Building Regulatory Capacity Indian Experience

BuildingRegulatory Capacity Indian Experience

Debasish PandaJoint Secretary

MINISTRY OF HEALTH, GOVT. OF INDIA.E-mail: [email protected] / www. cdsco.nic.in

mailto:[email protected]

Strong Pipeline

Good Quality

First on Market

International Sales Network

Low cost supply

Best People

Develop Products for

Markets

Strong External Growth

KEY EMPHASIS

SUCCESS

INDIAWorld’s largest democracy

Population: > 10,00,00,00,00

Area: 3,287,263 sq. km.Age distribution:

<14 yrs=33% 15-64 yrs=60% >65%=7%

China

US

India

JapanGermany

India

BrazilChinaRussia

India is an emerging economic superpower…

India would become the third largest economy after USA and China by 2050.

India's GDP will reach •$ 1 trillion by 2011•$ 2 trillion by 2020

•$ 3 trillion by 2025


•$ 10 trillion by 2038, and


In terms of GDP, India will overtake

• Italy by the year 2016•France by 2019

•UK by 2022

•Germany by 2023, and

•Japan by 2032

Among the BRIC group India alone has the potential to show the highest growth (over 5 percent) over the next 50 years.

China Overtakes the G3; India is Close Behind

India Shows Most Rapid Growth Potential of the BRICS

The Largest Economies in 2050

Changing Scenario in the Drug Sector

1947 1970 1990 2000 2006No. of Units

100 2000 6000 9000 10000

Volume of BusinessLocal $ 2.5 million $ 200

million$ 3 billion $ 5 billion $ 9billion

Export Nil $ 0. 5 billion

$ 1. 5 billion $ 3 billion $ 6 billion

Types / Categories of products

Tablets, Liquids Capsules Powders & Tinctures

APIsVaccines

MDIs, Injectables, LVP with FFS Technology

Biotech Products, Prefilled Syringes, NDDS

Biotech Products, Prefilled Syringes, NDDS, Medical Devices

Indian Pharmaceutical IndustryIndian Pharmaceutical Industry

Global ranking in volume terms 4th , Value terms 13th

Amongst top 3 worldwide API production centersProducts sold to over 100 countries World Class quality products

The size of Indian Pharmaceutical industry is about $15billion.

Indian Pharmaceutical IndustryIndian Pharmaceutical Industry

The domestic market is about $9billionExport of generics accounts for 40% of the Pharma sector revenuesMost competitive prices in the world ~ 8-10% of international pricesLargest number of USFDA approved site out side USALarge number of Drug Master File (DMF) filed by Indian pharmaceutical company to USFDA and got approval

Indian Pharmaceutical Industry: Indian Pharmaceutical Industry: EXPORTSEXPORTS

$6 bn

$0.01bn

$2.94bn$2.9bn

$3.53bn

$4.25bn

0

5000

10000

15000

20000

25000

30000

1980-81

1990-91

2000-01

2001-02

2002-03

2003-04

2004-05

2006-07

1980-811990-912000-012001-022002-032003-042004-052006-07

$2.10bn

$0.19bn$0.5bn

$1bn

$1.5bn

$2bn

$2.5bn

$3bn

$3.5bn

$4bn

$4.5bn

Current Growth Rate

Local Market 8-10%

Exports 10-15%

Clinical Research 30%

Impact on Globalization

Requirements due to GlobalizationGMPDMF ConceptNational Pharmacovigilance ProgrammeIndependent agency for standardsEffective market surveillanceConsumer Information (Package Insert)Registration of Foreign Site/Mutual RecognitionParticipation in Global Harmonization

DRUGS CONTROLLER (INDIA)

HEAD QUARTER SUB ZONALOFFICE (3)

ZONALOFFICE (4)

LABORATORY(6)

PORT OFFICE(7)

•New Drugs•CLLA•Imports•DTAB•I.P.•Parliament•Misc.

