Jumping Through the Shifting Hoops of Biosimilarity:
A Primer for U.S. and South Korean Companies©
By Lawrence A. Kogan, Esq.
Track 12 - Biotech Patenting & Licensing:
Strategic Response in New Legal Environment and New Market
Session 2 - Regulatory Approval on Biosimilars
Presented at
BIOKorea 2011
Conference and Exhibition
Seoul, Korea
September 30, 2011
Abridged Version
Jumping Through the Shifting Hoops of Biosimilarity:
A Primer for U.S. and South Korean Companies©
TABLE OF CONTENTS
I.
II.
III.
IV.
V.
VI.
VII.
VIII.
Economic Profile of the Biologics/ Biosimilars Industry
Intro to Biologics Price Competition and Innovation Act of 2009 (‘BPCIA’)
Overview of the BPCIA’s Provisions
BPCIA’s Implications for Patent Licensing
Key Hatch-Waxman Act IP Provisions
High Profile Post-Enactment Interpretational/Implementation Debates About
Reference Product Exclusivity
BPCIA’s Impact on International Trade
Conclusion
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I. Economic Profile of the Biologics/ Biosimilars Industry
A.
Macro Data
–
–
–
–
–
B.
Biotech product sales (100 world drugs) to increase from 33% in 2010 to 45% by 2016
U.S. share of world biosimilar market – 72.2% (2013), 82.9%(2014); Europe share of
world biosimilar market – 76.3% (2012), 26.4% (2013), 16.3% (2014)
South Korea IP and data exclusivity laws will tighten, inhibiting new product
opportunities for generics producers. Crowded domestic market, growing pricing &
cost pressures, drives South Korean companies to produce super-generics and
biosimilars (follow-on biologics – ‘FOBs’)
“[T]he [Korean] biosimilar industry depends on the U.S. market in which many
popular biotechnology drugs ... will see their patents expire between 2012 and 2019.”
“‘The U.S. market won’t be easy for Korean firms to penetrate...”
Micro Data
–
–
–
C.
$1.2 billion+ development cost for innovator biologic product + $450 million to build
specialized manufacturing facilities
In US, 8 to 10 years for biosimilar development, at cost of $100-$200 million
Several studies show biosimilar cost discount to biological reference product will be
no more than 10%-30% due to smaller # of FOB market entrants
Anecdotal Data/Prediction
–
US & European biotech drug sales not in line with prior chemical drug sales
•
–
Dendreon (Provenge ), Seattle Genetics (Adcetris ), Human Genome Sciences (Benlysta ),
Bristol Myers Squibb (Yervoy ), Genentech/Roche (Zelboraf ), and Centocor Ortho
Biotech/Johnson & Johnson (Zytiga)
High cost/lack of automatic substitution between FOB & pioneer biologic drugs will
slow FOB market penetration and revenues
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II. Intro to Biologics Price Competition and Innovation Act of 2009 (‘BPCIA’)
A.
General Issues for Consideration
– Signed into law 3/23/10, as part of Patient Protection and Affordable Care Act of 2009
(PPACA); amends Sec. 351 of Public Health Services Act (PHSA)
– Creates an abbreviated approval pathway for generic ‘biological products’ that are
demonstrated to be highly similar (i.e., biosimilar) to or interchangeable with an FDAlicensed reference biological product
– Since enactment, USFDA has worked to establish complete and final guidance on such
pathway – many difficulties & unanswered questions remain due to the relative
complexity of biologics compared to chemically based drugs
• USFDA officials have looked to Europe for ideas; some suggest promulgating rules that
significantly resemble European Medicines Agency (EMA) biosimilar guidelines
• USFDA has no simple way to answer the critical question of how similar a biosimilar must be to
the branded product
B.
Brief Overview of EU Biosimilars Pathway
– Directive 2004/27/EC, amending Directive 2001/83/EC – Article 10.4
– European Medicines Agency (EMA) biosimilar guidelines
• Authorization - Application submitted to secure authorization for a product claimed to be
‘similar’ to another biological medicine – the ‘reference product’.
• The licensing route for biosimilars is based on the principle that:
biologics are not chemical
drugs - biologics similar to a reference product “do not usually meet all the conditions to be
considered as a generic”
• EMEA/CHMP/42832/2005; EMEA/CHMP/BWP/49348/2005, etc.
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II. Intro to Biologics Price Competition and Innovation Act of 2009 (‘BPCIA’)
B.
