Transcript The Patented Medicines (Notice of Compliance) Regulations

The Patented Medicines (Notice
of Compliance) Regulations
Don Cameron
Bereskin & Parr LLP
April 17, 2014
The Canadian Pharmaceutical Regulatory Regime
– The PM(NOC) Regulations
I. A Brief History of the PM(NOC) Regulations
II. The Drug Approval Process in Canada
III. Pharmaceutical Patent Law – The Current
System
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Overview
Patent Register
PM(NOC) Regulations
Litigation under the PM(NOC) Regulations
Data Protection
I. A BRIEF HISTORY OF THE
PM(NOC) REGULATIONS
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Compulsory Licences
• 1923:
– Compulsory licences provided for food and drugs.
• Iff active ingredients were made in Canada
• 1969:
– Compulsory licences granted for imported active
ingredients
– The birth of Apotex and Novopharm (now part of
Teva)
Compulsory Licences
By early 80’s:
• Generic companies could manufacture, sell and import a
patented medicine before the expiry of a patent, provided:
– drug was shown to be “safe and effective”
– paid a royalty to patent owner: always 4%
• Result:
– Pharma patents were virtually useless
– Scared away drug research in Canada
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I. A Brief History of the PM(NOC)
Regulations
1980’s:
• USFTA negotiations:
– Pressure on Canada to remove our “third world” compulsory licensing system
• Parliament began re-vamping patent laws to rebalance the compulsory
licensing regime in order to generate growth in the pharmaceutical
industry and in light of international trade obligations
• Led to major overhaul of the patent system in 1987-1989
1987: Bill C-22
• Introduced:
– deferral of 7-10 years before compulsory licence could be granted (further
protection for drugs invented in Canada)
– Patents on the pharmaceutical product itself, not just the process of making it
– Patented Medicine Prices Review Board
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I. A Brief History of the PM(NOC)
Regulations
1991-1993: NAFTA/GATT TRIPS
• Minimum standards of IP for all nations participating
• International pressure on Canada to terminate compulsory
licensing
NAFTA/TRIPS:
• Exclusive right to make, use, sell, import and licence
patented product
1992 – Bill C-91
• Abolished prospective compulsory licences post 1991
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1992: Bill C-91
• Bill C-91 established “early working” and
“stockpiling” exceptions to patent infringement
• “Early Working” – Section 55.2(1) of the Patent Act (for
obtaining regulatory approval)
• “Stockpiling” preceding the expirty of the patent (to hit the
ground running)
• exception was abolished in 2001 as being inconsistent with Canada’s
international treaty obligations
• PM(NOC) Regulations brought into force
I. A Brief History of the PM(NOC)
Regulations
PM(NOC) Regulations:
• Link the drug regulatory approval system and
the patent system
• Enhance protection for pharmaceutical
patents by requiring a generic drug
manufacturers to “clear” relevant patents
prior to obtaining regulatory approval
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I. A Brief History of the PM(NOC)
Regulations
2006: Major amendments to the PM(NOC)
Regulations brought into force to address
perceived deficiencies in the regime
• Operation of the Regulations reaffirmed and clarified
• Established an 8-year data protection for patented
medicines to guarantee a minimum term of market
exclusivity to patentees
• Protected data is the bundle of confidential information that
is submitted to Health Canada to obtain market
authorization
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II. THE DRUG APPROVAL PROCESS
IN CANADA
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II. The Drug Approval Process in
Canada
• All drugs sold in Canada must be authorized for sale by Health
Canada
• For a “new” drug, the manufacturer submits a New Drug
Submission (“NDS”) setting out all data establishing the safety and
efficacy of the drug (obtained through rigorous clinical testing)
• Health Canada reviews the submitted information and evaluates
the drug’s safety, efficacy and quality
• At the completion of the review, if Health Canada has approved the
new drug, it issues a Notice of Compliance (“NOC”) which permits
the drug to be marketed in Canada
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II. The Drug Approval Process in
Canada
• Innovative pharmaceutical company is typically the first person to
discover/develop a drug and/or a new therapeutic indication
• Therefore, an NDS is typically filed by an “innovative”
pharmaceutical company
• Generally, an innovator will have one or more patents pertaining to
a new drug
• Any changes to the approval (change of name, packaging, product
