Overview of Regulatory Affairs and Worldwide Regulatory

bodies

Rajashri Survase-Ojha(Founder & Director, Raaj GPRAC)www.raajpharmaelearning.comrajashrio@gmail.comraajgprac@gmail.com

Disclaimer Contents of this presentation are the

presenters personal views and do not necessarily represent any companies policies and position.

Some images are taken – freely available from the internet for a diagrammatic representation of the content and the source is acknowledged.

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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

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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.

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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

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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 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

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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. 

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Different Regulatory Bodies

Different Regulatory Bodies

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US Regulatory Environment

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 is FDA?What does FDA 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?

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 game 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 county 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 Reglatory initiatives, some going beyond the intent of the original laws

Drug Registration in the US = one of the most rigorous systems in the world

Overview of FDA Organization – top level Office of the Commissioner (OC) Office of Regulatory Affairs (ORA) Centers for Product Jurisdiction

CDER (Center for Drug Evaluation and Research) CBER (Center for Biologics Evaluation and Research) CDRH (Center for Devices and Radiological Health) CVM (Center for Veterinary Medicine) CFSAN (Center for Food Safety and Applied Nutrition) NCTR (National Center for Toxicological Research)

The US Regulatory Environment (2)

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

EU Regulatory Environment [EMA]

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European Union

05/01/23

Evolution of the European Regulatory Environment since 1995…

1995 2000 2003 2004 2005 2006 2007

EMEA Centralised Procedure Mutual Recognition Procedure

Orphan Drugs Regulation

Annex I(to Directive 2001/83/EC)(CTD)

New Legisl. Title IV of Reg. 726/04 immediate

NewLegisl.fully into force

PaediatricRegulation

Legisl.on Advanced Therapy

Enlargement(to 15 MS)

Enlargement to 25 MS(CY, CZ, EE, HU, LT, LV, MT, PL, SI, SK)

Enlargement to 27 MS(BG & RO)

Birth of the Birth of the EMEAEMEA

2008

Enlarged Scopeof CP

2010

New Variation Regulation

New Pharmacovigilance legislation

Future…Accession of Croatia

2012

Implem.of New PVLegisl.

PRAC(July2012)

Austria (1995) Belgium (1952) Bulgaria (2007) Cyprus (2004) Czech Republic (2004) Denmark (1973) Estonia (2004) Finland (1995) France (1952) Germany (1952) Greece (1981) Hungary (2004) Ireland (1973) Croatia (2013)

Italy (1952) Latvia (2004) Lithuania (2004) Luxembourg (1952) Malta (2004) Netherlands (1952) Poland (2004) Portugal (1986) Romania (2007) Slovakia (2004) Slovenia (2004) Spain (1986) Sweden (1995) United Kingdom (1973)

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Member states of the European Union

05/01/23

COMP Committee on Orphan Medicinal Products

CHMPCommittee for Medicinal Products for Human Use

HMPCCommittee on Herbal Medicinal Products

NATIONAL COMPETENT AUTHORITIES ( > 3 500 EUROPEAN EXPERTS )

Structure of the European Medicines Agency (EMA)

PRACPharmacovig. and Risk Assessment Committee

CVMP Committee for Medicinal Products for veterinary use

Expe

rts

appo

inte

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NCA

EXECUTIVE DIRECTORGuido Rasi

COMMUNICATIONS AND NETWORKING

ADMINISTRATIONVETERINARY MEDICINESAND INSPECTIONS

PATIENT HEALTH PROTECTION

HUMAN MEDICINES DEVELOPMENT AND EVALUATION

EMA

Perm

anen

t St

aff

PDCOPaediatric Committee

CATCommittee for Advanced Therapies

• 27 MSs + NO/IS (EEA Countries) - 22 Languages (Working Language EN) • 1 scientific expert member nominated by each MS and 1 alternate • 1 scientific expert member from NO and IS and 1 alternate (observers)• 5 co-opted members as appointed by Management Board• 3 years Mandate renewable

Composition

            

Chairman (Dr. T. Salmonson; SE)

&

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

CHMP (Committee for Human Medicinal Products)

