Good Clinical Practices

Dr. Fardan QadeerJR I, Department of Pharmacology

Moderator: Dr. Ali AhmadHead Dept. of Pharmacology

Basic Research Disease Recovery Drug Recovery Preclinical

Development Clinical Trials Manufacturing

Not regulated

GLP

GCPGMP

Drug discovery and development

PRE CLINICAL TRIAL CLINICAL TRIAL

HUMANS

Adverse Effect

Ethical issues

Drug Toxicity

Phase I

• Checking for safety

• 10-20 healthy volunteers

• Unexpected side effects may occurs

Phase II

• Checking for efficacy

• ~ 200 samples

• How good is the intervention

• If not good, normally detect here

Phase III

• Checking effectiveness

• ~ 1000s samples

• Looking for rare side effect

Phase IV

• Test long term safety

• Real patients• Involve

untested group of people

Good Clinical Practices (GCP) is an international ethical &

scientific quality standard for designing, conducting,

recording & reporting trials that involve the participation of

human subjects.

It ensures theRIGHTSSAFETY

WELL BEING

Clinical Trials or Studies

Designing

Conducting

Monitoring

Recording

Analysis

Reporting

HISTORICAL BACKGROUND

Nuremberg Code, 1946Kefauver Amendments, 1962 – ThalidomideDeclaration of Helsinki, 1964National Research Act, 1974 - Tuskegee Syphilis Study (1932-1972)

Belmont Report, 1979

Nuremberg Code:1946

German Physicians conducted medical experiments on prisoners of war without their consent in during the time of Nazi rule.

Most of the participants of these experiments died or were permanently crippled.

• In December 9, 1946 - American military tribunal opened criminal proceedings against 23 leading German physicians and administrators for crimes against humanity – 16 of them were found guilty• The Nuremberg Code was established in

1948, stating that "The voluntary consent of the human participant is absolutely essential," • It did not carry the force of law, but the

Nuremberg Code was the first international document which advocated voluntary participation and informed consent.

Kefauver Amendments-1960• Thalidomide was as a sedative

during pregnancy in Europe but was not approved by US FDA• This lead to deformities in foetus • 1962 US Senate hearings Kefauver

Amendments passed into law - For the first time, drug manufacturers were required to prove to the FDA the effectiveness of their products before marketing them

Declaration of Helsinki-1964 • World Medical Association - recommendations guiding medical doctors in

biomedical research involving human participants1. Research with humans should be based on the results from laboratory and

animal experimentation2. Research protocols should be reviewed by an independent committee prior

to initiation3. Informed consent from research participants is necessary4. Research should be conducted by medically/scientifically qualified

individuals5. Risks should not exceed benefits

• Revised - 1975, 1983, 1989, 1996, 2000, 2002, 2004, 2008

Tuskegee Syphilis Study- 1932 to 1972

• The US Public Health Services conducted a Syphilis Study on 600 low income African-American individuals • During this study many people died of syphilis• Stopped in 1973 by the U.S. Department of Health,

Education, and Welfare• 1974 National Research Act passed - National Commission

for the Protection of Human Subjects of Biomedical and Behavioural Research established• The commission produce Belmont Report (1979)

Belmont Report-1979 National Commission for the Protection of Human Subjects of Biomedical and Behavioural Research

Key points:• To make sure the study is approved by an IRB•Get informed consent from the patient• Be sure that the patient understands the full extent to the experiment, and if not contact the study coordinator•Make sure the patient wasn't coerced into doing the experiment by means of threatening or bullying• Be careful of other effects of the clinical trial that was not mentioned, and report it to the proper study coordinator• Support the privacy of the patients identity, their motivation to join or refuse the experiment.• Ensure all patients get at the least, minimal care needed

ICH• The International Conference on Harmonisation of Technical

Requirements for Registration of Pharmaceuticals for Human Use (ICH) is a joint initiative the experts in pharmaceutical industry of Europe, Japan and the United States to discuss scientific and technical aspects of pharmaceutical product registration.

• 1980s-The European Union began harmonising regulatory requirements.

• 1989- Europe, Japan, and the United States began creating plans for harmonisation;

• 1990-ICH was created in April 1990 at a meeting in Brussels

Harmonisation would lead to a more economical use of human, animal and material resources, and the elimination of unnecessary delay in the global development and availability of new medicines while maintaining safeguards on quality, safety, and efficacy, and regulatory obligations to protect public health.

Co s

pons

ors

Observers

Non voting member

coordinates its technical input to ICH through its Scientific and Regulatory Section

Steering Committee

Drug Regulatory authority of India is also invited in ICH bi-annual meetings. • DRH representatives participate in the

Global Cooperation session of the ICH Steering Committee (SC) to discuss capacity-building and share experience/challenges on the implementation of ICH Guidelines.

