Overview of Regulatory Overview of Regulatory Environment in USA, Europe & Environment in USA, Europe &

India India

Dijo Mathew JohnDijo Mathew JohnPharm.D Post BaccalaureatePharm.D Post Baccalaureate

Need For Therapeutic Good Need For Therapeutic Good RegulationRegulation

Protect health and safety of population.

By ensuring the safety, quality and efficacy of therapeutic

goods covered under the scope of regulation.

Clinical Research Regulation in Clinical Research Regulation in USAUSA

Food & Drug Food & Drug AdministrationAdministration

The US FDA is a scientific, regulatory and public health agency under the United States Department of Health and Human Services.

It is led by the Commissioner of Food and Drugs, appointed by the President with the advice and consent of the Senate.

Comprised of several offices and centers.

Primary Responsibility of FDAPrimary Responsibility of FDA

For protecting and promoting public health through the

regulation and supervision of food safety, tobacco

products, dietary supplements, prescription and over-the-

counter pharmaceutical drugs (medications), vaccines,

biopharmaceuticals, blood transfusions, medical devices,

electromagnetic radiation emitting devices (ERED),

veterinary products and cosmetics.

Agency scientists evaluate applications for new human drugs and biologics, complex medical devices, food and color additives, infant formulas and animal drugs.

The FDA monitors the manufacture, import, transport, storage and sale of about $1 trillion worth of products annually.

Centre for Drug Evaluation and Centre for Drug Evaluation and Research Research (CDER)(CDER)

CDER is one of the centers of US FDA that

Reviews NDAs and ANDAs for their safety and efficacy

manages US cGMP regulations for pharmaceutical

manufacturing

Review advertising and promotion of drugs

collects and analyses safety data about pharmaceuticals that

are already on the market.

Selected regulations and guidance for drug studies

Code of Federal Regulations (CFR)

CFR Title 21: clinical trials related regulations. (revised frequently and published yearly): Part 11: Electronic records Part 50: Protection of human subjects Part 54: Financial disclosure by clinical investigators Part 56: Institutional Review Boards Part 312: Investigational new drug application Part 314: Applications for FDA approval to market a new drug

New Drug Approval Process at FDA

1. Sponsor/FDA Meetings (Pre-IND)2. Submission of IND to FDA3. Sponsor/FDA Meetings (End of Phase 2)4. Accelerated Drug Review 5. Parallel Track6. Clinical Hold Decision7. Notification to Sponsor (i.e for deficiencies)8. Sponsor/FDA Meetings (Pre-NDA)9. New Drug Application10. Final Meetings with Sponsor11. Permission for marketing12. Post marketing review

Clinical Research Regulation in Europe – Clinical Research Regulation in Europe – The European Agency for the Evaluation of The European Agency for the Evaluation of Medicinal Products (EMEA)Medicinal Products (EMEA)

Decentralized scientific body of the European Union

Protection and promotion of public and animal health through the evaluation and supervision of medicines for human and veterinary use.

Scientific opinions of the agency are prepared by 3 committees: CPMP: medicines for human use CVMP: veterinary medicines COMP: designation of orphan medicines for rare diseases

Clinical Research Regulation in UK – Clinical Research Regulation in UK – Medicines & Healthcare products Regulatory Medicines & Healthcare products Regulatory Agency (MHRA)Agency (MHRA)

MHRA – competent authority of authority for the medical

devices and the Licensing Authority for pharmaceuticals

advised by Committee on Safety of Medicines (CSM)

Key Activities of MHRA

Regulating medical devices.

Licensing of medicines before marketing and subsequent

variations.

Regulation of clinical trials.

Operating adverse incident reporting system for medical devices.

Issuing safety warning.

Responsibility for reporting, assessment and communications of

defective medicines.

Monitoring of medicines and acting on safety concerns after

marketing.

Evaluating medical devices to inform purchasing and encourage safe

use.

Managing the General Practice Research Database (GPRD).

Setting quality standards for drug substances through the ‘British

Pharmacopoeia’.

Providing advice and guidance on medicines and medical devices.

Drug Regulatory System in Drug Regulatory System in IndiaIndia

Health is in concurrent list of Indian Constitution

It is governed by both central and state governments

Clinical Research Regulation in India – Clinical Research Regulation in India – Drug Controller General of India (DCGI) Drug Controller General of India (DCGI)

Legislation is enforced by Central Govt (Dept of Chemicals

and Fertilizers, Ministry of Chemicals and Petrochemicals).

Drug Controller General of India (DCGI) under Central drug

Standard Control Organization (CDSCO) has prime

responsibility for regulating Clinical trials in India.

DCGI: matters related to product approval and standards,

clinical trials, introduction of new drugs and import licenses

for new drugs.

Approvals for setting up manufacturing facilities, obtaining

licenses to sell and stock drugs are provided by the State

Governments.

2 drug organizations to exercise control over drugs:

Central Drug Standard Control Organization (CDSCO)

State Drug Control Organizations

Central Drug Standard Control Central Drug Standard Control Organization (Organization (CDSCOCDSCO)) Controlling the quality of imported drugs. Co-ordinating the activities of the States and advising them on

matters relating to the uniform administration of the Act in the country.

Laying down Rules and ancillary provisions of Drugs Control and standards of drugs.

Controlling the quality of drugs moving in inter-state commerce jointly with Drug Control Organizations.

Granting approval to ‘New Drugs’ proposed to be imported or manufactured in the country.

Controlling the quality of drugs which are exported. Arranging meetings of 2 statutory bodies, DTAB and DCC .

Drugs Technical Advisory Board (DTAB): Technical experts and advises the Central and State Governments on all technical matters arising out of the enforcement of drug control.

Drug Consultative Committee (DCC): To ensure that the Drug Control measures are enforced uniformly in all States.

Genetic Engineering Approval Committee (GEAC): authority to approve rDNA pharmaceutical products.

Assess the bio-safety/environmental product.

Clinical Trials Guidelines in IndiaClinical Trials Guidelines in India

The guidelines that govern the conduct of Clinical trials in India include:• Schedule Y of Drugs and Cosmetics Act, 1940.• Ethical Guidelines for Biomedical Research on

Human Subjects, 2000.• Good Clinical Practices, 2001.

Schedule Y of Drugs and Cosmetics Schedule Y of Drugs and Cosmetics Act, 1940Act, 1940

Requirement and guidelines on clinical trials for import and manufacture of new drug in India.

Recommendations for carrying out Clinical Trials in India:• The clinical trials required to be carried out in the country

before a new drug is approved for marketing depend on the status of the drug in other countries.

• Phase III trials are usually required for the drugs which are already approved/marketed in the country of origin.

If the drug is not approved/marketed, trials are generally allowed to be initiated at one phase earlier to the phases of trials in other countries.

For new drug substances (IND) discovered in other countries phase I trials are not usually allowed to be initiated in India, unless phase I data from other countries are available.

If the drug is of unmet therapeutic need, such trials may be permitted even in the absence of phase I data from other countries.

For new drugs having potential for use in children, permission for clinical trials in the pediatric age group is normally given after phase III trials in adults are completed.

However, if the drug is of value primarily in a disease of children, early trials in the pediatric age group may be allowed.

CDSCO

Application Requirements

Application for permission to conduct clinical trials is made to the office of DCGI in Form 44.

Permission to import drug may be obtained by applying in Form 12 for a test license.

Permission to carry out clinical trials with a new drug is issued in Form 11 along with a test license

Data requirements under Data requirements under schedule Yschedule Y

Thank you…