Clinical Trials in Colombia

MEDICAL DEVICE
AND BIOPHARMA
1. Introduction
3. Clients
4. Regulatory Approval
2. Colombia
Interventional Concepts, Inc. is a full
service CRO (Contract Research
Organization) focused on the medical
device and biopharmaceutical
industry. We help you reach your
clinical development and research
goals by partnering you with our
extensive clinical research site
network in the U.S. and Latin America.
Regulatory consulting, sanitary
registration, and marketing
assistance for drug , and medical
device commercialization.
1. Introduction
We focus on helping highly innovative biopharmaceutical
and medical device companies
bring their life-changing developments from initial strategy
through clinical development to market.

What we do Who we are

All phases of medical device and
biopharma clinical trials.
Medical device feasibility trials.
Trial design, and protocol regulatory
submission.
Medical device or component
shipping, importation, logistics, and
distribution.
Animal research, cadaver, and
animal medical device training.
1.
We believe that Latin America
represents an untapped opportunity
for medical device and biopharma
companies to conduct cost-eective
clinical trials with the same quality
standards that they would nd in the
U.S. Our mission is to bring together a
vast network of capable Latin
American research sites to the medical
device and biopharma industry in the
US.
1. Introduction
Our history Why we do it
Interventional Concepts, Inc. was
founded in 2010 by Pedro
Martinez-Clark, M.D., an interventional
cardiologist trained at Harvard
University's Beth Israel Deaconess
Medical Center, who later became
Assistant Professor at the Miller
School of Medicine at the University of
Miami, where he worked side-by-side
with the internationally renowned Dr.
William O'Neill, who is part of our
advisory board. Interventional
Concepts, Inc.
OUR PURPOSE
AND BEGINNING
Dr. Martinez-Clark was part of the
University of Miami's International
Medicine Institute were he acquired
extensive experience in international
clinical trials and program
development. Dr. Martinez-Clark
currently serves as Chief Medical
Ocer for Interventional Concepts,
Inc.
More information about
Dr. Martinez- Clark is available at
http://martinezclark.com/
2.
1. Introduction
OUR VALUE
PROPOSITION
Interventional Concepts, Inc.'s value
proposition is built on the fact that most
Colombian clinical research sites are
simply not ready to deal directly with
sponsors from the U.S. Clinical research
has been conducted in Colombia for
over 20 years (mostly for pharma trials),
and Colombia is one of the top
destinations along with Mexico,
Argentina, Brazil and Peru for pharma
trials (as of August of 2013, there were
almost 200 simultaneous pharma trials
running in Colombia), however, sites in
Colombia, for the most part, do not deal
directly with foreign sponsors, much less
with sponsors seeking to conduct early
stage medical device trials, which are
very few in Colombia and involve a
heavier logistical operation.
Most sites in Colombia deal mostly with
large CROs (Quintiles, PPD, Covance,
ICON, Parexel, etc.), which in turn have
large contracts with the major drug
manufacturers and have oces in Bogota
and their relationship (oral and written) is
mostly in Spanish (Colombias English
prociency is one of the lowest in the
world according to the global English
Prociency Index: http://www.ef.edu/epi/
and they get paid mostly by the CRO in
local Colombian pesos (Colombias export
of health services related to clinical trials
is almost zero); furthermore, these CROs
for the most part, manage for their U.S.
sponsors all matters related to regulatory
aairs, logistics, etc., and they become the
point of contact for all communication to
and from the U.S. sponsor so that the
sites concentrate only on their clinical
duties related to providing medical
services for the pharma trial subjects
there are no large independent
(non-hospital) clinical research sites in
Colombia; most sites in Colombia are
part of medium to large hospital
institutions that have an interest for
clinical research, and the other sites are
independent medium to small medical
practices led by one physician-owner
who has a personal interest in research
and has found that he or she can
diversify his or her practices income by
running some clinical trials.
The typical prole of the clinical research
site that we have aliated to our
network is of the latter type; these are
sites with very little English skills and with
no experience doing international
business (i.e. invoicing in U.S. dollars,
communicating professionally in
american English, reading and executing
customary U.S. clinical trial contracts,
obtaining importation permits, securely
storing investigational medical devices,
3.
