Federal Court of Appeal upholds Health Canada’s requirement for additional information on testing data integrity

The Federal Court of Appeal (FCA) has dismissed Apotex’s appeal arising from its application to end Health Canada’s requirement for additional information establishing the integrity of data from Indian drug manufacturing facilities. The FCA found that the Federal Court (FC) properly considered the evidence and that it did not err in finding that the decision to implement the requirement for additional information was not improperly motivated.


This appeal arises from the third in a series of judicial-review applications by Apotex Inc. (Apotex) concerning regulatory intervention by Health Canada against drugs manufactured at facilities owned by Apotex affiliates in India.

The first two applications concerned an import ban on drugs manufactured at these facilities, implemented by the Health Products and Food Branch Inspectorate (Inspectorate) of Health Canada after Apotex informed the Inspectorate of issues concerning the integrity of testing data from these facilities. The FC quashed both the decision to impose the import ban, as well as a subsequent decision to vary the terms and conditions of establishment licences for these facilities, on the basis that they were motivated by an improper purpose.

The third application concerned additional limitations that were imposed with respect to approval of drugs manufactured at the Indian facilities. In November 2014, after being informed by the Inspectorate about the data integrity concerns, the Therapeutics Product Branch (TPD) of Health Canada told Apotex that it would not issue a Notice of Compliance (NOC) for drug submissions with data from these facilities, but would request further information as required. Apotex generally complied with the TPD’s requests for additional information relating to data integrity, and NOCs were issued for drug submissions with data from the two Indian facilities. In May 2015, the TPD implemented a general policy requiring additional information to establish the reliability of data from facilities where there were data integrity concerns.

In October 2015, Apotex asked the TPD to remove the requirement for additional information in light of the FC quashing the import ban. The TPD refused to do so on the basis that the Court’s decision did not address the reliability of data from the Indian facilities before Apotex implemented corrective and preventative measures, and because it was required by the general policy applicable to any drug submission for which there were concerns about data integrity.

Apotex applied for an order quashing the TPD’s decision refusing to end the requirement and sought approval of other products obtained from these facilities. As we previously reported, the Federal Court dismissed Apotex’s application, finding that the requirement for additional information to establish data integrity was not improperly motivated by the import ban. The Federal Court also found that maintaining the requirement for additional information was reasonable in light of genuine concerns about data integrity.

Standard of review

The FCA agreed with Apotex that the normal civil standard of review for findings of fact, i.e., palpable and overriding error, applied to the FC’s decision regarding Health Canada’s motivations. The Court rejected the Minister’s submission that the proper standard of review was reasonableness, holding that the standard was appropriate on review of the administrative decision but not for findings of fact or mixed fact and law made in the first instance.

All of the Minister’s evidence was considered

In response to the application, the Minister relied upon evidence from the Director General of the TPD. While the application was under reserve following the initial hearing, the Minister provided a correction to the Director General’s evidence and produced additional documents, leading to further cross-examination and a hearing on the additional evidence. Apotex argued that the FC erred by considering the initial evidence separately from evidence that was later produced, testing conclusions regarding the former with the information in the latter. The FCA rejected this argument, holding that there is no prescriptive methodology for a judge at first instance to follow and finding that all of the evidence was considered.

No error in failing to draw an adverse inference from the Minister’s evidence

The FCA held that the FC did not err by failing to draw an adverse inference against the Minister for not producing contemporaneous documents to establish the basis for the 2014 decision to require additional information and for not leading evidence from a witness with first-hand knowledge. Noting that the decision to draw such an inference is discretionary, the FCA held that Apotex did not ask the FC to do so regarding the evidence of witnesses and held that the scope of documentary production was appropriate.

No error regarding the motivation not to end the data integrity requirement imposed in 2014

The FCA held that the FC did not err in finding that the TPD’s 2014 decision to require additional information to address data integrity was not improperly motivated, unlike the import ban, on the evidence before the Court. As there was no support for the proposition that the 2015 decision to maintain the requirement was tainted independently of the 2014 decision, there was no need for the FCA to consider this issue further.

