Regulatory Affairs

Definition

• Regulatory Affairs (RA) is all about paper work

How the drugs are being approved, safety standard and information
database.

• RA is a comparatively new profession

which developed from the desire of
governments to protect public health by controlling the safety and
efficacy of products in areas including pharmaceuticals, veterinary
medicines, medical devices, pesticides, agrochemicals, cosmetics
and complementary medicines.
History: Regulatory Affairs

Circumstances faced by Health Authority (HA)

USA – “Cutter Incident”
Live Poliovirus instead of attenuated vaccine was
inoculated to patients (new polio infection, 200
children with paralysis and 10 people killed)

more effective regulation

History: RA

Europe - Thalidomide tragedy

Drug used as sedative and anti-cancer drug was negatively
impacting the foetus development (infants with malformation of the
limbs).

Pharmaceutical legislations become clear and transparent. EMA

committee was developed for drug assessment in the EU
Why regulating drugs?
Drugs are not ordinary consumers‟ products!
In most instances, consumers are not in a position to make decisions about
when to use drugs
which drugs to use
how to use them
to weigh potential benefits against risks as no medicine is completely safe

1937 – Elixir Sulfanilamide

71 adults and 34 children died
1957 – Thalidomide/Softenon
40 % died/malformation of limbs
1990 – 2001 – Cerivastatin (Baycol) – cholesterol treatment-rhabdomyolysis
Why RA??

The Pharmaceutical sector has been ever growing and with

globalization the race to lead to be first is no more restricted by
boundaries, companies need to dominate on a global level to
stay on top. As a result of this competitiveness companies
success lies in the “time taken” by the product to reach the
market.
The companies responsible for the discovery, testing,
manufacture and marketing of these products and also want to
ensure that they supply products that are safe and make a
worthwhile contribution to public health and welfare. Most
companies, whether they are major multinational
pharmaceutical corporations or small, innovative biotechnology
companies, have special departments of Regulatory Affairs
professionals.

6
Why RA??

On an average it takes 15-20 years for a

new drug development, and it cost around
$800-1000 million. With such an
expensive and time consuming activity,
companies cannot afford a single day
delay in getting the product to the market.

RA Professional play the very important

role in getting the product to market,
improper data reporting can delay
evaluation of a positive marketing
authorization.
7
What is RA?

Regulatory Affairs (RA) is a profession within the health care industry

namely, Pharmaceutical, Medical Device, Biologics, & Functional Food.

Regulatory Affairs is a profession which has developed from the desire of

governments to protect public health, by controlling the safety and efficacy
of products in areas including pharmaceuticals, veterinary medicines,
medical devices, pesticides, agrochemicals, cosmetics and complementary
medicines.

RA profession at its heart is all about Collecting, Analyzing and

Communicating the Risks and Benefits of health care products to

regulatory agencies and public all over the world.

RA can be defined as :

It means government affairs

Role of RA Professionals

RA as profession is broader than registration of products, they advise companies

both strategically and technically at the highest level. Their role begins right from

development of a product to making, marketing and post marketing.

They advice at all stages both in terms of legal and technical requirements and
restrains help companies save a lot of time and money in developing the product

and marketing the same.

They have a major contribution in company‟s success both commercially and

scientifically.

Their main role is to comply with Safety & Efficacy of the products as per

regulation laid down by the government.

Role of RA Professionals cont..

In an organization their prime responsibilities involves

preparation and presentation of registration documents to
regulatory agencies and carry out all following discussion to
obtain and maintain marketing authorization (MA) for the
products concerned.
They need to keep a track on ever changing legislation in all
countries where the companies is looking to market their
product.
They are responsible for the presentation of registration
documents to regulatory agencies in India and importing
countries and carry out all the subsequent negotiations
necessary to obtain and maintain marketing authorization for the
products concerned in country of origin as well as importing
countries.

5
Different Regulatory Bodies
Various Regulatory Authority

Country Regulatory Authority

India Central Drugs Standard Control Organization
(CDSCO)
US United States Food and Drug Administration
(USFDA)
Australia Therapeutic goods administration (TGA)
UK Medicines and Healthcare Products Regulatory
Agency (MHRA)
Europe European Medicines agency (EMA)
South Africa Medicines control council (MCC)
Brazil Advisory council and office of Ombudsman
(ANVISA)
Canada Health canada
Different Regulatory Bodies

