History and Principles of Good Clinical

Practices (GCP)
 Learning Objectives

• Define GCP

• Know History of GCP

• Understand Principles of GCP

• Describe Standards of GCP

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 Concept of GCP

• Good Clinical Practice (GCP) is an international ethical and scientific

quality standard for

• Trials that involve human participants.

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 Concept (cont.)

GCP is:
• Outline of responsibilities for engaging in clinical trials.
• Shared responsibilities.
• Individual responsibilities.
• a process that makes all parties to a study responsible for patient
safety and study quality.

• A set of standards incorporating scientific and ethical perspectives

into shared practice.

• A basis for trust and acceptance of clinical trials.

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GCP: Intercept for all Stakeholders of
Research

GCP

Protection of Human Participants and Credible Data Common Good

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 History of GCP

• A number of medical events and other legislative actions led to

guidelines on ICH-GCP in 1996. These include:

• In 1906, the US took action with “The Pure Food and Drug Act”
– To control the way drugs were put on the market
– The Act Imposed regulations on products whose labeling contained
alcohol, opium, morphine, cocaine and other substances

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 History of GCP

• In 1937, the sulfanilamide incident occurred which put the “Act” in

question:

• Sulfanilamide was a product used against streptococci

• It was sold as child's syrup in ethylene glycol → the disaster
• US then revised “Pure Food and Drug Act of 1906”
• This became the Food, Drug and Cosmetic Act of 1938
–Requirement for safety test of any drug before marketing

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 History of GCP

• Following WW II in Nuremberg trials, atrocities by Nazi doctors

became clear in the name of medical research

• In 1947 two US doctors who worked for the prosecution on the trials,
submitted a text with 6 points defining legitimate research

• These 6 points became 10 latter and known as “The Nuremberg Code”

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 History of GCP

• In 1964, 10 items of the Nuremberg Code incorporated in Declaration

of Helsinki by WMA

• The declaration was a guideline that provided highest ethical

standards at that time

• All these documents formed basis of GCP

• Thalidomide incident, however, led to issue of Harmonization

• During the 1960s, Thalidomide was used in Europe for insomnia,

mainly in pregnant women
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 History of GCP

• After marketed in US, discovered that it caused birth defects leading

to
 Tightening and amending of the Food, Drug and Cosmetic Act of the 1938

• Starting in mid-1970, FDA started to reject clinical trials from other

countries if their ethical and safety standards were not same

• Starting in mid-1980s, Europe and Japan each developed their own set
of GCP guidelines

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 History of GCP

• But differences between US, Europe and Japan remained and did not
contribute to economic efficiency of clinical trials.

• In 1996, an ICH was called consisting of authorities of Europe, US

and Japan and experts from pharmaceutical industries.

• This led to international uniform standard to accept results of CTs so

long conducted as per ICH-GCP guidelines.

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 History of GCP

• Recently ICH - GCP guideline has evolved from an economic to a

political and legal incentive.

• Several countries, with EU in the lead, are incorporating GCP in their

legislation these days.

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 Principles of GCP

1. Ethical conduct
 CTs should be conducted in accordance with basic ethical
principles, consistent with GCP and applicable regulatory
requirements
2. Research described in the protocol
 should be scientifically justified and described in a clear detailed
protocol
3. Risk identification
 Before initiating CT, foreseeable risks and inconveniences should
be weighed against anticipated benefits for trial participant and
society

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 Principles of GCP (cont.)

4. Benefit-Risk assessment

• A trial should be initiated and continued only if anticipated

benefits justify risks

• The rights, safety, and well-being of trial participants are most

important considerations and should prevail over the interests of
science and society

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 Principles of GCP (cont.)

5. Review by EC/IRB
 A trial should be conducted in compliance with the protocol that
has received prior IRB/EC approval

6.Protocol compliance
 Should be conducted in compliance with the approved protocol

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 Principles of GCP (cont.)

7. Informed consent (IC)

• Freely given IC should be obtained from every participant/legal
guardian prior to trial participation

8. Continuing review/ongoing benefit/risk assessment

• Should continue only if benefit/risk profile remains favorable

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 Principles of GCP (cont.)

9. Investigator qualifications
• Medical care given and decisions made on behalf of participants
should always be responsibility of a qualified physician/dentist

10. Staff qualifications

• Each individual involved in conducting trial should be qualified
by education, training, and experience

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 Principles of GCP (cont.)

11. Records
• All trial information should be recorded, handled, protected and
stored in a way that allows accurate reporting, interpretation and
verification.

12. Confidentiality/privacy
• Confidentiality of records that could identify participants should
be protected, respecting privacy and confidentiality rules in
accordance with applicable regulatory requirements.

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 Principles of GCP (cont.)

13. Good Manufacturing Practice

• IPs should be manufactured, handled, and stored in accordance
with applicable GMP
• They should be used in accordance with approved protocol

14. Quality Systems

• Systems with procedures that assure quality of every aspect of the
trial should be implemented

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GCP Standards
 GCP Design Standards

• Written protocol

• Investigator brochure

• Scientific soundness

• Feasibility

• Adequate resource

• Randomization/blinding

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 GCP Conduct Standards

• IRB and regulatory approval

• Compliance with protocol
• Informed consent
• Data confidentiality
• Medical management of adverse events
• Product accountability
• Qualification and training

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 GCP Recording Standards

• CRF completion

• Data handling

• Security maintenance

• Audit requirements

• Product accountability

• Management of study files/essential documents

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 GCP Reporting Standards (cont.)

• Whom to Report
 Sponsors
 IRB/EC
 Regulatory body
 DSMB
 Other investigators

• What to report
 Interim reviews (data and AEs/SAEs)
 Progress reports
 Final reports
 Monitoring/Audit Reports
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 Summary

• GCP is a set of responsibilities, standards and trust

• A number of medical events and other legislative actions led to

development of GCP

• GCP principles revolve around:

 Protection of rights, safety and well-being of trial participants

 Credible clinical trial data

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