GCP Compliance Part 1

Your Health and
Safety... Our priority
Votre santé et votre
Securité… notre priorité
Health Canada’s
GCP Compliance Program
GCP Information Sessions
November 2010
Objective
• To describe the role that Health Canada plays in
clinical research in Canada
• To provide an overview of the GCP compliance
monitoring program in Canada
• To explain the process by which clinical trial
inspections are conducted in Canada
• To provide a summary of findings from inspections
conducted since 2002
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Overview
• Structure and Responsibilities
• Clinical Trials Regulatory Framework
• Inspection Program
- Inspection Strategy
- Inspection Stages
• Inspection Findings
• Going Forward
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Structure and Responsibilities
Our Mandate:
• Minimizing health risk factors to Canadians while
maximizing the safety provided by the regulatory
system for health products and food; and
• Promoting conditions that enable Canadians to make
healthy choices and providing information so that
they can make informed decisions about their health.
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Structure and Responsibilities (cont’d)
Partial Structure:
Health Canada
Health Products and Food Branch
(HPFB)
Regions And Programs Branch
(RAPB)
Since April 1st, 2010
HPFB Inspectorate
Operational Centres
Good Clinical Practices
Compliance Unit
Halifax, Nova Scotia
Montreal, Quebec
Toronto, Ontario
Winnipeg, Manitoba
Vancouver, British Columbia
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Structure and Responsibilities (cont’d)
• Overview of Clinical Trial Oversight
CTA
Approval
Clinical Trial
Oversight
Adverse
Event
Monitoring
Clinical Trial
Inspections
Operational
Centres (RAPB) in
collaboration with
the Inspectorate
(HPFB)
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Structure and Responsibilities (cont’d)
Alberta Operational
Centre, Edmonton,
AB
Western
Operational Centre,
Vancouver, BC
Compliance
Quebec Operational
Coordination and Centre, Montreal, QC
Licensing Division,
Ottawa, ON
Manitoba and
Saskatchewan
Operational
Centre, Winnipeg,
Ontario and Nunavut
MB
Operational
Centre, Toronto, ON
Atlantic Operational
Centre, Halifax, NS
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Structure and Responsibilities (cont’d)
• The Inspectorate’s primary role, in collaboration with
the operational centres, is to deliver a national
compliance and enforcement program for drugs,
natural health products, medical devices, including
biologics and genetic therapies.
• This includes a GCP program for the verification
against and the enforcement of the regulatory
framework for clinical trials involving human subjects.
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Structure and Responsibilities (cont’d)
• The Inspectorate’s role is accomplished through 4
core functions:
–
–
–
–
Inspection
Compliance Verification/Investigation
Establishment Licensing
Laboratory Functions
• There is no establishment licensing requirement for
clinical trials.
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Structure and Responsibilities (cont’d)
• The Inspectorate’s guiding principles are:
– Transparency
• Compliance and Enforcement Policy
– Fairness
• Predictable and uniform national approach
– Based on Risk Management
• Decisions based on level of risk
– Commitment to Quality
– Qualified Staff
• Continuous Training
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Clinical Trials Regulatory Framework
• Food and Drugs Act (FDA)
• Food and Drug Regulations (FDR), Division 5
“Drugs for Clinical Trials Involving Human
Subjects”
- Came into force on September 1, 2001
- These regulations are not applicable to Medical
Devices or Natural Health Products (NHPs) (other
requirements apply)
- Integrate Good Clinical Practices (GCP).
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Clinical Trials Regulatory Framework (cont’d)
• Overview of Division 5 of the FDR:
–
–
–
–
–
–
–
–
C.05.001 (Interpretation)
C.05.002 (Application)
C.05.003 (Prohibition)
C.05.005 (Application for Authorization)
C.05.006 (Authorization)
C.05.007 (Notification)
C.05.008 (Amendment)
C.05.009 (Additional Information and Samples)
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Clinical Trials Regulatory Framework (cont’d)
• Overview of Division 5 of the FDR (cont’d):
– C.05.010 (Sponsor’s Obligations – GCP)
• Clinical trials regulatory framework is harmonized
through the principles of good clinical practices, as
described by ICH E6 “Guideline for Good Clinical
Practices”.