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

CHMP main tasks & responsibilities

Working Party Constellation

CHMP

QWP*

SWP*

BWP*Sci Adv

PhVig*

Patients & Consumers

Biosimilars tWPBiostatistics tWP

Blood Prod. tWP

Cardiovascular tWP

CNS tWP

RheumatologyImmunologytWP

Infectious Diseases tWP

Oncology tWPPharmacokinetics tWP

Pharmacogenomics tWP

Vaccines tWP

Gastroenterology DG

Respiratory DG

Urology DG

Radiopharmaceuticals DG

QSE standards Evaluation of Medicines

* 1 / MS representation

SAG diagnostics

SAG CVS

SAG Neurology

SAG Psychiatry

SAG Diabetes

SAG HIV / Antiviral

SAG Anti-Infectives

SAG Oncology

DG = drafting groupstWP = temporary working party

SAG Vaccines

                                                                                                                                 

CompositionCompositionChair and Vice Chair+ 1 member/MS+ 3 reps patient organizations+ 3 EMA reps

+ 3 patient organisations + 3 EMA

COMP (Committee for Orphan Medicinal Products)

Dr. Westermark

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Composition:Chair and Vice Chair+5 CHMP members +1 member/MS (not yet represented by member appointed by CHMP) + 3 reps patient organizations+ 3 reps healthcare professionals

+ 3 patient organisations+ 3 healthcare prof.

Dr. D. Brasseur

PDCO (Paediatric Committee)

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Registration in Europe Post Nov 2005 : Three European Systems

Centralised Procedure(via EMA)

Mutual Recognition procedure

Decentralised Procedure

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(27MSs) + 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 Optional for:

Any Other New Active Substance significant innovation (therapeutic, scientific or technical) in the interests of patients at community level Generic of Centralised reference prod. (may use CP or MRP/DCP)

Project management and co-ordination

Industry

•Rapporteur/Co-rapporteur•Scientific evaluation - experts•Opinion and assessment report•Working parties

EMACHMP

EUCommissionDriving & adoptionof the decision(EU license)

Members states1 per MS + 5 Co-opted members. Each MS has an Alternative.

Applicant MAH

Procedures for evaluating medicinal products and granting marketing authorization

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:

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Centralised procedure

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.

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MRP & DCP The mutual recognition procedure, which is applicable to the

majority of conventional medicinal products, is based on the 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.

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The 3 steps of the Centralised Procedure

Step IPre-submission to application• Early advice• Rapporteur/C-rapporteur appoinmt• Assessment team• Application• Validation

Step IIScientific evaluation• Assessment Reports• List of Questions (+ clock stop)• CHMP Opinion• Possibility to appeal• Transfer to EU Commission

Step IIIDecision Making Process

-120 days

210 days

67 days

Notify the EMARequest Rapporteur/co-Rapporteur

Submit the MAA

CHMP Opinion

Draft EC Decision

EC DecisionCommunity Licence

favourable

Answer to questionsOral hearing

Clock stop for answer to questions

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 Most significant difference with MRP = consultation

between MS‘s before 1st MA issued

&:

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 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

Application to Reference Member State (RMS)

RMS Approval (Day 210)

Submit MR application to Member States

National Submission210 days

MutualRecognition90 days

Closure of procedure(AR, SPC, labelling, PIL)

Arbitration by CHMP (Art.32, 33, 34) 60 days (CHMP opinion) + 30 days (Commission decision)

National licencesgranted within MSs

Approval

ArbitrationBy CMDh(60 days)

CMDh

National Step(30 days)

Serious objectionsReferral to CMDh

ApprovalSerious objectionsReferral to CHMP

Overview of the DCP

Submission of dossier to Reference Member State (RMS)and Concerned Member States (CMSs)

RMS starts evaluation, and issues preliminary Assessment Report (AR) for comments by CMSsRMS sends consolidated list of questions to Applicant

RMS prepares draft AR, draft SPC and draft labelling/package leafletSubmit MR application to Member States

Closure of procedure(AR, SPC, labelling, PIL)

Arbitration by CHMP (Art.32, 33, 34) 60 days (CHMP opinion) + 30 days (Commission decision)

National licencesgranted within MSs

Approval

DCP Step1120 days

DCP Step 290 days

ArbitrationBy CMDh(60 days)

CMDh

Clock stop

National Step(30 days)

