Regulatory Decision Summary for Micro+6 Regular

The purpose of this Supplemental New Drug Submission (SNDS) was to obtain market authorization, pursuant to section C.08.004 of the Food and Drugs Regulations, for “Micro+6 Regular”, filed by Sandoz Canada Inc.

This Supplement was filed for Micro+6 Regular for a new strength that has the identical 6 trace elements as the currently marketed Micro+6 Concentrate but at 1/5th of the concentrations. The Supplement was also filed to change the composition of the solution dosage form, with pH adjuster changed from nitric acid to sulfuric acid, and for a change in vial from untreated Type I amber glass vials to clear and coated Type I plus silicon dioxide coated glass vials.

Upon review of the submitted data package, Health Canada authorized Micro+6 Regular as filed.

There were no proposed changes to the drug substance. The drug product is manufactured by dissolving the active pharmaceutical ingredients (APIs) and excipients in water. The solution is filtered through a 0.22 µm filter and then terminally sterilized.

A request for waiver to perform comparative in vivo bioequivalence studies was provided for the proposed product (i.e., an injectable aqueous solution). The sponsor followed the principles outlined in the Health Canada Pharmaceutical Quality of Aqueous Solutions guidance document. It should be noted that this guidance describes conditions to be met to support a biowaiver request between a test product and a reference product containing identical amounts of the identical medicinal ingredients to establish bioequivalence. The sponsor compared the physicochemical properties of the proposed product against the current marketed product “Micro+6 Concentrate”. The qualitative composition for the proposed “Regular” formulation contained comparatively lower concentrations of elements and differed in the pH adjusters (sulfuric acid versus nitric acid) but was otherwise identical to the current “Concentrated” formulation. While a physicochemical comparative analysis showed comparable results, the products were considered as two different products (different strengths) and did not strictly meet the definition for “pharmaceutical equivalence” per Health Canada guidance and regulations. Therefore, the quality justification could not be the sole basis for deciding the acceptability of the biowaiver request. BGIVD/Gastroenterology Division (GD) was consulted. In their response, the Clinical Reviewer confirmed that the differences in the concentrations would have no impact on the safety and efficacy of the proposed product, when used in accordance with the prescribing information. Therefore, the biowaiver request was acceptable from a clinical perspective.

Overall, while Micro+6 regular is not considered equivalent to the currently marketed Micro+6 Concentrate based on Quality review, it is not expected to impact the safety and efficacy of the proposed product, when used in accordance with the prescribing information. The proposed change in vial was adequately justified. Therefore, a Notice of Compliance (NOC) was recommended.

For further details about Micro+6 Regular, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.