Saturday, November 14, 2015

Data Protection Regulations Apply to Post-NDS Supplementary Information

Hospira Healthcare Corporation v Canada (Health) and Sanofi-Aventis Canada Inc 2015 FC 1205, 2015 FC 1206 Gagné J
            2,196,922 / oxaliplatin / ELOXATIN

The main decision in these companion cases is the 1205 decision, in which Gagné J held that the data protection provisions of the Food and Drug Regulations (C.08.004.1) apply to supplementary submissions made after the filing of an NDS. In my view this holding was clearly correct, though the unusual facts may illustrate some problems with other aspects of Canada’s drug approval regime.

Oxaliplatin has long been a “standard of care” drug in the treatment of colorectal cancer. Oxaliplatin was discovered in Japan and subsequently licensed to and acquired by Sanofi [14].* However, until 2006 Sanofi did not seek an NOC for its oxaliplatin product, ELOXATIN, which had been sold in Canada since 1999, but only under the Special Access Program [14]. From 2004 to 2006, Hospira sought to file an NDS for its OXALIPLATIN FOR INJECTION product. However, Hospira did not have clinical trial data, and because by that time oxaliplatin was internationally recognized as the most therapeutically effective treatment for colorectal cancer, clinical trials could not ethically be performed. Nor could it file an ANDS referencing Sanofi’s product, because Sanofi had not yet obtained an NOC for sale in Canada. Consequently, in late 2006 Hospira filed its NDS without any clinical data, but only literature references and reports of post-marketing experience.

After various exchanges and litigation, Hospira’s NDS was rejected in 2012 because the literature references were not sufficiently robust to establish the clinical safety and efficacy required under C.08.002(2)(g), (h) [31]. Meanwhile, in the fall of 2006, within a month Hospira’s submission, Sanofi also filed an NDS which did include clinical trial data [18]. Sanofi’s submission was given priority status and an NOC was issued for ELOXATIN in 2007 [18], [21]. Hospira responded to the 2012 Notice of Noncompliance with new information, including, ultimately, the ELOXATIN Product Monograph [33], [34]. While this was enough to satisfy the safety and efficacy requirements, Hospira was then informed that because Hospira had made comparisons in its submission to ELOXATIN which was listed on the Register of Innovative Drugs by 2012 (though not in 2006), the data protection provisions Food and Drug Regulations (C.08.004.1) applied and the NOC for OXALIPLATIN FOR INJECTION would not be issued until the expiry of the term of market exclusivity for ELOXATIN [40].

It was uncontested that Hospira had indeed made comparisons in its submission to ELOXATIN [75], but Hospira argued that the data protection provisions, in particular C.08.004.1(3) do not apply to post-filing amendments made pursuant to subsection C.08.004(2), which permits the manufacturer to file additional information. The basic argument was textual: C.08.004.1(3) provides that data protection is invoked if a manufacturer “seeks a notice of compliance” for a new drug on the basis of a direct or indirect comparison with an innovative drug, and para (a) provides it cannot “file a new drug submission” until the data protection period expires. Since Hospira did not originally “seek” its NOC on the basis of a comparison, it was not barred from submitting its NDS and so, argued Hospira, the Minister could not refuse to issue the NOC under para (b), even though the approval would ultimately have been granted on the basis of such a comparison [65], [75].

Gagné J applied the standard approach to statutory interpretation, which requires consideration of the text, context and purpose surrounding the provisions at issue [77]. She noted that the purpose of the data protection provisions is in part to prevent unfair use of undisclosed clinical or other data generated by an innovative manufacturer to support its drug submission [73], [83]. This purpose clearly supports the view that the data protection provisions should apply to supplementary information, and the text was not sufficiently clear to override this purposive analysis, particularly when read in context [79], [83].

Because of the unusual facts, Hospira was in a difficult position, and it does seem problematic that Sanofi enjoyed a de facto market exclusivity under the SAP program from 1999 to 2007, and then obtained an additional 8.5 years of data protection starting from 2007 when its NOC was issued (though I’m not familiar with the background, so perhaps there is some good reason for this). But as a matter of statutory interpretation and the policy underlying the NOC Regulations, Gagné J’s holding is certainly correct.

Note that Gagné J also re-affirmed that the applicable standard of the Minister’s interpretgation of the data protection provisions is correctness [49], relying primarily on Takeda Canada 2013 FCA 13 [26]-[30], and also Pfizer Canada 2014 FC 1243 [57]-[104].

The sister decision 2015 FC 1206 concerned Hosipra’s difficulties with the PM(NOC) Regulations. Injectable oxaliplatin was also covered by the ‘922 patent, and the Minister had required Hospira to address that patent before an SNDS for Hospira’s ready-to-use injectable oxaliplatin solution would be considered [12]. Gagné J held that the refusal was moot issue, as the patent has expired and in any event the Mininster is prevented from issuing the NOC due to the data protection provisions, as discussed above.

*While not specified in the 1205 decision, when Gagné J stated that Sanofi “acquired” oxaliplatin, presumably she meant it acquired the ‘922 patent.

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