Serious objectionsReferral to CMDh

ApprovalSerious objectionsReferral to CHMP

(recommended 3 mths)

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 Chair: June M. Raine (UK – MHRA) Vice-Chair: 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

N.B. 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 systemAssessment on MAA (Agencies-EMEA)[www.eudra.org/emea]

EDQM/Ph.Eur(Council of Europe)[www.pheur.org]

Volume 1: Pharmaceutical Legislation for MedicinalProducts for Human useVolume 2: Notice to Applicants for MP for Human use

2A Procedures for marketing Authorization2B Presentation and format of the dossier(CTD)

Volume 3: Guidelines3A Quality and Biotechnology3B Safety, environment and information3C Efficacy

Volume 4: Good Manufacturing PracticesVolume 5: Pharmaceutical Legislation for MedicinalProducts for Veterinary use

Volume 6: Notice to Applicants for MP for Veterinary use Volume 7: Scientific guidelines for MP for Veterinary use Volume 8: Maximum residue limitsVolume 9: Guidelines for PV for MP for Human and Veterinary useVolume 10: Guidelines for Clinical Trial

Laws, Directives, regulations (EU institutions)[http://pharmacos.eudra.org]

Relevant EU legislation/ Guidelines

Maintenance of Marketing Authorizations (Variations, Renewals)

EU Variations Commission Guideline on Dossier Requirements for Type IA & IB

Notifications, July 2006 Categories of Variations

Minor ChangesType IAIN variation and Type IA

Type IB variation (Notify, wait for 30 days )

Type II variation (Needs prior approval, 60 days evaluation time period)

Major Changes

Differences between the categories

• Approval time

• Documentation to be submitted

• Money(Fees)

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

A F R IC A N T R A D IT IO N A L M E D IC IN E S C O M M IT T E EC ha irpe rs on

V ice -C h a irpe rs on

C O M P L E M E N T A R Y M E D IC IN E S C O M M IT T E EC ha irpe rson

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V E T E R INA R Y C L IN ICA L C O M M IT T E EC ha irpe rs on

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A N A L Y T IC A L C O M M IT T E EC ha irpe rson

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B IO LO G IC A L C O M M IT T E EC ha irpe rs on

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C L IN IC A L C O M M IT T E EC ha irpe rson

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C L IN IC A L T R IA L S CO M M IT T E EC ha irpe rs on

V ice -C h a irpe rs on

P H A R M A C E U T IC A L / B IO A V A ILA B IL IT Y CO M M IT T E EC ha irpe rson

V ice -Ch a irpe rson

P H A R M A C O V IG ILA N C E C O M M IT T EC ha irpe rs on

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S C H E D U L IN G CO M M IT T E EC ha irpe rson

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M E D IC IN E S CO N T RO L C O U N C ILC ha irpe rson

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South Africa : MEDICINES CONTROL COUNCIL(MCC)

MHRA-UK, UK-MHRA: Medicines and Healthcare products Regulatory AgencyThe MHRA regulates a wide range of materials like; Medicines Devices Tissue Engineering Nanotechnology BloodThe 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, condoms and surgical dressings.

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 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 standards

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).

WHO: World Health Organization

Japanese Regulatory Environment

Japanese law and relevant authorities for medicines registration

Pharmaceutical Affairs Law (PAL) – April 2005 MHLW (Ministry of Health, Labour and Welfare)

– Responsibility for approvals and licensing– http://www.mhlw.go.jp/english/index.html

PMDA (Pharmaceuticals and Medical Devices Agency)– Responsibility for scientific review (incl. audit for GMP, GLP,

GCP)– Branch under MHLW, created in 2004– http://www.pmda.go.jp/english/index.html

NIID (National Institute of Infectious Diseases)– Responsibility for national testing– http://www.nih.go.jp/niid/index-e.html

Relationship between MHLW and PMDA

Applicant MHLW Advisory Committee

Consultation

AdviceApproval

Pharmaceuticals and Medical Devices Agency (PMDA)

Consultation and Review(Single Review Team) External Experts

Compliance Review etc

Questionsand Responses

Consultation and NDA

Review Report

Instruction

Expert Discussion

INTERNATIONALREGULATORY

ENVIRONMENT

Scope

192 countries 23 time zones

Between 4000 and 6000 languagesMore than 150 monetary currencies

More than 70% of the world’s population are:Asia Pacific and Emerging Markets (APEM )