Links to decisions:

FCA Decision: Apotex Inc v Canada (Health), 2018 FCA 147

FC Decision: Apotex Inc v Canada (Health), 2017 FC 315

Pharma in Brief – Federal Court dismisses application for a prohibition order regarding prasugrel hydrochloride under the old PM(NOC) Regulations

The Federal Court dismissed an application by Eli Lilly Canada Inc., Ube Industries, Ltd., and Daiichi Sankyo Company, Limited (the Applicants) seeking a prohibition order regarding Apotex’s generic version of Lilly’s EFFIENT® (prasugrel hydrochloride). While the Court rejected Apotex’s allegations of overbreadth, insufficiency, and non-patentable subject matter, it held that the claims were obvious.


The claims of Canadian Patent No. 2,432,644 (the 644 Patent) relate to pharmaceutical compositions comprising prasugrel and aspirin. Prasugrel is a member of the thienopyridine family of compounds. The asserted claims of the patent claimed the use of prasugrel for simultaneous or sequential, separate administration with aspirin and the compound prasugrel for use in combination with aspirin, in preventing or treating a disease caused by thrombus or embolus.


In its obviousness analysis, the Court accepted the Applicants’ construction of the inventive concept: the combination of prasugrel plus aspirin with an antithrombotic effect that is greater than the sum of the effects of each agent alone. The Court also found that this inventive concept had not previously been disclosed and therefore differed from the state of the art.

However, in applying the “obvious-to-try” test, the Court held that the claims were obvious finding that there was a motivation in the art to try the combination of prasugrel with aspirin and that there was a “reasonable expectation” that combining prasugrel, a thienopyridine, simultaneously or sequentially with aspirin would produce a beneficial, complementary mechanism of action.

The Court acknowledged that:

Central to the Court’s analysis was evidence that the prior art had shown that the substitution of one thienopyridine (ticlopidine) for another (clopidogrel) to use in combination with aspirin had been positive.

Despite finding that one of only two thienopyridines approved for sale did not consistently demonstrate synergy with aspirin and that there was no information in the state of the art regarding the mechanism by which clopidogrel and aspirin had developed a synergy, the Court nevertheless concluded that there was a reasonable expectation that the combined use of prasugrel and aspirin could reasonably be expected to achieve a synergy similar to the combination of clopidogrel with aspirin.

This analysis minimizes the well-known unpredictability of structural changes on biological effect. In combination with the “obvious to try” test, this may create a low bar to obviousness that disproportionately impacts pharmaceutical inventions.

Patentable Subject Matter

The Court held that the patent disclosed that the use of prasugrel combined with aspirin results in an effect on platelet aggregation that is new, useful, and more than the mere sum of the effects of the two agents taken alone. The Court accepted as sufficient, data showing that the combination produced a numerically greater inhibition rate than prasugrel or aspirin alone and did not require a more formal statistical analysis.

Insufficiency & overbreadth

The Court rejected Apotex’s argument that the patent failed to disclose how to administer prasugrel and aspirin sequentially. Although time intervals were not specified in the patent, the experts were able to determine an appropriate interval using the patent and common general knowledge. The Court similarly rejected the argument that claim 29 of the 644 Patent was overly broad for failing to include a maximum time interval.


Link to Decision:

Eli Lilly Canada Inc., Ube Industries, Ltd. and Daiichi Sankyo Company, Limited v. Apotex Inc., 2018 FC 736

Health Canada Releases Updated Guidance on Amended PM(NOC) Regulations

As we reported, Canada implemented sweeping amendments to the Patented Medicines (Notice of Compliance) Regulations on September 21, 2017. Health Canada has now issued an updated guidance document on the administration of the Regulations in light of these amendments. The update also reflects administrative practices. The guidance document is effective as of May 11, 2018 and is applicable to all drugs that receive a notice of compliance (NOC).

