Regulations Guidelines &

Ethics in Clinical Research

Dr. Harisha.SICBio Clinical Research Pvt. Ltd

An Overview of

“A Clinical Trial (Clinical Research) is

controlled by the Regulations (laws) and is Conducted based on the prescribed Guidelines and ethical considerations”.

Anonymous

Regulations : The act of controlling, managing or directing according to the rules

led by the laws Governed by the Regulatory bodies

Guidelines: The written instructions to be followed for the credible and

standardized act Prescribed by different Organizations

Ethics: “Whatever our society accepts; after all we are human beings"

The Worldwide RegulationsUSA : United States Food and Drug Administration (USFDA) India : Central Drug Standard Control Organization (CDSCO)Canada : Health Canada - Santé CanadaAustralia : Therapeutic Goods Administration (TGA)UK : Medicine and Healthcare Products Regulatory Agency (MHRA)Europe : European Medicines Agency (EMEA)Switzerland : SwissmedicJapan : Ministry of Health, Labour and Welfare (MHLW)

International and Indian Guidelines International Guidelines:• ICH GCP (International Conference on Harmonization Good

Clinical Practice)• CIOMS (Council for International Organizations of Medical

Sciences) Guidelines (Jointly by WHO and UNESCO)

Indian Guidelines:• Indian GCP• ICMR (Indian Council of Medical Research) Guidelines for

Biomedical Research on Human Subjects

Ethics in Clinical ResearchEthics:

• Refers to moral principles governing human character and conduct

• Covers the analysis and employment of concepts such as right and wrong, good and evil, responsibility and values and customs of a person or group

• Look after by Ethics Committee

Institutional Review Board (IRB) Independent Ethics Committee (IEC)

The Indian Regulation

Central Drug Standard Control Organization

• The Central Governing Body responsible for approval of New Drugs Clinical Trials in the country laying down the standards for Drugs control over the quality of imported Drugs

• Functions under the Directorate General of Health Services,Ministry of Health and Family Welfare, India

• CDSCO office is located at Nirman Bhawan, New Delhi 110011 • Head of the CDSCO: Drug Controller General of India (DCGI)

(Current DCGI : Dr. G N Singh)

• Has four Zonal Offices (Mumbai, Kolkata, Chennai, and Ghaziabad) Central Drugs Laboratories (CDL) Kolkata, Central Drugs Testing Laboratories (CDTL) (Chennai, Mumbai and Guwahati) and Central Indian Pharmacopoeia Laboratory (CIPL), Ghaziabad. 

Schedule Y

• Law for permission to import and / or manufacture of new drugs for sale or to undertake clinical trials

• The Schedule Y laws have rooted out from the Drugs and Cosmetics Act of 1940 and are based on Rules 122A, 122B, 122D, 122DA, 122DAA and 122E of Drugs and Cosmetics Act,1940

• Schedule Y has 12 appendices starting with roman letters I to XII

• Form44 : Application form to be submitted to the DCGI office for the grant of permission to import or manufacture a new drug or to undertake clinical trial.

Contd..

Schedule Y APPENDIX I:

DATA TO BE SUBMITTED ALONG WITH THE APPLICATION TO CONDUCT CLINICAL TRIALS / IMPORT / MANUFACTURE OF NEW DRUGS FOR MARKETING IN THE COUNTRY.

APPENDIX I-A: DATA REQUIRED TO BE SUBMITTED BY AN APPLICANT FOR GRANT OF PERMISSION TO IMPORT AND / OR MANUFACTURE A NEW DRUG ALREADY APPROVED IN THE COUNTRY.

APPENDIX II: STRUCTURE, CONTENTS AND FORMAT FOR CLINICAL STUDY REPORTS

Contd..

APPENDIX III: ANIMAL TOXICOLOGY (NON-CLINICAL TOXICITY STUDIES)

APPENDIX IV: ANIMAL PHARMACOLOGY

Appendix V: INFORMED CONSENT

Contd..

APPENDIX VI: FIXED DOSE COMBINATIONS (FDCs)

APPENDIX VII: UNDERTAKING BY THE INVESTIGATOR

APPENDIX VIII:ETHICS COMMITTEE

APPENDIX IX: STABILITY TESTING OF NEW DRUGS

APPENDIX X:CONTENTS OF THE PROPOSED PROTOCOL FOR CONDUCTING CLINICAL TRIALS

APPENDIX XI:DATA ELEMENTS FOR REPORTING SERIOUS ADVERSE EVENTS OCCURING IN A CLINICAL TRIAL

The International RegulationFood and Drug Administration (FDA)

An agency of the United States Department of Health and Human Services (DHHS / HHS)

Responsible for regulating: Food Dietary supplements Drugs Biological medical products Blood products medical devices Radiation-emitting devices Veterinary products Cosmetics

Central Evaluation Laboratories under FDA

The Center for Drug Evaluation and Research (CDER) The Center for Biologics Evaluation and Research (CBER)

FDA Laws:

Code of Federal Regulations (CFR) Rooted out from Food, Drug and Cosmetic Act, chapter 1, Title

21(So called 21 CFR) 21 CFR is divided into total 1499 parts starting from 1.

Some important regulations of FDA required for conduction of Clinical Trial and Drug Approval Process are:

21 CFR Part-11: ELECTRONIC RECORDS; ELECTRONIC SIGNATURE

21 CFR Part-50: PROTECTION OF HUMAN SUBJECTS 21 CFR Part-54: FINANCIAL DISCLOSURE BY CLINICAL

INVESTIGATORS 21 CFR Part-56: INSTITUTIONAL REVIEW BOARDS 21 CFR Part-312: INVESTIGATIONAL NEW DRUG

APPLICATION 21 CFR Part-314: APPLICATIONS FOR FDA APPROVAL TO

MARKET A NEW DRUG

The Indian GuidelineIndian GCP Good Clinical Practice (GCP) is a set of ethical and scientific

quality standard guidelines for biomedical studies which encompasses the design, conduct, termination, audit, analysis, reporting and documentation of the studies involving human subjects

Establishes two cardinal principles: protection of the rights of human subjects authenticity of biomedical data generated

Formulated by Expert Expert Committee set up by Central Drugs Standard Control Organisation (CDSCO)

Endorsement is done by The Drug Technical Advisory Board (DTAB)

(Dr. S.P. Agarwal Director General of Health Services and Chairman, DTAB)

Indian GCP is divided into seven headings:

1. Definitions2. Pre-requisites for the study3. Responsibilities4. Record Keeping and Data Handling5. Quality Assurance6. Special Concerns7. Statistics