Brief Overview of EU Biosimilars Pathway (cont’d)
–
Data Exclusivity - ‘8+2+1’
•
•
•
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8 years - Biosimilar application first accepted only after 8 years from initial ‘reference’
product authorization
2 years - Once biosimilar application is accepted, market authorization of biosimilar must
wait another 2 years – i.e., placement in market NOT permitted until after 10 years total
following initial ‘reference’ product authorization (‘8+2’)
1 year - If, during the first 8 years of data exclusivity reference product sponsor obtains an
authorization for new therapeutic indication(s) which bring(s) ‘significant clinical benefit’ in
comparison with existing therapies, data exclusivity extended 1 year = 11 years total (‘8+2+1’)
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III. Overview of the BPCIA’s Provisions
A.
Biosimilarity and Other Information
– 42 USC 262(a) & (k); Public Health Service Act (PHSA), Sect. 351(a)&(k)
– ‘Biosimilar’ Product - “a biological product that is the subject of an application under
subsection (k) which “is ‘highly similar’ to the ‘reference product’ notwithstanding
minor differences in clinically inactive components” and with respect to which “there
are no clinically meaningful differences between the biological product and the
reference product in terms of the safety, purity, and potency of the product”
– ‘Biological’ Product - “any virus, therapeutic serum, toxin, antitoxin, vaccine, blood,
blood component or derivative, allergenic product, protein (except any chemically
synthesized polypeptide) or analogous product, or arsphenamine or derivative of
arsphenamine (or any other trivalent organic arsenic compound), applicable to the
prevention, treatment, or cure of a disease or condition of human beings”
– ‘Reference’ Product - the single biological product licensed under subsection (a) against
which a biological product application submitted under subsection (k) is evaluated
– USFDA two-step approach to reviewing claim of ‘biosimilarity’:
• First - Will review “analytic data showing how similar [company] compounds are to an
FDA-approved innovator version
• Second – Will “determine on a case-by-case basis how much animal and clinical data are
required for approval.”
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III. Overview of the BPCIA’s Provisions
– Also, a biosimilar application must show that:
• “Biological product and reference product use the same mechanism(s) of action for the
condition(s) of use prescribed, recommended, or suggested in the proposed labeling, but
only to the extent the mechanism(s) of action are known for the reference product;
• “The condition(s) of use prescribed, recommended, or suggested in the labeling proposed
for the biological product were previously licensed for the reference product”;
• “The route of administration, dosage form, and strength are the same for the biological
product and the reference product”; and
• “The facility in which the biological product is manufactured, processed, packed, or held
meets standards designed to assure that the biological product continues to be safe, pure,
and potent.”
B.
Interchangeability
– Once ‘Biosimilarity’ is determined can seek ‘Interchangeability’ determination
• Must show that the proposed biological product “can be expected to produce the same
clinical result as the reference product in any given patient”
• Where a proposed “biological product is administered more than once to an individual”:
– Must demonstrate that “the risk in terms of safety or diminished efficacy of alternating or
switching between the use of the biological product and the reference product is not
greater than the risk associated with using the reference product without such alteration or
switch”
• An Interchangeability determine permits presciption of biosimilar by pharmacy; NO
approval of physician required
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III. Overview of the BPCIA’s Provisions
C.
Exclusivity
– BPCIA provides for both marketing exclusivities and data protection for brand-name
biological reference products
• ‘Marketing Exclusivity’ - an FDA-administered proprietary right that prevents others from
filing an application for approval of a follow-on product
– Blocks competitors wishing to develop their own clinical data in support of marketing
approval application
• ‘Data Protection’ - prevents competitors from relying upon clinical data developed by the
brand-name firm in support of FDA approval of a competing version of the product
– Does NOT block competitors wishing to develop their own clinical data in support of
marketing approval application
– i.
General Exclusivity
• 4 years - NO acceptance of FOB ‘biosimilarity’ or ‘interchangeability’ application until 4
years after ‘reference’ product authorization/license [**European Union – 8 years]
• 12 years – NO approval of ‘biosimilarity’ or ‘interchangeability’ application until 12 years
after date of ‘reference’ product authorization/license (+ 8 years) [**European Union + 2
years]
– BPCIA – 12 years total exclusivity - NO market entry (without extension)
– EU EMA – 10 years total exclusivity - NO market entry (without extension)
• MARKETING EXCLUSIVITY or DATA EXCLUSIVITY??