The guidance document elaborates on a number of elements of the new regime, including:

  • The scope and application of section 5 of Regulations, including providing clarification for the types of submissions that will be captured by the provision when a second person applies for an NOC.
  • Information on the TPD’s process for assessing submissions (including supplements) under the new regime. This includes details on the process for submitting Form Vs and addressing additions to the Patent Register, as well as certification letter issuance and service.
  • Situations in which a second person must retract a notice of allegation, including screening rejections, notices of non-compliance-withdrawal, and notices of deficiencies-withdrawal.
  • How parties are to disclose litigation information to the TPD given that the Minister of Health is no longer a party to actions commenced under the amended Regulations. Health Canada has emphasized the importance of complying with this procedure in order to avoid the issuance of an NOC while a proceeding under the Regulations is still ongoing.
  • The TPD’s process for assessing CSPs under the Regulations, and in particular the manner and circumstances in which CSPs will be added to the Patent Register.
  • The process for placing submissions on Intellectual Property Hold.
  • The process for requesting that the TPD verify portions of a submission or supplement under the Regulations
  • The process for a first person to renounce the twenty-four month stay .
  • The TPD’s procedure for maintaining the Patent Register, including the removal of patents and CSPs that are found to be ineligible for listing. Notably, the guidance document states that patents and CSPs declared invalid or void will be deleted after an initial finding and will be added back to the Patent Register if the decision is subsequently reversed. Second persons who file submissions while the patent or CSP is not on the Patent Register will not need to address that patent or CSP.

Link to Guidance Document:

Guidance Document: Patented Medicines (Notice of Compliance) Regulations

Advisory Council on the Implementation of National Pharmacare – Consultation with Canadians

Advisory Council on the Implementation of National Pharmacare – Consultation with Canadians

The Advisory Council on the Implementation of National Pharmacare (“Council”) is consulting with Canadians on the implementation of a national program to fund prescription drugs.  The consultation is open until September 28, 2018.

The Council, which reports to the Minister of Health and the Minister of Finance, was created following an announcement in the 2018-2019 federal budget (reported here).

Canadians can provide their views on national pharmacare through various means, including: (i) an online questionnaire; (ii) by providing written submissions to the Council; and (iii) by engaging in the discussion through an online discussion forum.

To guide the consultation, the Council has published a discussion paper entitled Towards Implementation of National Pharmacare.  In the paper, the Council has identified the following key issues for consideration and questions for discussion:

  • Issue: Who will be covered and under what circumstances
    • Who should be covered under national pharmacare?
    • How should national pharmacare be delivered?


  • Issue: Which drugs will get coverage
    • Which drugs should be covered as part of a national pharmacare plan?
    • How much variability across different drug plans or jurisdictions should there be in the list of drugs covered by national pharmacare?


  • Issue: Who pays
    • Should patients pay a portion of the cost of prescription drugs at the pharmacy (e.g., co-payments or deductibles)?
    • Should employers, who currently play a significant role in funding drug coverage for their employees, continue to do so (either through contributions to a private plan or through a public plan)?


Canadians invited to share their views with the Advisory Council on the Implementation of National Pharmacare


First motion for early patent dismissal fails to meet high burden under newly-amended PM(NOC) Regulations

On July 6, 2018, the Federal Court dismissed the first motion brought under section 6.08 of the newly-amended Patented Medicines (Notice of Compliance) Regulations (the Regulations). The Court’s public reasons were released July 30, 2018. The moving party, Amgen Canada Inc. (Amgen), was seeking an order dismissing the Plaintiffs’ action in respect of two of the patents in suit on the ground that the action is redundant, scandalous, frivolous or vexatious or is otherwise an abuse of process. Amgen contended that it was plain and obvious that the Plaintiffs’ infringement allegations had no chance of success.

Norton Rose Fulbright Canada LLP represented the Plaintiffs, Genentech, Inc. and Hoffmann-La Roche Limited.


Amgen is seeking Health Canada’s approval to market a biosimilar version of HERCEPTIN® for the same indications as HERCEPTIN®.  The Plaintiffs commenced an action against Amgen seeking a declaration that the making, constructing, using or selling of Amgen’s biosimilar would infringe four patents. Amgen brought a motion to dismiss the action in respect of two of the patents, Canadian Patents No. 2,376,596 (596 Patent) and 2,407,556 (556 Patent). Amgen argued that the Plaintiffs’ allegations that Amgen would induce infringement of the 596 Patent and the 556 Patent were clearly futile.

Motion to dismiss under section 6.08

This was the first motion to dismiss brought under section 6.08 of the newly-amended Regulations. The Court found, however, that the jurisprudence under section 6(5)(b) of the previous Regulations – which had essentially the same language as section 6.08 – was applicable.

