protection & anti-counterfeit
Merck KGaA ................................................ 68
tesa scribos GmbH ..................................... 68
chemicals, raw materials & ingredients
Merck KGaA ................................................ 68
Mettler-Toledo AG ..................................... 81
ROQUETTE .................................................. 40
Umicore ...................................................... 31
clinical trials
DHL Healthcare Logistics ......................... 55
Elpro-Buchs AG .......................................... 61
Harrison Clinical Research ....................... 99
LifeConEx ...................................................... 4
Mettler-Toledo AG ..................................... 81
Oncology Services GmbH ......................... 91
cold chain
DHL Healthcare Logistics ......................... 55
Elpro-Buchs AG .......................................... 61
Envirotainer ................................................ 57
Exam Packaging......................................... 62
Tinytag (Gemini Data Loggers (UK) Ltd) ..... 64
Hameln Pharmaceuticals GmbH ............ 107
LifeConEx ...................................................... 4
Sensitech .................................................... 67
SOFRIGAM ................................................. 60
Tecnosoft srl .............................................. 60
compound screening
Mettler-Toledo AG ..................................... 81
contract services
Ferro Pfanstiehl Laboratories inc ............. 39
Hameln Pharmaceuticals GmbH ............ 107
Harrison Clinical Research ....................... 99
INC Research Inc ....................................... 96
Lomapharm
®
- R Lohmann GmbH KG .... 135
Nycomed .................................................. 109
Oncology Services GmbH ......................... 91
Pharmatest Services Ltd .......................... 93
Presspart Manufacturing Ltd ................. 117
Rechon Life Science ................................. 110
TNO ............................................................ 121
Unither Pharmaceuticals ......................... 100
Xceleron Inc ................................................ 45
drug delivery systems
Cafosa Gum SAU ...................................... 123
CIMA Labs Inc .......................................... 112
Crossject SA .............................................. 124
Do-Coop Technologies Ltd ...................... 118
Ferro Pfanstiehl Laboratories inc ............. 39
Haselmeier GmbH .................................... 112
LTS Lohmann Therapie-Systeme AG ..... 115
Patheon Inc ............................................... 105
Pevion Ltd .................................................. 11
Presspart Manufacturing Ltd ................. 117
SOFRIGAM ................................................. 60
Unither Pharmaceuticals ......................... 100
drug development
Do-Coop Technologies Ltd ...................... 118
Ferro Pfanstiehl Laboratories inc ............. 39
Mettler-Toledo AG ..................................... 81
Oncology Services GmbH ......................... 91
Patheon Inc ............................................... 105
Pevion Ltd .................................................. 11
Rechon Life Science ................................. 110
TNO ............................................................ 121
Umicore ...................................................... 31
Xceleron Inc ................................................ 45
drug discovery
Mettler-Toledo AG ..................................... 81
informatics
Thermo Fisher Scientifc ........................... 46
it & data management
Oncology Services GmbH ......................... 91
laboratory technology
Ferro Pfanstiehl Laboratories inc ............. 39
GE Analytical Instruments ....................... 84
HAMILTON Bonaduz AG ........................... 44
Mettler-Toledo AG ..................................... 81
Ove Arup & Partners Ltd........................... 83
Tecnosoft srl .............................................. 60
logistics
DHL Healthcare Logistics ......................... 55
Elpro-Buchs AG .......................................... 61
Envirotainer ................................................ 57
FedEx ........................................................... 58
LifeConEx ...................................................... 4
Ove Arup & Partners Ltd........................... 83
Patheon Inc ............................................... 105
manufacturing & Processing
Ferro Pfanstiehl Laboratories inc ............. 39
Hach Company .......................................... 88
Hameln Pharmaceuticals GmbH ............ 107
HAMILTON Bonaduz AG ........................... 44
Haselmeier GmbH .................................... 112
Lomapharm
®
- R Lohmann GmbH KG ..... 135
Ove Arup & Partners Ltd........................... 83