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III. Overview of the BPCIA’s Provisions
•
•
‘Reference Product’ Exclusivity Coverage Unavailable:
NO ‘reference’ product 4year/12year exclusivity coverage for a subsequent application
(made by reference product sponsor, manufacturer, licensor, predecessor in interest, or
other related entity) for:
–
–
•
YES ‘Reference Product’ 4 year/12 year exclusivity coverage for a subsequent
application will be extended to:
–
–
“a change (not including a modification to the structure of the biological product) that
results in a new indication, route of administration, dosing schedule, dosage form,
delivery system, delivery device, or strength” or
“a modification to the structure of the biological product that does not result in a change
in safety, purity, or potency.”
“a modification to the structure of the biological product resulting in a change in safety,
purity, or potency” – essentially a new biological product deserving of its own license
‘Orphan’ Drug Exclusivity
•
•
•
•
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If ‘reference product’ is designated for a rare disease or condition – Exclusivity Period = the
later of:
NO approval of biosimilar or interchangeable application relating to such disease or
condition for 7 years from reference product authorization/license (if reference product first
licensed under Section 526 of the Federal Food, Drug, and Cosmetic Act - Pre-BPCIA license)
or
NO approval of biosimilar or interchangeable application relating to such disease or
condition for 12 years from reference product authorization/license (if reference product
licensed under Section 351 of PHSA - post-BPCIA license)
** Because of BPCIA enactment, if ‘reference’ product first licensed under FFDCA has used
up all or some of its 7 years of exclusivity, it can receive up to 5+ years extra exclusivity but no
more than 12 years in total exclusivity
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III. Overview of the BPCIA’s Provisions
–
‘Pediatric Studies’ Exclusivity
•
‘Reference Product’ 4 year/12 year exclusivity coverage will be extended 6 months to 4.5
years /12.5 years if:
–
–
–
–
–
–
ii.
•
•
‘Interchangeability’ Exclusivity – 1 year
Protects 1st successful biosimilar applicant
NO FDA ‘interchangeability’ determination/approval for 2nd ‘biosimilar’ applicant
until earlier of:
–
–
–
–
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USFDA determines that information relating to use of ‘reference product’ will produce
health benefits in pediatric population;
USFDA makes a written request for pediatric studies;
Reference product sponsor agrees to such request;
Such studies are timely completed using appropriate formulations for each age group for
which the study is requested; and
Reports of such studies are submitted and accepted by USFDA
1 year after 1st commercial marketing of the 1st interchangeable biosimilar or
18 months after a final court decision on all patents in [a patent infringement] instituted
under BPCIA procedure against the 1st interchangeable biosimilar applicant or dismissal
of such action (with or without prejudice) or
42 months after approval/licensure of 1st first interchangeable biosimilar product where
such product’s applicant has been sued under under BPCIA procedure and such
litigation is still ongoing within such 42-month period
or
18 months after approval/licensure of 1st interchangeable biosimilar, if such applicant
was not sued
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III. Overview of the BPCIA’s Provisions
D.