1. Introduction
importing/exporting equipment and
devices, etc.) and are far from being a
world class operation costs at these
sites are low compared to costs at sites
belonging to larger hospital institutions.
When a sponsor in the U.S. trusts us for
their clinical trial, our Director of Clinical
Studies, and our Director of Clinical
Operations, respectively, are the U.S.
sponsors point of contact for all clinical
and logistics matters related to the trial.
Since the typical research sites in our
network are relatively small
administrative local operations albeit
with large volume of patients they
have with very little interest in investing
the funds necessary to becoming a fully
bilingual, internationally competitive and
world class clinical research site.
The model of having a global CRO with a
local oce in Colombia, creates very little
incentives for a Colombian site to
become a world class operation; the
global CROs local oces feed them
frequently with mostly phase II, III and IV
pharma trials, all negotiations and
contracts are done locally in Spanish, and
they are locally and conveniently
compensated in Colombian pesos due
to the daily U.S.
dollar uctuation relative to the
Colombian peso, it's not nancially
advantageous for these sites to contract
with CROs and sponsors in U.S. dollars
because they cannot predict the nal
sum of colombian pesos that they will
receive from their bank at the moment of
payment Colombian law prevents
banks from opening checking accounts in
foreign currency. For a Colombian
research site to break that pattern and to
diversify its income beyond local pharma
trials, it has to look overseas to attract
sponsors from the U.S. or Europe to
conduct their trials at their facility; this
will require a signicant personnel (with
world class bilingual and research/clinical
skills) and business
development/marketing investment to
promote their clinical research
capabilities overseas. Furthermore, the
business customs in Colombia are largely
dierent from the ones in the U.S.;
business values such as accountability,
punctuality, integrity, reliability, etc. are
not commonly found in Colombia and
the rest of Latin America.
We strive to create a buer zone
between the site in Colombia and the
sponsor in the U.S.
The typical sponsor that we attract is a
small startup typically backed with
venture capital funds; these companies
seek to conduct fast, cost eective and
ethical clinical trials for their innovation,
and by nature, are very dynamic and
require speed in regulatory approval,
product importation, patient recruitment,
etc. The U.S. sponsors that we have
brought to Colombia to conduct their
early stage medical device clinical trials
have understood our value proposition
and trust us to manage their trials from
EC and INVIMA regulatory approval to
trial closeout (we essentially become a
sponsor's feet on the ground in
Colombia).
4.
These are some of the trial and site
management activities that we typically
perform on behalf of a U.S. sponsor:
Even before we obtain regulatory
approval, we do all the preliminary
groundwork at the site digging into their
patient database to ensure that we have
candidate subjects.
We gather the paperwork and apply for
import permit right after INVIMA
approval.
We manage, on behalf of the site, the
budget and contract drafting and
negotiation with the US sponsor.
When needed, we design and
implement a patient referral campaign
that reaches out (with one-to-one
meetings) to potential local specialists
that could refer patients to the study at
the site.
We gather and submit on behalf of the
site the ongoing quarterly
reporting/regulatory paperwork
required by INVIMA.
We report to INVIMA all the study
activities as required by law: reporting
of adverse events, quarterly reporting
of patients enrolled, reporting of
devices used, dispossessed, returned to
the sponsor, etc.
We make sure that any amendments to
the protocol are approved by the local
EC and INVIMA.
Any other related activity that could
benet a sponsor in ensuring that its
trial is a success in Colombia.
Overall, we assume the role of project
and site managers for a trial and become
the only clinical, logistical and regulatory
point of contact between the Colombian
site and a U.S. sponsor. Without our
direct involvement as project managers,
the trial at a small site in Colombia will
very likely not be satisfactory to the
sponsor. Weve had cases where a US
sponsor has decided to deal directly with
a small site in Colombia; most of these
cases have ended in horror stories;
we'd be glad to provide, upon request,
names and contact information of
sponsors that have tried this approach so
that they can give their testimonial of how
bad their experience has been.
Our local entity in Colombia, by the name
of Health Quality Services and Products
S.A. (aka HQSP), is the title holder of the
U.S. sponsor's INVIMA protocol approval,
thus HQSP becomes the ocial importer
of record of all medical product related to
the trial and the party responsible for
complying with INVIMAs regulations
(reporting of adverse events, quarterly
reporting of patients enrolled, reporting
of devices used, dispossessed, returned to
the sponsor, etc). Technically and legally
for INVIMA, we, under HQSP, become the
U.S. sponsor's legal representative and
agent in Colombia.