9
US Regulatory
Environment
What is FDA?
What does FDA regulate?
FDA is the federal agency responsible for ensuring that foods are
safe, wholesome and sanitary; human and veterinary drugs,
biological products, and medical devices are safe and effective;
cosmetics are safe; and electronic products that emit radiation
are safe.
FDA also ensures that these products are honestly, accurately
and informatively represented to the public.
• Biologics
Cosmetics
Drugs
Foods
Medical devices
Radiation Emitting Electronic products
Veterinary Products
 What FDA does not regulate?
• Advertising
The Federal Trade Commission is the federal agency which regulates all
advertising, excluding prescription drugs and medical devices. FTC ensures that
advertisements are truthful and not misleading for consumers.
• Alcohol
The labeling and quality of alcoholic beverages are regulated by the Treasury
Department's Bureau of Alcohol, Tobacco, and Firearms (ATFs).
• Consumer Products
While FDA regulates a large portion of the products that consumers purchase,
the agency has no jurisdiction over many household goods. The Consumer
Product Safety Commission (CPSC) is responsible for ensuring the safety of
consumer goods such as household appliances (excluding those that emit
radiation), paint, child-resistant packages, and baby toys.
• Drugs of Abuse
Illegal drugs with no approved medical use--such as heroin and marijuana--are
under the jurisdiction of the Drug Enforcement Administration.
• Health Insurance
• FDA does not regulate health insurance, the cost of health care products or
procedures, or reimbursement for health and medical expenses. Questions about
Medicare should be directed to the Centers for Medicare and Medicaid Services.
 What FDA does not regulate?
Contd…
Meat and Poultry
The U.S. Department of Agriculture's Food Safety and Inspection Service is
responsible for the safety and labeling of traditional meats and poultry. (FDA
regulates meats, such as venison, ostrich and snake.)
• Pesticides
FDA, USDA, and the Environmental Protection Agency share the responsibility
for regulating pesticides. EPA determines the safety and effectiveness of the
chemicals and establishes tolerance levels for residues on feed crops, as well as
for raw and processed foods.
• Restaurants and Grocery Stores
Inspections and licensing of restaurants and grocery stores are typically handled
by local country health departments.
• Water
The regulation of water is divided between the Environmental Protection Agency
and FDA. EPA has the responsibility for developing national standards for
drinking water from municipal water supplies. FDA regulates the labeling and
safety of bottled water.
 The US Regulatory Environment (1)

The US Food and Drug Administration (FDA)

FDA’s Role and Responsibilities:

– FDA is regulating drugs, foods, cosmetics, biologics, medical
devices
– FDA is responsible for administration, enforcement,
interpretation of US drug law and has power to establish
regulations which have the force and effect of law
– FDA has developed policies, procedures and regulations to
implement its Regulatory initiatives, some going beyond the
intent of the original laws
Drug Registration in the US = one of the most
rigorous systems in the world
 FDA Advisory Committees

Overview of FDA Organization (FDA Advisory Committees)

• Office of the Commissioner (OC)
- Science board to FDA
- Risk communication advisory committee
- Pediatric advisory committee
• Office of Regulatory Affairs (ORA)
• CBER (Center for biologic Evaluation and Research)
- Allergenic products advisory committee
- Cellular, tissue and gene therapies advisory committee
- Blood products advisory committee
- Transmissible spongiform encephalopathies advisory
committee
- Vaccines and related biological products advisory
committee
 FDA Advisory Committees

• CDER (Center for Drug Evaluation and research)

- Anesthetic and life support drugs advisory committee
- Antiinfective drugs drugs advisory committee
- Antiviral drugs advisory committee
- Arthritis drugs advisory committee
- Cardiovascular and renal drugs advisory committee
- Dermatologic and ophthalmic drugs advisory committee
- Drug safety and risk management advisory committee
- Endocrinologist and metabolic drugs advisory committee
- GI drugs advisory committee
- Non-prescription drugs advisory committee
- Oncologic drugs advisory committee
- Peripheral and CNS drugs advisory committee
- Psychopharmacologic drugs advisory committee
- Pulmonary-allergy drugs advisory committee
 FDA Advisory Committees

• CDRH (Center for Devices and Radiological Health)

• CVM (Center for Veterinary Medicine)
• CFSAN (Center for Food Safety and Applied Nutrition)
- Food advisory committee
• NCTR (National Center for Toxicological Research)
 EU Regulatory
Environment [EMA]
European Union

08/25/16 18
Member states of the European Union

Austria (1995) Italy (1952)

Belgium (1952) Latvia (2004)
Bulgaria (2007) Lithuania (2004)
Cyprus (2004) Luxembourg (1952)
Czech Republic (2004) Malta (2004)
Denmark (1973) Netherlands (1952)
Estonia (2004) Poland (2004)
Finland (1995) Portugal (1986)
France (1952) Romania (2007)
Germany (1952) Slovakia (2004)
Greece (1981) Slovenia (2004)
Hungary (2004) Spain (1986)
Ireland (1973) Sweden (1995)
Croatia (2013) United Kingdom (1973)

08/25/16 20
 EMEA Committee-Management Board

• Chairman
• Two members of european parliament
• Two members of european commisssion
• One representative of each country
• Two representative of
- patients’ organizations
- Doctors’ organizations
- Veternarians’ organizations
• One representative of observer countries
- Bulgaria
- Iceland
- Norway
- Liechtenstein
- Romania
 Role of EMEA in regulation of
medicines

• Taking decisions about authorization of medicines

based on an objective, scientific assessment of
their quality, safety and efficacy.
• Conducting these assessment is primary goal of
EMEA.-decisions on granting, refusing, revoking
or suspending marketing authorizations.
• Communicating authoritative and objective
information about medicines to patients,
healthcare professionals and other audiences.
 Role of EMEA in regulation of
medicines

