The reference standard should contain the same active ingredient as the test product under investigation. The reference standard should be the formulation that has the highest bioavailability for the same active ingredient.

The reference standard should be administered by the same route as the formulation under investigation.

The reference standard for a drug is usually a formulation currently approved and marketed which is well accepted by the medical profession and has a long history of clinical use. The reference standard is usually the innovator's or the original manufacturer's product.

In the crossover design, each subject receives all the products under investigation at different occasions. In this case, each subject will act as his/her own control. Time should be allowed between the administration of each product, to make sure that all the drug from the previous administration has been completely eliminated.

To design a study to compare the bioavailability of two different products A and B, subjects involved in the study will be divided into two groups I and II. Group I receives product A and group II receives product B. After one week (or more, if complete drug elimination requires more than a week), group I should receive product B, and group II should receive product A. This way individual variation and variation due to sequence of drug administration can be eliminated.