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Good Clinical Practice Presented by:- Mr. Swapnil L. 1
Good Clinical Practices Presented by:- Mr. Swapnil L. Patil M.Pharm Department of Pharmaceutics Pad. Dr. D. Y. Patil College of Pharmacy, Akurdi, Pune, Maharashtra, India, 411018 . Mob.09730306520 2
Contents Glossary Principles of GCP IEC/IRB Responsibilities Investigator Responsibilities Sponsor Responsibilities Protocols and Amendments Investigator’s Brochure Essential Documents 3
GlossaryAdverse drug reaction (ADR)Serious Adverse Event (SAE) AuditBlinding/maskingInvestigatorProtocolSponsor 4
History 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 WWII 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. 5
GOOD CLINICAL PRACTICE FDA ICH 21 CFR International• Electronic Docs. • glossary• Inf. Consent • principles• Financial Disclosure • IRBs• IRBs • Investigator• IND regs. • Sponsor • Essential Docs 35
ICH Guidelines ICH Guidelines are divided into 4 main topics: Quality Topics – relate to chemical and pharmaceutical quality assurance e.g. Q1 Stability Testing Safety Topics – relate to preclinical studies e.g. S1 Carcinogenicity Testing Multidisciplinary Topics – cross-cutting topics which don’t fit into one of the other categories e.g. M1 Medical Terminology Efficacy Topics – relate to clinical studies in human subjects e.g. E6 Good Clinical Practice; e.g. E2A Clinical Safety Data Management: 7 e.g. E9 Statistical Principles for Clinical Trials
FDA Regulations21 C.F.R. Part 312, Subpart D (Duties ofSponsors, Investigators)– 21 C.F.R. Part 50 (Informed Consent)– 21 C.F.R. Part 56 (Institutional ReviewBoards)– 21 C.F.R. Part 54 (Investigator FinancialDisclosure) 8
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’ 9
Good Clinical Practice (GCP) is aninternational ethical and scientific qualitystandard for designing, conducting,recording, and reporting trials that involvethe participation of human patients.Compliance with this standard providespublic assurance that the rights, safety andwell-being of trial patients are protected andclinical trial data are credible. 10
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. 11
Principles of ICH GCP1. 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 Benefits RISK S weighed against the anticipated benefit for the individual trial subject & society.A trial should be initiated and continued only if the anticipated 12 benefits justify the risks.
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 13 protocol that has received prior IRB (or IEC) approval.
Principles of ICH GCP Continued7. 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. 14
Principles of ICH GCP Continued10. 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. 15
Principles of ICH GCP Continued12. 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. 16
Institutional Review Board (IRB), 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. 17
IRB Function•The primary function of an IRB/IEC is to safe guard therights ,safety ,and well being of all trial subjects. This isaccomplished by initial, continuing and annual review.•An IRB should consist of members who collectively havethe qualifications and experience to review and evaluatethe science , medical aspects, and ethics of the proposedtrial. 18
IRB Members 1.A minimum of five (5) members. 2.One member whose concern is not scientific. 3.One member who has no personal or familialrelationship to the institution or trial site.4.Any member with a conflict of interest may notparticipate in any part of the review or vote (except toprovide requested information).5.Individuals with special expertise may be invited to assistwith areas of unique or complex nature. These will not bevoting members.6.A list of IRB/IEC members and their qualifications 19should be maintained.
IRB/Ethics CommitteeAll studies must be approved prior to recruitingparticipantsIRB must review all documents given to participantsReporting AEs and Deviations from protocol to the IRBMaintenance of Records 20
Investigator ResponsibilitiesAdequate Resources Recruitment Time Qualified Staff Facilities Training 21
Investigator ResponsibilitiesMedical Care A qualified MD (or dentist) responsible for trial-related medical decisions Provide adequate medical care for AEs or other significant medical condition Inform PCP about participation in trial Make a reasonable effort to ascertain why participant withdrawals from study 22
Investigator ResponsibilitiesCompliance with Protocol Investigator 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 23
Investigator ResponsibilitiesProgress Reports Safety Monitoring Written summary of trial SAEs should be reported status to the IRB immediately Written reports to the AEs should be reported sponsor or regulatory according to sponsor authority of any changes guidelines affecting the trial Supply sponsor & IRB with requested materials on participant deaths 24
Investigator ResponsibilitiesPremature Termination Final Reportingor Suspension Inform IRB of study Promptly inform trial completion & a summary subjects of the trial’s outcome Assure appropriate Provide sponsor & therapy & follow-up regulatory authorities Inform sponsor, with all required reports regulatory authorities & IRB 25
Investigator’s BrochureDefined as a compilation of theclinical and nonclinical data onthe investigational product(s)that are relevant to the study ofthe product(s) in humansubjects. 26
Clinical Trial ProtocolGeneral InformationBackground InformationTrial Objectives & PurposeTrial DesignSelection & Withdrawal of ParticipantsTreatment of SubjectsAssessment of EfficacyAssessment of Safety 27
Sponsor ResponsibilitiesQuality Assurance & Quality Control Provide written SOPs Secures agreement between all parties Data handlingContract Research Organization (CRO) Hired by the sponsor to implement trial-related dutiesMedical Expertise Designated medical personnel to advise on trial-related medical questions and problems 28
Sponsor ResponsibilitiesTrial Design Designs CRFs Planning analysesTrial Management, Data Handling,Recordkeeping, & Independent Data MonitoringCommittee (DMC) Qualified personnel to supervise overall conduct of the study DMC assesses the progress of the clinical trial Maintain SOPs for electronic data processing Inform Investigator of guidelines for record retention 29
Essential Documents for the Conduct of a Clinical TrialPreclinical trialcommencementDuring clinical conductof trialAfter completion ortermination of trial 30
Storage of Essential DocumentsSponsor Rule: refer to study protocol FDA Rule: 2 options 2 years following marketing of the drug or, 2 years after IND application is withdrawn if drug was not marketed 31
Referenceshttp://www.fda.gov/oc/gcp/guidance.htmhttp://www.clinicaltrials.gov/http://www.fda.gov/oc/ohrt/irbs/websites.htmlhttp://ohrp.osophs.dhhs.gov/http://privacyruleandresearch.nih.gov/http://en.wikipedia.org/wiki/ICH-GCPHandbook: good laboratory practice (GLP): qualitypractices for regulated non-clinical research anddevelopment -2nd ed., WHO Library Cataloguing-in- 33Publication Data, 2nd ed., 7,15-20.
ReferencesOECD Principles of Good Laboratory Practice (asrevised in 1997)". OECD Environmental Healthand Safety Publications (OECD) 1. 1998.http://www.oecd.org/document/63/0,2340,en_2649_34381_2346175_1_1_1_37465,00.html.Schneider, K (1983(Spring)). "Faking it: The caseagainst Industrial Bio-Test Laboratories". AmicusJournal (Natural Resources Defence Council): 14-26.http://planetwaves.net/contents/faking_it.html. 34
ReferencesTweedale, AC (2011). "Uses of ‘Good LaboratoryPractices’ by regulated industry and agencies, andthe safety of bisphenol A". J EpidemiolCommunity Health (BMJ Group) Online First: 15February 2011. doi:10.1136/jech.2010.127761.Webster, Gregory K. et al. (2005). "JALATutorial: Considerations When ImplementingAutomated Methods into GcP". Journal of theAssociation for Laboratory Automation (Elsevier)10 (3): 182–191. doi:10.1016/j.jala.2005.03.003 35