Parenteral solutions: excipients and bioavailability [Regulatives / Guidelines]
Dear forum members
According to the Guideline "bioequivalence studies are generally not required if the test product is to be administered as an aqueous intravenous solution containing the same active substance as the currently approved product. However, if any excipients interact with the drug substance (e.g. complex formation), or otherwise affect the disposition of the drug substance, a bioequivalence study is required."
I guess the reference "or otherwise affect the disposition of the drug substance" is a kind of killer criterion in case you have different excipients than the reference product because how can you exclude that there is a possible affect?
For example sucrose is used to ensure the stability of a lyophilisat and to avoid aggregation during lyophilisation. IMHO in cases where sucrose does not form a complex (as e.g. in iron sucrose formulations) the drug should be 100% bioavailable once the lyophilisat is reconstituted with water and given parenteral even if it is known that sucrose has an influence on drug bioavailability when given peroral (Impact on intestinal absorption).
So how can I argue with a regulatory authority if the reference product contains another excipient with the same pharmaceutic-chemical properties than sucrose?
Your valuable input would be highly appreciated.
Thanks in advance.
Kind regards
Dr_Dan
According to the Guideline "bioequivalence studies are generally not required if the test product is to be administered as an aqueous intravenous solution containing the same active substance as the currently approved product. However, if any excipients interact with the drug substance (e.g. complex formation), or otherwise affect the disposition of the drug substance, a bioequivalence study is required."
I guess the reference "or otherwise affect the disposition of the drug substance" is a kind of killer criterion in case you have different excipients than the reference product because how can you exclude that there is a possible affect?
For example sucrose is used to ensure the stability of a lyophilisat and to avoid aggregation during lyophilisation. IMHO in cases where sucrose does not form a complex (as e.g. in iron sucrose formulations) the drug should be 100% bioavailable once the lyophilisat is reconstituted with water and given parenteral even if it is known that sucrose has an influence on drug bioavailability when given peroral (Impact on intestinal absorption).
So how can I argue with a regulatory authority if the reference product contains another excipient with the same pharmaceutic-chemical properties than sucrose?
Your valuable input would be highly appreciated.
Thanks in advance.
Kind regards
Dr_Dan
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Kind regards and have a nice day
Dr_Dan
Kind regards and have a nice day
Dr_Dan
Complete thread:
- Parenteral solutions: excipients and bioavailabilityDr_Dan 2016-03-10 09:39 [Regulatives / Guidelines]