Patheon Inc ............................................... 105
Presspart Manufacturing Ltd ................. 117
Rechon Life Science ................................. 110
Umicore ...................................................... 31
Packaging solutions
Constantia Flexibles GmbH .................... 139
DHL Healthcare Logistics ......................... 55
Exam Packaging......................................... 62
LifeConEx ...................................................... 4
Lomapharm
®
- R Lohmann GmbH KG ..... 135
Patheon Inc ............................................... 105
Rechon Life Science ................................. 110
rommelag ag .................................................. 102
SOFRIGAM ................................................. 60
Process analytical technology
Ferro Pfanstiehl Laboratories inc ............. 39
GE Analytical Instruments ....................... 84
Hach Company .......................................... 88
HAMILTON Bonaduz AG ........................... 44
Process automation
HAMILTON Bonaduz AG ........................... 44
Process equipment
Advanced Cyclone Systems SA ............... 77
HAMILTON Bonaduz AG ........................... 44
Quality assurance & control
Elpro-Buchs AG .......................................... 61
Ferro Pfanstiehl Laboratories inc ............. 39
GE Analytical Instruments ....................... 84
Hach Company .......................................... 88
Harrison Clinical Research ....................... 99
LifeConEx ...................................................... 4
Lomapharm
®
- Rudolf Lohmann
GmbH KG .................................................. 135
Mettler-Toledo AG ..................................... 81
Patheon Inc ............................................... 105
Rechon Life Science ................................. 110
Sensitech .................................................... 67
regulatory & compliance
Ferro Pfanstiehl Laboratories inc ............. 39
Hach Company .......................................... 88
Harrison Clinical Research ....................... 99
LifeConEx ...................................................... 4
Lomapharm
®
- R Lohmann GmbH KG ..... 135
Oncology Services GmbH ......................... 91
Patheon Inc ............................................... 105
Rechon Life Science ................................. 110
Sensitech .................................................... 67
rFid
Sensitech .................................................... 67
site selection
Harrison Clinical Research ....................... 99
Oncology Services GmbH ......................... 91
Ove Arup & Partners Ltd........................... 83
supply chain management
DHL Healthcare Logistics ......................... 55
Elpro-Buchs AG .......................................... 61
FedEx ........................................................... 58
LifeConEx ...................................................... 4
Ove Arup & Partners Ltd........................... 83
Rechon Life Science ................................. 110
Sensitech .................................................... 67
Validation
Exam Packaging......................................... 62
Ferro Pfanstiehl Laboratories inc ............. 39
GE Analytical Instruments ....................... 84
Lomapharm
®
- R Lohmann GmbH KG .... 135
Patheon Inc ............................................... 105
Rechon Life Science ................................. 110
Sensitech .................................................... 67
Tecnosoft srl .............................................. 60
Buyers guide
Directory > Index
Directory > Index
WorldPharmaceuticalFrontiers
|
www.worldpharmaceuticals.net 138
suppliers guide
aBB engineering services ........................... 79
www.abb.com/consulting
advanced cyclone systems sa .................. 77
www.acsystems.pt
alfa Wassermann spa............................... oBc
www.alfawassermannmanufacturing.it
alpex Pharma sa ......................................... 116
www.alpex.com
cafosa Gum sau .......................................... 123
www.cafosa.com www.healthingum.com
cima labs inc ............................................. 112
www.cimalabs.com
constantia Flexibles Gmbh ...................... iBc
www.constantia-fexibles.com
crossject sa ................................................. 124
www.crossject.com
dhl healthcare logistics ............................. 55
www.dhl-healthcare.co.uk
do-coop technologies ltd ........................ 118
www.docoop.com
elpro-Buchs aG .............................................. 61
www.pdf-datalogger.com www.elpro.com
envirotainer .................................................. 57
www.envirotainer.com
exam Packaging ........................................... 62
www.exampackaging.com
Fedex 58
www.fedex.com
Ferro Pfanstiehl laboratories inc ............... 39
