A Descriptive Analysis of the

Regulatory Framework in South

Africa and China
Guided by Presented by
Dr. S. G. Vasantharaju Vanga Harika Sri Bhavani
Associate Professor 120616012
Department of Pharmaceutical M. Pharm II, Drug Regulatory
Quality Assurance Affairs
Manipal College of Manipal College of Pharmaceutical
Pharmaceutical Sciences, Manipal Sciences, Manipal

Industry guide
Imtiyaz Basade
Senior Vice President
Drug Regulatory Affairs
Mylan Laboratories Ltd
 Introduction
 Two big challenges faced by the drug
industry
a) declining prescription drug sales
b) losing patent protection for many
profitable drugs
 Industry’s new markets – China and Africa
 South African market is one of the
established markets in Africa
 China forms the major part of the
pharmerging market
Manipal College of Pharmaceutical Sciences 5/20/19 2
List of Pharmerging Countries
Tiers Countries 2009 GDP based on PPP Incremental Pharma
valuation (trillion USD) market growth from
2009-13 (billion USD)

Tier 1 China 9 40B+

Tier 2 Brazil 2-4 5-15B
Russia
India

Tier 3 Venezuela <2 1-5B

Poland
Argentina
Turkey
Mexico
Vietnam
S. Africa
Thailand
Indonesia
Romania
Egypt
Pakistan
Ukraine

Manipal College of Pharmaceutical Sciences 5/20/19 3

 Objective
 To examine the regulatory frameworks
and present the key features of the
drug regulatory systems of China and
South Africa
 To evaluate the challenges faced in
obtaining marketing authorization in
China and South Africa
 To identify the differences in regulatory
requirements between China and South
Africa
Manipal College of Pharmaceutical Sciences 5/20/19 4
Medicines
Regulation in
South Africa
 The Medicines Control Council – in
terms of the Medicines and Related
Substances Control Act, (Act 101 of
1965)

Manipal College of Pharmaceutical Sciences 5/20/19 5

 Application and approval procedure (Routine review)

Applicati
on
Pre-screening
(Screening number
allocation)
Screening Accepted Final
submission
Hold
Evaluation ( 24
months for
Return as innovative
Incomplete products; 12
months for
generics) of
Approval
the application

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 Expedited review process (Fast-track)
 Products that will be considered for expedited review
are:
 Medicines on the Essential Drugs List (EDL)
 New Chemical Entities that are considered
essential for national health but do not appear on
the Essential Drugs List
Abbreviated medicine
 9 months

review process (AMRP)

 Only new chemical entities registered with one or
more of the authorities with which the Council aligns
itself will qualify for AMRP
 AMRP is an abbreviated evaluation process and not
an abbreviated application
 Based mainly on the expert reports of the pharmaco-
toxicological and clinical data
Manipal College of Pharmaceutical Sciences 5/20/19 7
 Challenges in the
regulatory framework of
South Africa
 Delay in the registration timeline hence
delaying the marketing of essential
drugs.
 Lack of experienced and qualified staff.
 Lack of transparency in registration
systems/practices
 High costs of GMP inspections.
 Inadequate legislation and regulations.

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 Organizational capacity
problems
 Widespread legislative reform and
affirmative action
 Legal conflict over regulatory
policy leading to poor
relationships
 Medicines Control Council situated
within the Department of Health
 Inadequate regulatory skills of
human resources
Manipal College of Pharmaceutical Sciences 5/20/19 9
 Strategies to overcome
the challenges
 A few strategies set up by the organization:
• promotion of the ITG (Industry Task Group);
• use of a consultancy firm to improve
organizational processes;
• establishing more formal contracts with part-
time evaluators;
• developing legislation to make the
regulatory agency a statuary body separate
from the Department of Health; and,
• establishing strong new leadership.