• ICH E6 was adopted by Health Canada in 1997.
• ICH E6 outlines requirements for the design, conduct
and recording of trials.
• Consistent with the Declaration of Helsinki.
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Clinical Trials Regulatory Framework (cont’d)
• Overview of Division 5 of the FDR (cont’d):
– C.05.010 (Sponsor’s Obligations – GCP)
• It is the sponsor’s responsibility to ensure adherence to
good clinical practices, including those requirements
outlined in this section.
• Few requirements are “black and white”
– The need for no more than one QI.
• ICH E6 provides interpretation.
• Some requirements differ from ICH E6
– The duration of record retention (C.05.012).
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Clinical Trials Regulatory Framework (cont’d)
• Overview of Division 5 of the FDR (cont’d):
– C.05.010 (Sponsor’s Obligations – GCP)
• The clinical trial is scientifically sound and clearly
described in a protocol;
• The clinical trial is conducted, and the drug is used, in
accordance with the protocol and this Division;
– Refer to ICH GCP sections 4.5 and 4.6.5.
– Deviations from or changes to the protocol should not be done
without Sponsor agreement and REB/Health Canada approval,
as needed.
– Any deviation from the approved protocol should be
documented and explained.
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Clinical Trials Regulatory Framework (cont’d)
• Overview of Division 5 of the FDR (cont’d):
– C.05.010 (Sponsor’s Obligations – GCP)
• Systems and procedures that assure the quality of
every aspect of the clinical trial are implemented;
– Refer to ICH GCP sections 5.1, 5.18 and 5.19.
– QA and QC requirements, including:
» Written SOPs to ensure compliance with the protocol,
GCP, and regulatory requirements;
» At a minimum, SOPs should cover informed consent
process, AE reporting, handling of the drug, record
retention;
» Written agreements, made by the sponsor with any
party(ies) involved with the clinical trial.
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Clinical Trials Regulatory Framework (cont’d)
• Overview of Division 5 of the FDR (cont’d):
– C.05.010 (Sponsor’s Obligations – GCP)
• For each clinical trial site, the approval of a research
ethics board is obtained before the clinical trial begins
at the site;
– Refer to definition of REB under C.05.001.
– Refer to ICH GCP sections 4.4 and 5.14.2.
• At each clinical trial site, there is no more than one QI;
– Refer to definition of QI under C.05.001.
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Clinical Trials Regulatory Framework (cont’d)
• Overview of Division 5 of the FDR (cont’d):
– C.05.010 (Sponsor’s Obligations – GCP)
• At each clinical trial site, medical care and medical decisions,
in respect of the clinical trial, are under the supervision of the
QI;
– Refer to ICH GCP sections 2.7 and 4.3.
– Provide adequate medical care to a subject for any AEs,
including clinically significant laboratory values.
– Inform a subject when medical care is needed for intercurrent
illness(es).
– Make a reasonable effort to ascertain the reason(s) for
withdrawal, while fully respecting the subject's rights.
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Clinical Trials Regulatory Framework (cont’d)
• Overview of Division 5 of the FDR (cont’d):
– C.05.010 (Sponsor’s Obligations – GCP)
• Each individual involved in the conduct of the clinical trial is
qualified by education, training and experience;
– Refer to ICH GCP sections 2.8, 4.1.1-3, 4.2.4, 5.5.1 and
5.18.2(b).
– There must be evidence of such qualifications.
– Includes knowledge by all trial personnel of:
» the protocol, the investigational product(s) and their trialrelated duties and functions;
» GCP and the applicable regulatory requirements.
– Includes supervision of the overall conduct of the trial, handling
and verifying the data, conducting the statistical analyses,
preparing the trial reports and monitoring the trial.
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Clinical Trials Regulatory Framework (cont’d)
• Overview of Division 5 of the FDR (cont’d):
– C.05.010 (Sponsor’s Obligations – GCP)
• Written informed consent, given in accordance with the
applicable laws governing consent, is obtained from
every person before that person participates in the
clinical trial but only after that person has been
informed of:
» the risks and anticipated benefits to his or her health
arising from participation in the clinical trial, and
» all other aspects of the clinical trial that are necessary for
that person to make the decision to participate in the
clinical trial
– Refer to ICH GCP sections 2.9 and 4.8.
