The Patented Medicines (Notice of Compliance) Regulations - PowerPoint Presentation

Slide1

The Patented Medicines (Notice of Compliance) Regulations

Don CameronBereskin & Parr LLP

April 17, 2014Slide2

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The Canadian Pharmaceutical Regulatory Regime – The

PM(NOC) Regulations

A Brief History of the PM(NOC) Regulations

The Drug Approval Process in Canada

Pharmaceutical Patent Law – The Current System

Overview

Patent Register

PM(NOC) Regulations

Litigation under the PM(NOC) Regulations

Data ProtectionSlide3

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

)Slide5

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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 CanadaSlide6

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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 BoardSlide7

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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 c

ompulsory licensing

NAFTA/TRIPS:

Exclusive right to make, use, sell, import and licence patented product

1992 – Bill C-91

Abolished prospective compulsory licences post 1991Slide8

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 forceSlide9

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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 approvalSlide10

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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 authorizationSlide11

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 CanadaSlide13

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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”)Slide14

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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 low-cost, 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)Slide18

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) proceedingSlide19

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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. 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). Slide21

III. Pharmaceutical Patent Law – The Current System

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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 RegisterSlide23

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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

See

Ratiopharm v. Wyeth

, 2007 FCA 264 Slide24

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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 requirementsSlide25

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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 ingredientSlide26

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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 ingredientSlide27

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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 symptomsSlide28

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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 derivativesSlide29

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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 forSlide30

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III. Pharmaceutical Patent Law – The Current System

PM(NOC) Litigation – Sequence of Events

“First Person” (e.g. Innovator) files a New Drug Submission (NDS) and has patents listed on the Patent Register.

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 triggeredSlide31

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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:

Await expiry of all listed patents before receiving a NOC;

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 allegationsSlide32

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III. Pharmaceutical Patent Law – The Current System

Section 6

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.

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 listedSlide33

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III. Pharmaceutical Patent Law – The Current System

Section 7

Once an application for an order of prohibition is filed, the Minister may not issue a NOC until the expiry of 24 months, unless:

the

court finds in favour of the generic, or

(

ii) the patent expires

Effectively

an interlocutory injunction without preconditions having been metSlide34

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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.

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 NOCSlide35

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III. Pharmaceutical Patent Law – The Current System

PM(NOC) Litigation – Burden of Proof

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 ProceedingsSlide36

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III. Pharmaceutical Patent Law – The Current System

PM(NOC) Litigation

Parties exchange pleadings, expert affidavits, conduct witness cross examination and file legal briefs.

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.Slide37

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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

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.)Slide38

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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.Slide39

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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 applySlide40

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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 jurisdictionsSlide41

Biologics

Drugs derived from the biological activity of living organismsPer Hughes: “bugs or bug poop”Heterogeneous, sensitive to manufacturing conditions

Examples:

Produced through recombinant DNA

Hormones

Gene therapy productsSlide42

Subsequent Entry Biologics

Demonstrated similarity to the reference biologic drugNot necessarily pharmaceutical or therapeutic equivalencesDifferences 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

R

egs

.Slide43

Thank You

Don Cameron

dcameron@bereskinparr.com

Bereskin & Parr LLP