The document provides an overview of ICH GCP (International Council for Harmonisation Good Clinical Practice) guidelines. ICH GCP guidelines were developed to harmonize clinical trial standards and processes across regions. They establish international ethical and scientific quality standards for designing, conducting, and reporting clinical research involving human subjects. Adherence to ICH GCP provides public assurance that the rights, safety, and well-being of clinical trial subjects are protected.

1. Overview of ICH GCP Syed Sarfaraz Uddin e-mail: syed.sarfaraz.uddin@gmail.com

2. What is ICH? ICH is a joint initiative involving both the regulators and the industry as equal partners in the scientific and technical discussions of the testing procedures which are required to ensure and assess the safety, quality and efficacy of medicines.

3. How did it evolve? The need to harmonize Public disasters, serious fraud and abuse of human rights. Trials of War criminals-Nuremberg code 1949 Thalidomide- Declaration of Helsinki 1964 Belmont report 1978( Ethical Principles and guidelines for the protection of human subjects of research)- Tuskegee syphilis study

4. History 1962 US FDA IND Guidelines 1964 Declaration of Helsinki 1968 Committee on Safety of Medicines, uk 1978 GCP, US FDA 1991 GCP, Europe 1996 ICH GCP 1997 ICH GCP Guideline

5. When did it begin? I st conf. in 1990 in Brussels 3 regions participated Representatives from Industry Academia Ministry of health

6. ICH parties 6 parties EU EFPIA European federation of pharmaceutical industries’ associations MHLW Ministry of health, Labor and welfare, Japan JPMA Japan Pharmaceuticals manufacturers Association US FDA PhRMA Observers : WHO, TPP(canada) International federation of Pharmaceutical manufacturer’s association

7. Key objective To discuss and define the minimum standards for the development and registration of investigational products

8. The result? Many guidelines made Most important- ICH GCP guidelines Evolved in several steps Consolidated guideline ICH E6 Sept 1997

9. ICH Guidelines: examples Efficacy: clinical trials etc Safety: pharmacovigilance, adverse drug reaction reporting Quality: raw materials, impurities, residual solvents etc Multidisciplinary: common technical document, electronic submission, coding systems

10. The ICH Story Through the development of science-based, international guidelines and standards How: Reduce unnecessary duplication and thereby contribute to the efficiency of drug development and registration for new pharmaceuticals Why: Regulatory authorities and research-based industry of the EU, US and Japan; WHO, EFTA and Canada observers Who:

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

12. Why is it needed? To ensure the rights, safety and well being of the trial subjects are protected Ensure the credibility of clinical trial data

13. The ICH GCP guideline Provide a unified standard for the EU, Japan and USA regions to facilitate mutual acceptance of clinical trial data by the regulatory authorities in these regions . ?The need No acceptance of foreign clinical data Regional variation in reg guidelines Escalating costs Extended time for registration ICH region covers 85% of Pharm. sales

14. ICH GCP guideline 8 sections

15. ICH GCP guideline 1. Glossary Common language for investigators/sponsors/ethics committees 2.Principles of Good Clinical Practice 13 tenets of ICH GCP 3.Requirements for IRB/IEC Roles responsibilities and composition

16. ICH GCP guideline 4.Responsibilities of the investigator 5.Responsibilities of the sponsor 6.Requirements for clinical trial protocol and protocol amendments 7.Responsibility of the sponsor in the development of investigator’s brochure. 8.Essential documents

17. Principles of ICH GCP Ethical conduct as per Declaration of Helsinki GCP Regulatory Requirements Risk- Benefit Primary concern- Subject

18. Principles of ICH GCP Supportive data Protocol Scientifically sound, clear, detailed Ethical Clearance Study to be conducted in compliance to the protocol which has received EC approval

19. Principles of ICH GCP Subject Care Medical decisions responsibility of qualified physician Qualified staff By education, training, experience in their area of responsibility Informed Consent

20. Principles of ICH GCP Clinical Trial data Recorded, handled and stored to enable accurate reporting, interpretation and verification Confidentiality

21. Principles of ICH GCP Investigational Product Manufactured, handled and stored as per GMP Used as per the protocol

22. Principles of ICH GCP Quality Assurance Systems and procedures to ensure the Quality of every aspect of the trial

23. Concerns about ICH Industry driven agenda or public health oriented approach Public health implications- inability to achieve standards and withdrawal of essential drugs Misdirecting national priorities

24. ICH vs. non-ICH ICH: 17 countries 15% world population 82% drug production 90% drug sales 95% R&D New Chemical Entities Chronic & lifestyle diseases Strong DRAs $$$$$ “ non-ICH”: 176 countries 85% world population 18% drug production 10% drug sales 5% R&D Mainly generics Life-threatening diseases Weak DRAs $

25. Indian GCP guidelines Released in Dec 2001(Developed by CDCSO and endorsed by DCGI) In general, in line with ICH GCP Has Revised Schedule Y (Jan 2005) addressed discrepancies?

26. Issues in Developing Countries The informed consent process Economic Vulnerability Patient doctor relationship Education level

27. ROLE OF GCP ? Good clinical practice (gcp) is an international ethical & scientific standard for conducting clinical trials that involve the participation of human subjects Compliance with this standard provides public assurance that the rights, safety & well-being of trial subjects are protected, which is consistent with the principles outlined in the declaration of helsinki GCP also ensures the credibility of clinical trial data.

