GCP For M.Pharm

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Good Clinical Practice

Presented By SARFRAJ AHMAD.M.Pharm1st Semester

Guided By MR. AMIT VERMA

(Lecturer)

Department of Pharmaceutical Sciences.

BBAU- Lucknow

ContentsContents

Introduction History Principles of GCP IEC/IRB Responsibilities Investigator Responsibilities Sponsor Responsibilities Differences Between Indian-GCP and ICH-GCP

Protocols of Clinical Trials Clinical Trials Essential Documents

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Why we need guideline and Why we need guideline and regulationregulation

To ensure that the rights, safety and well

being of trial subjects are protectetd.

The clinical data is credible.

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Good Clinical PracticeGood Clinical Practice

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A Set of Responsibilities ‘a process that makes all parties to a study responsible for patient safety and study quality’

Good Clinical Practice (GCP) is defined as 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’

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Are mainly focused on the protection of human rights in clinical trial.

Provide assurance of the safety of the newly developed compounds.

Provide standards on how clinical trials should be conducted.

Define the roles and responsibilities of - Clinical Sponsors, Clinical Research Investigators, Clinical Research Associates, And Monitors.

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The Objectives of Clinical The Objectives of Clinical ResearchResearch

1. To Contribute to Public Health

2. To Contribute to Health Science

3. To Contribute to Economic Development

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Dimensions of GCPDimensions of GCP

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General Frameworks•WHO GCP•ICH GCP

Regional/Applied Frameworks•EU GCP•US CFRNational/Applied GCP GuidelinesChina, India, Russia, Singapore, Malaysia, Indonesia, South Korea Argentina, Brazil, Mexico, South America, South Africa, Turkey

Historical perspectiveHistorical perspective

Tuskegee Experiment 1932-1970

Sulphanilamide disaster 1937

Thalidomide Tragedy 1950/60s

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Tuskegee ExperimentTuskegee Experiment

From 1932 -1970 with approval from the US Department of Public Health.

Poor black men with syphilis were regularly examined and the progress of their disease documented.

The “subjects "believed they were receiving optimal medical treatment.

The reality was that either inadequate or no treatment at all was being given.

As a direct result of this study at least 40 men lost their lives

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Sulphanilamide disaster 1937Sulphanilamide disaster 1937

Sulphanilamide widely available and useful antibiotic.

Manufacturer dissolved the compound in diethylene glycol to make it in elixir. ( DEG is poisonous to humans and other mammals)

Following acceptable testing for flavour, appearance and fragrance it was distributed.

But toxicity profile was not done.

1937 – in the United State 107 deaths (primarily children) directly attributable to the elixir sulphanilamide.

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Thalidomide Tragedy 1950/60sThalidomide Tragedy 1950/60s

Compound prescribed for nausea in pregnancy throughout Europe

No teratogenic testing performed in appropriate animal models

Early reports of patients suffering from peripheral neuritis were largely ignored

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Estimated 10,000 phocomelics born

Despite the evidence the drug manufacturers fought to keep the compound on the market.

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History of Good Clinical PracticeHistory of Good Clinical Practice Prior to an actual set of guidelines to follow for good

clinical practice, clinical studies were dangerous and could result in serous disease, or possibly death.

The Nuremburg Code of 1947 Experiments performed in Germany during WW-II opened the

eyes of the world for guidance for clinical testing on humans. The code did set ethical guidelines, but it lacked legislation to

back it up. Declaration of Helsinki

▪ In 1964, the World Medical Association established recommendations guiding medical doctors in biomedical research involving human subjects. These guidelines influenced national legislation, but there was no set standard between nations.

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ICHICH

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.

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http://en.wikipedia.org/wiki/Europe

http://en.wikipedia.org/wiki/Japan

http://en.wikipedia.org/wiki/United_States

13 Principles of ICH GCP13 Principles of ICH GCP

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 requirements.

2. Before a trial is initiated, foreseeable

risks and inconveniences should be

weighed against the anticipated benefit

for the individual trial subject & society.

A trial should be initiated and continued only if the anticipated benefits justify the risks. 17

Benefits RISKS

13 Principles of ICH GCP Continued13 Principles of ICH GCP Continued3. The rights, safety, and well-being of the trial subjects are

the most important considerations and should prevail over interests of science & society.

4. The available non-clinical & clinical information on an investigational product should be adequate to support the proposed clinical trial.

5. Clinical trials should be scientifically sound, and describe in a clear, detailed protocol.

6. A trial should be conducted in compliance with the protocol that has received prior IRB (or IEC) approval.

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13 Principles of ICH GCP Continued13 Principles of ICH GCP Continued

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.

8. Each individual involved in conducting a trial should be qualified by education, training and experience to perform his or her respective tasks.

9. Freely given informed consent should be obtained from every subject prior to clinical trial participation.

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10. All clinical trial information should be recorded, handled, and stored in a way that allows its accurate reporting, interpretation, and verification.

