1. Assessing the Viability of
FDA’s Biosimilars Pathway
Donald R. Ware
February 18, 2016
Petrie-Flom Center for Health Law
Policy, Biotechnology, and Bioethics,
Harvard Law School

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Enactment of BPCIA
Until recently, FDA’s statutory authority was limited to
approval of new biologic medicines, not “biosimilar”
versions of approved biologics
– Biologics are very large, complex molecules, often
antibodies, produced in living cells
•Different manufacturing processes produce different
molecules
•Biologics are among the most expensive therapeutics on the
market, sometimes costing >$100,000/year
–Hatch-Waxman pathway for approval of generic drugs
covers chemically synthesized small molecule drugs
having same active ingredient as innovator product
European Union created regulatory approval pathway
for biosimilar biologics in 2003

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Enactment of BPCIA
After EU pathway created, legislation proposed in U.S.
Biotech industry initially opposed
–Safety issues were paramount in early hearings
–Industry also raised issues about proprietary data,
patents, and economics, emphasizing $1 billion cost of
developing biologics through phase 3 clinical trials
Biologics Price Competition and Innovation Act
(“BPCIA”) enacted March 23, 2010 as part of Affordable
Care Act
–Added new section 351(k) of Public Health Services Act to
create abbreviated approval pathway for biological
products that are “biosimilar” or “interchangeable” with an
FDA-approved biological product

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Applicability
Applies to licensure of a “biological product,” as
distinguished from a drug:”
–virus, therapeutic serum, toxin, antitoxin, vaccine, blood,
blood component or derivative, allergenic product, or
–protein (except any chemically synthesized polypeptide)
Applicant must show that biological product is
“biosimilar” to a “reference product”
“Reference product” for purposes of BPCIA is a single
biological product licensed under PHS Act, i.e., under a
Biologics License Application (“BLA”)

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Approvable as “Biosimilar”
Must be “highly similar” to the reference product
–“No clinically meaningful differences between the
biological product and the reference product in terms of
safety, purity and potency of the product”
Must be based upon data from a clinical study, subject
to waiver by the Secretary
Must have same condition of use in labeling as
approved for reference product
Must utilize same mechanism of action for use listed in
labeling
Must have same route of administration, dosage form,
and strength as reference product

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“Interchangeable Biosimilar”
Heightened Requirements:
 “Biosimilar” to reference product
 Expected to produce the same clinical result in any given
patient
 No risk in switching between reference product and
biosimilar
Benefits of Interchangeability:
 If conditions met, biosimilar may be substituted for reference
product without intervention of prescribing physician (like a
generic drug)
 First interchangeable biosimilar has some market exclusivity
before FDA can approve second interchangeable product

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FDA Implementation
CDER, CBER Biosimilar Review Committees (BRC)
FDA-EMEA-Health Canada “Cluster” to align concepts
Issued 8 draft or final guidances, several others expected
this year, including interchangeability
Currently 59 proposed biosimilar products for 18 different
reference products enrolled in Biosimilar Product
Development Program
Public meetings, public presentations, conferences
Congressional and concurrent Federal (FTC) oversight

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Continuing Debate Over Data
Exclusivity Period
“Data exclusivity”: the period when FDA cannot rely on
its prior finding of safety, purity, and potency of the
reference product based on BLA holder’s clinical data
to support approval of a biosimilar
Under BPCIA, biosimilar applicant may not submit
application for 4 years after date when reference
product first licensed
Also, FDA may not approve application until 12 years
after date when reference product first licensed
12-year exclusivity period was the most contentious
issue in the legislative history of BPCIA
–Obama administration wants to shorten period to 7 years.
Negotiated 7-year period in TPP agreement

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Patent Enforcement Overview
 Unlike Hatch-Waxman, no Orange Book
– Instead, requires exchange of information to identify relevant patents
 Timing of patent litigation relative to approval date
– Unlike Hatch-Waxman, no automatic 30-month stay of approval upon
filing of patent litigation
– Two waves of pre-launch litigation
– Complicated procedure to select patents for earliest litigation
– Potential for at-risk biosimilar product launch
– Implications of eBay for grant of injunctive relief
 Notification to third party patent owners and standing
requirements
– Practical issues raised by necessary participation of third party patent
owners
– Effect on rights of third party patent owners

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No later than 180
days prior to launch
(k) applicant must
give notice to RPS of
expected launch.
RPS may seek
preliminary injunction
1st Wave of Litigation 2nd Wave of Litigation
Within 20 days after FDA
notice, (k) applicant must
provide a copy of (k)
application to RPS
Good Faith negotiation of patents for
immediate litigation
The Pre-Launch Patent Dance
Within 30 days after negotiated list or
short list exchange, RPS must file
immediate litigation on list(s)
Within 60 days
after receiving
BLA Patent List,
(k) applicant must
provide Patent
Statement and
may provide
Patent List
Within 60 days
after receiving
application, RPS
must provide
Patent List
If (k) applicant
does not provide
180 day notice,
RPS may bring DJ
action on any
listed patent
If RPS fails to sue
within 30 days,
remedy limited to
reasonable royalty
If (k) applicant does not
provide Statement,
RPS can bring DJ
action
If patent is omitted
from list, RPS
cannot sue for
infringement of
that patent
If (k) applicant
does not provide
(k) application,
RPS can bring DJ
action on any
patent
FDA notice:
(k) app.
accepted for
filing
Anticipated
launch of
biosimilar
If no agreement after 15 days of negotiation,
RPS and (k) applicant exchange short list of
patents for immediate litigation
= 30 days
Within 60 days after receiving
List and Statement, RPS must
provide Patent Statement

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Partial List of Open Questions
 Will information exchange requirements and costs of
litigation create a disincentive to filing a (k) application?
 Will (k) applicants choose to sidestep the patent dance after
the Federal Circuit’s decision in Amgen v. Sandoz?
 Will (k) applicants have an incentive to challenge many
patents or just one during first phase litigation?
 What will be the interplay of the patent dance with USPTO
proceedings (Inter Partes Review and Post-Grant Review)
and ITC investigations?
 Will FDA ever approve a biosimilar as interchangeable?
 How will approval of biosimilars affect pricing models?

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Thank you!
Donald R. Ware
Partner and Chairman
Intellectual Property Department
617 832 1167
dware@foleyhoag.com