• Continuously monitoring and assessing the safety

of medicines on the market (Pharmacovigilance)
• The designation of medicines for rare diseases
(orphan medicines).
• Asssessing pediatric investigational plans
• Drafting regulatory and scientific guidance to
assist companies in all areas for development and
marketing of medicines.
• Providing scientific advice and protocol to
companies submitting applications to EMEA.
 Structure of the European Medicines Agency
(EMA)
xperts appointed by NCA EMA Permanent Staff

EXECUTIVE
DIRECTOR
Guido Rasi

COMMUNICATIONS HUMAN PATIENT HEALTH VETERINARY

VETERINARY ADMINISTRATION
AND NETWORKING MEDICINES PROTECTION MEDICINES
MEDICINES
AND
AND
DEVELOPMENT
INSPECTIONS
INSPECTION
AND EVALUATION S

CHMP CVMP COMP HMPC CAT PDCO PRAC

Committee for
Committee for Committee for Committee Committee Committee Paediatric
Paediatric Pharmacovig.
Pharmacovig.
Medicinal
Medicinal Medicinal on Orphan on Herbal for Committee
Committe and
and Risk
Risk
Products
Products for
for Products for Medicinal Medicinal Advanced e Assessment
Assessment
Human
Human Use
Use veterinary use Products Products Therapies Committee
Committee

NATIONAL COMPETENT AUTHORITIES ( > 3 500 EUROPEAN EXPERTS )

CHMP and CVMP

Composition
Chairman (Dr. T. Salmonson; SE )

&

Vice-Chairman (Dr. I. Hudson; UK)

• One representative per EU member state plus one representative for

Iceland and one for Norway. Each committee member has an alternate.
• 5 co-opted members as appointed by Management Board to gain
additional expertise in particular scientific areas.
 CHMP main tasks & responsibilities

Delivering opinions to the European Commission

on new medicinal products/variation/renewal/line extension
on arbitration/referral procedures
 Advising on general EU guidelines/policies
 Scientific Advice & guidelines to companies
 Opinions on Compassionate Use to MSs
 Contribution to ICH process
 Establish Working Parties, SAGs & Expert Groups
 Delivering opinions to WHO
 Working Party Constellation

QSE
standards
Pharmacogenomic Biosimilars tWP Evaluation of
s tWP
Radiopharmaceuticals DG Biostatistics tWP Medicines

Gastroenterology DG Blood Prod. tWP

SAG
CVS
QWP* Cardiovascular
Respiratory DG Patients & tWP
Consumers SAG
Urology DG Neurology
CHMP CNS tWP
SAWP*(S
cientific
advice
PhVig* working SAG
party)
Vaccines Rheumatology Psychiatry
tWP Immunology
BWP* tWP
Sci Adv SAG
SAG= Pharmacokinetics Diabetes
Scientific tWP Oncology tWP
advisory Infectious
SAG
groups Diseases tWP
DG = drafting
Oncology
groups
SAG SAG
tWP = temporary SAG SAG
working party HIV / Antiviral diagnostics
* 1 / MS representation
Anti-Infectives Vaccines
 COMP (Committee for Orphan Medicinal
Products)

Composition
Chair and Vice Chair person
+
1 member/MS
+
3 reps patient organizations
+
3 EMA reps
Dr. Westermark

+ 3 patient organisations + 3 EMA

 PDCO (Paediatric Committee)

Composition:
Chair and Vice Chair person
+
5 CHMP members
+
1 member/MS
+
Dr. D. Brasseur 3 reps patient organizations
+
3 reps healthcare
professionals

+ 3 healthcare
26 + 3 patient organisations prof.
 Registration in Europe Post Nov 2005 :
Three European Systems

Centralised Mutual
Decentralised
Procedure Recognition
Procedure
(via EMA) procedure

27
Procedures for evaluating medicinal products
and granting marketing authorization

'©"Raaj GPRAC, Mumbai 2010-2016. All rights reserved.''

The European system for the authorisation of
medicinal products for human and animal use
was introduced in January 1995 with the
objective of ensuring that safe, effective and
high quality medicines could quickly be made
available to citizens across the European Union.
The European system offers several routes for
the authorisation of medicinal products:

30
 EU Centralised Procedure

Legal Basis: Regul. (EC) No 726/2004 (also establishing “EMA” European Medicines
Agency)
Principle: single application / evaluation single authorisation
direct access to all EU(28MSs) + Norway, Iceland and Liechtenstein
Scope:
Compulsory for:
Biotech (recombinant DNA, gene expressed proteins, hybridoma &
monoclonal antibodies)
New Active Substances in Specific Therapy Areas: AIDS, Cancer,
Neuro-degenerative disorder, Diabetes, Auto-immune disease, other
immune deficiencies, Viral diseases
Orphan Drugs
 Centralised procedure

'©"Raaj GPRAC, Mumbai 2010-2016. All rights reserved.''

