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GLOBAL REGULATORY
ASPECTS
By Poonam Bhardwaj
JANUARY 2012
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Where have the regulations come
from?
3,500 years ago ancient Egyptians were strict
Rules of medicines were to be followed
Reflected
Quality, Safety & Efficacy
Vigorously enforced
Vi l f d
If followed & patient died – absolution
If b k & patient di d – d h penalty!
broken i died death l !
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REGULATORY
Regulatory Affairs (RA)
Regulatory Authority
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REGULATORY AFFAIRS
The Pharmaceutical Biotechnology and
Pharmaceutical,
Medical device, and Research &
Development industries are most highly
regulated industries in the country.
As India is growing very rapidly in the
pharmaceutical sector, there is a
growing need of “Regulatory Affairs” to
Regulatory Affairs
cater the current needs of industries for
the global competition
competition.
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5. REGULATORY TERRITORIES
North America (US , Canada)
Europe (Europe Union, Eastern Europe)
Japan
J
Rest Of the World i.e. ROW
(Asia Pacific Region, ANZ, LATAM, CEE,
GCC, CIS)
, )
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REGULATORY TERRITORIES
Business Boundaries are dissolving
dissolving.
The world pharmaceutical regulations
are in continues process of
harmonization.
harmonization
“Regulatory” is the key to enter into the
market of any Country.
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REGULATORY TERRITORIES
Based on the “Economy” and
Economy
“Regulatory Control” of the countries,
these are grouped into:
Regulated M k t
R l t d Markets
Semi Regulated Markets
Non Regulated Markets
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REGULATORY TERRITORIES
Based on the “Economy” and
Economy
“Regulatory Control” of the countries,
these are grouped into:
Regulated M k t
R l t d Markets
Semi Regulated / Emerging Markets
Non Regulated Markets
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REGULATORY TERRITORIES
Regulated Markets
US
EU
Japan
ANZ (Australia, NewZealand)
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REGULATORY TERRITORIES
European Union Member States
Austria Greece Netherlands
Belgium Hungary Norway
Bulgaria Iceland Poland
Cyprus
C Ireland
I l d Portugal
P t l
Czech Republic Italy Romania
Denmark Latvia Slovakia
Finland Liechtenstein Slovenia
Estonia Lithuania Spain
France Luxembourg Sweden
Germany Malta United Kingdom 10

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REGULATORY TERRITORIES
Emerging Markets
Asia Pacific ASEAN
GCC (Gulf Co operation Council)
Co-operation
LATAM (Latin America)
CEE (Central East Europe)
CIS (Commonwealth Independent States)
Africa
Af i
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REGULATORY TERRITORIES
REGION COUNTRIES
Asia Pacific -- ASEAN Indonesia, Malaysia, Philippines, Singapore ,
Thailand, Brunei, Myanmar, Cambodia, Laos,
Vietnam.
GCC Bahrain, Kuwait, Oman, Qatar, Saudi Arabia,
(Gulf Co-operation Council) and UAE.
LATAM (Latin America) Brazil, Mexico, Venezuela
Argentina, Chile, Columbia, Ecuador
Guatemala, Barbados, Bolivia
CEE (Central East Europe) Belarus, Bulgaria, Czech Republic, Hungary,
Poland, Romania, Sl
P l d R i Slovakia.
ki
CIS (Commonwealth Armenia, Azerbaijan, Belarus, Kazakhstan,
Independent States) Kyrgyzstan, Moldova, Russia, Tajikistan,
Turkmenistan, Ukraine Uzbekistan,
Turkmenistan Ukraine, Uzbekistan Georgia
Africa South Africa, Ghana, Ethiopia, Kenya, 12
Tanzania, Luanda, Zambia, Sudan ..

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REGULATORY AUTHORITY
Regulatory Agency
Regulatory Body
Regulatory Authority
Government Body
Health A th it
H lth Authority
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REGULATORY AUTHORITY
Country Regulatory Authority
Argentina National Administration of Drugs, Food &
Medical Technology (ANMAT)
Brazil Agência Nacional deVigilância
Sanitária (ANVISA)
National Health Surveillance Agency
Bulgaria
B l i Bulgarian D
B l i Drug Agency (BDA)
A
Canada Health Canada
China State Food and Drug Administration (SFDA)
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REGULATORY AUTHORITY
Country Regulatory Authority
Denmark Danish Medicines Agency
Europe European Directorate for the Quality of
Medicines and Healthcare (EDQM) &
M di i dH l h
European Medicines Agency (EMA)
Germany Federal Institute for Drugs and Medical
Devices (BfArM)
India Central Drug Standard Control
Organization (CDSCO)
Food and Drug Administration (FDA)
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Ireland Irish Medicines Board