11. The confidentiality of records that

could identify subjects should be

protected, respecting the privacy

and confidentiality rules in accordance

with the applicable regulatory

compliance.

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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

13. Systems with procedures that assure the quality of every aspects of the trial should be implemented.

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Institutional Review Board (IRB),Institutional Review Board (IRB),Independent Ethics Committee (IEC)Independent Ethics Committee (IEC)

A formally designated group that oversees research

involving human subjects. Approves and disapproves human subject research. According to the standards of the community or the

institution, the IRB/IEC may require modifications to a protocol to ensure patient safety.

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IRB FunctionIRB Function

•The primary function of an IRB/IEC is to safe guard the rights ,safety ,and well being of all trial subjects. This is accomplished by initial, continuing and annual review.

•An IRB should consist of members who collectively have the qualifications and experience to review and evaluate the science , medical aspects, and ethics of the proposed trial.

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IRB MembersIRB Members

1. A minimum of five (5) members.

2. One member whose concern is not scientific.

3. One member who has no personal or familial relationship to the institution or trial site.

4. Any member with a conflict of interest may not participate in any part of the review or vote (except to provide requested information).

5. Individuals with special expertise may be invited to assist with areas of unique or complex nature. These will not be voting members.

6. A list of IRB/IEC members and their qualifications should be maintained.

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IRB/Ethics CommitteeIRB/Ethics Committee

All studies must be approved prior to recruiting participants

IRB must review all documents given to participants

Reporting Adverse Events and Deviations from protocol to the IRB

Maintenance of Records

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Investigator ResponsibilitiesInvestigator Responsibilities

Adequate ResourcesRecruitment

Time

Qualified Staff

Facilities

Training

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Medical CareA qualified Physician (or dentist) responsible for trial-related medical decisions

Provide adequate medical care for Adverse Events or other significant medical condition

Inform SPP about participation in trial

Make a reasonable effort to ascertain why participant withdrawals from study

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Compliance with ProtocolInvestigator should sign off on protocol

Investigator should not implement deviations from protocol

If deviations occur, they should be documented and reported at once to the sponsor, the IRB and other regulatory authorities

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Progress ReportsWritten summary of trial status to the IRB

Written reports to the sponsor or regulatory authority of any changes affecting the trial

Safety MonitoringSAEs should be reported immediately to sponsor

AEs should be reported according to sponsor guidelines

Supply sponsor & IRB with requested materials on participant deaths

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Investigator ResponsibilitiesInvestigator ResponsibilitiesPremature Termination or Suspension

Promptly inform trial subjects

Assure appropriate therapy & follow-up to subject

Inform sponsor, regulatory authorities & IRB

Final ReportingInform IRB of study completion & a summary of the trial’s outcome

Provide sponsor & regulatory authorities with all required reports

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Sponsor ResponsibilitiesSponsor Responsibilities

Quality Assurance & Quality ControlProvide written SOPs

Secures agreement between all parties

Data handling

Contract Research Organization (CRO)Hired by the sponsor to implement trial-related duties

Medical ExpertiseDesignated medical personnel to advise on trial-related medical questions and problems

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Sponsor ResponsibilitiesSponsor Responsibilities

Trial DesignDesigns of protocol and CRFsPlanning analyses to analysing

Trial Management, Data Handling, Recordkeeping, & Independent Data Monitoring Committee (IDMC)

Qualified personnel to supervise overall conduct of the studyDMC assesses the progress of the clinical trialMaintain SOPs for electronic data processingInform Investigator of guidelines for record retention

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Differences between Indian-GCP and ICH-GCP

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Clinical Trial ProtocolClinical Trial Protocol

General InformationBackground InformationTrial Objectives & PurposeTrial DesignSelection & Withdrawal of ParticipantsTreatment of SubjectsAssessment of EfficacyAssessment of Safety

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Essential Documents for the Conduct of a Essential Documents for the Conduct of a Clinical TrialClinical Trial

Preclinical trial commencement

During clinical conduct of trial

After completion or termination of trial

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Clinical TrialsClinical TrialsThe trials are conducted in 4 phases. Phase 1 trials are for determining dosing, document how a drug is metabolized and identify side effects. Phase 2 trials gather further safety data and evidence of the drug's efficacy.Phase 3 further tests the product's effectiveness on a greater number of participants, and monitors side effects.Phase 4 trials can be conducted after a product is already approved and on the market to find out more about the treatment's long-term risksIt is estimated that only 5 in 5,000 compounds that enter preclinical testing make it to human testing, and only 1 of those 5 may be safe and effective enough to reach pharmacy shelves

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Storage of Essential Documents Storage of Essential Documents

FDA Rule: 2 options2 years following marketing of the drug or,

2 years after IND application is withdrawn if drug was not marketed

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Conclusion Conclusion

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