Therefore, as set out in the section 6(5)(b) case law, dismissing an action under section 6.08 remains an extraordinary remedy. The moving party bears the onus of demonstrating that the claim is so clearly futile that it has not the slightest chance of success. The Court is to determine whether the plaintiff raises an arguable case. In doing so, the Court  is not to embark on anything resembling a trial of the action in order to evaluate the strength of either party’s case.

The Court found that it should exercise a heightened level of caution in dismissing actions under the newly-amended Regulations, as – unlike the previous Regulations – if the action is dismissed, the plaintiff may be precluded from suing for patent infringement if the proposed product comes to market.

The Court also observed that, because the newly-amended Regulations provide for discovery, in cases that – like this one – concern induced infringement of use claims, there may be many key documents in addition to the proposed product monograph.

An arguable case of induced infringement

The Court found that it was not plain and obvious that the Plaintiffs’ allegations of induced infringement had no chance of success. With respect to the 596 Patent, the Court found that the parties had engaged in legal and factual disputes during the motion. The Court determined that it was at least arguable that Amgen would exert the requisite influence leading to direct infringement of the 596 Patent by physicians and patients. With respect to the 556 Patent, the Court determined that there was a debatable issue regarding claims construction and that the Plaintiffs had otherwise raised an arguable case of induced infringement.


Genentech, Inc. and Hoffmann-La Roche Limited v Amgen Canada Inc., 2018 FC 694

Getting the Deal Through – Pharmaceutical Antitrust

Norton Rose Fulbright has published a new edition of Getting the Deal Through – Pharmaceutical Antitrust. This edition is an updated, thorough overview of the application of antitrust law to the pharmaceutical sector worldwide. The pharmaceutical sector remains a priority area for antitrust enforcement in most major jurisdictions, where enforcement agencies have been increasingly prone to use antitrust rules to protect innovation and control drug prices along the value chain.

You may access a copy here.

Federal Court upholds patent validity and grants prohibition order against generic lisdexamfetamine in pre-CETA PM(NOC) application

The Federal Court dismissed Apotex’s action to invalidate the claims of Canadian Patent No. 2,527,646 (the 646 Patent), which was consolidated with Shire’s application to prohibit the Minister of Health from issuing a Notice of Compliance for Apotex’s generic version of VYVANSE® (lisdexamfetamine). Shire’s counterclaim for infringement in the action was dismissed but the Court granted the prohibition order against the Minister.

Patent found to be valid

Amphetamines are used to treat attention deficit and hyperactivity disorder (ADHD), but are controlled substances because they can be abused for their euphoric effect. Abuse typically occurs when tablets are crushed into a powder that is snorted or dissolved and injected. Sustained-release formulations improve convenience for patients but are more susceptible to abuse because they contained greater amounts of amphetamines.

Invention of the 646 Patent

The 646 Patent claimed prodrugs of amphetamines and derivatives or analogs formed by covalent attachments of chemical moieties to the amphetamine. These prodrugs are converted in the body to the active amphetamine over time, providing sustained release of amphetamine while reducing abuse potential. The asserted claims of the 646 Patent covered lisdexamfetamine (LDX), consisting of d-amphetamine conjugated to the amino acid L-lysine. The claims at issue also cover certain salts of LDX, pharmaceutical compositions containing LDX, and use of LDX to treat ADHD.

Not a selection patent

Shire argued that LDX is selected from the class of amphetamine amino acid conjugates encompassed by Australian Patent No. 54168/65 (the AU 168 Patent). Apotex disagreed. Justice Fothergill doubted that the 646 Patent may be properly characterized as a selection patent. However, he found that nothing turned on this point because the outcome of his anticipation and obviousness analyses were not affected by it. In coming to his conclusion, he distinguished and rejected Apotex’s reliance on Hoffmann-La Roche Ltd. v Apotex Inc., 2013 FC 718, noting that there may be reason to approach this decision with caution.

Not anticipated

The Court held that the 646 Patent was not anticipated. Justice Fothergill found that the expert evidence raised many unanswered questions regarding the prior art, which did not clearly relate to prodrugs, did not disclose the process of making LDX, and did not teach that the compounds it disclosed provide a sustained release treatment for ADHD with, or even without, a reduced potential for abuse.