monograph) requires a Supplementary New Drug Submission
(“SNDS”)
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II. The Drug Approval Process in
Canada
• “Me too”
– Unlike innovator, a generic manufacturer need not
establish safety and efficacy of a generic drug
– Generic need only demonstrate bioequivalence to
a drug which is already on the market and has
been approved by Health Canada
• “Bioequivalence” = the active ingredient of a generic drug be
absorbed into the body and metabolized in approximately
the same amount over approximately the same period as
the active ingredient of the innovator drug
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II. The Drug Approval Process in
Canada
• To obtain marketing approval for a generic drug, the generic
manufacturer submits an Abbreviated NDS (“ANDS”)
demonstrating that the generic formulation is “bioequivalent”
to the brand formulation
– ANDS typically does not contain clinical data
• By establishing bioequivalence, generic demonstrates safety
and effectiveness by comparison, without having to do
extensive clinical trials
– Significantly less money and time required to bring generic drug
to market
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III. PHARMACEUTICAL PATENT LAW
– THE CURRENT SYSTEM
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III. Pharmaceutical Patent Law – The
Current System
• The current system reflects Parliament’s attempt to strike a
balance between two competing objectives: (i) provision of lowcost, high-quality pharmaceuticals, and (ii) protection of
innovation and stimulation of R&D
• Generic manufacturers are given the benefit of “early working”
for a drug approval prior to patent expiry but must address
patent issues prior to obtaining marketing approval
• Innovators are given the benefit of 8-years of data protection
– Generic manufacturers are prohibited from filing an ANDS or
triggering litigation under the PM(NOC) Regulations for the first 6
years of the 8 year term (except for submissions made under the Jean
Chrétien Act)
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III. Pharmaceutical Patent Law – The
Current System - Linking
Patent status
• Valid, infringed patents can
block entry of generic
• Register of patents relating to
an approval
• No practical was to get an
interlocutory injunction
• Q: Are the generic’s allegations
of non-infringement and
invalidity justified?
HPB Approval
• Can’t grant approval until
patent issues are resolved
on a preliminary basis
• Minister can’t grant a
generic approval for 2 years,
pending PM(NOC)
proceeding
III. Pharmaceutical Patent Law – The
Current System
Overview
Astra Zeneca Canada Inc. v. Canada (Minister of Health), 2006 SCC 49 at para. 12:
The NOC Regulations lie at the intersection of two regulatory systems with sometimes
conflicting objectives. First, is the law governing approval of new drugs, which seeks to
ensure the safety and efficacy of new medications before they can be put on the market. The
governing rules are set out in the Food and Drugs Act, R.S.C. 1985, c. F-27 (“FDA”), and the
Food and Drug Regulations, C.R.C. 1978, c. 870. The FDA process culminates (if successful) in
the issuance of a NOC to an applicant manufacturer by the Minister of Health on the advice
of his officials in the Therapeutic Products Directorate. The FDA objective is to encourage
bringing safe and effective medicines to market to advance the nation’s health. The
achievement of this objective is tempered by a second and to some extent
overlapping regulatory system created by the Patent Act, R.S.C. 1985, c. P-4. Under that
system, in exchange for disclosure to the public of an invention, including the invention of a
medication, the innovator is given the exclusive right to its exploitation for a period of 20
years. Until 1993, the two regulatory systems were largely kept distinct and separate.
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III. Pharmaceutical Patent Law – The
Current System
Overview
Astra Zeneca Canada Inc. v. Canada (Minister of Health), 2006 SCC 49
at para. 13:
The problem perceived by Parliament in 1993 was that if a generic
manufacturer waits to begin its preparation of a copy-cat medicine for
regulatory approval until the patent expires, the FDA approval process will
likely add at least two years to the effective monopoly of the patent
owner, which is two years of monopoly longer than the Patent Act
contemplates. On the other hand, if the generic manufacturer tries to
work the patented invention prior to the expiry of the patent, even if
solely to satisfy the FDA requirements for a NOC, it will infringe the patent,
thus inviting litigation by the patent owner (and this is a very litigious
industry).
