Health Canada Interim Policy Clarifies Interpretation of "Medicinal Ingredient," Product Labelling, and Pharmaceutical Equivalence

On June 16, Health Canada announced an interim policy regarding the interpretation of "identical medicinal ingredient" as it applies to product labelling and determinations of pharmaceutical equivalence for Abbreviated New Drug Submissions (ANDSs).¹

What You Need To Know

• Health Canada will interpret "medicinal ingredient" to mean the Active Pharmaceutical Ingredient (API) used as the raw material in the manufacture of the finished drug product.
• A drug product label must identify the API raw material as the "medicinal ingredient."
  • If the API raw material undergoes an in situ change to a new chemical form during the manufacturing process (e.g., conversion to salt form), the label should further identify the chemical form in the finished product, in addition to identifying the API raw material.
• When evaluating whether a submission should be assessed as an ANDS with reference to a previously approved drug product, Health Canada will determine pharmaceutical equivalence at the following stages:
  • the manufacturing input stage (whether the same medicinal ingredients are used as raw materials for manufacturing);
  • the manufacturing process stage (if the same medicinal ingredients diverge into different chemical forms during manufacturing); and
  • the finished dosage form stage (if the medicinal ingredients appear in different chemical forms before or during manufacturing, but converge into the same chemical form in the finished dosage form).
• If a proposed drug product uses the same medicinal ingredient as a previously approved drug product at the manufacturing input stage, but those ingredients diverge into different chemical forms at the finished dosage form stage, then assessment as an ANDS may not be appropriate, and Health Canada may require additional safety, effectiveness, and quality data.
• The interim policy does not apply to biological or radiopharmaceutical products, or medicinal ingredients without a single defined chemical structure (e.g., polymers with varying molecular weights).

Background

In Apotex Inc. v. Canada (Health), 2013 FC 1217, Apotex submitted an ANDS regarding its product Apo-Telmisartan. The Apotex ANDS referenced Micardis, the product label of which identified the medicinal ingredient as "telmisartan." Apo-Telmisartan included potassium hydroxide in the manufacturing process, while Micardis used sodium hydroxide, resulting in different salt forms being found in the finished dosage forms for each product (telmisartan-potassium and telmisartan-sodium respectively).

Health Canada required Apotex to submit additional safety, effectiveness, and quality data for its ANDS, citing the different salt form as the basis for its decision. Health Canada stated that Apo-Telmisartan and Micardis contained different "medicinal ingredients," and therefore were not pharmaceutically equivalent products. Apotex applied for judicial review, noting that the API raw material in both products was simply "telmisartan," and that the label for Micardis (and labels for other generic telmisartan products) identified the medicinal ingredient only as "telmisartan" without reference to any salt forms. The Federal Court agreed, noting that Health Canada’s interpretation of "medicinal ingredient" was applied inconsistently, and ordered Health Canada to reconsider its decision on the Apotex ANDS.

Analysis

The new interim policy from Health Canada clarifies both the interpretation of "medicinal ingredient," and how that interpretation impacts both product labelling requirements and the determination of pharmaceutical equivalence in an ANDS. It is now clear that a product label must identify both the API as used as a manufacturing input and any alternative chemical form found in the finished dosage form. With respect to ANDS submissions, Health Canada may require additional safety, efficacy, or quality data even where the same medicinal ingredient is used at the manufacturing input stage, if there is evidence that different chemical forms appear during the manufacturing process. Given this flexibility, manufacturers are encouraged to discuss pharmaceutical equivalence with Health Canada before filing an ANDS.

Further, Health Canada has made clear that any findings of pharmaceutical equivalence, or lack thereof, will not impact the application of the Patented Medicines (Notice of Compliance) Regulations. These Regulations will apply whenever a drug submission makes a direct or indirect reference to a drug on the Patent Register, regardless of whether the products are pharmaceutically equivalent.

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¹ http://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/pol/notice_im_pol_mi_avis-eng.php.

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