Regulatory Decision Summary for Micro+6 Concentrate
Review decision
The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.
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What was the purpose of this submission?
The purpose of this Supplement to a New Drug Submission (SNDS) was to seek approval of a new strength of Micro+ 6 Concentrate (6 Trace Elements Injection USP), containing lower concentrations of copper and manganese.
Why was the decision issued?
In this SNDS, the sponsor proposed the addition of a new strength for Micro+6 Concentrate (6 Trace Elements Injection USP), containing lower concentrations of manganese (55 mcg/mL instead of 500 mcg/mL) and copper (300 mcg/mL instead of 1000 mcg/mL).
No new clinical studies were required for the proposed decrease in concentrations of copper and manganese, as this was a result of concerns regarding the potential toxicity of the currently approved concentrations as raised by the American Society for Parenteral and Enteral Nutrition (ASPEN) 2012 guidelines. The guidelines recommended that daily doses of manganese and copper in adult parenteral trace element (TE) products be decreased to 55 mcg/day and 300 mcg/day, respectively, as there were case reports of manganese-associated neurotoxicity and copper toxicity (i.e., significantly elevated levels of hepatic and/or renal copper) in patients receiving total parenteral nutrition (TPN) at the doses used in the currently approved TE products. The effectiveness and more favourable risk-benefit profile of the proposed new strength is further supported by the published dose-range finding studies in the ASPEN (2012) guidance document. In these studies, the optimal daily dose of manganese and copper to achieve stable blood levels without any potential toxic effects were 55 mcg/day and 300 mcg/day, respectively.
The recommended daily doses were updated according to Health Canadas request, and other revisions were made to the Product Monograph to adequately mitigate the risks associated with manganese and copper toxicity, especially, as these risks are further increased in patients with hepatic dysfunction, cholestasis, or biliary obstruction.
Overall, the new proposed strength of Micro+6 Concentrate, containing reduced concentrations of manganese (55 mcg/mL) and copper (300 mcg/mL), is expected to have an improved benefit-harm-uncertainty profile compared to the currently approved strength when used in accordance with the updated Product Monograph.
Decision issued
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.
Related Drug Products
| Product name | DIN | Company name | Active ingredient(s) & strength |
|---|---|---|---|
| MICRO+6 CONCENTRATE | 02507587 | SANDOZ CANADA INCORPORATED | CHROMIUM (CHROMIC CHLORIDE) 10 MCG / ML COPPER (CUPRIC SULFATE) 300 MCG / ML IODINE (SODIUM IODIDE) 75 MCG / ML MANGANESE (MANGANESE SULFATE) 55 MCG / ML SELENIUM (SELENIUM DIOXIDE) 60 MCG / ML ZINC (ZINC SULFATE) 5 MG / ML |