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 Regulation
of Subsequent Entry Biologics in Canada
Tanya Weston
Health Canada released, for public comment
only, a
revised version of the Draft Guidance for
Sponsors: Information and Submission Requirements for
Subsequent Entry Biologics (“SEBs”)
on March
27, 2009.
The
revised version is in respect of a proposed
regulatory approval process for SEB’s and reflects comments
received from stakeholders during a public consultation held
in June 2008. The revised version was released in conjunction
with Proposed Revisions to Guidance Document: Data Protection
under C.08.004.1 of the Food and Drug Regulations and
Proposed Additions to Guidance Document:
Patented Medicines (Notice
of Compliance) Regulations (“PM(NOC)
Regulations”).
As described by Health
Canada, biologic products as those derived through the
metabolic activity of living organisms. These products are
listed on Schedule D of the Food and Drugs Act (i.e.,
blood products, cells and tissues, gene therapies, vaccines,
etc.). An SEB is
defined as a biologic product that would enter the market
subsequent to, and “similar” to, an approved innovator
biologic product by relying, to some extent, on the safety and
efficacy data of an approved innovator product where they
could demonstrate similarity with the approved product.
Key elements of the revised
version of the draft guidance document are briefly described
below:
-
Proposed Regulatory Framework for SEB’s:
It is apparent from the revised version of the draft
guidance document and the public consultation held in June
2008 that Health Canada proposes to regulate SEB’s through
guidance documentation and without amendments to the Food
and Drug Regulations or the PM(NOC) Regulations.
More particularly, Health Canada proposes to utilize the
existing regulatory framework for pharmaceuticals and
biologics (i.e., Part C, Division 8 of the Food and Drug
Regulations) with some modification. A manufacturer of
an SEB will be required to submit a New Drug Submission,
which may be based on reduced clinical data where the
manufacturer can demonstrate similarity between the SEB and
a chosen reference product. Health Canada has also indicated
that it will undertake regulatory review of SEB submissions
prior to finalizing the guidance documentation.
-
Similarity: The guidance
document indicates that a manufacturer must demonstrate
similarity through extensive data, including side-by-side
characterizations of the SEB and the reference product.
Similarity will primarily be deduced from comprehensive
quality studies. Manufacturers will be required to
demonstrate that the SEB and reference product are
comparable in terms of quality, safety, and efficacy. It is
important to note, however, that manufacturers will not be
required to demonstrate that the two products are identical.
Rather, the manufacturer will be required to establish that
the two products are similar enough that the existing
knowledge of both products sufficiently indicates that any
quality attribute differences should have no adverse impact
on the safety or efficacy of the SEB and that the
non-clinical and clinical data in respect of the reference
product is relevant to the SEB.
-
Reference Product: The
reference product should be an approved biologic product
marketed in Canada with “a suitable duration and volume of
marketed use such that a demonstration of similarity will
bring into relevance a substantial body of acceptable data
dealing with safety and efficacy.” The Minister of Health
may consider an approved reference product from another
jurisdiction (“foreign reference product”) upon request.
Where a foreign reference product is used to demonstrate
similarity to an authorized biologic product, the submission
must provide a link between the foreign reference product
and the product authorized for sale in Canada. More
particularly, the SEB submission must document that the
foreign reference product is either “marketed by the same
innovator company or corporate entity which is approved to
market the medicinal ingredient in the same dosage form in
Canada, or is marketed through a licensing arrangement with
the innovator company or corporate entity which currently
markets the version of the product approved in Canada.” It
is important to note that an SEB cannot be used as a
reference product for subsequent submissions since it will
not have been authorized on the basis of a complete quality
and clinical data package.
-
Differences in Manufacturing Process:
Health Canada will not approve an SEB whose manufacturing
process clearly differs from that of the chosen reference
product (e.g., use of transgenic organisms versus cell
cultures). The impact of any process differences will be
assessed taking into consideration factors such as the
specific process, the product, the extent of the
manufacturer’s knowledge of and experience with the process
and the development data generated.
-
Data
Protection: Amendments to
data protection under c. 08.004.1 of the Food and Drug
Regulations are not proposed at this time. Health Canada
has proposed revising the guidance document in respect of
data protection to specify that a submission for an SEB that
makes a direct or indirect comparison to an innovative
biologic product cannot be filed until six years after the
innovative biologic product in question has been approved.
-
PM(NOC)
Regulations: Amendments to
the PM(NOC) Regulations
are not proposed at this time. Health Canada has proposed
revising the guidance document in respect of the
PM(NOC) Regulations
to specify that section 5 of the
PM(NOC) Regulations will apply to
SEB submissions which seek approval based on a direct or
indirect comparison to a reference product that has patents
listed on the Patent Register (e.g., the sponsor of the
SEB submission
must address each patent listed on the Patent Register in
respect of the reference product before regulatory approval
will be granted). In the case of foreign reference products,
if the Canadian version of the reference product has patents
listed on the Patent Register, section 5 will also apply to
the SEB
submission.
For a discussion regarding the
implications of the proposed regulatory framework for
intellectual property protection of biologics in Canada,
please contact Tanya Weston (tweston@mbm.com).
For a discussion of the original
draft guidance document, please refer to
http://www.mbm.com/News/Quarterly%20e-Newletter/Articles/HTML/Jun%202008%20Articles/Biologics.html
dated June 2008.
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