Inspection Planning - University of Manitoba

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
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Process for selecting the target
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Factors that may impact the target
• Site Selection
• Going Forward
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
GCP Inspection Target
• Process for selecting the target
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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
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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.
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
GCP Inspection Target (cont’d)
• Factors that may impact the target
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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
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Site Selection
• Inspection Strategy for Clinical Trials (POL-0030)
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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
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Started January 1, 2002.
A final implementation phase
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Started January 1, 2003.
The Inspectorate is responsible for site selection.
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Site Selection (cont’d)
• Voluntary and Confidence Building Phase
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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.
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Site Selection (cont’d)
• "Horizontal" Inspections
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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.
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Site Selection (cont’d)
• REB Assessments (2002-2008)
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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.
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Site Selection (cont’d)
• Selection Process
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Lists of approved CTAs are generated by SIPD
(Submission and Information Policy Division) for the
GCP Compliance Unit in Ottawa
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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.
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Site Selection (cont’d)
• Selection Criteria (current strategy)
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Number of clinical trials conducted at the site
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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
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Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Site Selection (cont’d)
• Selection Process (cont’d)
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Inspections may be conducted at the following
sites:
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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.
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Going Forward
• Vision for a “representative” site selection that
would include:
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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
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Going Forward (cont’d)
• Selection Criteria (examples)
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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:
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Sponsors
Qualified Investigators (QI)
Central Research Organizations (CROs)
Site Management Organizations (SMOs)
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Going Forward (cont’d)
• Selection Criteria (cont’d)
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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
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Going Forward (cont’d)
• Should also consider…
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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
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
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
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments