In certain scenarios, in vitro dissolution tests can replace in vivo bioequivalence studies. This is particularly true when a drug product, though available in varying strengths, maintains proportional similarity in its active and inactive ingredients. In such cases, the need for in vivo bioequivalence studies for lower strength variants may be waived, provided dissolution tests and in vivo studies on the highest strength yield satisfactory results.
Bioequivalence can be indicated through comparative dissolution tests, especially if there's a strong correlation between a drug's dissolution and its bioavailability. However, most drugs, like immediate-release tablets and capsules, don't exhibit this correlation, necessitating in vivo bioequivalence studies.
For oral solid dosage forms, at least one dose strength of the product, typically the highest dose strength, must be supported by an in vivo bioequivalence study. If lower-dose-strength products demonstrate substantial similarity in active and inactive ingredients, comparative in vitro dissolution may suffice.
The FDA allows waivers for bioequivalence studies for products where bioequivalence is self-evident, including solutions for parenteral, oral, or local use, provided they share identical ratios of active and inactive ingredients. To grant biowaivers to non-biostudy strengths of a generic immediate-release solid oral dosage form drug product line, the FDA requires certain criteria to be met, including conducting an acceptable bioequivalence study on at least one strength, proportional similarity, and acceptable in vitro dissolution for the strength(s) seeking the biowaiver. Generic modified-release products are generally ineligible for biowaivers.
In vitro dissolution testing can be used instead of in vivo bioequivalence studies under certain conditions.
When a drug has the same ratio of active and inactive ingredients across all strengths, in vivo bioequivalence testing for the lower strengths can be waived—provided the highest strength passes dissolution and in vivo tests.
Comparative dissolution tests are adequate to indicate bioequivalence when a strong correlation exists between a drug’s dissolution and bioavailability.
Most drugs, like immediate-release tablets and capsules, lack such a correlation and require in vivo studies to establish the bioequivalence of the highest-strength dosage.
If lower-dose-strength products show similarity in active and inactive ingredients, only a comparative in vitro dissolution may be needed.
The FDA permits waiving bioequivalence studies for products where it is self-evident, like solutions for parenteral, oral, or local use, provided they have identical ratios of active and inactive ingredients as the reference products.
繁體中文