Patent Protection
–
BPCIA defines an ‘act of patent infringement’ as also including:
•
•
–
The BPCIA creates a new extensive mandatory statutory patent dispute procedure:
•
–
–
to resolve potential patent disputes (i.e., issues of patent validity/infringement) between a
brand name biologic drug (‘reference product’) sponsor and a biosimilar applicant before an
FDA-approved biosimilar product is commercially marketed
This procedure is triggered by the USFDA’s acceptance for review of a submitted
biosimilar application
BPCIA’s patent dispute procedure consists of three stages:
•
•
•
–
the submission of a biosimilar application with respect to a patent included in the reference
product sponsor’s initial and supplementary patent lists compiled pursuant to the BPCIA’s
patent dispute procedure AND
the submission of a biosimilar application with respect to a patent that the reference product
sponsor could reasonably assert would be infringed by the commercialization or importation
of the applied-for biosimilar product, even though the biosimilar applicant failed to comply
with its statutory obligation to provide a copy of the biosimilar application to the reference
product sponsor
Pre-litigation information exchange
Early stage litigation
Late stage litigation
BPCIA’s dispute procedure is intended to reduce patent litigation through long cooling-off
period; however whether this objective will be met is highly questionable
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III. Overview of the BPCIA’s Provisions
– i. Pre-Litigation Information Exchange (Takes place over 6 month period)
• Biosimilar Applicant provides ‘information’ - confidentially to reference product sponsor
within 20 days of USFDA notifying it received biosimilar application, including:
–
–
–
–
A copy of the biosimilar application;
Information describing the process of manufacture of proposed biological product;
Additional information reference product sponsor or representative requests; and
Other information biosimilar applicant deems relevant & appropriate
• ‘Information’ shall be given to:
– Reference product sponsor;
– Reference product sponsor’s ‘outside’ counsel; and
– Reference product sponsor’s ‘inside’ counsel;
• ‘Information may be given to:
– The owner of a patent exclusively licensed to the reference product sponsor, if the
owner retains a right to assert the patent or participate in litigation
• Reference Product Sponsor provides ‘information’ – to biosimilar applicant, no later than
60 days after receiving biosimilar application, including:
– A list of reference product patents ‘believed’ to be infringed if biosimilar product would
be used, sold or imported into the US; and
– Specific patents on such list that the reference product sponsor would be prepared to
license
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III. Overview of the BPCIA’s Provisions
• Biosimilar Applicant responds to reference product sponsor not later than 60 days after
receipt by:
– Responding to each identified patent on reference product sponsor’s list; or
– Providing own list of reference product sponsor patents against which it believes a claim
of patent infringement could reasonably be asserted
– At a minimum, must submit a detailed statement substantiating, claim by claim, its
position concerning why the patent is invalid or unenforceable, or will not be infringed
• Reference Product Sponsor responds to biosimilar applicant no later than 60 days by:
– Providing, with respect to each patent reference product sponsor has listed, a detailed
statement substantiating, claim by claim, its own position why each listed patent is valid
and enforceable and will be infringed if biosimilar product is commercialized
– ii. Early Patent Litigation Negotiations/Information Exchange (45 day process if agree)
• Both Parties have 15 days from reference product sponsor’s last information dispatch to
negotiate in good faith which patents to litigate
• If Agreement is reached, reference product sponsor commences a patent infringement
action not later than thirty (30) days from the date of such agreement, based on the agreed
upon list of patents;
– Reference Product Sponsor must effectively litigate 2x patents listed by biosimilar
applicant (can’t decline to litigate designated patents or else may lose rights)
• Biosimilar applicant must notify FDA within thirty (30) days of receiving complaint
• If NO Agreement is reached, biosimilar applicant must notify the reference product
sponsor of the number of patents it believes should be litigated.
• Within five (5) days of such notice, BOTH PARTIES simultaneously exchange their
respective lists of specifically identified patents which each party seeks to litigate
• Reference Product Sponsor’s list cannot exceed # of patents on biosimilar applicant’s list
– Thus, biosimilar applicant’s patent list effectively controls total # of patents to be litigated
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III. Overview of the BPCIA’s Provisions
– iii. Late Stage Patent Litigation/Pre-Commercialization
• The BPCIA patent dispute procedure makes available to the Parties the following judicial
remedies, with conditions:
– Preliminary Injunctions
– Declaratory Judgments
– Permanent Injunctions
• Preliminary Injunctions (PRI)
– Reference Product Sponsor may seek a PRI after receiving the biosimilar applicant’s 180day advance notice of biosimilar product’s 1st commercialization, but before the actual
commercial marketing occurs (during this 180 day/6 month window)
– Reference Product Sponsor may use a PI to add to the list of patents for litigation, any
patents it has acquired or exclusively licensed (‘subsequently acquired/licensed patents’)
since it first exchanged patent lists, against which it could reasonably assert a claim of
patent infringement, if:
» Timely notified - within thirty (30) days of execution of acquisition/licensing
agreement – (if not timely notified, such patents CANNOT be asserted by Reference
Product Sponsor in subsequent infringement litigation)
– PRI is effective until a court determines patent validity, infringement or enforcement
– PRI applies to patents of both parties on pre-litigation initial patent lists that could
reasonably be asserted as having been infringed, but were not included in the early stage
patent suit (if patent not on initial list, cannot obtain PRI with respect to it)
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III. Overview of the BPCIA’s Provisions
• Declaratory Judgments (DJ)
– DJs are NOT available to either Party, when biosimilar applicant has timely provided a
copy of the biosimilar application & other information to the reference product sponsor,
UNTIL AFTER reference product sponsor receives biosimilar applicant’s 180-day advance
commercialization notice
– The DJ may seek a determination of infringement, validity or enforceability with respect
to (i.e., DJ applies to:) any patents included in either the initial patent list or a
supplementary patent list of subsequently acquired or licensed patents
– Reference Product Sponsor may seek a DJ where the biosimilar applicant failed:
» To timely provide the reference product sponsor with any of the required
information; or
» To timely fulfill its obligations to the reference product sponsor or to the FDA
Secretary under these patent dispute proceedings:
» To timely exchange patent lists
» To timely notify USFDA of its receipt of RPS’ complaint
» To timely respond to RPS’ supplementary list of subsequently licensed patents
» To notify RPS prior to biosimilar product’s 1st commercial marketing
– Biosimilar applicant may seek DJ after it files 180 day notice of commercialization in an
effort to control litigation
• Permanent Injunctions (PMI)
– Reference Product Sponsor may seek and court may grant PMI after the biosimilar
applicant product’s 1st commercialization but before the reference product sponsor’s patent
expires
– A PMI can only follow a final, non-appealable court decision of infringement obtained in
an ‘Immediate Action for Patent Infringement’ initiated under the BPCIA’s dispute
procedure
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IV. BPCIA’s Implications for Patent Licensing
A.