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III. Pharmaceutical Patent Law – The Current System
PM(NOC)
Regulations
Patent Listing
ss. 3-4
Generic
Notice of Allegation
s. 5
Proceedings for a
Prohibition Order
s. 6
Damages
s. 8
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III. Pharmaceutical Patent Law – The Current System
Patent Listing and The Patent Register (sections
3 & 4)
• Minister of Health maintains a public register of patents based
on patent lists submitted by patentees/licensees who file an
NDS and to whom an NOC have been issued
– “linchpin” of the PM(NOC) Regulations
• Patents which are listed on the Patent Register are entitled to
protection under the PM(NOC) Regulations
• Minister has a duty to determine what patents are listed and
to remove patents that have been listed improperly
– f(timing, subject matter & relevance)
• Generic drug manufacturers have no say on the listing or
delisting of a patent on the Patent Register
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III. Pharmaceutical Patent Law – The
Current System
Patent Listing cont’d
• To have a patent listed a “first person” (e.g. an innovator) who
files or has filed a NDS or SNDS submits a patent list in respect
of the drug to the Minster of Health
• Not all patents are eligible for listing. To qualify for listing, the
patent must meet three (3) key requirements:
– (1) Timing
– (2) Relevance
– (3) Subject matter
•
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See Ratiopharm v. Wyeth, 2007 FCA 264
III. Pharmaceutical Patent Law – The
Current System
Patent Listing cont’d - Timing
• Patent list must be filed
– (1) at the time the NDS or SNDS is filed for a drug;
or
– (2) within 30 days of the grant of the patent
• There is no mechanism for listing a patent on the Patent
Register if a patent list is submitted outside of these timelines
• Only patent lists submitted in accordance with the above
timelines will be accepted. Patent lists submitted separately
will be refused as not meeting the timing requirements
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III. Pharmaceutical Patent Law – The
Current System
Patent Listing cont’d – Subject Matter
• Eligible patents listed in respect of a NDS must
contain:
– (1) a claim for the approved medicinal ingredient;
– (2) a claim for the approved formulation containing
that medicinal ingredient;
– (3) a claim for the approved dosage form containing
that medicinal ingredient; or
– (4) a claim for the approved use of that medicinal
ingredient
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III. Pharmaceutical Patent Law – The
Current System
Patent Listing cont’d – Subject Matter
• Eligible patents listed in respect of a SNDS
must contain:
– (1) a claim for the approved change in
formulation;
– (2) a claim for the approved change in dosage
form; or
– (3) a claim for the approved change in use of that
medicinal ingredient
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III. Pharmaceutical Patent Law – The
Current System
Section 2 definitions:
• "claim for the medicinal ingredient" includes a claim in the patent for the
medicinal ingredient, whether chemical or biological in nature, when
prepared or produced by the methods or processes of manufacture
particularly described and claimed in the patent, or by their obvious
chemical equivalents, and also includes a claim for different polymorphs of
the medicinal ingredient, but does not include different chemical forms of
the medicinal ingredient;
• "claim for the formulation" means a claim for a substance that is a
mixture of medicinal and non-medicinal ingredients in a drug and that is
administered to a patient in a particular dosage form;
• "claim for the dosage form" means a claim for a delivery system for
administering a medicinal ingredient in a drug or a formulation of a drug
that includes within its scope that medicinal ingredient or formulation;
• "claim for the use of the medicinal ingredient" means a claim for the use
of the medicinal ingredient for the diagnosis, treatment, mitigation or
prevention of a disease, disorder or abnormal physical state, or its
symptoms
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III. Pharmaceutical Patent Law – The
Current System
The Patent Register – Ineligible Subject Matter
• Patents which may not be listed on the Patent
Register include:
– (1) a purely process patent
– (2) a patent for a medical device
– (3) a patent claiming only an active metabolite of a
medicine contained in a drug for which a NOC is
sought
– (4) a patent for an impurity present in the final drug
product
– (5) a patent for a difference chemical form of the
medicinal ingredient or uses thereof
– E.g. salts, esters, other derivatives
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III. Pharmaceutical Patent Law – The
Current System
Patent Listing cont’d – Relevance
• To be eligible for listing on the Patent Register a
patent must be relevant to the drug which is the
subject of the submission against which the
patent is to be listed
• i.e. the patent must claim the specific product which the
innovator is seeking to sell
• Therefore, a patent listed with respect to a SNDS
must claim the change in use of the medicinal
ingredient, formulation or dosage form applied
for
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III. Pharmaceutical Patent Law – The
Current System
PM(NOC) Litigation – Sequence of Events
1. “First Person” (e.g. Innovator) files a New
Drug Submission (NDS) and has patents listed
on the Patent Register.
2. When a “Second Person” (e.g. generic
manufacturer) files an ANDS referencing the
Innovator’s drug, and the innovator drug has
associated patents listed on the register,
PM(NOC) Regulations are triggered
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III. Pharmaceutical Patent Law – The
Current System
Section 5
3.
Generic manufacturer must address each patent which is
listed for the referenced drug at the time of filing of the ANDS
.Generic only has to address patents listed on the Register at the
time the ANDS is filed (“frozen register”)
4.
Generic can:
i. Await expiry of all listed patents before receiving a
NOC;
ii. Allege invalidity or non-infringement of the patent at
issue by filing a Notice of Allegation to the innovator
setting out the basis of its allegations
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III. Pharmaceutical Patent Law – The
Current System
Section 6
5. Upon receiving NOA, Innovator may, within
45 days, apply to the Federal Court for an
order prohibiting the Minister of Health from
approving the sale of the generic drug.
