Good Clinical practice

PREPARED BY:SOMNATH NAVGIREM. PHARM II: (PHARMACEUTICS) DEPARTMENT OF PHARMACEUTICAL SCIENCES, RASHATRASANT TUKDOJI MAHARAJ NAGPUR UNIVERSITY,NAGPUR.

What is GCP?

Good Clinical Practice

Refers to

Good Clinical (Research) Practice

GCP (GOOD CLINICAL PRACTICE) is a

standard for the design, conduct,

performance, monitoring auditing,

recording, analyses, & reporting of

clinical trial that provides assurance

that the data and reported result are

credible and accurate and the rights

integrity, and confidentiality of trial

subjects are protected.

OBJECTIVEIt ensure that the studies are scientifically and ethically sound and that the clinical properties of the pharmaceutical substances under investigation are properly documented.

The guidelines seek to establish two cardinal principles:1. protection of the rights of human subjects and 2.authenticity of biomedical data generated.

•These guidelines have been evolved with consideration of WHO, ICH, USFDA and European GCP guidelines as well as the Ethical Guidelines for Biomedical research on Human Subjects issued by the Indian Council of Medical Research •The objective of this ICH GCP Guideline is to provide a unified standard for European Union (EU), Japan and the United States to facilitate the mutual acceptance of clinical data by the regulatory authorities in these jurisdictions.

International Scientific & Ethical quality Standard

DESIGN

REPO

RT

REC

OR

D

COLLECT

Patient Safety Credibility of Data

The Concept of Good Clinical Practice

Tuskegee trials - 1930s German prisoners trials - 1940s Thalidomide Disaster – 1960s Sulfanilamide disaster of 1937

Why GCP?

Tuskeegee Trial (Alabama, U.S.A., 1932-1972) > 600 men with syphilis

50% randomized to treatment 50% randomized to NO TREATMENT

◦Result: Untreated patients fared poorly A significant number of patients died

No information given to patients; no permission was sought to withhold treatment; no clear endpoints.

Outcome: Litigation, financial settlements

Why GCP? Case #1

German prisoner research trials (1940’s) Objectives of various trials:

◦ Effect of cold, heat, chemicals on men, women and children

◦ “Time to death” testing in response to stressors in healthy “volunteers”

◦ Organ transplant experiments on healthy “volunteers” Any information given (some?) is irrelevant because

prisoners were forced to participate Outcome:

◦ 25 German scientists taken to court, 7 acquitted, 9 imprisoned, 9 given death sentence

◦ Nuremberg Code of 1947

Why GCP? Case #2

In 1962 , thalidomide, a sleeping pill developed & widely used abroad, was being studied for used in U.S.

William S.Merrell company of Cincinnati was using drug investigationally

Dr. Frances Kelsey at the FDA delayed approval of the NDA by asking the sponsor for more information about neuritis as a possible side effect

Thalidomide disaster of 1962

However, even though the NDA was withdrawn, the FDA discovered that 2.5 million tablets of thalidomide were distributed to 1,270 U.S. physicians as samples

200,000 American patients received thalidomide By the mid-1960s, 10,000 birth defects occurred

worldwide approximately 10,000 children were born with severe

malformities, including phocomelia, because their mothers had taken thalidomide during pregnancy

This resulted in Kefauver-Harris Amendment of 1962,which address the issue of effectiveness and safety

Sulfanilamide drug used to treat a staphylococcal infection. drug shown dramatic curative effect & have been used for sometime in tablet & powdered form, but in southern estate it demand as liquid form

Watkins experimented & found that Sulfanilamide dissolve in diethylene glycol

New formulation had not been tested for toxicity

Sulfanilamide disaster of 1937

Catalyst Event Sulfanilamide Tragedy

Nazi Physicians Trial

Thalidomide Tragedy

Syphilis Study

Unethical Research Events

Regulatory Milestone

Food, Drug, and Cosmetic Act

Nuremberg Code

Kefauver-Harris Amendments

National Research Act

Untested AIDS Vaccine in Human Trials. ◦Good Clinical Practice Journal 6(3):5-6, 1999

Case background:◦Dr. Ishwar Gilada, Indian Health Organization◦Administered untested vaccine to 10 HIV-

positive patients (Manisyl, a bovine immunodeficiency virus vaccine)

◦No permission sought from DCGI◦Patient took case to court

Scientific Misconduct: India

History – the regulation were originally concerned with “ Quality, Identity & purity” of product not with efficacy & safety of drug substance /product

The regulation of GCP start after some dangerous event occur

Evolution of Regulation of GCP

1. Event occur-when more than 100 children die after taking strep-elixir (sulfanilamide & diethylene glycol)

Reaction of event -1938 Federal Food Drug & cosmetic Act required that drug to be tested for safety

2. Event –between 1950-1960 thousand of children born with Phocomelia (seal limbs) when taken by a pregnant women during pregnancy

Reaction of event- the kefauver Harris amendment of 1962 passed by U.S. congress. It include

Evidence of efficacy of drug before approval Evidence of safety before testing in human Give protection to human in research

It all began when….

The rights, safety,& wellbeing of trial patient are most important

The trial should be conducted with the ethical principle of Declaration of Helsinki and consistent with GCP & regulatory environment

Clinical trial should be scientifically sound & describe in a clear detail protocol

The risk of patient should be less &benefit should be more

Principles of GCP

All clinical trail information should be recorded handled & stored in way that allow its accurate reporting interpretation verification

Medical care of patient should be taken by qualified physician

Each individual involved in a clinical trial should be qualified by education training & experience

Before the start of clinical trial participation informed consent of every patient is necessary

Trial must be conducted to protocol that has received prior approval of an IRB/IEC

Principles of GCP

1. Federal Food & Drugs act, 19062. Sulfanilamide Disaster, 19373. Food, Drug & Cosmetic act, 19384. The Nuremberg Code, 19485. Durham Humphrey Amendment, 19516. Thalidomide Disaster, 19517. Kefauver Harris Amendment 19628. Declaration of Helsinki, 19649. Medical Device Amendment, 197610. Good clinical practice (1980s1990s) 11. ICH-GCP, 1997

The Milestones in Evolution of GCP

Medical research must.. Conform to generally accepted scientific principles & be

based on thorough knowledge of scientific literature Caution should be exercised in the conduct of research that

may affect the environment Welfare of the animals must be respected Importance of the objective should outweigh 5risks & burden

to subjects Be described in a protocol Be considered by an ethical review committee Be conducted by scientifically qualified persons supervised by

clinically competent medical person Subjects must be volunteers & informed participants

World Medical Association Declaration of Helsinki

Physician must: Protect the life,health,privacy & dignity of the human

subject Cease any investigation if the risks outweigh any

potential benefits Inform adequately each potential subject & obtain

his/her freely given consent, preferably in writing Obtain consent from a legally authorized

representative if subject legally incompetent

World Medical Association Declaration of Helsinki

‘A need was, however, felt to develop our own Indian Guidelines to ensure uniform quality of clinical research throughout the country and to generate data for registration for new drugs before use in the Indian population.’

Indian GCP – CDSCO(central Drug Standard Control organization)

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