Manipal College of Pharmaceutical Sciences 5/20/19 10

 South African Health
Products Regulatory
Authority (SAHPRA)
 More independent with stronger self-governance
 Regulation of drugs, biologics, medical devices, in
vitro diagnostics, complementary medicinal
products, food, and cosmetics.
 Mutual recognition agreements with other
regulatory agencies, such as the FDA, to reduce the
registration approval times for products approved
by those agencies.
 Designed to reduce the time medicinal products
spend in review and get safe and effective drugs
and medical devices approved for use in South
Africa.
Manipal College of Pharmaceutical Sciences 5/20/19 11
 Medicines regulation in
China
 The China Food and Drug
Administration (CFDA) and its affiliates
play a key role

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 Application and approval procedure for imported drugs
(Clinical trial approval)
Application submission

Dossier content and format checking, notification of quality test and specifications
verification, by SDA (30 days)

Technical evaluation by CDE (120/100 days*) Samples testing and standards

verification by NICPBP (85 days)

Complementary data from applicant within 4 months

Supplementary data evaluation by CDE (40/25 days*)

Rejection Final approval by CFDA (40/20 days*)

or return *Notes: Days before slant line
refers to timeline for ordinary
approval and that after is the
timeline for fast track
Approval for clinical trials approval. All in working days.

Notification of clinical trial protocol Commencement of the clinical

and the list of investigators to CFDA trial
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Application and approval procedure for imported drugs

Submission of clinical trial results and other amended or supplementary data by

applicant

Acceptance by CFDA

Technical evaluation by CDE Complementary data from applicant

(120/100 days*) within 4 months by a whole

Supplementary data evaluation by

CDE (40/25 days*)

Rejection or return Final decision by CFDA (40/20 days*)
Approval of import drug application
*Notes: Days before slant line
refers to timeline for ordinary
approval and that after is the
timeline for fast track approval.
All in working days.

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 Special review and approval
procedure
 The following maybe applied for special review and
approval:
(1) active ingredients and their pharmaceutical
preparations made from any plant, animal,
mineral, or other raw material, including newly-
discovered crude herb medicines and their
preparations, provided that they have not been
previously marketed in China;
(2) chemicals, preparations containing such
chemicals, and biotechnology products, provided
that they have not been authorized for marketing
in China or any other country;
(3) new Manipal
drugs used to diagnose,
College of Pharmaceutical Sciences 5/20/19
treat, or prevent
15
 Challenges in the
regulatory framework of
China
 Lack of transparency.
 Lack of familiarity with the laws and regulations in
China as most of the guidelines are available only in
Mandarin (Chinese)
 The translation of all the materials in Mandarin
(Chinese) may include translational errors into the
submissions.
 In China, it is not possible to get marketing
authorization without local registration clinical trial.
 Long registration lag compared to other countries
because of the long regulatory process and duration.