Our clinical research model has been very
successful; we have tight contracts with
our aliated sites in Colombia and they
trusts us with managing trials on their
behalf. Proexport (Colombias ocial
export promoting agency) has recognized
our organization as pioneers in bringing
medical device clinical trials to Colombia,
and we are working very closely with
Proexport to promote Colombia as the
best destination
We translate by certied ocial
translators and to the local Colombian
Spanish dialect all the study
documents.
We import and store whats needed
for the trial at our INVIMA certied
facility in Bogota and provide monthly
inventory reports to the sponsor.
We assign one of our Clinical Research
Coordinators to the site to ensure that
what was contracted gets done
properly.
We participate, on behalf of the site, in
frequent calls with the sponsor to
report on the progress of the trial.
When needed, we call candidate and
enrolled subjects to their homes to
make sure they show up for their
appointments.
5.
in Latin America for U.S. sponsors to
conduct their medical device and
biopharma early stage clinical trials
(press release available here:
http://goo.gl/f1O75E).
Proexport has recognized that Colombia
oers excellent clinical expertise that can
be exported to U.S. sponsors of clinical
trials, and its now a national interest to
promote Colombia to the medical device
and biopharma industry in the U.S., thus
increasing Colombias export numbers
and the countrys GDP; we are the only
company assisting Proexport on this
matter as advisors for their plan.
Furthermore, we work closely with
Colombia's ocial country brand
(http://www.colombia.co/en/) and have
entered into a cooperation and licensing
agreement to use the brand to promote
the name of Colombia to the medical
device and biopharma industry in the
U.S.
A U.S. sponsor is free to choose to
conduct its trial in Colombia and not use
our organization as project and site
managers for its trial.
Wed recommend that the U.S. sponsors
establishes a direct line of communication
with a larger hospital institution with an
established research department. Large
institutional hospital sites are somewhat
readier to deal directly with a U.S.
sponsor than a small independent site,
however, their speed is much lower than
what is needed to conduct early stage
medical device clinical trials typically
these sites will not sign a Clinical Trial
Agreement (CTA) in a foreign language, so
the U.S. sponsor will have to translate the
CTA to Spanish according to the site's
specic and strict guidelines, negotiate
the language of the CTA in Spanish, and
be subject to Colombian contracting laws
(its advisable that a U.S. sponsor
contracts the services of a local attorney
to adapt its CTA to Colombian legal
language and local business customs),
and be prepared to deal with the site
personnel with poor English skills.
Our organization has specialized in
providing early stage/rst-in-man clinical
research services to U.S. sponsors looking
to conduct cost eective and ethical
trials in Colombia. We seek to provide
end-to-end services from study and
protocol design, document translations,
regulatory assistance, logistics (import,
inventory control, distribution, export),
site and trial management, and any other
related activity that could benet a
sponsor in ensuring that its trial is a
success in Colombia. We split our service
oering in two separate entities that
work together to bring to U.S. sponsors
the best clinical research sites that
Colombia has to oer. Our sister Site
Management Organization entity is called
Latin American Clinical Research Alliance,
LLC (LACRA), while our CRO services are
provided by Interventional Concepts, Inc.
1. Introduction
6.
We typically execute two agreements
with sponsors: 1) a Clinical Services
Agreement (CSA) that lies the foundation
of our overall relationship, 2) and 1 or
more Clinical Trial Agreements (CTA)
depending on the number of sites that
the sponsor seeks to bring to its study.
The CTA is typically executed between
the sponsor and LACRA since we already
have tight underlying agreements
(Master Hospital Agreements or MHA)
with each site; with this model, we bring
speed to the negotiation and the study
budget then becomes an attachment to
our MHA with a site and an attachment
to the CTA that we execute with the
sponsor.
Our budgets are clear, transparent and
are specic to each individual site. We
add the site startup costs, our startup
costs and an industry standard and
customary 20% (of the site's per subject
clinical costs) professional and
administrative overhead fee in
compensation for our site/trial/project
management services
We work in unison with the smaller
sites to provide a professional interface to U.S. sponsors so
that their clinical trials can be conducted satisfactory
following world-class U.S. business practices.
