Good Clinical Practices for drug discovery and development

1. Good Clinical Practices
Dr. Fardan Qadeer
JR I, Department of Pharmacology
Moderator: Dr. Ali Ahmad
Head Dept. of Pharmacology

2. Basic Research
Disease
Recovery
Drug Recovery
Preclinical
Development
Clinical Trials Manufacturing
Not regulated
GLP
GCP
GMP

3. Drug discovery and development
PRE CLINICAL TRIAL CLINICAL TRIAL
HUMANS
Adverse
Effect
Ethical
issues
Drug Toxicity

4. 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

5. 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 the
RIGHTS
SAFETY
WELL BEING
Designing
Clinical Trials
or Studies
Conducting
Monitoring
Recording
Reporting
Analysis

6. HISTORICAL BACKGROUND
Nuremberg Code, 1946
Kefauver Amendments, 1962 – Thalidomide
Declaration of Helsinki, 1964
National Research Act, 1974 - Tuskegee Syphilis Study
(1932-1972)
Belmont Report, 1979

7. 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.

8. • 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.

9. 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

10. Declaration of Helsinki-1964
• World Medical Association - recommendations guiding medical doctors in
biomedical research involving human participants
1. Research with humans should be based on the results from laboratory and
animal experimentation
2. Research protocols should be reviewed by an independent committee prior
to initiation
3. Informed consent from research participants is necessary
4. Research should be conducted by medically/scientifically qualified
individuals
5. Risks should not exceed benefits
• Revised - 1975, 1983, 1989, 1996, 2000, 2002, 2004, 2008

11. 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)

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

13. 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

14. 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

15. 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 sponsors
Observers
Non voting member
coordinates its technical input to ICH through its
Scientific and Regulatory Section
Steering Committee

16. 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.

18. 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.

19. • 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.

20. • 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.

21. • 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).

22. • 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.

23. • 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.

24. GCP in India
The 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

25. 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

26. Pre-requisites for the study
Investigational Pharmaceutical Product
Pre-Clinical supporting data
Protocol
Ethical & Safety Considerations
Record Keeping
and Data
Handling
Statistics
Responsibilities
Sponsor
The Monitor
Investigator
Quality
Assurance
All research involving
human subjects should
be conducted in
accordance with the
ethical principles
contained in the current
revision of Declaration
of Helsinki

27. 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 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

28. 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

29. 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

30. • “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)