BPCIA Patent Dispute Resolution Process Will Feature Patents Not Included in
FDA Orange Book) Portending More Extensive Litigation
–
–
BPCIA does not exclude process patents from the patent dispute procedure
But FDA Orange Book’s exclusion of process patents renders ‘prior art’ searches more
difficult, and patent litigation more likely for biosimilar applicants
•
B.
FDA Orange Book contains a list of all approved products, including their composition &
method patents
Patent Owners May Be Included in Reference Product Sponsor Litigation
Without Prior Notice
–
–
–
–
BPCIA’s patent dispute procedure permits, but does NOT require, a biosimilar
applicant to provide certain information directly to the owner of a patent exclusively
licensed to the reference product sponsor with respect to the reference product
BPCIA’s patent dispute procedure requires a biosimilar applicant to provide
confidential information to a reference product sponsor and its ‘inside’ & ‘outside’
counsel, but does not require any of them (indirectly) to share such information with
third-party owners of patents exclusively licensed to the reference product sponsor
BPCIA’s patent dispute procedure requires a reference product sponsor to include in
its follow-up lists to the biosimilar applicant subsequently acquired or exclusively
licensed patents within 30 days of the exclusive licensing agreement’s execution, but
does not ensure that the patent owner will be apprised of such submission or of any
subsequent patent litigation
BPCIA’s patent dispute procedure does not require patentees to participate in the
confidential disclosure process, which could encourage their nonparticipation
9/30/11
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IV. BPCIA’s Implications for Patent Licensing
C.
Reference Product Sponsor’s Failures May Trigger Forfeiture of Patent Rights
–
i. Denial of Preliminary Injunction to Reference Product Sponsor–
•
–
May result from reference product sponsor’s failure to include a patent on the initial
pre-litigation patent list it previously provided to the biosimilar applicant
ii. Denial of Preliminary Injunction to Reference Product Sponsor–
•
Only a ‘reasonable royalty’ can be awarded by a court in a successful reference product
sponsor patent infringement action against a biosimilars applicant, if a reference
product sponsor failed:
–
–
–
To timely commence such action (within the prescribed 30 days where both parties agree
on patents to be litigated) with respect to a patent identified in the reference product
sponsor’s pre-litigation or early litigation patent list provided to the biosimilar applicant;
or
To prosecute an otherwise timely filed patent infringement action to judgment in good
faith (i.e., it sought dismissal of the action)
iii. Denial of ‘Standing’ to Patent Owner to Bring Patent Infringement Action
•
9/30/11
A reference product sponsor’s failure to include an exclusively licensed patent on an
initial or supplementary patent list provided to the biosimilar applicant pursuant to
the BPCIA dispute procedure will preclude the owner of such patent from bringing a
patent infringement action with respect to potentially infringing biosimilar product
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IV. BPCIA’s Implications for Patent Licensing
D.
