1. Quality Assurance & Quality Control in Pharmaceuticals & Healthcare Industries By- Dr. Sushrut Varun Satpathy MBBS, MD Assistant Professor Department of Pharmacology Sikkim Manipal Institute of Medical Sciences

2. Good Clinical Practices: An overview 28 th of January 2016 2

3. Good Clinical Practice (GCP): Meaning 3  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.

4. The objective of this ICH GCP Guideline is to provide a unified standard for the European Union (EU), Japan and the United States to facilitate the mutual acceptance of clinical data by the regulatory authorities in these jurisdictions. 4

5. History Why Do We Need Guidelines? Why Are We Regulated?

6. Nazi Medical War Crimes: during World War II Experiments conducted by Nazi physicians during World War II were unprecedented in their scope and the degree of harm and suffering to which human beings were subjected

7. 7

8. 8 THE DOCTORS TRIAL

9. The Tuskegee Syphilis Study

10. Belmont report 1978 (Ethical Principles and guidelines for the protection of human subjects of research)-Tuskegee syphilis study

11. The Jewish Chronic Disease Hospital Study

12. The Willowbrook Study

13. Thalidomide tragedy 13

14. The thalidomide tragedy marked a turning point in toxicity testing, as it prompted United States and international regulatory agencies to develop systematic toxicity testing protocols The thalidomide tragedy also brought into sharp focus the importance of rigorous and relevant testing of pharmaceuticals prior to their introduction into the market place 14 Thalidomide tragedy

15. Codes and Guidelines  Nuremberg Code (1947).  W.M.A’s Declaration of Helsinki (1964). Belmont Report (USA) (1979)-Tuskegee syphilis study  Council for International Organizations of Medical Sciences (CIOMS) 1993.  International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH), in 1996, Guideline on Good Clinical Practice,E6 (GCP).

16. Overview of ICH GCP

17. What is ICH? The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH)- is unique in bringing together the regulatory authorities and pharmaceutical industry of Europe, Japan and the US to discuss scientific and technical aspects of drug registration. 17

18. What is ICH? Since its inception in 1990, ICH has gradually evolved ICH's mission is to ensure that safe, effective, and high quality medicines are developed and registered in the most resource-efficient manner

19. How did it evolve? The need to harmonize Public disasters, serious fraud and abuse of human rights. Trials of War criminals-Nuremberg code 1947 Thalidomide- Declaration of Helsinki 1964 Belmont report 1978 ( Ethical Principles and guidelines for the protection of human subjects of research)-Tuskegee syphilis study

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

21. The result? Many guidelines made Most important- ICH GCP guidelines Evolved in several steps

22. Sources and development of GCP guidelines

23. 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.

24. Why is it needed ? To avoid research misconduct and fraud as this is a growing public and professional concern nowadays 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 Helsinski

25. Why is it needed? To assure that the clinical trial data are credible To provide a unified standard for different countries to facilitate the mutual acceptance of clinical data by regulatory authorities

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

27. 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

28. 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

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

30. Principles of ICH GCP Investigational Product  Manufactured, handled and stored as per GMP Quality Assurance  Systems and procedures to ensure the Quality of every aspect of the trial

31. Indian GCP guidelines Released in Dec 2001(Developed by CDSCO and endorsed by DCGI) In general, in line with ICH GCP

32. The Players Under the GCP guidelines- Institutional Review Board/ Ethics Committee, Investigators Sponsor(s)

33. Institutional Review Board/Ethics Committee Responsibilities : Safeguard rights, safety and well being of all trial subjects Trial protocol(s)/ amendment(s), written informed consent form(s), subject recruitment form(s), written information to be provided to the subjects, investigator’s bronchure(IB), available safety information, information about payments and compensation, investigator’s CV

34. IRB/EC…responsibilties..cont.. Review a proposed clinical trial within a reasonable time Review each ongoing trial at intervals appropriate to the degree of risk to human subjects, but atleast once per year Address relevant ethical concerns and meet applicable regulatory requirements for such trials Review both amount and method of payment to subjects*

35. Investigator Qualified by education, training and experience Appropriate use of the investigational product(s), aware of and comply with GCP and regulatory requirement(s) Permit monitoring and auditing by the sponsor, and inspection A qualified physician (investigator/sub- investigator) – responsible for trial related decisions

36. Investigator …..cont… Comply with the sponsors for timely completion of the project and recording of all clinical and non-clinical data ADR- managed appropriately and reported On Trial completion - * inform institution * documents/records – sponsor * IRB/EC- summary

37. 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

38. 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 – Completion or withdrawal (reason) from the study

39. 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

40. Sponsor Responsiblities : Quality assurance and Quality control : responsible for implementing and maintaining quality assurance and quality control systems with written SOPs to ensure that trials are conducted and data generated, documented and reported in compliance with the protocol, GCP and the applicable regulatory requirement(s)

41. Sponsor….responsibilities…cont… Contract Research Organization (CRO): May transfer any or all of sponsor’s trial- related duties and functions to a CRO, but the ultimate responsibilty for the quality and integrity of trial data always resides with the sponsor

42. Sponsor…respon…cont… Medical expertise Trial design Trial management, data handling, record keeping Independent data monitoring committee Investigator selection Allocation of duties and functions Compensation to subjects and investigators

43. Sponsor…respon…cont… Financing Notification/submission to regulatory authority Information on investigational product Manufacturing, packaging, labeling, coding, supplying and handling investigational product Record access Safety information ADR monitoring Trial monitoring and audit Premature termination or suspension of a trial

44. Conclusion Scientific community involved in all types of clinical trials must be aware of and comply with the specification described in details in the guidelines for GCP before conducting any trial

45. Conclusion 45 Thanks..... “When a doctor [goes] wrong, he is the first of criminals. He has nerve and he has knowledge.” - Sherlock Holmes

46. References:  http://www.wma.net/e/policy/b3.htm http://www.wma.net/e/policy/b3.htm  www.hhs.gov/ohrp/humansubjects/guidance/belmont.html www.hhs.gov/ohrp/humansubjects/guidance/belmont.html  www.hhs.gov/ohrp/references/nurcode.html www.hhs.gov/ohrp/references/nurcode.html  www.icmr.nic.in/guidelines/GCLP www.icmr.nic.in/guidelines/GCLP  www.cdsco.nic.in/ www.cdsco.nic.in/  www.ub.edu/recerca/Bioetica/doc/Declaracio_Helsinki_2013 www.ub.edu/recerca/Bioetica/doc/Declaracio_Helsinki_2013  www.jewishvirtuallibrary.org/jsource/Holocaust/nazi_experime nts www.jewishvirtuallibrary.org/jsource/Holocaust/nazi_experime nts  www.ich.org/fileadmin/Public_Web.../ICH.../E6_R1__Guideline www.ich.org/fileadmin/Public_Web.../ICH.../E6_R1__Guideline