The centralised procedure, which is compulsory for
products derived from biotechnology, for orphan
medicinal products and for medicinal products for human
use which contain an active substance authorised in the
Community after 20 May 2004 (date of entry into force of
Regulation (EC) No 726/2004) and which are intended
for the treatment of AIDS, cancer, neurodegenerative
disorders or diabetes. The centralised procedure is also
mandatory for veterinary medicinal products intended
primarily for use as performance enhancers in order to
promote growth or to increase yields from treated
animals. Applications for the centralised procedure are
made directly to the European Medicines Agency (EMA)
and lead to the granting of a European marketing
authorisation by the Commission which is binding in all
Member States.
31
MRP & DCP
The mutual recognition procedure, which is applicable to the
majority of conventional medicinal products, is based on the

'©"Raaj GPRAC, Mumbai 2010-2016. All rights reserved.''

principle of recognition of an already existing national marketing
authorisation by one or more Member States.
The decentralised procedure, which was introduced with the
legislative review of 2004, is also applicable to the majority of
conventional medicinal products. Through this procedure an
application for the marketing authorisation of a medicinal product is
submitted simultaneously in several Member States, one of them
being chosen as the "Reference Member State". At the end of the
procedure national marketing authorisations are granted in the
reference and in the concerned member states.
 The 3 steps of the Centralised Procedure

Step I Notify the EMA

Pre-submission of application Request Rapporteur/co-Rapporteur
• Early advice
• Rapporteur/Co-rapporteur appoinmt 120 days
• Assessment team
• Application
• Validation
Submit the MAA
Step II
Scientific evaluation Answer to questions
• Assessment Reports Clock stop for
210 days answer to questions Oral hearing
• List of Questions (+ clock stop)
• CHMP Opinion
• Possibility to appeal
CHMP Opinion
• Transfer to EU Commission
favourable

Step III Draft EC Decision

67 days
Decision Making Process

EC Decision
Community Licence
 Two options

Mutual Recognition Procedure

Art. 28 para. 2 of Dir. 2001/83/EC
For products with an existing MA

Decentralised Procedure
Art. 28 para. 3 of Dir. 2001/83/EC
Only possible, if no authorisation has already been
granted
 MRP & DCP: key authority stakeholders

CMDh ("Coordination group for mutual recognition and decentralised procedure for
human medicinal products"):
Mixed responsibilities: procedural, regulatory and scientific
One representative from each MS, appointed for 3 years (renewable)
+ observer from EMA and Commission
CMD(h) Chair person appointed for 3 years
+ Vice-chair representative of MS that has presidency of Council

RMS ("Reference Member State")

Selected by the applicant
Has to prepare the assessment report (AR)
Acts as central point between MS and MAH

CMS ("Concerned Member State(s)")

All other MS„s where the Company has submitted the dossier
 Overview of the MRP

National Application to Reference Member State (RMS)

Submission
210 days
RMS Approval (Day 210)

Mutual Submit MR application to Member States

Recognition
90 days

Serious objections Closure of procedure Approval National

CMDh Referral to CMDh (AR, SPC, labelling, PIL) licences
Arbitration granted within
By CMDh Approval MNSastional Step
(60 days)
(30 days)

Arbitration by CHMP (Art.32, 33, 34)

60 days (CHMP opinion) + 30 days (Commission decision)
 Overview of the DCP

Submission of dossier to Reference Member State ( RMS)

DCP Step1 and Concerned Member States ( CMSs)
120 days
RMS starts evaluation, and issues preliminary
Assessment Report (AR) for comments by CMSs
RMS sends consolidated list of questions to Applicant
Clock stop
(recommended 3 mths)
RMS prepares draft AR, draft SPC and
DCP Step 2 draft labelling/package leaflet
90 days Submit application to Member
States

Serious objections Closure of procedure Approval National

CMDh Referral to CMDh (AR, SPC, labelling, PIL) licences
Arbitration granted within
By CMDh Approval MNSastional Step
(60 days)
(30 days)

Arbitration by CHMP (Art.32, 33, 34)

60 days (CHMP opinion) + 30 days (Commission decision)
 The “Pharmacovigilance and Risk Assessment
Committee” (PRAC)

Replacing Pharmacovigilance Working Party (PhV WP)

Mandate: Risk detection, Benefit-Risk Assessment, Communication of risk and
benefit/risk, Risk Minimisation and Analysis Impact, Design and Evaluation of PASS
CHMP & CMDh to “rely upon” recommendations from PRAC but retain responsibility
for benefit-risk assessments
PRAC started in July 2012
Membership:
1 member (& 1 alternate) from each MS
One Chair person: June M. Raine (UK – MHRA)
Vice-Chair person: Almath Spooner (Ireland – IMB)
Interaction between PRAC & CHMP:
About 30% of CHMP agenda would go to PRAC
Aiming that PRAC Rapporteur could come from same MS as CHMP Rapporteur
Chalenge with timing of PRAC opinions: i.e. trying to fit the PRAC 60 day review
timeframe into overall timelines and still allow CHMP time to consider PRAC
input before adopting their opinion
New requirements for the Marketing Authorisation
Application (MAA)

Pharmacovigilance System Master File (PSMF)

