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Clinical Trial Review and Approval: New Regulations and their implications Siddika Mithani, Ph.D Clinical Trials & Special Access Programme Therapeutic Products Directorate February, 2003 Health Products and Food Branch Direction generale des produits de sante et des aliments Overview Clinical Trial Reform New Regulations for Clinical Trials implemented September 1, 2001 Clinical Trial Applications – filing requirements Health Products and Food Branch Direction generale des produits de sante et des aliments Objectives of CT Framework Maintain protection of research subjects Enhance competitiveness of the research environment Assure growth of the Canadian research environment Key Considerations… Risk management is of paramount importance Research subjects should not be exposed to undue risk Shared responsibility of study sponsors, investigators, Research Ethics Boards and Health Canada Evolution of the clinical trial review process Clinical Trial Review and Approval (1997) ICH adopted guidelines including the Good Clinical Practice Consolidated Guidelines TPD guidelines for studying of special populations (women, children, etc.) Need for change…. Canadian Context Review period viewed as internationally noncompetitive by industry Canadian R&D industry interested in establishing Phase 1 CT research facilities in Canada leading to more R&D Phase 1 represents only 4% of clinical research conducted by manufacturers of patented medicines in Canada New Regulatory Framework 30 day default review period for clinical trial applications [C.05.006(1)(b)] 7 day administrative target for bioequivalence and appropriate Phase 1 clinical trial applications [policy statement] Framework for inspection program for all clinical trials against generally accepted principles of Good Clinical Practices 30-day Default System Scope [C.05.002] - clinical trials in Phases I, II, III - applications for Phase IV trials not required [DIN/NOC] - Clinical trial amendments [C.05.008] Application requirements the same for all sponsors [industry and independent investigators - [C.05.005] Additional information must be submitted within 2 days [C.05.009] 7-day Target System [Policy] Scope - Bioequivalence trials - Phase I trials in healthy adult volunteers Exemptions - Phase I trials in patients - Phase I trials involving: somatic cell therapies, gene therapies, xenografts, prophylactic vaccines or reproductive & genetic technologies Sponsors must receive No Objection Letter prior to initiation of the trial Regulatory Requirements Research Ethics Boards (composition and mandate) Qualified Investigator defined in the regulations Sponsor’s Obligations: - Good Clinical Practices [C.05.010] - Labelling of Clinical Trial Supplies [C.05.011] - Record keeping requirements [C.05.012] - ADR Reporting [C.05.014] Additional Reporting Requirements Prior to commencement of the clinical trial [C.05.006(1)(d)]: - information on clinical trial site and qualified investigator - information on REB for each clinical trial site - information on REB refusal if applicable - proposed date for commencement of the clinical trial at each site Suspension and Cancellation Suspension [C.05.016] - reasonable grounds - written notice indicating applicable site[s] - 30 day window with opportunity to be heard Cancellation [C.05.017] - safety concern - written notice indicating applicable site[s] - 60 day window Review Process Pre-CTA meeting Filing of CTA Clinical Trial Site Information Form Notification - Administrative changes to protocol - Discontinuation not related to safety - Some Quality changes Clinical Trial Applications (CTAs) Regulatory Requirements - HC 3011 Form - Investigator’s Brochure - Proposed Protocol(s) including rationale for study Operational Requirements - WP format - For pharmaceuticals - PCERT Investigator-Initiated CTAs Requirements - HC 3011 - Investigator’s Brochure (or Product Monograph - Rationale for proposed study - Informed Consent - Quality information, if drug not marketed in Canada Continuous Assessment Premature discontinuation of trial - detailed rationale - impact on proposed/ongoing trials - confirm that distribution stopped, unused drug returned and investigators notified Serious and Unexpected ADRs to be faxed to appropriate Directorate Continuous Assessment Other Expedited Reports include: - for expected serious ADRs, an increase in the rate of occurrence - significant hazard to patient – eg., drug does not appear to be working in life-threatening disease - major safety finding from newly completed animal study Safety Updates/ IB Updates Required on a annual basis, or as requested Processed as Notifications - Investigator’s Brochure annually - New IB should reflect all safety information - Global status of drug More Information….. TPP Website: www.hc-sc.gc.ca/hpb-dgps/therapeut Guidance Documents: …../htmleng/draft_guide_industry.html Contact: [email protected]