Generic Drug Applications 

Comparing dissolution profiles of your generic drug with its originator in Biorelevant Media can increase your chances of achieving bioequivalence.

The challenge

For a generic drug product to be approved by regulatory authorities it must share the same pharmacokinetic profile as its originator with and without food (fasted and fed states respectively). Regulators demand the in vivo bioavailability of the products must be statistically bioequivalent. Bioequivalence studies are mandatory for all poorly soluble drugs in BCS Class II and BCS Class IV. Some countries additionally demand Food Effect clinical studies.

The existing approach

Prior to clinical bioequivalence studies, comparative dissolution of the generic test product and its originator is currently performed in buffers which may contain synthetic surfactants such as sodium lauryl sulphate. These buffer systems and synthetic surfactants do not represent the fluids found in the human gut accurately enough. Testing in them may therefore not provide representative results of what happens in vivo. Misleading results could have very costly consequences such as testing a non-bioequivalent formulation. 

The Biorelevant approach 

Biorelevant Media are typically used for in vitro dissolution testing of product performance using USP equipment. These tests are intended to identify generic formulations bioequivalent to the reference listed drug product.

Comparing the dissolution profiles of the generic formulation with the originator reference drug in Biorelevant Media can increase your chances of achieving bioequivalence. This is because Biorelevant Media are physiologically discriminating. They contain bile salts and lecithin and are much more representative of conditions in the human gut than buffers containing synthetic surfactants. This is in terms of their composition, osmolarity, pH, buffer capacity and solubilizing properties. 

Biorelevant dissolution studies simulate what the release rate of the drug would be like in intestinal fluids that are found in the various sections of the gastro-intestinal tract. Formulations that have matching release rates and solubilities in Biorelevant Media compared to the originator reference listed drug are more likely to be bioequivalent than those formulations where there is a difference. This is particularly true of drugs that are solubility or dissolution rate limited. By testing your generic drug product in Biorelevant Media, you can decide if it’s worth proceeding with a clinical bioequivalence study.