Bioequivalence





What is it?

When developing a generic drug product it has to be pharmaceutically equivalent to the original product. This means that the application form (e.g. swallowable dosage form), the drug and the dose have to be the same for the test and the reference products. On the other hand the two have to be biologically equivalent. This so-called bioequivalence is typically tested on humans. In these studies test individuals usually have to swallow the reference (original) and the test (generic) product and the outcomes have to be very similar. These outcomes are measured in blood-concentration profiles (not therapeutic ourcomes). Only if the outcomes of the test product are within 80-125% of the outcomes of the reference product, the two can be called interchangeable, or bioequivalent. Then the test product is qualified to become a generic.

Concept of waiving bioequivalence

For some drugs such costly and time intensive studies can be waived. In these cases the bioequivalence studies can be exchanged with simple dissolution tests of the reference and test products. These products have to fulfill certain criteria regarding the kind of drug and dosage form used. Only if they satisfy the requirements (high solubility of the drug, rapid drug dissolution from the dosage form, wide therapeutic window of the drug, etc.) they will qualify for a so-called biowaiver. Instead of running studies on humans, dissolution tests are performed on the reference and test products in different solutions. Only if both products show a rapid (within 30 minutes) or a very rapid dissolution (within 15 minutes) in all solutions they can be regarded as interchangeable, or bioequivalent.

Use of biorelevant solutions to assess bioequivalence

Since biorelevant media (such as FaSSIF, FeSSIF, FaSSGF) describe the conditions of the gut more accurately than any other solution, they can be used as tools to assess bioequivalence of drugs. The biorelevant concept can therefore be used to reduce unnecessary bioequivalence studies, which will cut down development time and costs. Additionally, if applied in a right way, biorelevant solutions will become an essential tool for biowaivers on all kinds of drug products. This will not only reduce development costs of generic drugs, but also increase the availability of more affordable medicines.



Publications

FDA guidance on Nitazoxanide tablets (2011)

Daniel Rosside Campos et al.: Bioequivalence of Two Enteric Coated Formulations of Pantoprazole in Healthy Volunteers under Fasting and Fed Conditions (2007)