Gcp,glp,gclp presentation

Good clinical practice guidelines

1. GCP, GLP and GCLP guidelines 1 Dr. Ssuna Bashir Clinical Epidemiology and Biostatistics MBCh.B (MUST) Msc . (MAK) Fellowship in Mixed methods Research (MAK) Email: [email protected] Mob. [phone]

2. GCP: Good Clinical practice ICH: International Conference on Harmonization GLP: Good Laboratory Practice GCLP: Good Clinical Laboratory Practice OECD – Economic Co-operation and Development 2

3. GOOD CLINICAL PRACTICE (GCP) Good Clinical Practice (GCP) is an international ethical and scientific quality standard for designing, conducting, recording and reporting trials that involve the participation of human subjects. Compliance with this standard provides public assurance that the rights, safety and well-being of trial subjects are protected, consistent with the principles that have their origin in the Declaration of Helsinki, and that the clinical trial data are credible INTRODUCTION 3

4. To Provide a unified standard for Europe, Japan and US To facilitate the mutual acceptance of clinical data Note: This guideline should be followed when generating clinical trial data that are intended to be submitted to regulatory authorities. May also be applied to other clinical investigations that may have an impact on the safety and well-being of human subjects OBJECTIVES OF ICH-GCP 4

5. ICH GCP CONT… Good Clinical Practice guidelines include protection of human rights as a subject in clinical trial. It also provides assurance of the safety and efficacy of the newly developed compounds. Good Clinical Practice Guidelines include standards on how clinical trials should be conducted, define the roles and responsibilities of clinical trial sponsors, clinical research investigators, and monitors. 5

6. Nuremberg Code, 1946 – voluntary consent of the human subject is absolutely essential, animal experimentation results and a knowledge of the natural history of the disease Kefauver Amendments, 1962 (Thalidomide) – Drug manufacturers should prove to the FDA the effectiveness of their products before marketing them Declaration of Helsinki, 1964 – The fundamental principle is respect for the individual, their right to self determination and the right to make informed decisions regarding participation in research, both initially and during the course of the research. National Research Act, 1974 - Tuskegee Syphilis Study (1932-1972) Belmont Report, 1979 – respect for persons, beneficence, and justice HISTORY OF ICH GCP 6

7. THE PRINCIPLES OF ICH GCP Conduct trials according to GCP Weigh risks vs benefits Protect the subjects (rights, safety and wellbeing of participants) Have adequate information to justify trial (nonclinical and clinical) Write a scientifically sound protocol Receive IRB/IEC approval Use qualified physicians Use qualified support staff Obtain informed consent Record information appropriately Protect confidentiality Handle investigational products appropriately Implement quality systems 7

8. THE INSTITUTIONAL REVIEW BOARD/INDEPENDENT ETHICS COMMITTEE (IRB/IEC) An independent body constituted of medical, scientific, and non-scientific members Main responsibility – To ensure the protection of the rights, safety and well-being of human subjects involved in a trial IRB also reviews, approves, and provides continual review of trial protocol and amendments and of the methods and material to be used in obtaining and documenting informed consent of the trial subjects. 8

9. KEY PERSONS/TERMS IN A TRIAL Investigator – A person responsible for the conduct of the clinical trial at a trial site. If a trial is conducted by a team of individuals at a trial site, the investigator is the responsible leader of the team and may be called the principal investigator Sponsor – An individual, company, institution, or organization which takes responsibility for the initiation, management, and/or financing of a clinical trial Protocol – A document that describes the objective(s), design, methodology, statistical considerations, and organization of a trial. Independent Data-Monitoring Committee (IDMC) – An independent data-monitoring committee that may be established by the sponsor to assess at intervals the progress of a clinical trial, the safety data, and the critical efficacy endpoints, and to recommend to the sponsor whether to continue, modify, or stop a trial Essential documents – Documents which individually and collectively permit evaluation of the conduct of a study and the quality of the data produced. 9

10. GOOD LABORATORY PRACTICE (GLP) GLP is a quality system concerned with the organizational process and the conditions under which non-clinical health and environmental safety studies are planned, performed, monitored, recorded, archived and reported. (OECD GLP Guideline). INTRODUCTION 10

11. OBJECTIVES OF GLP: GLP makes sure that the data submitted are a true reflection of the results that are obtained during the study. GLP makes sure that data is traceable. Promotes international acceptance of tests. 11

12. The formal regulatory concept of “Good Laboratory Practice” (GLP) originated in the USA in the 1970’s The FDA’s publication of Proposed Regulations on GLP in 1976, with establishment of the Final Rule in June 1979 . In 1981, OECD produced GLP principles that are international standard. GLP - HISTORY 12