28. INTERNATIONAL ETHICAL STANDARDS Professional standards for the protection of human subjects in research did not exist till late 1940’s. Nuremberg tribunal held in 1945 and 1946 that “voluntary consent of the human subject is absolutely essential” The Declaration of Helsinki outlines 12 principles by which physicians must conduct research in therapeutic & non-therapeutic interventions.

29. Fundamental Ethical Principles Guiding Protection Of Human Subjects In Biomedical Research RESPECT FOR PERSONS : Acknowledges the dignity & autonomy of individuals. This principle requires that subjects give their informed consent prior to participating in research. BENEFICENCE : Obligates researchers to treat subjects fairly. JUSTICE : requires the equitable selection of subjects in light of research setting & research purposes.

30. PRINCIPLES BEHIND GCP Before initiating any clinical trial, ANTICIPATED RISKS should be weighed against EXPECTED BENEFITS for the trial subject & society The RIGHTS, SAFETY & WELL BEING of trial subjects are the most important considerations & should prevail over the interests of science & society. The entire study procedure should be scientifically sound & detailed in a trial protocol. This protocol should receive a prior APPROVAL FROM AN INDEPENDENT ETHICS COMMITTEE.

31. ETHICAL REVIEW SHOULD DEFINE JUSTIFIABLE BOUNDARIES BETWEEN THE RIGHTS OF THE SUBJECT AND THE BENEFITS THAT MIGHT ACCRUE TO SOCIETY THROUGH SCIENTIFIC INFORMATION DEVELOPED IN CLINICAL TRIALS. Regulations have been established internationally, to ensure ethical & scientific conduct of trials

32. GOALS OF INTERNATIONAL HARMONIZATION OF REGULATORY REQUIREMENTS SAFEGUARD PUBLIC HEALTH ASSURE CONSUMER PROTECTION STANDARDS FACILITATE AVAILABILITY OF SAFE AND EFFECTIVE PRODUCTS ELIMINATE INCONSISTENT STANDARDS INTERNATIONALLY FACILITATE MUTUAL ACCEPTANCE OF DATA FROM CLINICAL TRIALS

33. STAKEHOLDERS & THEIR RELATIONSHIPS MONITOR DATA SUBJECT REGULATORY AUTHORITY SPONSOR ETHICS COMMITTEE INVESTIGATOR

34. ROLE OF ETHICS COMMITTEES Play a vital role in protecting human subjects in clinical trials. They review trial protocols to ensure that …. informed consents are obtained from the subjects subjects are not exposed to unreasonable risks Establishment of EC’s has become a cornerstone of protection of human subjects in clinical research

35. Protection of Human Subjects Prior To Study Start The investigator must request ethics approval for: Protocol Informed Consent Form/Advertisements/Other Information Protocol amendment and /or Informed Consent Amendments All sites at which patient activity will occur

36. Protection of Human Subjects During the study The investigator must request ethics approval for any change in the research activity The investigator must submit progress reports to the IRB as required The subject must be informed of any new information which might affect their decision to continue participation in the trial

37. RESPONSIBILITIES OF THE INVESTIGATOR Conduct the research in accordance with the protocol and Good Clinical Practice (GCP) Protect the rights, safety, and welfare of the subjects Report all adverse events (serious and non-serious) Retain study documents and medical records Control the distribution and use of the study medication

38. RESPONSIBILITIES OF THE SPONSOR The sponsor is responsible for implementing and maintaining quality assurance of data generated in compliance with the protocol Sponsor is responsible for securing agreement from all involved parties to ensure direct access to all sites, source data & reports for the purpose of monitoring & auditing by regulatory authorities Agreements made by the sponsor with the investigator should be in writing

39. MEDICAL CARE OF TRIAL SUBJECTS During and following a subject’s participation in a trial, the investigator & institution should ensure that adequate medical care is provided to deal with adverse events related to the trial The investigator should inform the subject’s primary physician about the trial & the subject’s participation

40. Protection of Human Subjects Informed Consent Must be signed and dated by the subject prior to study start Language understandable to the subject Subject Information Sheet approved by the Ethics Committee The Consent Form must contain the elements required by GCP Subject must be given a copy

41. Study Documentation Before the study starts IRB approval letter Members of IRB and their qualifications/affiliation Normal ranges of clinical laboratory

42. Study Documentation During the study The investigator must keep: Source documents Medical records (including access to computer records) Laboratory reports ECGs, X-rays, etc. Any other medical records, reports or notes (hospital admissions and discharges) A subject identification list Copies of all study related documentation

43. Medical Records In particular, they should contain notes on: Sufficient information to support subject eligibility This should be well documented (signed and dated) Subject’s participation in the study Dates of visits Procedures, investigations done Observations, diagnoses Medications taken (including study medication) Adverse events / SAE’s Completion or withdrawal (reason) from the study

44. Study Documentation After the study The sponsor needs from the investigator: Final drug accountability records All used and unused supplies and medication All required documents completed

45. The trial subjects should be explained the correct use of the investigational product and compliance to these instructions should be checked periodically Investigator should maintain records of the delivery of the product, the inventory, use by each subject as per protocol INVESTIGATIONAL PRODUCT

46. MONITORING The rights & well-being of human subjects are protected The reported data are accurate, complete & verifiable from source documents The conduct of the trial is in compliance with approved protocol & with applicable regulatory requirements THE PURPOSES OF MONITORING ARE TO VERIFY THAT…

47. Questions?