MAH must prepare and maintain “Pharmacovigilance system master
file” (PSMF): replaces former “Detailed Description of Pharmacovigilance
System” (DDPS), and must be held at MAH site
Summary of the Pharmacovigilance System must be included in the MAA
dossier
Full PSMF to be provided within 7 days of request from a competent
authority
Risk Management Plan (RMP)
„detailed description of risk management system‟
RMPs to be included in MAAs for all new products
Authorities can impose need for Risk Management System on already
authorised products if concerns about Benefit/Risk balance
Format and content of RMPs addressed in Commission‟s implementing
measures
 Overview of the Regulation-EU

EU Regulatory system
EDQM/Ph.Eur Assessment on MAA

(Council of Europe) (Agencies-EMEA)

[www.pheur.org] [www.eudra.org/emea]

Laws, Directives, regulations (EU institutions)

[http://pharmacos.eudra.org]
Relevant EU legislation/ Guidelines

Volume 1: Pharmaceutical Legislation for Medicinal
Products for Human use
Volume 2: Notice to Applicants for MP for Human use
2A Procedures for marketing Authorization
2B Presentation and format of the dossier(CTD)
Volume 3: Guidelines
3A Quality and Biotechnology
3B Safety, environment and information
3C Efficacy
Volume 6: Notice to Applicants for MP for Veterinary
use
Volume 7: Scientific guidelines for MP for Veterinary
use
Volume 8: Maximum residue limits
Volume 9: Guidelines for PV for MP for Human and
Veterinary use
Volume 10: Guidelines for Clinical Trial

Volume 4: Good Manufacturing Practices

Volume 5: Pharmaceutical Legislation for Medicinal
Products for Veterinary use
 Maintenance of Marketing Authorizations
(Variations, Renewals)

EU Variations
Commission Guideline on Dossier Requirements for Type IA & IB
Notifications, July 2006
Categories of Variations
Type IA variation
Minor Changes
Type IB variation (Notify, wait for 30 days )
Major Changes Type II variation (60 days evaluation time
period)
South Africa : MEDICINES CONTROL
COUNCIL(MCC)

The Medicines Control Council (MCC) is a statutory

body that was established in terms of the Medicines
and Related Substances Control Act, 101 of 1965, to
oversee the regulation of medicines in South Africa.

It is appointed by the Minister of Health and its main

purpose is to safeguard and protect the public
through ensuring that all medicines that are sold and
used in South Africa are safe, therapeutically
effective and consistently meet acceptable standards
of quality.
South Africa : MEDICINES CONTROL
COUNCIL(MCC)

MCC Structure
MEDICINES CONTROL COUNCIL
Chair person
Vice- Chair person

AFRICAN TRADITIONAL MEDICINES COMMIT TEE COMPLEMENTARY MEDICINES COMMITTEE

Chair person Chair person
Vice- Chair person Vice-Chairperson

VETERINARY CLINICAL COMMI TTEE A NALYTI C L COMMITTEE

Chair person Chair pei rs on
Vice-Chairperson V ce - h r p r on
C a s
BIOLOGICAL COMMITTEE C LINICAL COMM TT EE
Chair person Chair pers on
Vice-Chairperson Vice - h p r on
C ai s
CLINICAL TRIALS COMMITTEE PHARMACEUTICAL /B I AVA LAB LITY COMM ITTEE
Chair person Chair per on
Vice-Chairperson Vice - h p on
C ai s
PHARMACOVIGILANCE COMMITTE SCHEDULING COMMITTEE
Chair person Chairperson
Vice-Chairperson Vice-Chairperson
 MCC-Structure

• The skills of council and its committees are

written into law and include expertise in
toxicology, and medicine safety, clinical
pharmacology, biotechnology, pharmaceutics,
internal medicine, virology, phamaceutical
chemistry, neonatology, pediatrics, immunology,
veternary science, complementary medicines and
law.
• The council, in considering whether a medicine is
suitable for use for its intended purpose assesses
its relative risk against the benefits.
UK-MHRA: Medicines and Healthcare
products Regulatory Agency
The MHRA regulates a wide range of materials like;
Medicines
Devices
Tissue Engineering
Nanotechnology
Blood
The term “medicines” embraces both pharmaceutical and
biological medicines and vaccines.

The term “medical devices” includes medical equipment.