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REGULATORY AUTHORITY
Country Regulatory Authority
Italy Italian Pharmaceutical Agency
Japan Pharmaceuticals and Medical Devices
Safety Authority (PMDA)
Netherlands Medicines Evaluation Board
New Medsafe - Medicines and Medical Devices
Zealand Safety Authority
Pakistan
P ki t Drug C t l Organisation, Ministry of Health
D Control O i ti Mi i t f H lth
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REGULATORY AUTHORITY
Country Regulatory Authority
Philippines Philippine Council for Health Research and
Development (PCHRD)
Poland Ministry of Health & Social Welfare
Singapore Health Sciences Authority (HSA)
Sri Lanka
S iL k Ministry f Healthcare and Nutrition
Mi i t of H lth d N t iti
South Africa Medicines Control Council (MCC)
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REGULATORY AUTHORITY
Country Regulatory Authority
Switzerland Swiss Agency for Therapeutic Products
Uganda National Council for Science and Technology
(UNCST)
UK Medicines and Healthcare Products
Regulatory Agency (MHRA)
USA The Food and Drug Administration (FDA)
Yemen Ministry of Public Health and Population
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FDA Regulatory Pyramid
US Laws
L
Congress
Food, Drug &
Cosmetic Act
Regulations cGMP
GLP = GxP
21 CFR Part 11; GCP
21 CFR Part 210, 211, 820, etc.
Guidances
Part 211. Current Good Manufacturing Practice for
g
Finished Pharmaceuticals.
Standards
GAMP 4 Guide; ISO 9000, IEEE Standards; ASTM Standards; US
Pharmacopeia (USP); International Conference on Harmonization (ICH)
Slide 20

21. CFR = Code of US Federal Regulations Elder
Title 26 Internal Revenue
Title 1 General Provisions
Title 27 Alcohol, Tobacco Products and Firearms
Title 2 [Reserved]
Title 28 Judicial Administration
Title 3 The President
Title 29 Labor
Title 4 Accounts
Title 30 Mineral Resources
Title 5 Administrative Personnel
Title
Ti l 31 Money and Finance: Treasury
M d Fi T
Title 6 [Reserved]
Title 32 National Defense
Title 7 Agriculture
Title 33 Navigation and Navigable Waters
Title 8 Aliens and Nationality
Title 34 Education
Title 9 Animals and Animal Products
Title 35 Panama Canal
Title
Titl 10 Energy
E
Title 36 Parks, Forests, and Public Property
Title 11 Federal Elections
Title 37 Patents, Trademarks, and Copyrights
Title 12 Banks and Banking
Title 38 Pensions, Bonuses, and Veterans' Relief
Title 13 Business Credit and Assistance
Title 39 Postal Service
Title 14 Aeronautics and Space
p
Title 40 Protection of Environment
Title 15 Commerce and Foreign Trade
Title 41 Public Contracts and Property
Title 16 Commercial Practices
Management
Title 17 Commodity and Securities Exchanges
Title 42 Public Health
Title 18 Conservation of Power and Water
Title 43 Public Lands: Interior
Resources
R
Title 44 Emergency Management and Assistance
Title 19 Customs Duties
Title 45 Public Welfare
Title 20 Employees' Benefits
Title 46 Shipping
Title 21 Food and Drugs Title 47 Telecommunication
Title 22 Foreign Relations Title 48 Federal Acquisition Regulations System
Title 23 Highways Title 49 Transportation
Title 50 Wildlife and Fisheries Slide 21
Title 24 Housing and Urban Development
Title 25 Indians

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21 CFR Part ……
CFR Title 21 （Food and Drugs)
g )
1. General Enforcement Regulations
2. General Administrative Rulings and Decisions
3. Product Jurisdiction
:
11. Electronic Records and Electronic Signatures
:
58. G d L b
58 Good Laboratory Practice (GLP)
t P ti
:
210. Current Good Manufacturing Practice in
Manufacturing Processing, packing, or Holding of Drugs.
211. Current Good Manufacturing Practice for Finished
Pharmaceuticals.
:
820. Quality System Regulation (QSR) Device GMP
Slide 22

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ICH
International Conference on Harmonisation
of
Technical Requirements for Registration of
Pharmaceuticals
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ICH
Bringing together the
regulatory authorities and
pharmaceutical industry
of ………….???
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ICH
USA Europe
Japan
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Q S E M
"Quality" "Safety" "Efficacy" "Multi-
disciplinary
disciplinary"
Topics i.e. those Topics i.e. those Topics i.e. those Topics i.e.
relating to relating to in relating to cross-cutting
chemical and vitro and in vivo clinical studies Topics which
pharmaceutical pre-clinical in human do not fit
Quality studies subject (Dose uniquely into
Assurance (Carcinogenicity Response one of the
(Stability Testing, Testing Studies Good above
Impurity Testing G t i it
I it T ti Genotoxicity Clinical
Cli i l categories
t i
etc) Testing etc.) Practices etc.) 26