Not obvious

The Court held that the inventive concept for all the claims of the 646 Patent was a sustained-release formulation of a therapeutically useful dose of amphetamine that is resistant to abuse. Justice Fothergill found that the difference between the state of the art and the inventive concept was the compound LDX and its advantageous properties. He also found that the prior art did not indicate or suggest that LDX would provide sustained release of amphetamine with reduced abuse potential, and that the prior art did not suggest prodrugs would render a drug less susceptible to abuse.

The Court held that LDX was not obvious to try. There was no way to know the properties of LDX without testing, even if the testing was routine, and it was not more or less self-evident that the contemplated tests would overcome the differences between the starting point and the ending point

Not overbroad

Justice Fothergill found that the claims were not overbroad, as he construed  the term “L-lysine-d-amphetamine” as only LDX and a group of compounds.

Specification is not insufficient

Justice Fothergill held that the specification of the 646 Patent is not insufficient because LDX’s advantageous properties exist regardless of whether it is in a particular salt form, or as a free base. He also held that the invention of the 646 Patent does not relate to scale-up synthesis or to a particular crystal form, and that the skilled person was capable of making the claimed compounds by following the 646 Patent.

No reliance on foreign decisions

In reaching the foregoing conclusions, Fothergill J. rejected Shire’s position that the Court should regard foreign judgments involving comparable patents, which consistently affirmed the validity of the patents, as being instructive.

No infringement because of experimental or regulatory use exception

The Court found that Apotex obtained LDX for experimental or regulatory use, and that it was a sufficient defence for Apotex to have an internal policy that the approximately 900,000 capsules containing LDX dimesylate in its inventory would be used entirely for future research or making demonstration batches. As a result, the Court dismissed Shire’s infringement action.

Minister prohibited from granting Notice of Compliance

Having decided that the patent was valid, Justice Fothergill also granted a prohibition order against Apotex’s Apo-lisdexafetamine product as the proceeding under the Regulations was confined to the validity issues in the case.


Apotex Inc v Shire LLC, 2018 FC 637

Pan-Canadian Pharmaceutical Alliance (pCPA) releases draft brand process guidelines

On June 13, 2018, the pan-Canadian Pharmaceutical Alliance (pCPA) released its draft Brand Process Guidelines (Guidelines) for stakeholder feedback. As part of the consultation process, pCPA is planning a webinar for innovative manufacturers on June 22, 2018. The pCPA also released a Frequently Asked Questions (FAQ) document, and a Letter of Intent (LOI) template with the Brand Process Guidelines.

Brand Process Guidelines. The Guidelines are intended to promote a common understanding of the pCPA process, and provide an overview of the pCPA process broken down into the following phases: pre-pCPA, initiation, consideration, negotiation, completion, and post-pCPA. The Guidelines provide details on: (i)  initiation of the pCPA process for new drugs, existing drugs and line extensions, (ii) the content expectations for manufacturer proposals, (iii) negotiation format and negotiator expectations, as well as (iv) communication, confidentiality and disclosure requirements during negotiation. The Guidelines also include target completion timelines for the pCPA process, which sets out an estimated timeline of ≤ 140 days from initiation to completion.

Frequently Asked Questions (FAQ). The FAQ document provides an overview of some commonly asked questions such as: (i) factors that can impact negotiation timelines, (ii) whether a manufacturer can negotiate with individual jurisdictions after receiving a Close Letter (a letter indicating that the pCPA is not opening negotiation for a particular drug) from the pCPA, and (iii) whether a decision to close negotiations without an LOI can be reconsidered.

Letter of Intent (LOI) Template. The LOI template is a standard form document that will detail the agreed upon terms and conditions for funding reached between the lead province(s) and the manufacturer. Of note for manufacturers, the template sets out sample provisions for first dollar and incremental rebates. The template also states that participating jurisdictions may renegotiate the terms of the agreement through the pCPA where there are significant market changes or if expenditures for the drug product significantly exceed the participating jurisdictions’ budget impact. Finally, the template includes standard provisions for continued enrolment of patients in a manufacturer’s patient support program (PSP) for a specified period of time after listing or indefinitely where the patient does not meet the reimbursement criteria in the jurisdiction.

Interested stakeholders should consider attending the pCPA’s webinar for innovative manufacturers on June 22, 2018 as well as submitting additional comments on the Guidelines to the pCPA.