•GMP Audits•Coordinations with States

•GMP Audits•Coordinations with States

•Import•Export •Testing of drug

Samples•Validation of Test protocol

DRUGS CONTROLLER/ COMMISSIONER

DEPUTY DRUGS CONTROLLER

DRUGS TESTING LABORATOTY

DRUGS INSPECTOR

SUPPORTING STAFF

STATE DRUGS CONTROL ORGANISATIONSTATE DRUGS CONTROL ORGANISATION

GOVT. ANALYST

ANALYST

SUPPORTING STAFF

Drugs Inspectors About 1040Drugs Manufacturers : “ 9000Loan Licensees ” 2000cosmetics Manufacturers “: 2200Sales Premises “: 3,50,000

Strengthening of Drug Regulatory System

Capacity building of regulatory personnelAugmentation of manpower and infrastructure Legislative amendments

Penal ProvisionsCDA Bill

• Capacity building of regulatory personnel– Training under capacity building project at

National Institute of Pharmaceutical and Educational Research (NIPER) during Jan 2004 to June 2008.

– More than 500 Drugs Inspectors have been trained on GMP and other different aspects of Drug Regulations.

– More than 450 analysts from Govt. Testing laboratories have been trained on GLP and other aspects of Drug regulations.



• Augmentation of manpower and infrastructure– 68 new posts of Drugs Inspectors and 10 Posts of technical

officers have been created and steps are being taken to fill-up all these posts.

– New FDA building has been commissioned and started functioning.

– Process of bringing all the State and Zonal offices under a common server has been initiated.

– Five existing Drug Testing Laboratories under Central Govt. have been upgraded and created a new one.

– Modern equipment and financial assistance were provided to all 22 existing State Drug testing laboratories.


• Legislative amendments

– A bill has been introduced in the Parliament to amend Penal Provision (minimum 10 years which may extended to life imprisonment with fine of one million rupees for manufacture, sale and distribution of Spurious Drugs)

– A bill has been introduced in the Parliament to amend the Act for creation of “Central Drug Authority”

MINISTRY OF HEALTH, GOVT.OF INDIA

Central Drugs Authority

Chairman

Members (3-5)

Drugs Controller General (INDIA)

PROPOSED STRUCTURE OF CDA

Main divisions of CDA – 10Regulatory Affairs & EnforcementNew Drugs & Clinical TrialsBiological & Biotechnology ProductsDivision for PharmacovigilanceDivision for Medical Devises and Diagnostics

Contd..

Division for Imports Division for Organizational services Division for Training & Empowerment Division for Quality Control AffairsDivision for Legal & Consumer Affairs

Indian Pharmacopoeia Commission (IPC)

• IPC has been registered as a Society on 9th Dec. 2004.• It is an autonomous Institution under the Ministry of

Health and Family Welfare, Govt. of India.• Dedicated for setting of Standards for Drugs,

Pharmaceuticals and Health Care Devices/Technologies etc.

• To publish Indian Pharmacopoeia which is an official and legal book of Standards for Drugs (IP 2007 has been published in Dec 2007).

• Providing reference substances and training.

• Objective– To develop comprehensive monographs for Drugs to be

included in the Indian Pharmacopoeia (IP).– To develop monographs for Herbal Drugs, both raw

drugs and extracts/formulations therefrom.– To give special attention to detect impurity profile of

the raw materials.– Framing the monographs considering the level of

sophistication in analytical testing.



• Objective contd……– Distribution of IP Reference Standards including

Related Substances (RS), Impurities and degradation products.

– To collaborate with other International Pharmacopoeias to Harmonize with Global Standards (a MOU has been signed between IP Commission and USP Convention on 1st Aug. 2006).

– To review existing monographs periodically for up gradation/revision.


• Scientific Wing– Research and Development– Pharmaceutical Chemistry – Pharmacology– Microbiology – Pharmacognosy– Medical Devices– Library, Information and Publications– Sample Warden– Reference Standard.