(which ocially start right after INVIMA
approves the protocol); as described
above, our aliated sites are small
independent research sites that dont
have the international administrative
capabilities to manage a trial from a US
sponsor, so our 20% professional and
administrative fee is a fair compensation
for the value that we bring to the site and
to a U.S. sponsor, which equates to what
a large institutional site would have
charged any sponsor for its
administrative overhead. In other words,
if a U.S. sponsor deals directly with a site
in Colombia, the sponsor would have
been charged a customary 20% overhead
and administrative fee on top of the site's
clinical costs. The smaller sites aliated
to our network don't add that 20%
overhead and administrative fee to their
costs because they recognize that they
lack the capable bilingual and
experienced administrative sta needed
to conduct a worldclass clinical research
trial directly with a U.S. sponsor; that's
where we ll the gap.
We work in unison with the smaller sites
to provide a professional interface to U.S.
sponsors so that their clinical trials can
be conducted satisfactory following
world-class U.S. business practices.
7.
Colombia is a Latin-American leader
in volume of clinical research and
receives over 115 annual trials.
2. Colombia
Why Colombia
CONDUCT YOUR CLINICAL TRIAL IN COLOMBIA
one of the world's fastest growing
emerging economies.
Colombia excels in trials related to
diabetes, cardiology, oncology,
endocrinology, infectology,
vaccination, pneumology,
rheumatology, internal medicine,
hematology, ophthalmology, and
gynecology.
High enrollment rate, competitive
costs, highly motivated, and
bilingual investigators, and a fast
and predictable regulatory pathway
(1-3 months).
Colombian medicine is well known
in Latin America and the rest of the
world as a pioneer and leader in
health services, positioning the
country as one of the most
attractive destinations for medical
treatments.
Over 120 government-certied GCP
compliant clinical research sites
with over 20 years of experience
and with the same quality and
ethical standards that you would
nd in the U.S.
Fast product importation (Free
trade agreement with the U.S.)
Great geographical location: EST
time zone, fast, and direct airline
connectivity from the U.S.
Great healthcare infrastructure and
business environment for clinical
trials.
Great healthcare infrastructure and
business environment for clinical
trials.
8.
We are a full-service CRO (Contract
Research Organization) focused on
the medical device and biopharma
industry. We help you reach your
clinical development and research
goals by partnering you with our
extensive clinical research site
network in the U.S. and Latin America.
2. Colombia
Reach your clinical trial goals
With a high enrollment rate, fast and
predictable regulatory environment,
competitive rates, highly motivated
and bilingual investigators, Colombia
is the premier destination for
conducting clinical research.
Colombia is conveniently located at
just a short direct ight from Miami,
FL.
Colombia is a hidden gem
duties related to providing medical
services for the pharma trial subjects
there are no large independent
(non-hospital) clinical research sites in
Colombia; most sites in Colombia are
part of medium to large hospital
institutions that have an interest for
clinical research, and the other sites are
independent medium to small medical
practices led by one physician-owner
who has a personal interest in research
and has found that he or she can
diversify his or her practices income by
running some clinical trials.
The typical prole of the clinical research
site that we have aliated to our
network is of the latter type; these are
sites with very little English skills and with
no experience doing international
business (i.e. invoicing in U.S. dollars,
communicating professionally in
american English, reading and executing
customary U.S. clinical trial contracts,
obtaining importation permits, securely
storing investigational medical devices,
9.
WHO TRUST
US
3. Clients
Clients such as the University of Miami,
DirectFlow Medical, Mitralign, Roxwood
Medical, InterValve, Avinger, CeloNova
BioSciences, NeuroTronik, Syntheon
Medical, Corquest Medical, MitraSpan, Kona
Medical, among others, have trusted us with
their clinical trials.
10.
COLOMBIA IMPORTATION PROCESS
Investigational or Commercial
Medical Products
4. Schemes
(which ocially start right after INVIMA
approves the protocol); as described
above, our aliated sites are small
independent research sites that dont
have the international administrative
capabilities to manage a trial from a US
sponsor, so our 20% professional and
administrative fee is a fair compensation
for the value that we bring to the site and
to a U.S. sponsor, which equates to what
a large institutional site would have
charged any sponsor for its
administrative overhead. In other words,
if a U.S. sponsor deals directly with a site
in Colombia, the sponsor would have
been charged a customary 20% overhead
and administrative fee on top of the site's
clinical costs. The smaller sites aliated
to our network don't add that 20%
overhead and administrative fee to their
costs because they recognize that they
lack the capable bilingual and
experienced administrative sta needed
to conduct a worldclass clinical research
trial directly with a U.S. sponsor; that's
where we ll the gap.
