Federal Court Rejects Apotex’s Judicial Review Application for Apo-Omeprazole Magnesium Tablets

Federal Court Rejects Apotex’s Judicial Review Application for Apo-Omeprazole Magnesium Tablets

Apotex Inc v Canada (Health), 2017 FC 857

The Federal Court (“FC”) upheld the Minister of Health’s decision to cancel reconsideration for Apo-Omeprazole Magnesium Tablets manufactured by Apotex Inc. (“Apotex”). [8] This is the second time Apotex sought an application for judicial review that was dismissed by the FC, amounting to yet another failed attempt to obtain approval for the magnesium tablet form of its anti-ulcer drug (see also 2012 FCA 322; PCK Reporter summary available Here).

The decision to cancel reconsideration resulted from the inability of the parties to agree on an eligible question to be posed to the Reconsideration Panel. [6] The FC held that Apotex did not have a legitimate expectation to have its preferred question appear before the Panel, and the Minister did not fetter her discretion to focus the question on the regulatory requirement of bioequivalence. [8]

Background and Context

To market a drug in Canada, a manufacturer must obtain a Notice of Compliance from Health Canada. While innovators must file a lengthy New Drug Submission, a “fast-track” option is available for generic manufacturers via the Abbreviated New Drug Submission (“ANDS”). [10-12] The Food and Drug Regulations allow a generic product to be approved by demonstrating that it is bioequivalent to the “innovative drug,” referred to as the Canadian reference product (“CRP”), [15-16] meaning that their product can be expected to have the same effects as the CRP when administered to patients under specified conditions. [3] Apo-Omeprazole is a Proton Pump Inhibitor (“PPI”) that functions to lower gastric acid production in the treatment of ulcers. [42] The CRP is LOSEC, marketed by AstraZeneca, which can be taken without any meal restriction. [42] Apotex’s ANDS ultimately failed because it did not demonstrate bioequivalence under high fat meal conditions. [22]

Apotex’s first ANDS was filed in 2003 and was placed on patent hold, with an expectation to be approved upon expiration of the AstraZeneca patent. [4] However, as a result of greater experience with PPIs, Health Canada realized the necessity to additionally require study results under fed conditions, including high fat meals, which was not part of Apotex’s 2003 ANDS. [20] Health Canada indicated that all generic PPIs approved have met the requirement to account for the different conditions that affect the release of PPIs. [72, 74]

Apotex submitted a second ANDS in 2013 to include a study conducted in 1998 with high fat meals, but Health Canada considered the study unsatisfactory, citing a poor design and inadequate results. [87] Apotex sought reconsideration, a process that involves posing an appropriate question to an external expert panel, but Apotex and Health Canada were incapable of reaching an agreement on an eligible question. [30-36] Health Canada wanted to focus on “bioequivalence” whereas Apotex insisted on “safe and effective.” [43-58] The Minister eventually cancelled the reconsideration process in 2015, which was the decision Apotex challenged in this case. [59]

Legitimate Expectations Were Met and There was no Fettering of Discretion

The FC explained that the function of the Reconsideration Panel is technical in nature. [39] In this case, the Panel’s role would have been to respond to the reconsideration question and to make a recommendation to the Minister of Health as to whether the results of the 1998 fat fed study provided evidence on Apotex’s product being “bioequivalent” to the CRP, a regulatory requirement for ANDS approval. [95] As such, a question that instead focused on “safety and effectiveness” would have been not useful. [99]

Apotex argued that it had legitimate expectations to have the issues it wanted raised to go before the Reconsideration Panel. [65] The FC disagreed, stating that the reconsideration process is not to be treated like an appeal where each party is free to frame its issues before a court. [85] In this case, the FC considered the legitimate expectation to be concerned with Apotex having been given a fair opportunity to draft an eligible question and found that Apotex was indeed given a better than fair opportunity. [90]

Contrary to Apotex’s submissions, the FC also found that the Minister did not have the discretion to not consider bioequivalence, and the Minister did not restrict how bioequivalence should be assessed. [94-104] Fettering of discretion occurs when the decision-maker confines the exercise of discretion by refusing to consider factors that are legally relevant. [92] The Minister could not have fettered a discretion that she did not have, as in this case. [104] The FC further explained that the underlying rationale for this bioequivalence regulatory pre-condition is to allow a generic product to “piggy-back” on the CRP, which has already gone through the rigour of presenting “detailed reports of tests” and “substantial evidence” to demonstrate safety and effectiveness. [103] Fundamentally, the FC viewed Apotex’s application as an attempt to circumvent regulatory requirements that would not otherwise have been met with its 1998 fat fed study. [95]

Commentary

This is a case where Apotex did not want to be confronted with the task of demonstrating bioequivalence because that would entail conducting further studies, presumably a time-consuming and resource-intensive undertaking. Instead, Apotex chose to bring its case, twice, before the Federal Courts, both times unsuccessfully. Justice Roy went as far as describing this case as an “episode” [28] in “what is in the process of becoming a veritable saga” [1] and essentially a “last-ditch effort” to salvage something that should not succeed. [124] Nonetheless, Apotex has appealed. Perhaps Apotex’s frustration stems from the Minister’s initial “approval” of the ANDS in 2003, only to later revoke it with an additional request for further experimental results, at a time when the patent hold was over and Apotex was anticipating to have its product enter the market.

patent rules