A standard for the design, conduct, performance, monitoring, auditing, recording, analyses, and reporting of clinical trials that provides assurance that the data and reported results are credible and accurate, and that the rights, integrity, and confidentiality of trial subjects are protected.

1. Prepared By:- Rajeev Sahai
B.Sc, M.Pharmacy (Pharmacology)

2. GCP
“A standard for the design, conduct, performance,
monitoring, auditing, recording, analyses, and
reporting of clinical trials that provides assurance
that the data and reported results are credible and
accurate, and that the rights, integrity, and
confidentiality of trial subjects are protected.”
ICH–GCP [1.24]

4. Development of GCP guidelines
4
1938 – US Food, Drug, and Cosmetic Act
1947 – Nuremberg Code
1962 – Kefauver–Harris Drug
Amendment (USA) [IND]
1964–2000 – Declaration of Helsinki
1981 – US FDA regulation on informed consent
and IRBs
1997 – ICH–GCP guidelines
2001 – EU Clinical Trials Directive
1986 – National GCP guidelines
1968 – UK Medicines Act [CTC, CTX]
1977 – US FDA CFR: Obligations for Sponsors,
Monitors, Investigators
Elixir of sulfanilamide – 1937
Thalidomide – 1960s
Nuremberg Trials – 1940s
US FDA investigator inspections –
1972–74

5. The Elixir Tragedy, 1937
The US Food and Drug Administration’s role
in the regulation of novel medicines was
born out of tragedy. Seventy-one adults
and 34 children died in the fall of
1937 after taking a drug called Elixir
Sulfanilamide to treat a variety of
ailments, from gonorrhea to sore throat. At
that time, the FDA, which had been
launched in 1906 as the Bureau of
Chemistry, served simply to police claims
made about food and drug ingredients. No
formal government approval was required
to market new drugs.
There had to be some truth to what
[drug companies] were selling . . .
but in terms of safety, let alone
efficacy, that wasn’t part of the
equation.

6. The Elixir Tragedy, 1937
In 1937, the S.E. Massengill Company
of Bristol, Tennessee, began selling
bottles of Elixir Sulfanilamide, a liquid
version of a popular antibiotic of the
day. Investigators from the US Food
and Drug Administration (FDA)
identified the drug’s solvent,
diethylene glycol, as the killer. FDA
didn’t regulate drug safety at the time,
and therefore had no authority to
reprimand the company, the agency
was able to track down and seize
bottles of Elixir Sulfanilamide on a
technicality—“elixir” was a designation
reserved for drugs containing
ethanol—an operation that saved as
many as 4,000 lives.

7. 1938 – US Food, Drug, and Cosmetic Act
The disaster provoked a public outcry that led to the
passage of the 1938 Food, Drug, and Cosmetics Act,
which gave the FDA power to monitor the safety of new
drugs.

8. Nuremberg Code – Nazi Experiments

9. Nuremberg Code- 1947
The trials began on December
9, 1946 in Nuremberg,
Germany and were led
exclusively by the United
States.
The Nuremberg code (10
point) includes such
principles as informed
consent and absence
of coercion; properly
formulated scientific experime
ntation;
and beneficence towards
experiment participants.

10. Thalidomide Tragedy- 1960
The development and sale of thalidomide
• Thalidomide was developed in the 1950s. It was an anticonvulsive drug, but
instead it made users sleepy and relaxed. It seemed a perfect example of newly
fashionable tranquilizers.
• Animal tests did not include tests looking at the effects of the drug during
pregnancy. The apparently harmless thalidomide was licensed in July 1956 for
prescription-free over-the-counter sale in Germany and most European
countries. The drug also reduced morning sickness, so it became popular with
pregnant women.
First suspicions and the disaster
• By 1960 doctors were concerned about possible side effects. Some patients had
nerve damage in their limbs after long-term use. Pharmaceutical Company did
not provide convincing clinical evidence to refute concerns. In the United
States, the FDA did not approve the drug for use.
• There was an increase in births of thalidomide-impaired children in Germany
and elsewhere. However, no link with thalidomide was made until 1961.

11. Thalidomide Tragedy- 1960
The thalidomide disaster is one
of the darkest episodes in
pharmaceutical research
history. The drug was marketed
as a mild sleeping pill safe even
for pregnant women. However,
it caused thousands of babies
worldwide to be born with
malformed limbs. The damage
was revealed in 1962. Before
then, every new drug was
seen as beneficial. Now there
was suspicion and rigorous
testing.

12. Tuskegee Trial- 1932- 1972
• In 1932, the Public Health Service, working with the Tuskegee
Institute, began a study to record the natural history of syphilis in
hopes of justifying treatment programs for blacks. It was called
the "Tuskegee Study of Untreated Syphilis in the Negro Male."
• The study initially involved 600 black men – 399 with syphilis, 201
who did not have the disease. The study was conducted without
the benefit of patients' informed consent. Researchers told the
men they were being treated for "bad blood," a local term used to
describe several ailments, including syphilis, anemia, and
fatigue. In truth, they did not receive the proper treatment
needed to cure their illness. In exchange for taking part in the
study, the men received free medical exams, free meals, and
burial insurance. Although originally projected to last 6 months,
the study actually went on for 40 years.

13. Tuskegee Trial- 1932- 1972
• The men were never given adequate
treatment for their disease. Even
when penicillin became the drug of
choice for syphilis in 1947, researchers
did not offer it to the subjects. The
advisory panel found nothing to show
that subjects were ever given the
choice of quitting the study, even
when this new, highly effective
treatment became widely used.
• In October 1972, The advisory panel
concluded that the Tuskegee Study
was "ethically unjustified"--the
knowledge gained was sparse when
compared with the risks the study
posed for its subjects.