4. Schemes
Sequence Actvity Days (aprox.) Cost (USD) Required Documents Responsible Party
1
Import Permit
(Ministry of Industry and
Commerce/VUCE oce)
10 ~$1,300
1. Pro-Forma invoice
2. INVIMA approval
(protocol or sanitary
registration)
Sponsor
Interventional Concepts
2
Transportation from origin (major
city in the U.S.) to Bogota,
Colombia
(Fedex/UPS/DHL/TNT, etc.)
3 Based on size
and weight
Commercial invoice
Sponsor
3.1
Nationalization of medical devices
(ordinary importation)
(Customs Broker and Colombian
Customs Agency [DIAN])
4
~0%-30% of
CIF value
(Cost,
insurance,
and freight)
depending
on the type
of medical
product.
1. Commercial invoice
2. Product brochure (if
available)
Interventional Concepts local
logistics team in Colombia
Sponsor
3.2
Nationalization of supporting
medical equipment (temporary
importation)
(Customs Broker and Colombian
Customs Agency [DIAN])
4
~16% of CIF
value (Cost,
insurance,
and freight)
depending
on the type
of medical
product.
1.Commercial invoice
2. Local insurance
policy (obtained locally by
Interventional Concepts)
Interventional Concepts local
logistics team in Colombia
4
Local delivery to storage facility
(Local transportation provider)
1 N/A N/A logistics team in Colombia
5
Domestic delivery to research site
(Domestic overnight transportation
provider)
1
Based on size
and weight
N/A
Interventional Concepts local
logistics team in Colombia
12.
4. Schemes
Notes:
Customs broker fees, document
preparation fees, and Interventional
Concepts, Inc. professional fees
(billable at an hourly rate) are not
included in the above prices.
Sponsors will ship devices to our
INVIMA-approved storage facility in
Bogota, D.C., Colombia - not directly
to the research site.
An import permit is needed for each
shipment.
Unless it is absolutely necessary due
to an emergency procedure or
missing devices critical for a
procedure, we do not recommend
shipping anything by courier nor
bringing devices as part of a
traveller's personal luggage.
INVIMA keeps strict control of the
importation (and returns if
applicable) of devices that are
approved for importation and may
visit the site unannounced to check
on the proper proof and paper trail
of importation.
Contacts for all shipping,
importation and logistics related
questions:
Monica Mora, Vice President of
Clinical Operations:
mmora@interventionalconcepts.net
Bianka Sibilia, Director of Clinical
Operations - Colombia:
bsibilia@interventionalconcepts.net
duties related to providing medical
services for the pharma trial subjects
there are no large independent
(non-hospital) clinical research sites in
Colombia; most sites in Colombia are
part of medium to large hospital
institutions that have an interest for
clinical research, and the other sites are
independent medium to small medical
practices led by one physician-owner
who has a personal interest in research
and has found that he or she can
diversify his or her practices income by
running some clinical trials.
The typical prole of the clinical research
site that we have aliated to our
network is of the latter type; these are
sites with very little English skills and with
no experience doing international
business (i.e. invoicing in U.S. dollars,
communicating professionally in
american English, reading and executing
customary U.S. clinical trial contracts,
obtaining importation permits, securely
storing investigational medical devices,
13.
Colombia Investigational
Medical Device Protocol
APPROVAL PROCESS
Study
protocol
Application
package
Local EC meets
every 30 days
Approves
Approves Import permit
Study
begins
Request for aditional
documents
Sponsor
allowed to
ship medical
devices to
Colombia
Multiple
Documents
Regulatory
Agency - meets
every 30 days
Patient
recruitment
begins
Request for additional
documents
Multiple
Documents
4. Schemes
14.
