Download DIA Webinar, FDA`s Biosimilars Draft Guidance

FDA’s Biosimilars
Guidance -- Legal and
Regulatory
Considerations
James S. Cohen, Esq.
McDermott Will &
Emery
DIA Webinar
April 10, 2012
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Topics
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Biosimilar vs. Interchangeable
Use of Foreign Data
Post-Market Safety
Exclusivity/Intellectual Property
Combination Product/Device Delivery System
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Background
• Biologics Price Competition and Innovation Act
of 2009 (BPCIA) (part of Patient Protection and
Affordable Care Act) became law (3-23-12)
– Amends section 351 of the PHS Act to create
biosimilar pathway
• February 2012, FDA issues three draft guidance
documents
– This suggests it will be some time before proposed
and final regulations, and final guidance issue
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Background
• Provides current scientific, quality and regulatory
thinking on biosimilars, but little information on
interchangeability
• Biosimilar:
– “the biological product is highly similar to the
reference product notwithstanding minor differences
in clinically inactive components; and there are no
clinically meaningful differences between the
biological product and the reference product in terms
of safety, purity, and potency of the product”
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Biosimilar vs. Interchangeable
• Interchangeable:
– biological product “is biosimilar to the reference
product; and can be expected to produce the same
clinical result as the reference product in any given
patient; and
– … [if] administered more than once to an individual,
the risk in terms of safety or diminished efficacy of
alternating or switching between the two products is
not greater than the use of the reference product
without such alternation or switch”
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Biosimilar vs. Interchangeable
• Sponsors should use “stepwise approach” to
showing biosimilarity
– FDA will conduct “risk-based” review of “totality of
evidence” submitted
– Amount/type of analyses and testing required
determined on case-by-case (“product-specific”) basis
• “Extensive” comparative analytical data using
“state-of-the-art” technology expected
– If reference product cannot be adequately
characterized in this way, suggests meet with Agency
to assess whether appropriate for biosimilar pathway
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Biosimilar vs. Interchangeable
• FDA does discuss showing of interchangeability
• Will consider interchangeability at time of
original/supplemental application
– Says would be difficult at this time “as a scientific matter” to
establish interchangeability given statutory definition and
“sequential nature of that assessment”
• Unlikely to determine if product is
interchangeable in an original application
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Biosimilar vs. Interchangeable
• Like generics, interchangeable product may be
automatically substituted for reference product
without approval by prescriber (subject to state
laws)
• However, no similar provision for biosimilars
and, at least initially, unlikely will be eligible for
substitution under state laws
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Use of Foreign Data
• In general, sponsor needs to provide data
directly comparing products
• However, “under certain circumstances,”
sponsor can “seek to use” data from animal or
clinical studies
– Must provide adequate data to scientifically justify the
relevance of the non-U.S. comparative data
• Should discuss with FDA very early in
development phase
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Use of Foreign Data
• Factors FDA will consider include:
– Relevance of clinical program design to condition of use and
patient population
– Relationship between the two license holders, including whether
non-U.S. product, and/or any of its components, are
manufactured in the same facility
– Whether non-U.S. product was (a) manufactured in a facility
licensed/inspected by, and/or (b) licensed by, a regulatory
authority with similar scientific/regulatory standards as U.S. (e.g.,
ICH countries), and how long product marketed
– Scientific bridging between the products, including comparative
physico-chemical characterization, bioassays/functional assays
and comparative clinical and/or non-clinical PK and/or PD data,
as well as data to address labeling and packaging differences
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Use of Foreign Data
• “At this time” unlikely clinical comparisons with
non-U.S. product would be an adequate basis to
support “the additional criteria required” for
interchangeability
• FDA has suggested it would like to utilize
Europe’s biosimilar experience
– FDA has expanded its confidential information sharing
agreements with European and other regulatory
authorities for clinical data, inspection, and postmarket safety information
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Post-Market Safety
• Provides only general information, but
emphasizes need for robust program
• Post-market safety considerations have come
under increasing scrutiny
– Given FDA’s cautious approach to biosimilars, will
likely require (at least initially) enhanced
labeling/post-market surveillance as condition of
approval
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Post-Market Safety
• Should monitor/consider any particular safety
concerns associated with:
– use of reference product and its class, and
– product in its development/clinical use if marketed
outside U.S.
• Proposed product labeling should include clear
statement that approved:
– As biosimilar to reference product for the indication(s)
and route(s) of administration, and (has or has not)
been determined to be interchangeable
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Post-Market Safety
• May require post-market safety and
effectiveness studies, and Risk Evaluation and
Mitigation Strategies (REMS)
• Sponsors should consult with “appropriate FDA
Divisions” to discuss approach
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Exclusivity and Patent Disputes
• BPCIA has exclusivity provisions, and provisions for
resolution of patent disputes that differ from ANDA
process.
• Exclusivity for reference product:
– No 351(k) product can be approved until 12 years from first
licensure of reference product
– No 351(k) application can be filed until 4 years from first
licensure
• Also, 6 months exclusivity for pediatric studies, and
exclusivity provisions for first interchangeable approved
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Exclusivity and Patent Disputes
• Process for patent dispute resolution
– Unlike the public patent listing process for generic
drugs, the BPCIA provides for a detailed private
disclosure process in which -• Applicant provides copy of application and shares
manufacturing information with innovator
• Innovator identifies its patents, including process and
process patents
• The parties negotiate and reduce to patents in dispute for
litigation, innovator can sue towards end of this process
• Applicant gives 180 days notice before first commercial
marketing, and innovator can seek preliminary injunction
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Exclusivity and Patent Disputes
• FDA “is continuing to review” the reference
product exclusivity provisions, and has
requested pubic comment on factors to consider
in its interpretation of those provisions
– e.g., whether 12 years applies to market and data
exclusivity, or data exclusivity limited to 4 years
• Applicant may include a request for exclusivity
– Until further guidance available, “adequate data and
information’ should be included to support request
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Combination Product/Device Delivery
System
• Some biosimilars will be combination products
(e.g., biologic-device, biologic-drug)
• Biosimilar can have different delivery/containerclosure system
– pre-filled syringe or auto-injector vs. vial presentation
• Biosimilar in delivery device may require
separate device application
– FDA has limited the number of CPs for which it has
required separate INDs or marketing applications
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Combination Product/Device Delivery
System
• If different delivery/container closure system:
– for biosimilar, must show compatible for use with final
formulation through appropriate studies (including
extractable/leachable and stability studies), and for
certain design differences, performance testing and a
human factors study may be needed
– For interchangeable, FDA may consider whether
differences significantly alter critical design attributes,
product performance, or operating principles, or
would require additional instruction without the
intervention of prescriber. Additional performance
data may also be needed
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Contact Information
• Comments or questions welcome
James S. Cohen
McDermott Will & Emery, LLP
600 Thirteenth Street, N.W
Washington, D.C. 20005
[email protected]
202-756-8276
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