Proactive Measures for Counsels to Consider
–
Must carefully review clients’ license agreements to evaluate the likelihood that an
exclusively licensed patent will fall subject to a dispute involving a biosimilar
product
•
•
•
Undertake cost-benefit of securing exclusive vs. non-exclusive license in light of
litigation risk
Exclusive licensor (patent owner) should ensure that its licensee provides prompt
notice of a biosimilar legal challenge
Exclusive licensor (patent owner) should ensure that it retains for itself the right to
play an active role in the reference product sponsor’s:
–
–
–
•
Reference product sponsor-exclusive licensee should restrict the exclusive licensor’s
(patent owner’s) role in the patent dispute procedure:
–
–
–
•
•
9/30/11
Biosimilar application review;
Decision to include or not include the licensed patent on its patent list(s); and
Prosecution of an infringement action involving the licensed patent
To reduce the risk of procedural delay;
To retain discretion over whether to assert exclusively licensed patents
To control the prosecution of patent litigation and settlement
Determine how inclusive the list of patents to be litigated should be for purposes of
defining the initial scope of litigation
Weigh whether statements of facts and law concerning listed patents should be
intentionally obtuse given evidentiary value of statements in litigation
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V. Key Hatch-Waxman Act IP Provisions
A.
-
Exclusivity
The Hatch-Waxman Act established several different types of marketing
exclusivities:
–
i. New Chemical Entities
•
–
ii. New Clinical Studies
•
–
7 years for specific indication
iv. Pediatric Studies
•
B.
3 years from approval for NDA or supplemental NDA if reports of new studies
essential to FDA application
iii. Orphan Drug
•
–
5 years from approval of NDA for a particular active ingredient (moiety) – NO reliance
on data; NO generic application accepted
6 months
Patent Protection
–
i. Statutory Exemption from Patent Infringement Claims
•
•
9/30/11
To make, use or sell patented invention solely for uses relating to FDA marketing
approval
Generic mfrs can commence work on a generic version of an approved drug at any time
during the life of the patent so long as the work furthers compliance with FDA regs
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V. Key Hatch-Waxman Act IP Provisions
– ii. Patent Term Extension
• For lost time during regulatory review, provided patentee exercises due diligence
– Not to exceed 5 years
– Full remaining patent term not to exceed 14 years
– iii. Challenging Approved Drug Patents/Dispute Settlement
• Generic applicant that files certification stating that FDA Orange Book-listed patent for
approved originator drug is invalid or will not be infringed (“a paragraph IV
certification”) MUST NOTIFY patent owner, who may bring infringement suit with 45
days of receipt of such notice
• Automatic Stay of generic application if patent owner or original drug applicant timely
files infringement action
– iv. Rewards for Challenging Approved Drug Patents (FDA Orange Book-listed)
• 180 day exclusivity for FIRST generic to file “paragraph IV certification”
9/30/11
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VI. High Profile Post-Enactment Interpretational/Implementation Debates
About Reference Product Exclusivity
A.
B.
USFDA Federal Register Notice Description of Marketing Exclusivity and
Solicitation of Public Advice (10/5/10)
Congressional Research Service (CRS) Report Discusses Distinction Between
Market Exclusivity and Data Protection With Respect to What Type of
Exclusivity the BPCIA Provides (10/26/10)
•
C.
Letter From 3 Principal US House of Representatives /BCPIA Authors to
USFDA Discussing The Character & Period of Exclusivity (12/10/10)
•
D.
Data Exclusivity, NOT Market Exclusivity
Letters From BIO and PhRMA to USFDA Discussing Character, Period and
Extensions of Exclusivity to Supplementary Applications, ‘Related Entities’ and
Third-Party Transferees (12/23/10)
•
•
E.
Market Exclusivity & Data Protection/Exclusivity
No market authorization until after patent & all exclusivities expire
Non-qualifying supplemental filings of reference product sponsor AND
reference product affiliated entities are entitled to the remaining exclusivity
periods relating to the reference product - ‘Evergreening’ – “UMBRELLA”
EXCLUSIVITY
Letter From 5 US Senators to USFDA Discussing Distinction Between
Marketing Exclusivity and Data Protection With Respect to What Type of
Exclusivity BPCIA Provides (1/7/11)
•
•
9/30/11
Data Exclusivity NOT Marketing Exclusivity
NO Separate 12 year Data Exclusivity for same product or for product structurally
modified without a change in safety, purity or potency
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VI. High Profile Post-Enactment Interpretational/Implementation Debates
About Reference Product Exclusivity
F.