13. In the early 70’s FDA became aware of cases of poor laboratory practice (PLP) all over the United States. FDA decided to do an in-depth investigation in 40 toxicology labs. They discovered a lot fraudulent activities and a lot of poor lab practices. WHY GLP WAS CREATED 13

14. Personnel Sponsor Management Study director Quality Assurance Facility Laboratory Operation Characterization Animal care Equipment Reagents BASIC ELEMENTS OF GLP Documents Standard operating procedures (SOPs) Protocols Reports Archiving Test and Control Articles Characterization Handling Storage 14

15. GOOD CLINICAL LABORATORY PRACTICE (GCLP) GCLP applies those principles established under GLP for data generation used in regulatory submissions relevant to the analysis of samples from a clinical trial. At the same time it ensures that the objectives of the GCP principles are carried out. This ensures the reliability and integrity of data generated by analytical laboratories. 15

16. Provides a bridge between GCP and GLP Provides framework to organisations on facilities, systems and procedures Ensures the reliability, quality and integrity of the work and results Satisfies GCP expectations. GCLP Principles should be interpreted and applied to any laboratory that analyses samples generated during the conduct of a clinical trial SCOPE OF GCLP 16

17. THE GCLP PRINCIPLES Organisation and Personnel Facilities Equipment, materials and reagents Standard Operating Procedures (SOPs) Planning, conduct and reporting Quality Control and Quality audits Retention of study records and reports. 17

18. ORGANISATION & PERSONNEL Facility management Analytical Project Manager Analytical staff Archivist Quality Audit personnel 18

19. FACILITY MANAGEMENT Ensures that the principles of GCP,GCLP are complied with Provide sufficient, trained staff Appropriate & available facilities, equipment & materials SOPs are approved and in place Ensure Analytical Plan exists Quality audit and QC programs are in place 19

20. ANALYTICAL PROJECT MANAGER Responsible for the overall conduct of the analytical work Approve analytical plan & ensure plan is followed Ensure authorisation for any modification is obtained & documented Ensure results are accurately recorded Approve the issue of analytical results Ensure data are archived 20

21. ANALYTICAL STAFF Maintain awareness of GCP, GCLP which apply to their work Perform trial requirements in accordance with Trial Protocol, Analytical Plan & Standard Operating Procedures. Maintain prompt, accurate and complete records Responsible for the quality of their work & data 21

22. QUALITY AUDIT STAFF Independent monitoring of facility Performs quality audits review all aspects of the facility and work performed Reports findings to Analytical Project Manager and Facility Management 22

23. FACILITIES, EQUIPMENT & REAGENTS Demonstrably fit for purpose Facilities suitable size, structure and location space to avoid sample mix-up or contamination separation of activities limited access? storage areas temperature controlled, monitored, limits set, alarmed, back up good housekeeping 23

24. FACILITIES, EQUIPMENT & REAGENTS Equipment acceptance testing prior to use appropriately maintained & calibrated with records to demonstrate this trend analysis of calibration checks? validated computer systems in use may need to keep records of usage Reagents suitably labelled and stored 24

25. STANDARD OPERATING PROCEDURES Function of SOPs To establish standard procedures which will ensure quality and integrity of the data To communicate these procedures to those who will undertake them and underpin training To leave a permanent record of the methodology employed. 25

26. SOPs CONT… Approved by Management Controlled with historical file maintained To cover areas such as: Format, control and review of SOPs Sample handling- receipt, chain of custody, storage, repeat analysis, etc Methods or control of methods Equipment use and maintenance Record keeping QC procedures & Audit procedures 26

27. PLANNING Documented and approved plan for the work May form part of the contractual agreement with the sponsor Should reflect the requirements of the clinical protocol Should contain sufficient detail to provide clear instruction to staff Amendments and deviations documented 27

28. CONDUCT In accordance with the plan Data and results recorded promptly, indelibly, legibly, signed & dated Methods validated Uniform analytical platforms Definition of raw (source) data Documented procedure for repeat analysis 28

29. REPORTING Two types of report Analytical report: A formal report which may be issued on completion of the work detailed in the analytical plan. Analytical results : A document(s) containing just the results which is usually issued rapidly on completion of sample analysis on a given day Contain information as required by GCLP, Analytical plan and Sponsor clinical trial number, identity of the facility and APM, dates, results etc. QC to ensure accuracy Approved for issue 29

30. STORAGE AND RETENTION OF DATA Trial data, Analytical plan & Analytical results/reports Supporting data or information Organisation charts Staff records (training, job descriptions, CVs) Equipment records( maintenance & calibration) System validation records Historical file of SOPs Quality Audit reports Stored in appropriate facilities 30

31. SUMMARY -GCLP GCLP is concerned with producing reliable results which can be supported and are reconstructable To meet the challenge of GCP compliance 31