The Patented Medicines (Notice
of Compliance) Regulations
An Overview
Christina Capone Settimi
Associate, Cameron MacKendrick LLP
Toronto
January 23, 2009
 Cameron MacKendrick 2009
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
2
•
Overview
•
Patent Register
•
PM(NOC) Regulations
•
Litigation under the PM(NOC) Regulations
•
Data Protection
I. A Brief History of the PM(NOC) Regulations
3
I. A Brief History of the PM(NOC) Regulations
Pre-1993:
• Prior to 1993, pharmaceutical patents were subject to a
compulsory licensing regime
• Generic companies could manufacture, sell and import a
patented medicine before the expiry of a patent, provided the
drug is shown to be “safe and effective”
• Innovators paid fixed royalty of 4%
• Compulsory licenses were available virtually as of right and/or
generic drug manufacturers could enter the market at any time
• Result was that there was virtually no protection for
pharmaceutical patents in Canada
4
I. A Brief History of the PM(NOC) Regulations
1980’s:
• 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
• Let to major overhaul of the patent system in 1987-1989
• Various changes made to the regime over a number of years which
gradually increased the protection available to pharmaceutical
patents from compulsory licensing
• However, compulsory licensing regime viewed by international
community as being inconsistent with Canada’s trade obligations
under TRIPS and NAFTA
5
I. A Brief History of the PM(NOC) Regulations
1993:
• Compulsory licensing abolished
• New regime introduced to attempt to strike a balance
between encouraging innovation and providing access to
lower cost medicines.
• Bill C-91 established “early working” and “stockpiling”
exceptions to patent infringement
• “Early Working” – Section 55.2(1) of the Patent Act
• “Stockpiling” exception was abolished in 2001 as being
inconsistent with Canada’s international treaty obligations
• PM(NOC) Regulations brought into force
6
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
7
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
• To gain Health Canada authorization 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
10
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
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II. The Drug Approval Process in Canada
• 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
13
II. The Drug Approval Process in Canada
• Once a manufacturer has obtained its NOC, any changes
to the approval (e.g. change of name, packaging, product
monograph) requires the manufacturer to file a
Supplementary New Drug Submission (“SNDS”)
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III. Pharmaceutical Patent Law – The Current System
15
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)
16
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.
17
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
19
Generic
Proceedings for a
Notice of Allegation
Prohibition Order
s. 5
s. 6
Damages
s. 8
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
• Generic drug manufacturers have no say on the listing or
delisting of a patent on the Patent Register
20
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
• See Ratiopharm v. Wyeth, 2007 FCA 264
21
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
22
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
23
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
25
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
27
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
28
III. Pharmaceutical Patent Law – The Current
System
Section 5
• Generic manufacturer must address each patent which is
listed for the referenced drug at the time of filing of the
ADNS 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
29
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) the
patent expires
•
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Effectively an interlocutory injunction without preconditions
having been met
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
•
•
33
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:
34
•
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.
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
•
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.)
35
III. Pharmaceutical Patent Law – The Current
System
PM(NOC) Litigation – Implication of Decision
•
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.
36
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
• 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 (1999), 87 C.P.R. (3d)
29 (FCA)
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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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THANK YOU.
ANY QUESTIONS?
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