Your Health and Safety... Our priority Votre santé et votre Securité notre priorité Health Canada: Clinical Trial Inspection Planning GCP Information Sessions November 2010
Overview GCP Inspection Target Process for selecting the target Factors that may impact the target Site Selection Going Forward
GCP Inspection Target Process for selecting the target The objectives for the GCP Compliance Program are outlined in Operational Plan A2.4. The objectives are revised every fiscal year. Currently, 80 clinical trial sites per year are targeted for inspection On average, one inspection is conducted in relation to one CTA. An inspection will assess all parties (e.g., CRO). Each region is assigned a number of inspections based on the resource allocation.
GCP Inspection Target (cont d) Factors that may impact the target The complexity of the trial(s) being inspected The number of trials being inspected at one site (i.e., one trial versus multiple trials) The need for a lot of follow-up The need for compliance and enforcement action(s) (e.g., resulting from a NC ) The number of compliance verifications and/or investigations
Site Selection Inspection Strategy for Clinical Trials (POL-0030) POL-0030 was developed in consultation with TPD and BGTD. POL-0030 outlined the strategy for the effective and uniform implementation of the CT Regulations. Two phases to the implementation of inspections: A confidence building and voluntary phase Started January 1, 2002. A final implementation phase Started January 1, 2003. The is responsible for site selection.
Site Selection (cont d) Voluntary and Confidence Building Phase Phased-in approach used for the implementation of the inspection program; Inspections were performed upon invitation at sites of Sponsors and QIs; Inspections were limited in number (18) and no formal ratings were issued; Stakeholders acquired an understanding of the inspection process and inspectors gained experience; Inspectees were satisfied with the voluntary and phased-in approach.
Site Selection (cont d) "Horizontal" Inspections 5 leading paediatric institutions were inspected in 2003/04; Large university hospitals were inspected in 2004/05; Common quality systems and procedures were assessed, in addition to the selected clinical trials; REB and variety of QIs; This approach had a great impact on the entire center.
Site Selection (cont d) REB Assessments (2002-2008) Linked to a specific study; Assessed 34 sites; no formal rating was issued; Assessed REB operations, as per ICH E6, and confirmed conformance by Sponsors to the regulatory requirements involving REBs; The focus was on REB membership, member responsibilities, procedures and records; Canadian standard for REBs is being developed.
Site Selection (cont d) Selection Process Lists of approved CTAs are generated by SIPD (Submission and Information Policy Division) for the GCP Compliance Unit in Ottawa The lists are a snapshot in time. The lists include site information. The lists do not include information on enrolment. The GCP Compliance Unit maintains a list of previous and scheduled inspections to avoid duplication. Sites are selected for inspection based on these lists and following the selection criteria.
Site Selection (cont d) Selection Criteria (current strategy) Number of clinical trials conducted at the site Number of subjects enrolled in the specified clinical trial Status of the specified clinical trial Number of serious unexpected adverse drug reactions at the clinical trial site Compliance history of the sponsor and/or site Drug(s) involved in the specified clinical trial
Site Selection (cont d) Selection Process (cont d) Inspections may be conducted at the following sites: Qualified Investigator (QI) site Sponsor Contract Research Organization (CRO) Site Management Organization (SMO) The majority of inspections are done at the QI site. The Sponsor is ultimately responsible for ensuring adherence to the regulatory requirements, including GCP.
Going Forward Vision for a representative site selection that would include: Geographical spread Large centers and small clinics All therapeutic products Different therapeutic areas Different dosage forms Commercial versus non-commercial trials New parties Vulnerable populations (psychiatry, paediatrics, women) Flagged trials Different phases, including placebo trials
Going Forward (cont d) Selection Criteria (examples) Number of clinical trials conducted at the site Number of subjects enrolled Number of serious unexpected adverse drug reactions Number of protocol deviations Observations made during past inspections Different therapeutic areas Type of responsible party: Sponsors Qualified Investigators (QI) Central Research Organizations (CROs) Site Management Organizations (SMOs)
Going Forward (cont d) Selection Criteria (cont d) Identity of the sponsor Commercial vs non commercial organizations Appropriate balance between pharmaceuticals and biologics, therapeutic class Phase of a clinical trial (e.g., Phase I, bioequivalence study) Geographic spread (big city, small city, rural, etc.) Size of the site (University institutions vs. private clinics) New sponsors, QIs, CROs, SMOs International best practices in other jurisdictions where audits/inspections are conducted
Going Forward (cont d) Should also consider Targeted vs random inspections Inspections based on theme(s), trend(s) Inspections of ongoing vs closed clinical trials Regular vs horizontal inspections (e.g., large research institutions) Input from the review Directorates Simultaneous inspections of Sponsor and QI vs partial assessments Increased focus on data validation and BE trials Joint inspections with other regulatory authorities
QUESTIONS? Further information available online at: Health Canada Drugs and Health Products Compliance and Enforcement Good Clinical Practices www.healthcanada.gc.ca/gcp www.santecanada.gc.ca/bpc