www.ferro.com
Ge analytical instruments .......................... 84
www.geinstruments.com
Ge sensing & inspection technologies ... iFc
www.gesensing.com/kayeproducts/
tinytag (Gemini data loggers (uK) ltd) ...... 64
www.tinytag.info
Generex Biotechnology ............................... 114
www.generex.com
GöteborgBio .................................................. 35
www.goteborgbio.se
hach company ............................................. 88
www.hach.com/hua
hameln Pharmaceuticals Gmbh ............. 107
www.hameln-pharma.com
hamilton Bonaduz aG .............................. 44
www.hamiltoncompany.com
harrison clinical research......................... 99
www.harrisonclinical.com
haselmeier Gmbh ..................................... 112
www.haselmeier.com
inc research inc ............................................ 96
www.incresearch.com
lifeconex ......................................................... 4
www.lifeconex.com
lomaPharm
®
- rudolf lohmann
Gmbh KG .................................................... 135
www.lomapharm.de
lts lohmann therapie-systeme aG ....... 115
www.ltslohmann.com
medicilon/mPi Preclinical research -
shanghai ........................................................ 95
www.medicilon-mpi.com
medicofarma ................................................ 104
www.medicofarma.pl
merck KGaa ................................................... 68
www.merck-pigments.com
mettler-toledo aG ......................................... 81
www.mt.com/quantos
multipharma sa .............................................. 7
www.multipharma.ch
nycomed ....................................................... 109
www.nycomed.com
oncology services Gmbh ............................ 91
www.oncology-services.com
original1 ..................................................... 75
www.original1.net
ove arup & Partners ltd ............................. 83
www.arup.com
Patheon inc .................................................. 105
www.patheon.com
Pevion Biotech ltd ........................................ 11
www.pevion.com
Pharmatest services ltd ............................ 93
www.pharmatest.f
Presspart manufacturing ltd ................... 117
www.presspart.com
Quintiles ........................................ front cover
www.quintiles.com/newhealth
rechon life science .................................... 110
www.rechon.com
rommelag aG ............................................. 102
www.rommelag.com
roQuette ..................................................... 40
www.roquettepharma.com
sensitech ...................................................... 67
www.sensitech.eu
siemens it solutions and services ........... 72
www.it-solutions.siemens.com
sofrigam ........................................................ 60
www.sofrigam.com
taracell - r meiers söhne aG ..................... 63
www.taracell.com
tecnosoft srl ................................................. 60
www.tecnosoft.eu
tesa scribos Gmbh ...................................... 68
www.tesa.scribos.com
thermo Fisher scientifc .............................. 46
www.thermo.com/informatics
tno ................................................................. 121
www.tno.nl/pharma
umicore ........................................................... 31
www.chemistry.umicore.com
unither Pharmaceuticals ........................... 100
www.unither-pharma.com
Varaždin Park ................................................ 32
www.varazdinpark.com
Xceleron inc ................................................... 45
www.xceleron.com
Constantia Flexibles
Big enough to dare,
small enough to care.
Constantia Hueck Folien GmbH & Co KG
Pirkmühle 14-16
92712 Pirk
T +49 961 87 223
F +49 961 87 485
Pharma@constantia-flexibles.com
www.constantia-flexibles.com
Constantia Flexibles develops, manufactures and delivers flexible packaging solutions globally to
its portfolio of customers in the food, healthcare and beverage markets. We are a leading supplier
of aluminium based packaging for medicines and medical/cosmetic applications, including
tablets, capsules, powders or meditechnical products.
QUALITY ... is our mission
By selecting Constantia Flexibles as
your partner you will be working with
one of the world’s foremost suppliers
of aluminium-based flexible packaging
materials.
SERVICE ... is our motivation
Working with Constantia Flexibles will
give you access to a major global
manufacturing and customer service
network which will exceed your expec-
tations in terms of responsiveness,
flexibility and creativity.
INNOVATION ... is our challenge
As a leader in innovation, Constantia
Flexibles has a range of new technolo-
gies and processes to offer the very
best solutions for your business.
Packaging Solutions for the
Pharmaceutical and Healthcare Industry
Pharma_allg_2010_216x292mm.pdf 21.01.2010 11:01:15 Uhr

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