Requirements
for Investigational
Medical Device Clinical Trials
Documents Local Ethics Committee National Regulatory Agency
(INVIMA)
Protocol (see Notes & Recommendations)
Investigator's Brochure
Informed Consent
Schedule of Activities
Study Budget
Insurance Policy Certicate (must include name of the
protocol, investigator(s) name, site address, and must
be valid during the duration of the study (at least two
years is recommended and the policy doesnt have to
be issued by a Colombian insurance agency)

Resume/CV for the investigator(s) duly signed and

recently dated within the past 30 days prior to
submission.
Training certicate or letter issued by the Sponsor
that that states that the investigator(s) was trained on
the handling and use of the device.
Lab Test Results (issued by the lab that performed
the tests): a) Biocompatibility, sterility, pyrogenicity,
stability, performance, animal tests, etc. as applicable;
b) Electrical safety, electromagnetic compatibility, etc.
as applicable; c) Software test results as applicable.
Clinical Supply List: Detailed and denitive list of
medical devices and supplies required for the
execution of the protocol and to be imported in
Colombia.
Lab Test Results (issued by the lab that performed
the tests): a) Biocompatibility,
sterility, pyrogenicity, stability, performance, animal
tests, etc. as applicable; b) Electrical safety,
electromagnetic compatibility, etc. as applicable; c)
Software test results as applicable.
x
x
x
x
x
x
x
x
x
x
x
x
x
x
4. Schemes
16.
1. Cover Page
A. Name of the research protocol
A.1 Participating research
Notes &
institutions
Names of the investigator(s), A.2
A.3
A.4
A.3.1
co-investigator(s) and
consultants. Names of the
investigator(s),
co-investigator(s) and
General Information about the
clinical trial.
City
Address
Telephone number
Study initiation date
(aprox.)
Study termination date
(aprox.)
Version of the research
protocol
2. Summary
3. Formulation of the Problem
Problem statement
Justication for the study
Research questions
4. Theoretical Framework
5. Medical Device Information
Product name, manufacturer,
reference number
Description
Label(s)
User's manual or insertion manual
6. Research Hypothesis (if applicable)
7.Objectives
General objectives
Specic objectives

About the protocol
Research protocols for clinical trials
must follow this table of contents and
include the following information:
Recommendations
8. Methodology
9. Ethical Considerations
(It must include the Ethics Committees
evaluation for each of the participating
research institutions as well as the
patients Informed Consent, according to
Ministry of Healths Resolution No. 8430
of 1993)
B.1 Type of study (clinical trial or
B.2 Demographics
B.3 Sampling
B.4 Inclusion and exclusion criteria
B.5 Table of variables
B.6 Information collection technique
B.7 Information sources
B.8 Information collecting instrument
B.9 Information collecting process
B.10 Procedure description
B.11 Risk analysis, benets, and risk
observational trial)
(what, who, how, when)
mitigation
Identication, analysis, and
reporting of adverse events
(According to the Ministry of Social
Protections Resolution No. 4816
of 2008)
Pilot trial
Prevention of study bias
B.12
B.13
B.14
B.15
Technique for information
processing and analysis
10. Study Management
Schedule of activities
Budget
Bibliographic References (Vancouver System/ICMJE)
17.
Month Date of Meeting Deadline
(for document submission)
February 12 January 15
March 12 February 14
April 23 March 21
May 14 April 25
June 11 May 20
July 16 June 13
August 13 July21
September 17 August 18
October 15 September19
November 12 October 17
December 10 November 17
INVIMA
Meeting Dates (2014)
4. Schemes
Notes & Recommendations
About translations:
All documents must be translated to
the "Colombian" Spanish dialect. Its
recommended that translations are
done by native Colombian
Spanish-speaking translators certied
by the Colombian Ministry of Foreign
Aairs; the Spanish language changes
from country-to-country and INVIMA
has rejected documents (ie. Informed
Consent) that are not easily understood
by the average native Colombian
citizen.
Its recommended that a Translator
Adavit or Translation Certication be
attached to any translated document.
INVIMA: Instituto Nacional de Vigilancia
de Medicamentos y Alimentos.
18.
Clinical Trials in Colombia
MEDICAL DEVICE
AND BIOPHARMA
Interventional Concepts, Inc. - 2520 Coral Way - Suite 2120 - Miami, FL 33145-3438 USA - +1 (954) 903-7210
www.interventionalconcepts.net