•
•
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Innovator argues that the generic’s allegations of
invalidity and/or non-infringement are “not justified”
At this stage, generic can move to strike the
proceedings on the basis that an asserted patent was
improperly listed
III. Pharmaceutical Patent Law – The
Current System
Section 7
6. Once an application for an order of prohibition is filed, the
Minister may not issue a NOC until the expiry of 24 months,
unless:
(i) the court finds in favour of the generic, or
(ii) (ii) the patent expires
Effectively an interlocutory injunction without
preconditions having been met
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III. Pharmaceutical Patent Law – The
Current System
PM(NOC) Litigation
•
A proceeding under the PM(NOC) Regulations is a judicial
review proceeding to determine whether NOC should issue.
•
•
•
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NOT an action for patent infringement.
Proceedings are intended to be summary proceedings
governed by the Federal Court Rules regarding applications
Must be completed within 24 months. Once 24 month
period is over, MOH is no longer prevented from issuing NOC
III. Pharmaceutical Patent Law – The
Current System
PM(NOC) Litigation – Burden of Proof
•
•
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The first person has the legal burden to prove on a balance
of probabilities that none of the allegations in the Notice of
Allegation is justified
• Can rely on the presumption of validity, but to its peril
• Allegations in the Notice of Allegation are presumed to
be true until the contrary is proved
See Pfizer v. Minister of Health, 2008 FC 11 for a summary of
the jurisprudence as to the BOP in NOC Proceedings
III. Pharmaceutical Patent Law – The
Current System
PM(NOC) Litigation
7. Parties exchange pleadings, expert affidavits, conduct
witness cross examination and file legal briefs.
8. Following a hearing, the Court will either:
• Grant an order of prohibition preventing the
Minister from approving the sale of the generic
drug until expiry of the patent; or,
• Dismiss the application. The generic drug can be
manufactured and sold.
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III. Pharmaceutical Patent Law – The
Current System
Section 8
• If the Court dismisses the application for prohibition (or if the
application is otherwise discontinued), the second person may
recover any loss suffered as a result of being held off the market
•
•
•
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Second person is limited to its damages. It cannot claim the first
person’s profits
The second person bears no liability for compensation if the
application for prohibition is successful
First trial decision on section 8 damages: Apotex Inc. v. Merck &
Co., Inc. et al. (October 21, 2008), Ottawa, T-1144-05 (Fed. Ct.)
III. Pharmaceutical Patent Law – The
Current System
PM(NOC) Litigation – Implication of Decision
•
•
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If unsuccessful, the Innovator can appeal to the Federal
Court of Appeal; however, once the NOC has issued, any
appeal is moot.
Since the Court does not rule on the ultimate validity or
infringement of the patent, patent infringement and
impeachment proceedings under the Patent Act are still an
option.
III. Pharmaceutical Patent Law – The
Current System
Data Protection (pre – October, 2006)
• Based on international obligations imposed by NAFTA and TRIPS
• Require that where a company submits confidential data to a
regulatory authority when seeking approval for a new drug, the data is
protected from reliance by competitors for a certain period of time
after the date the drug is approved – then 5 years.
• Prior to the 2006 amendments, the data protection provision of the
Food and Drug Regulations was interpreted narrowly by the Courts
such that it was rarely, if ever, triggered
• See e.g. Bayer v. Attorney General of Canada (1998), 87 C.P.R. (3d)
29 (FCA)
– relied on bioequivalence - not on the underlying data, so they didn’t apply
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III. Pharmaceutical Patent Law – The
Current System
Data Protection (post – October 2006)
• Amended Food and Drug Regulations prohibit issuance of a NOC to
a manufacturer that makes a direct or indirect comparison to an
“innovative drug” until eight (8) years after issuance of the
innovators first NOC
• + additional 6 months for certain paediatric
submissions
• Applies to all drugs that have received a NOC on or after June 17,
2006
• A generic manufacturer may file an ANDS or trigger litigation under
the PM(NOC) Regulations after 6 years
• Amended regulations are more in line with comparable foreign
jurisdictions
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Biologics
• Drugs derived from the biological activity of
living organisms
– Per Hughes: “bugs or bug poop”
• Heterogeneous, sensitive to manufacturing
conditions
• Examples:
– Produced through recombinant DNA
– Hormones
– Gene therapy products
Subsequent Entry Biologics
• Demonstrated similarity to the reference
biologic drug
– Not necessarily pharmaceutical or therapeutic
equivalences
• Differences in quality should have no adverse impact on
safety and efficacy
• Data from reference biologic is relevant to the SEB
• Approved under the existing New Drug
Submission pathway under F&D Regs.
Thank You
Don Cameron
[email protected]
Bereskin & Parr LLP