Transcript Drug Submissions: Review Process

Drug Submissions: Review Process
Agnes V. Klein, MD
Biologics and Genetic Therapies Directorate
February, 2003
www/hc-sc.gc.ca/hpb-dgps/therapeut
Items for Consideration
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Introduction
Screening
In-depth evaluation
Assessment of Benefits and Risks
International Harmonization
Continuous Assessment
Introduction
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The Regulatory Organizations
The Regulatory review
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What is it?
Purpose?
Health of the Public
Information/Promotion
Processes
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Role of law, science and medicine
Role of Guidelines, Policies, Practices…
Applies to: drugs, biologics,
radiopharmaceuticals, medical devices…
Drugs are developed in a more or less linear
fashion
International linkages?
What is it we actually do…
(Demistifying the process)
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We ensure the safety, efficacy and quality of
‘drug products’ and the adequacy of their labeling
Why do we do it? For the benefit of Canadians…
We regulate only manufacturers of products (sponsors);
we do not regulate the practice of health professions;
however we use the guidelines drafted by the medical
profession in particular, to help us arrive at decisions….
The Review of Submissions
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Is the core function of the Regulatory Organizations
What is Submission: types as noted
Can we measure quality? By the completeness and
comprehensiveness of format and content.
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Format: ensures that data are organized in a manner that will allow,
quickly, to ensure that all necessary parts of a submission are present.
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Tools: Guidelines, Policies (Mgmt of Submissions Policy)
Structure currently governed by C.08,005.1 (format and content
acceptable to the Minister)
Administrative Screening: ensures accuracy of forms,
submissions, certification, legibility, pagination, general usability,
completeness of data, appropriate cross-referencing, presence of
pivotal trials, presence and completeness of Chem and Mfr.
Information, templates, etc…
The Review:
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New Drug Submissions and compliance with regulations:
A Drug may not be sold unless:
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A NDS has been filed, with sufficient information to assess
safety, effectiveness and quality…. ,a Notice of Compliance
(NOC) has been issued; the “Minister” must notify the
manufacturer is the material is insufficient…,additional
information may be requested…
A NOC may be suspended for a many reasons of safety, efficacy
or quality, of if the information provided turns out to be untrue
Time-frames
Types of submissions
In-depth Evaluation of a Submission
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Substance of a submission: special review paper
Who reviews submissions? How are they reviewed?
What are the possible outcomes?
What happens upon completion? Depends on the type of
submission
Aims of Review/Evaluation
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Establish whether data support claim(s)
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Define necessary safety measures reflected in the
appropriate sections of the PM
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Do not assume the new product is effective and safe, just
because it belongs to an already established class of drugs
Aims of Review/Evaluation
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Establish whether data support claim(s)
Define necessary safety measures reflected
in the appropriate sections of the PM
Do not assume the new product is effective
and safe, just because it belongs to an
already established class of drugs
In-depth Evaluation
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Substance of the clinical portion of a Submission:
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Original information generated by a sponsor for purposes of
demonstrating the properties (safety and efficacy or profile) of a
product and defining the instructions for its use. It can be
conceived as a “review paper” of a very specific nature
What is done?
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An assessment (validation) of the sponsor’s summary. This is
compared against the original database, ensuing summaries and
comment; based on rules of evidence, policies, guidances,
precedents, etc.
Applies to pre-clinical as well clinical data.
Expectations
Product Monograph/Package Insert/Instructions to Patients.
In-depth Evaluation
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The review process as a validation exercise that seeks to prove
consistency of conclusions from trials conducted and that needs to
place the new therapeutic entity within the context of existant
therapies for a disease.
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Benefit-risk assessment: a standard for the quality of the
information provided: This is where science and medicine meet
with statistics, where conclusions can be strengthened or
weakened; where reality and perception meet; where policy and
risk must be concordant; where ethics and regulation come to
forefront, where the Therapeutic Index and the Therapeutic
Window encounter patient outcomes, where clinical relevance
meets statistical significance, where the place of the ‘new product’
within extant therapies may be defined.
Outcomes:
Other comments:
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International collaborations:
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The Product Monograph:
Priority Reviews and NOC/Cs
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Regulatory agencies: FDA, EMEA, TGA,
Other: ICH, CIOMS, etc.
ICH: Purpose and Objective; accomplishments to date
Purpose, scope, status
Other collaborations
Post marketing issues: Adverse Reaction Monitoring: voluntary with
multiple limitations; Signal Generation: ( WHO, Cdn ADR program,
other Regulatory Agencies, publications, media;)
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Purpose: To have an up to date risk-benefit profile of a product, up to
date information in the Product Monographs; up to date information to
be provided to Health Professionals and Public.
Conclusions:
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We consider that, in general, we serve the
public well
Issues:
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Timeliness of Review
Occasional disagreements with Industry
Reality of Risks vs Perceptions of Risk
How to best communicate with public in
general and dispel misperceptions