Medical DevicesThe current Indian medical device market is estimated to be worth around 3 billion USD and out of these $2.5 billion worth devices are being imported. Presently regulated as Drugs (which are notified by Government of India)Step to form separate regulations as per international normsDevelopment on the basis of Global Harmonization Task Force ( GHTF)Guidelines being formulated with active participation of all stakeholdersCore groups formed for recommendations

Biotech ProductsAll Biotech Products considered as New DrugsRequire permission from DCG(I) Approval of Genetic Engineering Approval

Committee (GEAC)Approval of Review Committee on Genetic

Manipulation (RCGM) under DBT

Stem Cell ResearchRegulated on the basis of guidelines for Stem Cell

Research and Therapy issued by ICMRNational Apex Committee for Stem Cell Research

and Therapy (NAC-SCRT)Institutional Committee for Stem Cell Research

and Therapy (IC-SCRT)Health Minister’s Screening Committee ( HMSC)Institutional Ethics Committee( IEC)Institutional Animal Ethics Committee (IAEC)

Stem Cell Research

Two centers recognized by Federal Government for stem cell researchNational Centre for Biological Sciences, BangaloreReliance Life Science Laboratories, Mumbai

E-governance

• IT enabled services• E-Filing of All Applications • Resource Center• Legal Affairs and Consumer Cell

National Pharmacovigilance Programme

N N N N N S S S S SS E E E E E W W W W W

CDS OC

S S S S S W W W WEEEEENNNNN

NPAC = National Pharmacovigilance Advisory Committee(CDSCO), ZRP = Zonal Pharmacovigilance Centre (Delhi & Mumbai), RPC = Regional Pharmacovigilance Center

(Delhi,Kolkata,Mumbai,Nagpur & Pandicherry)PPC = Peripheral Pharmacovigilance Centre (26)

N N N N N S S S S SS E E E E E W W W W W

CDS OC

S S S S S W W W WEEEEENNNNN

Aims and Objectives of National Pharmacovigilance

Programme

To generate broad based ADR data on the Indian population and share the information with global health-care community through WHO.

To ensure optimum safety of drug products in the Indian market .

To provide technical expertise for evaluating statutory AE reports furnished by sponsors conducting clinical trials in India.

Responsibilities of National Pharmacovigilance Advisory

CommitteeExamine the ADR data generated by centersRisk-benefit analysis of drugs marketed in the countryAdvise Government regarding safe use of drugsMonitor functioning of National Pharmacovigilance Programme and give inputs for the better functioning of the programme from time to time.

INTERNATIONAL COLLOBORATION

WHOHealth CanadaMOU with Brazil/South AfricaTechnical Corporation with USFDA(Clinical Trail, Pharmacovigilance programme,

Medical Devices , IT-Enabled Services etc.)


WHO /Health Canada• A team of WHO (HQ) and Health Canada visited India to

develop the road map for strengthening the Indian NRA in two phases.

• Ist Phase To recognize the biological Department, Develop appropriate documentation against a Quality Assurance SystemDeliver the Ist training programme.

• IInd Phase To establish two expert committees to provide technical expertise in the area of Vaccine Licensing and oversight registration of Clinical trials.To develop a continuous education programme.


• Road map of the activities– Phase –I

• April 08 : formal agreement between WHO/Health Canada and Indian Govt. to implement the Institutional development plan.

• May 08: Development of the training module for the in Country licencing course.

• May/June 08 : reorganization of the Vaccine cell• July 08 : Training course on licensing to be

delivered by Health Canada and WHO at Ottawa and Geneva.


• Road map of the activities– Phase –II

• Aug 08: Further Training of CDSCO personnel in India.

• Sept./Oct. 08: observed review applying the revised licenced process.

• Nov. 08: Advance training on Regulatory Inspections.

• Dec 08 : tentative date for WHO formal reassessment

Global Pharmaceutical

Industry!

Global Destination To

India

Outsourcing Opportunities

Outsourcing Opportunities -

India

Bulk Drugs&

FormulationsManufacturing

BioinformaticsBiostatistics

SoftwareDevelopment

ContractMarketing &

Sales

International Clinical Trials

Technical Services

HerbalsNeutraceuticals

ContractR&D

TurnkeyProjects

Plant Machinery

&Pharma

Equipment

PrimaryPackaging Materials

Drivers of Growth

India — Gradually Building a Track Record

Advantage India!