Medical devices are all products, except medicines, used in
healthcare for the diagnosis, prevention, monitoring or
treatment of illness or disability. Examples include X-ray and
other imaging equipment, pacemakers, artificial joints,
anaesthetic equipment, pregnancy test kits, infusion
equipment, beds, wheelchairs and surgical dressings.
 MHRA-Structure

• The agency board: Non-executive

chairman, six non-executive members and
agency’s chief executive officer
• The executive board: agency’s directors
• Risk and audit committee: Chief executive
and management board
 MHRA-Structure

• MHRA’s main activities are supported by ten

divisions:
1. Licensing division
2. Vigilence risk management of medicines (VRMM)
3. Device technology and safety
4. Devices clinical
5. Inspection, enforcement and standards
6. Information management
7. Human resources
8. Operations and finance
9. Policy
10.Communications
 UK-MHRA: Aims and Objectives

• Protecting public health through regulation with acceptable

benefit-risk profiles for medicines and devices.
• Promoting public health by helping people who use these
products to understand their risks and benefits.
• Improving public health by encouraging and facilitating
developments in products that will benefit people.
• Safeguard public health through MHRA’s primary role in
ensuring that the products MHRA regulate meet required
standards that they work and are acceptably safe.
• Carry out communication role through the provision of
accurate, timely and authoritative information to healthcare
professionals, patients and the public.
UK-MHRA: Activities

• Assessing the safety, quality and efficacy of

medicines and authorizing their sale or supply in
the UK for human use.
• Overseeing the UK notified bodies that audit
medical device manufacturers.
• Operating post-marketing surveillance and other
systems for reporting, investigating and
monitoring adverse drug reactions to medicines
and adverse incidents involving medical devices
and taking any necessary action to safeguard
public health, for e.g. through safety warnings,
removing or restricting the availability of
products or improving designs.
UK-MHRA: Activities

• Operating a quality surveillance system to sample

and test medicines and to address quality
defects, monitoring safety and quality of
imported unlicensed medicines.
• Regulating clinical trials of medicines and medical
devices.
• Promoting good practice in safe use of medicines
and medical devices.
• Managing general practice research database and
BP and contributing to the development of
performance standards of medical devices.
UK-MHRA: Activities

• Offering scientific, technical, and

regulatory advice on medicines and
medical devices.
• Monitoring and ensuring compliance with
statutory obligations relating to medicines
and medical devices through inspection,
taking enforcement action where
necessary.
WHO: World Health Organization

WHO is the directing and coordinating authority for health

within the United Nations system.
It is responsible for providing leadership on global health
matters, shaping the health research agenda, setting norms and
standards, articulating evidence-based policy options, providing
technical support to countries and monitoring and assessing
health trends.
WHO is Geneva based.
Many countries follow the guidelines provided by WHO.
Food and Drugs Control Authority India follows WHO guidelines.
WHO GMP certification is a requirement and well accepted in
most of the countries across Asia, Africa, CIS and Latin America.
 How does WHO work and for whom?

WHO’s main functions:

- To give worldwide guidance in field of health.
- To act as the directing and coordinating authority on
international health work.
- To encourage technical cooperation for health with
Member States
- Has constitutional mandate to develop norms and global
standards for health.
- To co-operate with governments in strengthening
national health programme.
- To develop and transfer appropriate health technology
information.
 WHO: World Health Organization

Countries
All countries which are Members of the United Nations may
become members of WHO by accepting its Constitution. Other
countries may be admitted as members when their application
has been approved by a simple majority vote of the World
Health Assembly.
Territories which are not responsible for the conduct of their
international relations may be admitted as Associate Members
upon application made on their behalf by the Member or other
authority responsible for their international relations. Members
of WHO are grouped according to regional distribution (193
Member States).
INTERNATIONAL
REGULATORY
ENVIRONMENT
 Scope

192 countries
More than 70% of the
23 time zonesworld’s
population are:
Between 4000 and 6000 languages
Asia Pacific and
More than 150Emerging Markets
monetary currencies
(APEM )
 International & Emerging Regions

Key markets
Asia Pacific:

India, Philippines, South Korea, Taiwan

China / Hong Kong / Macau:

China
Latin America :

Argentina, Brazil, Chile, Mexico

Middle East and North Africa (MENA):

Egypt, Pakistan, Saudi Arabia, Turkey

Sub Saharan Africa (SSA):

South Africa
Eastern Europe
RoW = Rest of the World
What are the RoW countries?
World regions excluding US, CA, EU, CH, Au,
and Nz.

What are the regions and sub-regions?

AMEA – Asia Middle East and English-speaking
Africa
LATAM – Latin America
RIC+ - Russia & Former Soviet States, Greater
China, Greater India, Israel, French-speaking
Africa, South-east Europe
Regions and Sub-regions
- definitions
AMEA
ASIA
ASEAN (Association of South East Asian Nations)
Korea, Japan

MIDDLE EAST
Arabian Peninsula (Saudi Arabia)
Gulf (Bahrain, Kuwait, Qatar, UAE, Oman, Yemen)
Near East (Egypt, Jordan, Lebanon, Syria, Irak, Iran,
Afghanistan, Pakistan)

AFRICA
English-speaking Africa
ASEAN: 2 main areas of
Harmonisation
ACTD (ASEAN Common Technical
Dossier) : > Harmonize format

ACTR (ASEAN Common Technical

Requirement) :> Harmonize technical
content
Developed based on international guidelines such
as ICH, EMEA, FDA, WHO
ASEAN: Organization of Application Dossier
(ACTD)

