Canada: Federal Court Sets Aside Minister Of Health's Approval Of RUZURGI For The Second Time Over Data Protection Dispute

For the second time, the Federal Court (FC) has set aside the decision by the Minister of Health to issue market authorization for the amifampridine drug RUZURGI. In Catalyst Pharmaceuticals, Inc. v. Canada (Attorney General), 2022 FC 292, the FC held unreasonable the Minister's interpretation and application of the data protection provisions set out in the Food and Drug Regulations, and remitted the matter yet again for a new determination.

The data protection provisions of the Food and Drug Regulations (the Regulations) aim to protect and reward innovators and prevent unfair commercial use of data generated for regulatory approval. The Office of Submissions and Intellectual Property (the OSIP) is responsible for applying data protection provisions. Subsection C.08.004.1(3) provides:

(3) If a manufacturer seeks a notice of compliance for a new drug on the basis of a direct or indirect comparison between the new drug and an innovative drug,

In 2019, both Catalyst Pharmaceuticals, Inc. and Médunik Canada submitted a New Drug Submission (NDS) for amifampridine drugs for the treatment of an ultra-rare and debilitating autoimmune disorder called Lambert-Eaton myasthenic syndrome (LEMS). Catalyst's amifampridine drug (in phosphate salt form) is marketed under the name FIRDAPSE by KYE Pharmaceuticals Inc. in Canada. Médunik's amifampridine drug (a free base) is marketed under the name RUZURGI.

On July 31, 2020, the Minister issued a Notice of Compliance (NOC) to Catalyst for FIRDAPSE. FIRDAPSE was recognized as an innovative drug, was placed on the register, and was entitled to data protection under subsection C.08.004.1(3): an eight-year period of market exclusivity, during which time no drug submission that makes a "direct or indirect" comparison to FIRDAPSE can be approved.

On August 10, 2020, a NOC was issued to Médunik for RUZURGI. At the heart of the conflict between the parties is that, in its NDS, Médunik referenced both non-clinical and clinical FIRDAPSE safety and efficacy studies, that were required for FIRDAPSE to gain regulatory approval in the US and Canada (the "Impugned Information"). Catalyst challenged the Minister's decision to issue a NOC to Médunik for RUZURGI as contrary to the data protection provisions of the Regulations, and in particular, to paragraph C.08.004.1(3)(b). The Federal Court quashed the Minister's decision and sent the file back to the Minister for a new determination.

On June 24, 2021, the OSIP (on behalf of the Minister) issued its reasons (the "OSIP Reasons") which concluded that even though FIRDAPSE was designated an innovative drug as of July 31, 2020, the data provisions in section C.08.004.1(3)(b) did not prohibit the issuance of the RUZURGI NOC. The Minister then issued the RUZURGI NOC for the second time; Catalyst again sought judicial review.

Under the standard of reasonableness, the Federal Court found that the Minister's reasoning did not fall within a range of possible, acceptable outcomes that are defensible in respect of the facts and the law. At the heart of the Minister's decision to issue the RUZURGI NOC was the OSIP's interpretation of the data protection provisions. OSIP asserted that the RUZURGI NDS did not engage paragraph C.08.004.1(3)(b) because of two specific points of interpretation: the first relates to the timing of the drug submission, and the second, to the reliance on a comparison to an innovative drug. On both interpretive points, the FC found that the Minister's interpretation of C.08.004.1(3)(b) is unreasonable given the text of the regulations, as well as the context and purpose of the data protection regime.

Timing of the drug submission

The OSIP's position was that the data provisions must be interpreted to operate in a forward-looking manner in the sense that the manufacturer's conduct needs to be evaluated when it occurs. Thus, the OSIP had concluded that as the FIRDAPSE information was included in the RUZURGI NDS before FIRDAPSE was approved and designated as an innovative drug, because of the timing, the presence of the safety information could not have been to seek approval on the basis of a comparison to FIRDAPSE.

The FC clarified that actual regulatory text of C.08.004.1(3)(b) contains two clear and distinct prohibitions. The first is that "[i]f a manufacturer seeks a notice of compliance for a new drug on the basis of a direct or indirect comparison between the new drug and an innovative drug", the Minister "shall not approve that submission", which the FC defines as the approval prohibition. The second is that the Minister "shall not issue a notice of compliance in respect of the new drug", which the FC defined as the NOC issuance prohibition. Contrary to the OSIP's interpretation, the NOC issuance prohibition is not dependent on paragraph (a) for its application.

As for the timing of the filing of the NDS, the FC found that the Regulations do not indicate that the evaluation of a possible comparison with an innovative drug must be assessed strictly at the time of filing. On the contrary, the actual text of the Regulations suggests a continuous verification until the NOC is issued.

As a final note on the timing issue, the FC found that the OSIP's interpretation of the timing issue ignores the purpose of the Regulations, which is to protect drug manufacturers from the unfair commercial use of undisclosed test or other data that they are required to file with Health Canada to obtain a NOC for a drug that uses a new chemical entity.

Reliance on comparison to an innovative drug

Second, the OSIP asserted that Médunik was not relying on the FIRDAPSE studies in seeking an NOC for RUZURGI, because that information was included in the NDS simply by virtue of being publicly available safety information, and not because it formed part of the basis on which the RUZURGI NDS is being recommended for approval.

The FC found that the OSIP's interpretation that the manufacturer must rely on an innovative drug's data accords with the plain meaning of the regulatory text, and so this part of the OSIP Reasons is reasonable. However, the FC found that after setting that principle, the OSIP failed to apply its own interpretation to the RUZURGI NDS, imposing, de facto, the reliance requirement not to Médunik but to the Minister. The evidentiary record showed that both Médunik and the Minister actually relied on the FIRDAPSE studies, which were essential for market authorization.

Further, were it not for the timing, there would have been an issue with the data protection. The OSIP had concluded that Médunik could use the information as long as it was in before FIRDAPSE's approval as an innovative drug. Had the OSIP not considered the inclusion of the FIRDAPSE studies as a comparison to an innovative drug, the OSIP would not have been solely concerned with the timing of Médunik's NDS.

While Catalyst argued that the appropriate remedy is to quash the Minister's Decision, and not send it back for redetermination, the Court was not satisfied that there are exceptional circumstances and thus remitted the matter to the Minister for a new determination. The Attorney General of Canada has filed an appeal with the Federal Court of Appeal, and Catalyst has cross-appealed.

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