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ICH - Quality
ICH section Description
p
Q1 Stability Study
Q2(R1) Validation of Analytical Procedures
Q3A(R2) Impurities in New Drug Substances
p g
Q3B(R2) Impurities in New Drug Products
Q3C(R4) Impurities: Guideline for Residual Solvents
Q4 Pharmacopoeias
Q5 Quality of Biotechnological Products 27

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ICH
ICH section Description
p
Q6 Specifications
Q7 Good Manufacturing Practice Guide for Active
Pharmaceutical Ingredients
Q8(R2) Pharmaceutical Development
Q9 Quality Risk Management
Q10 Pharmaceutical Quality System
Q 11 Development and Manufacture of Drug
Substances 28

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REGULATORY SUBMISSIONS
Nomenclature of Documents:
DMF / ASMF (Drug Substance; DS)
(D S b t
Dossier (Drug Product; DP)
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REGULATORY SUBMISSIONS
Drug Master File (DMF) is a master
g ( )
document containing complete information
on API.
Drug Master File (DMF)
Compilation for open and closed part
It is a submission of documents, covering
factual and complete information on
chemistry, stability, purity, i
h i t t bilit it impurity profile,
it fil
packaging and cGMP status of any API. 30

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REGULATORY SUBMISSIONS
Drug Dossier is a document which consist of
complete information of Drug product
(Formulation). Viz:
Information on API and Excipients
Manufacturing process
M f t i
Quality documents
Pre-clinical study
P li i l t d
Clinical Study
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OK I am Ready to File
– No What?
Now
Its
It CTD
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REGULATORY SUBMISSIONS
WHAT IS CTD???
CTD (Common Technical Document) is an
application FORMAT prescribed
pp p
organization of the information required to
be submitted.
A harmonized format for a regulatory
dossier that is considered acceptable in
US, Japan Europe and other regulatory
also.
l
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REGULATORY SUBMISSIONS
TYPES OF CTD SUBMISSION
PAPER SUBMISSION
ELCTRONIC SUBMISSION
(eCTD)
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PAPER SUBMISSION
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ELECTRONIC SUBMISSION
(e
( CTD)
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Role of Regulatory Affairs
Professionals
“Regulatory Affairs Professional ”
is the crucial link between
pharmaceutical company, its
products and worldwide
regulatory authorities viz.
viz
USFDA, EMEA, etc.
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REGULATORY
AFFAIRS
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Role of Regulatory Affairs
Professionals
Regulatory Affairs Unit in a p
g y pharmaceutical company
p y
is a vital unit that drives the R & D efforts of the
company to the market successfully.
A Regulatory Affairs department is a dynamic
business unit which works with a focus to get
products to the market with a commercially viable
label in the least possible time and expenses.
The world has become a global village and many
companies are in a race to place many new products
in the world markets to gain market share and
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Role of Regulatory Affairs
Professionals
In such a scenario a small delay in gaining market
y g g
access means huge loss in terms of market share
and revenue generated.
The key to success for pharmaceutical companies
lies in obtaining timely marketing approval from
regulators.
regulators
So to obtain timely marketing approval companies
can either strengthen the regulatory department or
outsource the same to regulatory affairs consulting
firm.
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Role of Regulatory Affairs
Professionals
They ensure appropriate licensing, marketing and
y pp p g, g
legal compliance of pharmaceutical and medical
products.
They combine scientific knowledge, legal and
business issues and co ordinate the approval and
co-ordinate
registration.
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Role of Regulatory Affairs
Professionals
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IMPORTANT LINKS
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IMPORTANT LINKS
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IMPORTANT LINKS
http://www.fda.gov/default.htm
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IMPORTANT LINKS
http://www.edqm.eu/site/Homepage-
http://www.edqm.eu/site/Homepage-628.html
http://www.ema.europa.eu/ema/index.jsp?cu
p p j p
rl=pages/home/Home_Page.jsp&mid=
rl=pages/home/Home_Page.jsp&mid= 47

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IMPORTANT LINKS
http://www.pmda.go.jp/english/index.html
http://www pmda go jp/english/index html
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IMPORTANT LINKS
http://www.cdsco.nic.in/
http://www.drugscontrol.org/
http://www drugscontrol org/
http://www.fda-mah.com/ 49

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CONCLUSION
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