Letter From Generic Pharmaceutical Manufacturers, Healthcare Service
Providers, etc. to USDFA Discussing Character of Period of Exclusivities BPCIA
Provides (1/20/11)
•
Concurrent 4 year/ 8 year periods
–
–
G.
Letter From 4 Senators to USFDA Expressing Their Opposition to BPCIA’s 12year Exclusivity Period (1/24/11)
•
H.
4 years – Data Exclusivity & Marketing Exclusivity
8 years – Marketing Exclusivity – Data of reference product can be relied on
FDA can begin reviewing biosimilar applications during 12 years exclusivity
period
President Obama’s Line-By-Line 2012 Budget Review Proposing a Reduction to
the BPCIA Exclusivity Period For Reference Products – From 12-years to 7 years,
and the Denial of ANY Additional Exclusivity Period, to Reduce National
Healthcare Costs (2/15/11)
•
•
9/30/11
NO Evergreening
Saves $2.34 billion in US healthcare costs
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VII. BPCIA’s Impact on International Trade
A.
The Korea-US Free Trade Agreement (KORUS FTA)
–
Brief Chronology of the Signing and Amending of the Treaty (2007)
•
•
–
Brief Discussion of the ‘May 10 Agreement’ and USTR ‘Side Letter’ (2007)
•
•
–
Implementation of FTA Marketing/ Data Exclusivity & ‘Patent Linkage’ provisions
delayed for 18 months
Inclusion of WTO TRIPS Doha Declaration provisions/’flexibilities’ due to pressure of
110th Congress & health activist groups - (e.g., compulsory licensing for benefit of
developing countries)
Brief Discussion of Obama Administration’s Renegotiation of the Treaty (2009-2010)
•
•
–
April 2007 negotiations concluded
June 2007 FTA signed
December 2010 – Agreed to extend implementation of FTA Marketing/Data Exclusivity
& Patent Linkage provisions an additional 18 months (now a total of 36 months)
Environmental and labor provisions added to FTA
Discussion of Signing & Ratifying of EU-South Korea FTA (2010-2011)
•
•
•
•
•
9/30/11
5 years Data Exclusivity
European Commission signed Oct. 2010
European Parliament ratified Feb. 2011
EU-South Korea FTA in effect in July 2011
Creates added pressure for US to ratify KORUS-FTA – competitive disadvantage
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VII. BPCIA’s Impact on International Trade
– Discussion of Data Exclusivity & Patent Linkage Provisions of Final Text of
Renegotiated KORUS-FTA
• Article 18.9.1(a) - 5 years Data Exclusivity – NO reliance on original drug approval or data for 5
years in Korea
• Article 18.9.1(b) – NO reliance on original drug approval or data of prior marketing approvals of
original drug in another country for 5 years
• Article 18.9.2 – 3 years exclusivity in Korea or in another country for new clinical information
essential to the FDA regulator’s approval of a pharmaceutical product
• Article 18.9.4 – Prevents Korean regulators from terminating data protection period with the
expiration of a patent
• Article 18.9.5 – Patent Linkage – Korea must implement measures in its marketing approval
process to prevent generic drug approval during the term of the originator’s drug patent AND
must disclose identity of generic applicants seeking marketing approval during the patent term
• Articles 18.9.3/ 18.11 – WTO Doha Declaration on TRIPS Agreement on Public Health provisions
ensuring availability of ‘compulsory licenses’ to meet ‘public interest’ health needs
• Patent Linkage – Korean regulators must investigate and confirm that a generic drug applicant
seeking marketing approval does NOT infringe an existing patent – if a patent claim exists, the
regulator must deny marketing approval until the patent term expires
– Discussion of Ongoing US Ratification Delays (2010-2011)
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VII. BPCIA’s Impact on International Trade
B.