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Clinical Trials Regulatory Framework (cont’d)
• Overview of Division 5 of the FDR (cont’d):
– C.05.010 (Sponsor’s Obligations – GCP)
• The ICF must be approved, as well as any
amendments;
• It is to be revised whenever important new information
becomes available that may be relevant to the subject's
consent;
• The subject should be informed in a timely manner if
new information becomes available that may be
relevant to his/her willingness to continue (to be
documented);
• The subject should be fully informed of all pertinent
aspects of the trial;
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Clinical Trials Regulatory Framework (cont’d)
• Overview of Division 5 of the FDR (cont’d):
– C.05.010 (Sponsor’s Obligations – GCP)
• The language used should be as non-technical as
practical and should be understandable to the subject;
• Time must be afforded to the subject to inquire about
the trial and to decide whether or not to participate in
the trial. All questions about the trial should be
answered to the satisfaction of the subject;
• Prior to a subject's participation, the ICF should be
signed and personally dated by the subject and by the
person who conducted the informed consent
discussion.
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Clinical Trials Regulatory Framework (cont’d)
• Overview of Division 5 of the FDR (cont’d):
– C.05.010 (Sponsor’s Obligations – GCP)
• The subject must understand (via both the informed consent
discussion and the ICF):
– That the trial involves research
– The purpose of the trial
– The trial treatment(s) and the probability for random
assignment to each treatment
– The trial procedures to be followed
– The subject's responsibilities
– The alternatives that may be available to the subject, and their
important potential benefits and risks
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Clinical Trials Regulatory Framework (cont’d)
• Overview of Division 5 of the FDR (cont’d):
– C.05.010 (Sponsor’s Obligations – GCP)
– That their participation in the trial is voluntary and that they may
refuse to participate or withdraw from the trial, at any time
– Who may be granted direct access to their original medical
records for verification of clinical trial procedures and/or data
– That records identifying them will be kept confidential
– Whom to contact for further information
– The expected duration of their participation in the trial.
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Clinical Trials Regulatory Framework (cont’d)
• Overview of Division 5 of the FDR (cont’d):
– C.05.010 (Sponsor’s Obligations – GCP)
• The requirements respecting information and records set out
in section C.05.012 are met;
– Refer to Guide-0068
» Essential documents should be retained as per ICH E6
(REB: section 3.4, QI: section 4.9.5 and Sponsor: section
5.5.11).
» The original records need to be kept for 25 years.
• The drug is manufactured, handled and stored in accordance
with the applicable GMPs;
– Refer to Annex 2 to the Current Edition of the GMP Guidelines.
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Clinical Trials Regulatory Framework (cont’d)
• Overview of Division 5 of the FDR (cont’d):
– C.05.011 (Labelling)
• The sponsor shall ensure that the drug bears a label
that sets out the following information in both official
languages:
– a statement indicating that the drug is an
investigational drug to be used only by a qualified
investigator
– the name, number or identifying mark of the drug
– the expiration date of the drug.
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Clinical Trials Regulatory Framework (cont’d)
• Overview of Division 5 of the FDR (cont’d):
– C.05.011 (Labelling)
•
•
•
•
•
the recommended storage conditions for the drug
the lot number of the drug
the name and address of the sponsor
the protocol code or identification, and
if the drug is a radiopharmaceutical as defined in
section C.03.201, the information required by
subparagraph C.03.202(1)(b)(vi).
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments
Clinical Trials Regulatory Framework (cont’d)
• Overview of Division 5 of the FDR (cont’d):
– C.05.012 (Records)
– C.05.013 (Submission of Information and Samples)
– C.05.014 (Serious Unexpected Adverse Drug
Reactions)
– C.05.015 (Discontinuance of a Clinical Trial)
– C.05.016 & C.05.017 (Suspension & Cancellation)
Health Products and Food Branch
Inspectorate
L’Inspectorat de la Direction générale
des produits de santé et des aliments