Part I
* Upon Request
Administrative Data &
Product Information

Part III
Non-clinical Part IV
Part II Clinical
Quality Overview,
Summary Overview,
Overall Summary
& Reports & Study Reports* Summary
& Study Reports*
Region AMEA – definition
ENGLISH-SPEAKING AFRICA
Angola, Ethiopia, Ghana, Kenya, Malawi, Mozambique, Namibia,
Nigeria, Sierra Leone, Somalia, South Africa,Tanzania, Uganda,
Zambia, Zimbabwe
Region RIC+
RIC+
RUSSIA AND FORMER SOVIET UNION COUNTRIES
Russia
Ukraine
OFSUs (Armenia, Azerbaijan, Belarus, Georgia,
Kazakhstan, Kirghistan, Moldova, Tajikistan,
Turkmenistan, Uzbekistan)
GREATER INDIA (India, Sri Lanka, Bangladesh)
GREATER CHINA (China, Hong Kong, Taiwan)
ISRAEL
FRENCH-SPEAKING AFRICA
SOUTH-EAST EUROPE (Albania, Bosnia-Herzegovina,
Kosovo, Macedonia, Montenegro, Serbia, Srpska)
Region RIC+

RUSSIA AND FSU COUNTRIES

1.Armenia 2. Azerbaijan 3. Belarus 5. Georgia 6. Kazakhstan 7.
Kirghistan 10. Moldova 11. Russia 12. Tajikistan 13. Turkmenistan 14.
Ukraine 15. Uzbekistan
Region RIC+

FRENCH-SPEAKING AFRICA
Algeria, Benin, Burkina Faso, Cameroon, Chad, Congo Brazzaville,
Congo Kinshasa, Ethiopia, Gabon, Guinea, Ivory Coast, Madagascar,
Mali, Mauretania, Mauritius, Morocco, Rep. Central Africa, Senegal,
Togo, Tunisia (Arabic-speaking Africa : Libya, Sudan )
General Overview of specific
regional requirements
Regions, but all are national registrations
Enormous diversity of regulatory requirements
However, some harmonisation on some clusters e.g. ASEAN,
Gulf
Currently, the registration documentation can be either
EU-based files, complemented with additional HA’s
requirements, OR
CTD files specifically prepared for geographical expansion
in AMEA, LATAM, RIC+
CTD format is not accepted in all RoW countries but dossier
must be submitted as per respective HA guidelines.
General Overview of specific
regional requirements

When a standard file is sent to RoW countries for submission,

Regulatory dept. often receives a list of additional documents
needed before the file can be submitted to the HA. Collecting
these documents can take weeks/months and further delay
the submission.

Many countries insist on additional specific documentation for

product registration, variations, site changes, etc.

Mostly, the additional requirements are of a CMC nature,

although there are requests for extra certificates, statements,
CPPs, etc
GCC-Middle East Countries
Armenia Israel Syria

Azerbaijan Jordan Turkey

Bahrain Kuwait Turkmenistan

Egypt Lebanon United Arab Emirates

Georgia Oman Yemen

Iran Qatar

Iraq Saudi Arabia

Background:

Middle East countries developed

legislations for drug registrations,
inspection, drug control and life cycle.
Legislation and review process varies from
country to country.
Classification of the products varies to the
degree of development (new chemical
entities, generic, similar etc.)
 REGULATORY
SUBMISSIONS IN INDIA

69
Local (Domestic market)

Registration of products in our own

country India for selling to Local market

Regulatory Authority :Food and Drug

Administration (FDA)

Reference : Drugs and cosmetic Act 1940,

Rules 1945

70
Regulatory Bodies Governing & Controlling Clinical
Trials

Regulatory Ministry Location

Body

Drugs Ministry Central

Controller of Body
General Health (Delhi)
(India) and
(DCGI), Family
Directorate Welfare
General of
Health
Services
(DGHS)
Local (Domestic market) New
Molecule
Registration of new products in our own
country -India for selling to Local market

Regulatory Authority :Drug Control General

(DCGI),Delhi

Reference : Drugs and cosmetic Act 1940.

Rules 1945.

72
Global Harmonisation
Initiatives
What is ICH?
“International Council on Harmonization of
Technical Requirements for Registration of
Pharmaceuticals for Human Use”.

ICH is a joint initiative involving both regulators and

research-based industry representatives of the
EU, Japan and the US in scientific and technical
discussions of the testing procedures required to
assess and ensure the safety, quality and efficacy
of medicines.
 ICH Structure / Organisation

6 official parties (co-sponsors) directly involved :

Authorities and research based industry from
EU:- European Commission + EMA and CHMP
- EFPIA (Eur.Feder.Pharmac.Industries&Associations)
Japan:- MHLW (Ministry of Health and Welfare)
- JPMA (Japanese Pharmaceutical Manuf. Association)
USA:- FDA (US Food and Drug Administration)
- PhRMA (Pharmaceut. Research and Manuf. of America)
Official "Observers"
World Health Organisation (WHO)
European Free Trade Area (EFTA)
Canada (Health Protection Branch)
"Interested Parties" also involved
Pharmacopoeias (Eur.Ph., J.P., U.S.P.)
other industry sectors (OTC and Generics)
What is the purpose of ICH?
The objective of ICH is to increase
international harmonization of technical
requirements to ensure that safe, effective,
and high quality medicines are developed
and registered in the most efficient and cost
effective manner.
ICH Guidelines
The ICH Topics are divided into four major categories and
ICH Topic Codes are assigned according to these categories.

Q S E M
"Quality" Topics, "Safety" Topics, "Efficacy" "Multidisciplinar
i.e., those relating i.e., those relating Topics, i.e., y" Topics, i.e.,
to chemical and to in vitro and in those relating to cross-cutting
pharmaceutical vivo pre-clinical clinical studies in Topics which do
Quality studies human subject not fit uniquely
Assurance (Carcinogenicity (Dose Response into one of the
(Stability Testing, Testing, Studies, Good above categories
Impurity Testing, Genotoxicity Clinical Practices, (MedDRA,
etc.) Testing, etc.) etc.) ESTRI, M3, CTD,
M5)
"Quality" Topics
Stability - Q1A – Q1F
Analytical Validation – Q2
Impurities – Q3A - Q3C (Q3D – concept paper)
Pharmacopoeias – Q4A - Q4B (and annexes)
Quality of Biotechnological Products – Q5A – Q5E
Specifications – Q6A – Q6B
Good Manufacturing Practice – Q7
Pharmaceutical Development – Q8
Quality Risk Management - Q9
Pharmaceutical Quality System – Q10
Development and Manufacturing of Drug Substances – Q11
Efficacy Topics
E1: The Extent of Population Exposure to Assess Clinical Safety for Drugs Intended for Long-
Term Treatment of Non-Life-Threatening Conditions
E2A: Clinical Safety Data Management : Definitions and Standards for Expedited ReportingE3:
Structure and Content of Clinical Study Reports
E3: Structure and Content of Clinical Study Reports
E4: Dose-Response Information to Support Drug Registration
E5(R1): Ethnic Factors in the Acceptability of Foreign Clinical Data
E6: Good Clinical Practice : Consolidated Guideline
E7: Studies in Support of Special Populations : Geriatrics
E8: General Considerations for Clinical Trials
E9: Statistical Principles for Clinical Trials
E10: Choice of Control Group and Related Issues in Clinical Trials
E11: Clinical Investigation of Medicinal Products in the Pediatric Population
E12: Principles for Clinical Evaluation of New Antihypertensive Drugs
E14: The Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for
Non-Antiarrhythmic Drugs

E15: Definitions for Genomic Biomarkers, Pharmacogenomics, Pharmacogenetics, Genomic

Data and Sample Coding Categories

E16: Genomic Biomarkers Related to Drug Response: Context, Structure and Format of
Qualification Submissions
Multidisciplinary Guidelines

M1 MedDRA
Medical Terminology

M2 ESTRI
Electronic Standards for the Transfer of Regulatory Information

M3M3(R2)
Nonclinical Safety Studies for the Conduct of Human Clinical Trials
and Marketing Authorization for Pharmaceuticals

M4CTD
The Common Technical Document

M5M5
Data Elements and Standards for Drug Dictionaries
 ICH Now and in the Future

New areas to develop ICH guidelines:

Post-marketing pharmacovigilance
Pharmacogenomics
Biomarkers
Gene Therapy

Continued Harmonisation: prevention of new

interregional disharmony
Avoid unilateral development of requirements in specific areas
 …Globalising ICH

ICH Global Cooperation Group (GCG)

Representatives from other Regional Harmonisation initiatives
APEC (Asia-Pacific Economic Cooperation)
ASEAN (Association of the Southeast Asian Nations)
GCC (Gulf Cooperation Council)
PANDRH (Pan American Network for Drug Regulatory Harmonization)
SADC (Southern African Development Community)
Evolution in ICH and understanding that some non-ICH countries are
now major contributors/consumers to the global pharmaceutical market
Regulators Forum - started in 2008
Including representatives from Australia, Brazil, China, Taiwan,
India, Russia, Singapore and South Korea most of which are not
part of Harmonisation Initiatives already
Key areas of focus: API GMP; clinical trials; pharmacovigilance
Various links

USA : UNITED STATES FOOD AND DRUG ADMINISTRATION

http://www.fda.gov/
Europe : THE EUROPEAN AGENCY FOR THE EVALUATION OF
THE MEDICINAL PRODUCTS (EMEA)
http://www.emea.europa.eu/
Health Canada:
http://www.hc-sc.gc.ca/dhp-mps/index-eng.php
South Africa : MEDICINES CONTROL COUNCIL (MCC)
http://www.mccza.com/
United Kingdom : MEDICINES AND HEALTHCARE PRODUCTS
REGULATORY AGENCY (MHRA)
http://www.mhra.gov.uk/
Various links
New Zealand : NEW ZEALAND MEDICINES AND
MEDICAL DEVICES SAFETY AUTHORITY (MEDSAFE)
http://www.medsafe.govt.nz/
Australia : THERAPEUTIC GOODS ADMINISTRATION
(TGA)
http://www.tga.gov.au/
Brazil: ANVISA
http://www.anvisa.gov.br/eng/legis/index.htm#6
Thanks for your Attention!