The Trans-Pacific Partnership Agreement (TPPA)
–
–
4 Nations (Brunei, Chile, NZ, Singapore) signed in 2005; Took effect in Nov. 2006
Discussion of Original TPPA & Obama Administration’s Pursuit of Expansive TPPA
Negotiations, Focusing on Data Exclusivity and Patent Linkage Provisions (12/2009)
•
•
•
–
–
Letter From 18 House of Representatives Committee on the Judiciary Members to
President Obama Expressing the Need to Pursue the Highest Level American IP
Protections in TPPA Negotiations Using the Korea FTA as a Starting Point (KORUSplus) (2/4/11)
Discussion of Leaked TPPA Position Papers of New Zealand Government & US
Industry, and US Government Draft TPPA Text (12/4/10; 12/13/10; 2/10/11)
•
•
•
–
Notification to US Congress in Fed Register Notice seeking public comment
US to push for a truly Asia regional agreement to set benchmarks
9 countries now negotiating (5 new countries, besides US) – Australia, Malaysia, Peru,
Vietnam
Public Citizen NGO leak showing New Zealand support for ‘TRIPS-aligned’ position
opposing US ‘TRIPS-plus’ position
KEI NGO leak showing US position to use KORUS-FTA as baseline for TPPA
KEI NGO leak showing US proposed IP chapter leaving open provisions for
marketing/data exclusivity & patent linkage
Discussion About How USTR’s Announcement that it Would Table its Complete
TPPA IP Proposal for Negotiation by Mid-June 2011 to Speed Up Talks, Triggered
Heated Public Debate in the US About Which Negotiating Position USTR Should
Pursue - ‘May 10-KORUS’ or ‘KORUS-plus’ (April 2011)
•
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One pharma executive quoted as saying ‘KORUS-plus’ with 12 year Marketing/Data
Exclusivity for Biologics integrating BPCIA is needed as baseline with China and Asia
region
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VII. BPCIA’s Impact on International Trade
– Letter From 14 Democratic House Ways & Means Committee Members to USTR Kirk
Seeking for USTR to ‘Defend’ ‘KORUS-May 10’ as the US position in the TPPA
Negotiations (7/26/11)
– Letter From 40 Pro-Free Trade House Members to President Obama Urging TPPA IP
Chapter to Include 12 Years Marketing/Data Exclusivity Protection for New Biologic
Drugs (7/27/11)
– Letter From 10 Democratic House of Representative Members to USTR Kirk Urging that
‘May 10-KORUS be the Starting Point for US TPPA Negotiating Position and that Any
Data Exclusivity Provisions to be Included Should be Voluntary (8/2/11)
– Letter From 7 Democratic House of Representative Members to President Obama
Recommending that US Refrain From Negotiating Any TPPA IP Provisions Related to
Exclusivity for Biosimilars Medicines (8/4/11)
• BPCIA still too without full understanding of its impact, to call for 12 years Exclusivity
• Urging Adherence to Presidential Call for 7 Years Marketing/Data Exclusivity
– Letters From Group of 37 US Senators and 2 US House of Representatives Members
From Colorado to President Obama Calling For USTR To Secure 12 Years of
Marketing/Data Exclusivity Rather Than President’s Line-by-Line Review of 2012
Budget Plan Recommending 7 Years, and Rather Than 5 Years Marketing/Data
Exclusivity of KORUS-FTA’s “May 10 Agreement” (9/12/11)
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VIII. Tentative Conclusions
• The BPCIA:
– Is unquestionably a formidable and ambitious piece of legislation that aims to promote
scientific innovation and safe and cost-effective access to healthcare .
– Recognizes that biologic drugs and biosimilar products are far more technically complex
and economically costly and time-consuming to develop and market than conventional
pharmaceuticals and their generic counterparts, and that the scientific challenges and
associated risks regulators face when evaluating the biosimilar features of live biologic
proteins are far greater than those faced when assessing the bioequivalence of
chemically synthesized molecules.
– Provides a delicate, if not tenuous, balance between the rights and interests of patent
owners, biosimilar applicants and the public at large, that can potentially result in a
diversion of scarce economic, intellectual and social capital away from critical product
development efforts and towards ill-conceived and unproductive IP-based litigation at
administrative and judicial fora that could severely delay the introduction of badly
needed medicines.
– Compels US FDA officials to look toward Europe’s longer experience with establishing
a biosimilars pathway, and South Korean and other APEC member nation FDA
authorities to compare their emerging biosimilar pathways with those of Europe and the
US to ensure lessons learned and to facilitate greater harmonization.
– Reflects a shifting multipolar dynamic, that will likely need to be updated over time to
keep pace with new biotechnology discoveries and evolving manufacturing and
processing techniques, as well as, emerging life science business models.
– Has arguably already triggered domestic and cross-border R&D, manufacturing and
distribution realignments.
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Providing an Informed, Reasoned, Dispassionate Voice to the Global Public Debate ®
THE INSTITUTE FOR TRADE, STANDARDS AND SUSTAINABLE DEVELOPMENT, Inc. ©
www.itssd.org
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