Regulatory Decision Summary for BiCNU

The purpose of this Supplement to a New Drug Submission (SNDS) was to obtain market authorization, pursuant to section C.08.004 of the Food and Drugs Regulations, for BiCNU, filed by Marcan Pharmaceuticals Inc. This submission was filed to seek authorization for an additional dosage form, specifically a solution for intravenous infusion.

The purpose of this Supplement to a New Drug Submission (SNDS) was to obtain market authorization for an additional dosage form, a solution for infusion, of BiCNU. The currently approved formulation is a lyophilized powder that requires a diluent and an additional solvent for reconstitution prior to administration.

A Notice of Non-Compliance (NON) was issued by Health Canada on June 13, 2024, due to concerns identified during the review, including lower osmolarity and surface tension of the proposed formulation and insufficient stability data. In response, the sponsor submitted literature references, additional characterization data, and an animal toxicology study to address objections related to the safety and clinical pharmacology of BiCNU.

Additional characterization using a dissolution study demonstrated that the dissolution profile of the proposed drug product was similar to the reference product, indicating that the proposed formulation did not exhibit controlled-release behavior and that drug availability for absorption was not affected by differences in surface tension.

Literature references indicated that Polysorbate 80 micelles have a short terminal disposition half-life and are rapidly cleared from the central plasma compartment, suggesting minimal impact on clinical pharmacology compared to the lyophilized reference product.

The animal toxicity study showed no clinical signs, mortality, gross pathological findings, or body weight changes in animals dosed with either the proposed or reference product, supporting comparable safety profiles.

The chemistry and manufacturing information submitted for BiCNU solution demonstrated that the drug substance and drug product can be consistently manufactured to meet approved specifications.

Overall, the benefit-harm-uncertainty profile was favorable for BiCNU solution for intravenous infusion for the approved indication when used under the conditions recommended in the approved Product Monograph. Therefore, a Notice of Compliance (NOC) was recommended. Following review and requested revisions, the final Product Monograph dated January 31, 2025 (sequence 0047) and labelling materials were considered acceptable.

For further details about BiCNU, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.