Brand Process Guidelines, FAQ Document, LOI Template

CETA Tracker: Update on section 6 actions under the Patented Medicines (Notice of Compliance) Regulations

As we reported, Canada implemented a single-track pharmaceutical patent litigation regime through amendments to the Patented Medicines (Notice of Compliance) Regulations (the Regulations) on September 21, 2017. Below, we provide an update on new actions and decisions under the amended Regulations.

New actions under the amended Regulations

Nearly seven months after the amended Regulations came into force, litigation is gathering steam. As we reported, the first action under the new regime was commenced by Norton Rose Fulbright Canada LLP on behalf of Genentech, Inc. and Hoffmann-La Roche Limited (collectively, Genentech) in respect of trastuzumab biosimilars on December 11, 2017. This was followed by three more trastuzumab-related actions in late December 2017.

Since the beginning of 2018, ten more actions have been commenced, for a total of fourteen actions currently ongoing:

  • Genentech, Inc. et al. v Amgen Canada Inc., Court File No. T-1921-17 (trastuzumab)
  • Genentech, Inc. et al. v Celltrion Healthcare Co., Ltd., Court Files No. T-1969-17, T-1970-17, and T-1971-17 (trastuzumab)
  • Bristol-Myers Squibb Canada Co. et al. v Apotex Inc., Court Files No. T-350-18 and T-351-18 (apixaban)
  • Janssen Inc. et al. v Teva Canada Limited, Court File No. T-353-18 (paliperidone)
  • Hoffmann-La Roche Limited et al. v Pfizer Canada Inc., Court Files No. T-401-18 and T-402-18 (trastuzumab)
  • Allergan et al. v Tillots Pharma AG, Court File No. T-503-18 (mesalamine)
  • Shire LLC et al. v Apotex Inc., Court File No. T-641-18 (lisdexamfetamine)
  • Bayer Inc. v. Jamp Pharma Corp., Court File No. T-666-18 (vardenafil)
  • Eli Lilly et al v Apotex Inc., Court File No. T-724-18 (teriparatide)
  • Amgen Inc. et al v. Pfizer Canada Inc., T-741-18 (filgrastim)

In order to manage the significantly increased number of deadlines in actions under the amended Regulations compared to applications under the former regime, the Court has applied its “Guidelines for Actions under the Amended PMNOC Regulations”, reported here. This includes early scheduling of the steps leading up to trial using a checklist developed by the Court, early assignment of trial judges, and early booking of trial dates to occur within 21 months of the statement of claim being filed.

Two motions have been decided under the amended Regulations. The court dismissed a motion to vary unilaterally imposed confidentiality rules as premature. The court also dismissed a motion to stay a 6.08 motion until after discovery.


Standing Committee on Health releases report and recommendations on National Pharmacare

On April 18, 2018 the Standing Committee on Health tabled its report on national pharmacare entitled Pharmacare Now: Prescription Medicine Coverage for All Canadians.

The Committee believes that the best way to move forward in establishing a universal single payer public prescription drug coverage program is by expanding the Canada Health Act to include prescription drugs dispensed outside of hospitals as an insured service.  The Act establishes criteria and conditions for insured health services that must be met by provinces to receive payments from the federal government.  Federal government funding will be increased, although the Committee believes that the program should be cost-shared between federal, provincial and territorial governments.

In addition to amending the Act, the recommendations include:

  • Expanding the mandate of the Canadian Agency for Drugs and Technologies in Health (“CADTH”) to include maintaining the national formulary, as well as increasing its capacity to undertake therapeutic reviews of high cost specialty drugs, oncology drugs and drugs for rare diseases.
  • Developing a transparent decision-making framework for price negotiations for pharmaceutical drugs undertaken by the pan-Canadian Pharmaceutical Alliance and designating it as the common agent for the bulk buying of pharmaceuticals.
  • Amending the Patent Act to require manufacturers to reduce prices after 15 years if no generic substitute is available.
  • Investigating the market practices of the pharmaceutical sector, including those of patented and generic drug manufacturers, wholesalers and retail pharmacies, to identify opportunities to reduce prices.

As we reported, the government has also created an Advisory Council on the Implementation of National Pharmacare, which is expected to provide a report in 2019.


Pharmacare Now: Prescription Medicine Coverage for All Canadians