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 Strategies to improve
regulations
 Transparency initiatives
 An effective mechanism to discuss questions
related to submission requirements and issues
directly with the agency
 In-country representation
 Use of a common language (English) accepted
in other regions
 The regulatory pathway for category I, new
drug registration may offer advantages that
compensate for the additional time and
development work required
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 Differences in regulatory requirements and
approval in China and South Africa
Requirements China
NDA format CTD of CMC
NDA category 1) New chemical entity never
marketed in any country
2) Drug preparation with changed
administration route and not
marketed in any country
3) Drug marketed ex-China
4) Drug substance and its
preparation with changed acid
or alkaline radicals (or metallic
elements), but without any
pharmacological change, and
the original drug entity already
approved in China
5) Drug preparation with changed
dose form, but no change of
administration route, and the
original preparation already
approved in China
6) Drug substance or preparation
following national standard.
Requirement of CPP Import drug require CPP at NDA
Utilizing foreign clinical trial data Global / MRCT clinical data for
chemical drugs
Manipal College of Pharmaceutical are acceptable,
Sciences 5/20/19
South Africa
ZA CTD
1) New chemical entity
applications
2) Multisource/ generic
applications and innovator
product line extension
applications that include
clinical information in
support of efficacy and
safety
3) Multisource/ generic
applications and innovator
line extension applications
that include comparative bio
availability/ bioequivalence
studies as proof of efficacy
4) Multisource/ generic
applications and innovator
line extension applications
that include comparative
dissolution studies as proof
of efficacy
5) Biological medicines
Application is not dependent on
the
availability of a CPP
If already available, clinical
data is acceptable 18
 Differences in regulatory requirements
and approval in China and South Africa
Requirements China
Application fees Application fees of drugs
includes:- registration fee: IND:
45,300 RMB (import drug); NDA:
45,300 RMB (import drug); drug
quality test: around 50,000 RMB,
based on test items; GCP
inspection: free charge; GMP
inspection: free charge
Language Chinese
Review organization Review: CDE (Center for Drug
Evaluation), Decision: CFDA
(China Food & Drug
Administration), Inspection:
Regional Drug Administration
Review time Official timeline of CTA / NDA of
import drug from submission to
approval: 145working days
Priority review system Special review procedure exists
Orphan drug system No orphan drug designation
system
Manipal College of Pharmaceutical Sciences 5/20/19
South Africa
Application fees of NCEs,
including (first strength, first
dosage form): R50000;
Screening fee on receipt of an
application: R1500; Evaluation
of additional submitted clinical
data: R2500; Inspection: R600
per hour(Local manufacturing
sites), R3600 per
hour(International
manufacturing sites)
English (Britain)
Review: MCC (Medicines control
council), Decision: Minister of
Health, Inspection: The
Inspectorate and Law
Enforcement Unit of MCC
NME: 24 months
Generics: 12 months
Expedited review process
Abbreviated medicine review
process
South African Foundation for
Rare Disorders (SAFRD) but not
well established (No strength,
compliance, funding) 19
 Differences in regulatory requirements
and approval in China and South Africa
Requirements China
Pre-approval inspection On-site GMP inspection
Pharmacopoeial standards Chinese Pharmacopoeia
GMP system Chinese GMP 2010version(MOH order 79)
DMF system DMF system is investigated butnot yet
implement.
Contents of packaging label and The required contents are
language described in CFDA order 24.The
contents Should be written in
Chinese.
Manipal College of Pharmaceutical Sciences 5/20/19
South Africa
When acceptable evidence of
GMP compliance is not
available, manufacturers are
inspected
BP, USP and Ph Eur
Good Manufacturing Practice for
medicines in South Africa (2010)
A system known as technical package is
known
The required contents are
described in General
information guideline. Contents
should be written in English
20
 Conclusion
 South Africa and China have quite a
good regulatory framework
 A few challenges – if overcome, the
framework would be in-line with the
developed countries

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 References
 Narsai K, Williams A, Mantel-Teeuwisse AK. Impact of regulatory requirements on
medicine registration in African countries-perceptions and experiences of Pharma
companies in South Africa. Southern Med Review (2012) 5;1:31-37
 Guideline (MCC)- General information [Internet].2013 [cited 2013 Oct 6]. Available
from: http://mccza.com/genericDocuments/2.01_General_information_Jul12_v8.pdf
 Registration and licensing requirements for the manufacture and sale of
pharmaceutical products in South Africa [Internet].2013 [cited 2013 Oct 21].
Available from:
http://www.piasa.co.za/images/legislation/REGISTRATION%20AND%20LICENS
ING%20REQUIREMENTS%20in%20SA%202009.pdf
 Overview of Chinese Regulatory Framework [Internet]. [cited 2013 Nov 8].
Available from: http://www.tigermed.net/newsinfozz.php?newid=131
 Product Registration and Other Regulatory Issues in China [Internet]. 2014 [cited
2014 Jan 19]. Available from:
http://www.pacificbridgemedical.com/publications/product-registration-amp-other-r
egulatory-issues-in-china/
 South Africa tackles drug approval delays [Internet]. [cited 2014 Jan 22]. Available
from:
http://www.reuters.com/article/2012/05/29/ozatp-safrica-medicines-idAFJOE84S0
6820120529

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