14. 18th WMA General Assembly, Helsinki,
Finland, June 1964
Preamble
• The World Medical Association (WMA) has developed the
Declaration of Helsinki as a statement of ethical principles for
medical research involving human subjects, including research on
identifiable human material and data.
• The Declaration is intended to be read as a whole and each of its
constituent paragraphs should be applied with consideration of all
other relevant paragraphs.
• Consistent with the mandate of the WMA, the Declaration is
addressed primarily to physicians. The WMA encourages others
who are involved in medical research involving human subjects to
adopt these principles.

15. International guidelines
Nuremberg Code
Sets out standards for the review and conduct of research involving
human subjects, including:
– voluntary consent of subjects
– justifiable reason for experiment
– protection of participants
Published in 1947 in response to the discovery of unethical medical
experimentation by Nazi scientists during World War II

16. International guidelines
The Declaration of Helsinki
Sets out ethical standards for the conduct of human subjects
research:
– research with humans should be based on the results from
laboratory and animal experimentation
– research protocols should be reviewed by an independent
committee prior to initiation
– informed consent from research subjects is necessary
– research should be conducted by medically/
scientifically qualified individuals
– risks should not exceed benefits
Adopted by the World Medical Association in 1964

17. The International Conference on Harmonisation
Guidelines for Good Clinical Practice
International Conference on Harmonisation
The Provides guidelines for topics concerning:
– quality
– efficacy
– safety
– multidisciplinary issues
Formed in 1990 to provide a unified standard for the EU, Japan, and
the US to facilitate the mutual acceptance of clinical data by the
regulatory authorities in these jurisdictions

18. Principles of ICH–GCP
– trials should be conducted in accordance with the principles
that have their origin in the Declaration of Helsinki
– risks and benefits should be carefully evaluated
– the rights, safety, and wellbeing of trial subjects
are pre-eminent
– available information on the investigational product
should support the trial
– trials should be scientifically sound and described in a detailed
protocol
– protocols should be reviewed and approved by an IRB/IEC
– a qualified physician (or dentist, where appropriate) should
be responsible for all medical care of and decisions about study
subjects

19. Principles of ICH–GCP
– each individual involved in conducting a trial should be
qualified by education, training, and experience
– freely given informed consent is required before
entering a subject into a trial
– all clinical trial information should be recorded,
handled, and stored in a way that allows its accurate
reporting, interpretation, and verification
– confidentiality of records should be protected
– investigational products should be manufactured,
handled, and stored in accordance with GMP
– QA procedures should be implemented

20. National/regional guidelines, laws, and
regulations
The Federal Food, Drug, and Cosmetic Act, US, 1938
– drug manufacturers required to provide scientific proof that
new products were safe
– first ever regulation of cosmetics and therapeutic devices
– specific authority provided for factory inspections
Drafted in the wake of elixir of sulphanilamide tragedy

21. The Kefauver–Harris Drug Amendment,
US, 1962
– manufacturers had to prove efficacy as well as safety before
marketing a new product
– informed consent required from participants
– resulted in current format of clinical testing
Developed in response to the thalidomide tragedy

22. The National Research Act, US, 1974
 to identify basic ethical principles that should underlie the conduct of
biomedical and behavioral research involving human subjects
 to develop guidelines to ensure that such research is conducted in
accordance with those principles
 mandated establishment of an IRB at all institutions conducting
biomedical research
Created the National Commission for the Protection of Human
Subjects of Biomedical and Behavioral Research

23. The Belmont Report, US, 1979
– respect for persons
– Beneficence
– Justice
It also emphasizes the distinction between practice
and research
Summarized the basic ethical principles identified by the National
Commission

24. The Code of Federal Regulations, US
 21 CFR is concerned with interpretation of the Federal Food, Drug,
and Cosmetic Act
 21 CFR encapsulates FDA’s regulations relating to GCP, including:
• electronic records (Part 11)
• human subjects protection (Part 50)
• financial disclosure (Part 54)
• IRBs (Part 56)
• INDs (Part 312)
The codification of the general and permanent rules published in the
Federal Register by the executive departments and agencies of the
Federal Government

25. EU Clinical Trials Directive, 2001
– applies to all EU member states
– intended to harmonize laws, regulations, and procedures in the
member states
EU Clinical Trials Directive, 2005
Changes to the Clinical Trials Regulations include
– arrangements for payment of fees
– notifying the licensing authority of serious breaches of GCP and/or
the protocol, and
– extension of the infringement notices (warning notices) regime.
Intended to provide a legal framework for the application of GCP to all
European clinical trials through incorporation into the national laws of EU
member states by May 1, 2004

26. Drugs and Cosmetics Act 1940 and Rules 1945-
India
- Drugs and Cosmetic Act 1940 has been divided in Chapters, Rules and
Schedules and is amended from time to time to control the safety, efficacy and
quality of the drugs. It is an act to regulate the import, manufacture,
distribution and sale of the drugs and cosmetics.
- Amended (2005) Schedule Y- Development and marketing of Drugs in India
- The Central Drugs Standard Control Organization (CDSCO) under Ministry of
Health and Family Welfare (MoH and FW) prescribes standards for ensuring
safety, efficacy and quality of drugs, cosmetics, diagnostics and devices in India.
- Ethical guidelines for Biomedical Research on Human subjects by the ICMR in
2000
- CDSCO released Indian Good Clinical Practice (GCP) guidelines in 2001.
- Drugs and Cosmetics (First Amendment) Rules, Jan 2013
- Drugs and Cosmetics (Second Amendment) Rules, Feb 2013