International & Emerging Regions

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:

Russia

Key markets

Models for drug regulatory assessment

Countries can be categorised in 2 licensing models:

model of licensing system based upon submission of evidence of registration in reference countries

model of licensing system based upon a full assessment of new drug applications (including biological products)

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, Australasia (AUS, NZ), 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

Region ASEA – definition

ASEAN (Association of South East Asian Nations) Singapore, Malaysia, Thailand, Philippines, Indonesia, Laos, Cambodia,

Vietnam , Brunei Darussalam, Myanmar

ASEAN

Association of Southeast Asian Nations 10 member states : Indonesia, Malaysia, Philippines,

Singapore, Thailand, Brunei, Vietnam, Laos, Myanmar, Cambodia

Population of about 560 million, a total area of 4.5 million square kilometers, a combined GDP of US$ 1,100 billion, and a total trade of about US$ 1,400 billion

Objectives : To accelerate economic growth, social progress and cultural development in the region and to promote regional peace and stability

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)

* Upon RequestPart IAdministrative Data & Product Information

Part II Quality

Overall Summary& Reports

Part IIINon-clinical

Overview, Summary

& Study Reports*

Part IV Clinical

Overview, 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+

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

RUSSIA AND FSU COUNTRIES

Region RIC+

FRENCH-SPEAKING AFRICAAlgeria, 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 CountriesArmenia Israel Syria

Azerbaijan Jordan Turkey

Bahrain Kuwait Turkmenistan

Egypt Lebanon United Arab Emirates

Georgia Oman Yemen

Iran Qatar

Iraq Saudi Arabia

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.)

Background:

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REGULATORY SUBMISSIONS

IN INDIA

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

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INDIAN REGULATORY ENIVORNMENT

Regulatory Bodies Governing & Controlling Clinical Trials

Regulatory Body

Ministry Location

Drugs Controller General (India) (DCGI), Directorate General of Health Services (DGHS)

Ministry of Health and Family Welfare

Central Body (Delhi)

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.

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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 increaseinternational harmonization of technicalrequirements to ensure that safe, effective,and high quality medicines are developedand registered in the most efficient and cost

effective manner.

ICH GuidelinesThe ICH Topics are divided into four major categories and ICH Topic Codes are assigned according to these categories.

Q S E M"Quality" Topics, i.e., those relating to chemical and pharmaceutical Quality Assurance (Stability Testing, Impurity Testing, etc.)

"Safety" Topics, i.e., those relating to in vitro and in vivo pre-clinical studies (Carcinogenicity Testing, Genotoxicity Testing, etc.)

"Efficacy" Topics, i.e., those relating to clinical studies in human subject (Dose Response Studies, Good Clinical Practices, etc.)

"Multidisciplinary" Topics, i.e., cross-cutting Topics which do not fit uniquely into one of the above categories (MedDRA, ESTRI, M3, CTD, M5)

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

"Quality" Topics

Efficacy TopicsE1: The Extent of Population Exposure to Assess Clinical Safety for Drugs Intended for Long-

Term Treatment of Non-Life-Threatening ConditionsE2A: Clinical Safety Data Management : Definitions and Standards for Expedited

ReportingE3: Structure and Content of Clinical Study ReportsE3: Structure and Content of Clinical Study ReportsE4: Dose-Response Information to Support Drug RegistrationE5(R1): Ethnic Factors in the Acceptability of Foreign Clinical Data E6: Good Clinical Practice : Consolidated GuidelineE7: Studies in Support of Special Populations : Geriatrics E8: General Considerations for Clinical TrialsE9: Statistical Principles for Clinical TrialsE10: Choice of Control Group and Related Issues in Clinical TrialsE11: Clinical Investigation of Medicinal Products in the Pediatric PopulationE12: 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 MedDRAMedical Terminology  M2 ESTRIElectronic Standards for the Transfer of Regulatory Information  M3M3(R2)Nonclinical Safety Studies for the Conduct of Human Clinical Trials

and Marketing Authorization for Pharmaceuticals

M4CTDThe Common Technical Document  M5M5Data 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

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

Various links

Thanks for your Attention!