Tuesday, December 8, 2015

Whether HAL HCl is an ester of ALA HCl is a Matter of Fact

Photocure ASA v Canada (Health) 2015 FC 959 Kane J
            hexaminolevulinate hydrochloride / CYSVIEW [aka HEXVIX]

In this application for judicial review Kane J declined to interfere with the Minister’s decision refusing to add Photocure’s drug CYSVIEW to the Register of Innovative Drugs. The key issue was whether the Minister’s decision involved matter of law or matter of fact. The case does not really raise any questions of general legal interest, though there was some suggestion by Kane J that whether the Minister’s interpretation of the Data Protection Regulations is to be reviewed on a correctness standard turns on the particular legal issue.

Only an “innovative drug” can be listed on the Register. An innovative drug is defined in C.08.004.1(1) as follows:

a drug that contains a medicinal ingredient not previously approved in a drug by the Minister and that is not a variation of a previously approved medicinal ingredient such as a salt, ester, enantiomer, solvate or polymorph.

In Takeda 2013 FCA 13, (blogged here), the FCA held that everything specified by the “such as” provisio, including salts and esters, are per se ineligible for listing, regardless of how much effort might have been required in their development [125]; on the other hand, if a variant is of a type that is not specifically listed, then the question of whether it is "a variation of a previously approved medicinal ingredient" will depend, at least in part, on whether approval is being sought primarily on the basis of previously submitted clinical data [124-25]. The FCA in Takeda also held that the standard of review of the Minister’s interpretation of the Data Protection Regulations is correctness: [34], [111].

The active ingredient in CYSVIEW is hexaminolevulinate hydrochloride (HAL HCl). The drug aminolevulinic acid hydrochloride (ALA HCl) had previously been approved [2]. It was uncontroverisal that HAL is an ester of ALA, and HAL HCl is a salt of HAL, and neither ALA nor HAL had previously been approved. Photocure argued that but HAL HCl is not an ester of ALA HCl [22], and so consideration should be given to whether approval was being sought on the basis of previously submitted data in deciding whether to list CYSVIEW. The Minister however, decided that because the structure of HAL HCl is almost identical to ALA HCl, except for the addition of an ester group, HAL HCl is an ester of ALA HCl, and therefore per se ineligible for listing [2], [31].

The main thrust of Kane J’s analysis was straightforward: there was a question of law as to whether esters are per se ineligible for listing, but that question was decided by Takeda, and the question of whether a particular compound is an ester is a question of fact, on which the Minister is owed deference [130]. As Kane J pointed out, Photocure wanted to introduce scientific evidence to assist the court in determining whether HAL HCl is an ester of ALA HCl, and that in itself shows that the question is one of fact [144].

That analysis seems to me to have been sufficient to dispose of the issue. However Kane J went on to say that

[150] On a standard of review analysis, whether or not the issue is characterized as a question of statutory interpretation (a question of law) or a question of fact (or mixed fact and law), I would arrive at the same standard: the standard of review is reasonableness. Starting from a presumptive standard of reasonableness and conducting a contextual analysis to determine if that presumption is rebutted or starting from the established principle that questions of fact are reviewed on the standard of reasonableness, the nature of the question is a key factor.

This seems to suggest that in Kane J’s view if this were a question of law, it is a question of law that is to be decided on the reasonableness standard, notwithstanding that the FCA in Takeda held that the standard of review of the Minister’s interpretation of the Regulations is generally correctness. I don’t have any opinion as to whether this is sound on administrative law principles, but it does seem to me to have been an unnecessary refinement of Takeda in light of Kane J’s holding that the question was one of fact. She concluded the above paragraph by noting “This analysis becomes a bit circular in the present circumstances,” and rather than being a refinement to Takeda, I take this statement by Kane J as primarily being another way of illustrating that the question is better characterized as being one of fact. 

Once the standard of review was established, Kane J had no difficulty in concluding that the Minister's decision was reasonable [180].

(Note that HAL HCl is also sometimes abbreviated as HAL HCI, and similarly ALA HCl is sometimes abbreviated as ALA HCI. Presumably this is because “I” and “l” can look similar or even the same, depending on the font being used. If you can't tell, one is a capital i, and the other is a lower case L.)

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