• Representatives also listen to ICH technical topics discussed by the SC during meetings and are invited to nominate technical experts in Expert Working Groups/Implementation Working Groups to contribute to the development of ICH Guidelines.

GU

IDEL

INES

Principles of ICH GCP

• 2.1 Clinical trials should be conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki, and that are consistent with GCP and the applicable regulatory requirement(s).• 2.2 Before a trial is initiated, foreseeable risks and

inconveniences should be weighed against the anticipated benefit for the individual trial subject and society. A trial should be initiated and continued only if the anticipated benefits justify the risks.

•2.3 The rights, safety, and well-being of the trial subjects are the most important considerations and should prevail over interests of science and society.•2.4 The available nonclinical and clinical information

on an investigational product should be adequate to support the proposed clinical trial.

•2.5 Clinical trials should be scientifically sound, and described in a clear, detailed protocol.•2.6 A trial should be conducted in compliance with

the protocol that has received prior institutional review board (IRB)/independent ethics committee (IEC) approval/favourable opinion.

• 2.7 The medical care given to, and medical decisions made on behalf of, subjects should always be the responsibility of a qualified physician or, when appropriate, of a qualified dentist.• 2.8 Each individual involved in conducting a trial should be

qualified by education, training, and experience to perform his or her respective task(s).

•2.9 Freely given informed consent should be obtained from every subject prior to clinical trial participation.•2.10 All clinical trial information should be recorded,

handled, and stored in a way that allows its accurate reporting, interpretation and verification.

• 2.11 The confidentiality of records that could identify subjects should be protected, respecting the privacy and confidentiality rules in accordance with the applicable regulatory requirement(s).• 2.12 Investigational products should be manufactured, handled,

and stored in accordance with applicable good manufacturing practice (GMP). They should be used in accordance with the approved protocol.• 2.13 Systems with procedures that assure the quality of every

aspect of the trial should be implemented.

GCP in IndiaThe Main regulatory laws operating in India are the Drug and

Cosmetics Act (1940) and the Drugs and Cosmetics Rules (1945).

SCHEDULE Y

Import and/ or manufacture of new drugs

Clinical trials

The latest amendment in Schedule Y says:• The clinical trial Sponsor is responsible for implementing and

maintaining quality assurance systems to ensure that the clinical trial is conduced and data generated, documented and reported in compliance with the protocol and GCP Guidelines

Pre-requisites for the studyInvestigational Pharmaceutical Product

Pre-Clinical supporting data Protocol

Ethical & Safety Considerations

Statistics

Responsibilities Sponsor The Monitor Investigator

Quality

Assurance

Record Keeping and Data Handling

All research involving human subjects should

be conducted in accordance with the

ethical principles contained in the current revision of Declaration

of Helsinki

Principles of essentiality

• Whereby, the research entailing the use of human subjects is considered to be absolutely essential after a due consideration of all alternatives

Principles of voluntariness, informed consent and community agreement

• Full information about the study• Written and informed consent• Risk and harm arising from the study• Right to withdraw from the study voluntarily

Principles of human experimentation

Principles of non-exploitation

• Involvement in the research or experiment; and, irrespective of the social and economic condition or status, or literacy or educational levels attained by the research subjects

Principles of privacy and confidentiality

• The identity and records of the human subjects of the research or experiment are as far as possible kept confidential

Principles of precaution and risk minimisation

• It ensures that the research subject and those affected by it are put to the minimum risk, suffer from no irreversible adverse effects and, generally, benefit from and by the research or experiment.

Principles of professional competence

• The research is conducted at all times by competent and qualified persons

Principles of accountability and transparency

• The research or experiment will be conducted in a fair, honest, impartial and transparent manner

Principles of the maximisation of the public interest and of distributive justice

• The research or experiment and its subsequent applicative use are conducted and used to benefit all human kind

Principles of institutional arrangements

• All arrangements should be made in a bonafide and transparent manner; • Ensure that research reports, materials and data connected with the research are duly preserved and archived.

Principles of public domain

• The research is brought into the public domain so that its results are generally made known through scientific and other publications

Principles of totality of responsibility • whereby the professional and moral responsibility, for the due observance of all the principles, guidelines

or prescriptions laid down generally or in respect of the research or experiment

Principles of compliance

• there is a general and positive duty on all persons, conducting, associated or connected with any research entailing the use of a human subject to ensure that both the letter and the spirit of these guidelines

• “Let not hatred of any people keep you from dealing justly. Deal justly, that is nearer to your duty. Observe your duty to God. Lo! God is Informed of what ye do." (Quran 5.8)

Thank You