Driving forces behind expansion of the industry

Driving ForceAdvantages in cost structure

Process -environment equation

Development of NCEs/ preliminary testing

Growing demand for multi-source products in emerging economies

Price pressure in generic segment

Companies moving up the value chain

Source

Affiliates of MNCs

Established companies with R&D infrastructure

Companies with:

- Technological competence

- Export/international

orientation

- Strong process skills

Advantage India

- Established Strengths in Process Chemistry– Rich Pool of Scientists– Diverse genetic pool such as Caucasians, Mongoloids

and Australians– Networking Ease– Clinical Trial Research - Superior Benefits

- Huge Patient Data- Diversity of Diseases- High quality hospitals- Competent Medical Professionals- Timely regulatory approvals- Low cost services- Increasing Acceptance of IPR

India - Opportunities1. Skilled Manpower : Availability of a talented pool of

English speaking doctors, basic research scientists & life science personnel.

2. Patient Enrolment : India constitute 1/6th of the entire

globe and patient enrolment can be really fast thereby expediting the

new drug development process. Most of the patients are treatment

naive as well.

3. Wide Spectrum of Disease: Presence of tropical and sub-tropical diseases increases the scope of research across various therapeutic areas in India.

India – Opportunities…

4. Economy: The cost of Manufacturing, Research & conducting clinical trials in India is low.

5. Economic Environment: Indian economic environment is quite favorable for foreign direct investment andGovt. of India allows 100% subsidiary of a foreign company .

6. Data Quality: Over the years Indian investigators have participated in several US & European registration trials and the acceptance of data by the respective regulatory agency speaks about the quality of data generated by Indian investigators

India’s Clinical Trials Market

Source: CenterWatch, 2003; Company reports and interviews

• 2002 Industry Spending on CR Services and Investigator Grants $100 to $150 Million

• Estimated Number of Active ICH-GCP Clinical Studies Conducted in 2002 40 to 50

• Estimated Number of Active GCP Trained Principal Investigators in 2002 200 to 250

• 2010 Projected Industry Spending onCR Services and Investigator Grants ~ $ 2 Billion

Applicable GCP Guidelines in India

• ICH GCP Guidelines, 1997• Ethical Guidelines for

Biomedical Research on Human Subjects,2006 (ICMR Code)

• Indian GCP guidelines (2001)in line with the latest WHO, ICH, FDA, and MHRAguidelines

• Revision of Schedule Y(2005)

Emerging Scenario (Clinical Research & Industry)

Vigilant Ethics Vigilant Ethics CommitteesCommittees

Ongoing reviews

AE AE ReportingReporting

GCPGCP QCQC

Regulatory Regulatory InspectionsInspections

Trained Trained InvestigatorsInvestigators

Credible DataCredible Data

Safe Pharmaco-

therapeutics

EVOLUTION OF GCPs

Medicine

Science

Industry

Human RightsGCPs

Reason(s) why India is the choice for CT

Regulatory body Approval Average Time

Drugs Controller General of India (DCGI)

•For Global clinical study•For Investigational New Drugs (IND)

•For New Drug Approval

4 to 6 weeks12 weeks

6 to 8 weeks


Test license to import drugs for test and analysis

3 to 4 weeks


NOC for export of New Drugs

3– 4 weeks


Registration of foreign Mfg. Site and its products.

25 weeks

State Licensing Authority Grant of Mfg. License 12 to 25 weeks

- Typical Timelines for Regulatory Approvals -

Regulatory Approval

Recent India Regulatory Reform makes Approvals Possible within 6 weeks.

What India can offer to World market

Synthesis of Huge Quantities of APIs

for Clinical Trial Programs

Clinical Trials for a Large Number of

New Drugs

Software Solutions and Analysis of

Clinical Data

Toxicology & Pharmacology Studies

What India can offer to World market

Contract manufacturing for Global Supply of APIs

Quality Generic Products

Process Technologies

Pharmaceutical Manufacturing Equipment

Alternate Medicines - Ayurvedic & Herbal

MNC-India Partnership

MNCs who left earlier are back on

Indian shores.

World generic companies like

TEVA, Apotex, Hexal Pharma,

Altana Pharma have also set up

bases in India specially for

carrying out R&D in Pharma.

Government Policy Initiatives

Investment related

Technology related

Trade related

To summarize….

India has a great advantage to become a dominant player in the global pharmaceutical industry.

Compelling fundamentals will drive the growth of the clinical development sector in India

Potential for innovation & sector transformation

Documents

Building Regulatory Capacity Indian Experience