Drug product bioequivalence studies

The study design is dependent on the nature of the active drug. The bioequivalence study can be a comparative skin blanching study as in glucocorticoids (FDA, Topical Dermatological Corticosteroids In Vivo Bioequivalence, June 2,1995.) or a comparative clinical trial or any other appropriate vahdated bioequivalence study (e.g., dermatopharmacokinetic study) for the topical dermatological drug product. 

Bioavailahility studies are used to compare different formulations of the drug product, or different batches of the same formulation and, as discussed in Chapter 8, generic copies of a reference drug. Their comparative value is based on the premise that, if similar amounts of identical active substance are delivered to the site of action at similar rates, then a similar biological response can be expected, which leads to the conclusion that the two preparations are bioequivalent. 

Hard gelatin capsules are uniquely suitable for blinded clinical tests and are widely used in preliminary drug studies. Bioequivalence studies of tablet formulations may be conveniently blinded by inserting tablets into opaque capsules, often along with an inert filler powder. Even capsule products may be disguised by inserting them into larger capsules. 

The question that must be addressed is which molecular species should be quantified in a bioequivalency study of a product containing a chiral drug ... 

Other issues in veterinary bioequivalence which merit attention include policies to be followed when a product is to be used by more than one animal species. Is it sufficient to perform a bioequivalence study in only one species, or should studies be carried out in most or all the species for which the drug is recommended [46] There may be reason to believe that bioequivalence problems exist in some veterinary products [47,48]. 

C. T. Rhodes, Bioequivalence studies for veterinary drug products, Clin. Res. Drug. Affairs, 9, 1 (1992). 

Guidance for Industry Bioavailability and Bioequivalence Studies for Orally Administered Drug Products—General Considerations. Oct. 2000. 

FDA. Guidance for Industry Bioavailability and Bioequivalence Studies for Orally Administered Drug Products—General Considerations (Revised) (I). Rockville MD, USA U.S. Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER), 2003. 

FDA Guidance to Industry Bioavailability and bioequivalence studies for orally administered drug products — General considerations, 2002. 

Waiver of in vivo bioequivalence studies for major post approval manufacturing changes for the BCS Class I (Biopharmaceutics Classification System highly soluble, highly permeable and rapidly dissolving) solid oral products is NOT recommended for narrow therapeutic index drugs (17). 

Stereoisomer Assays. There are many drugs that are administered as racemic mixtures. They may undergo stereoselective metabolism and/or elimination, and one isomer may be more active than the other. Therefore, there is the need to develop and validate bioanalytical assays for stereoselective determination in bioavailability/bioequivalence studies. All methods used for measurement of stereoisomer should be validated (with emphasis on stereospecificity). For bioequivalence studies of an existing racemic product, a stereospecific assay is not required if the rate and extent of profiles are superimposable (within the usual statistical boundaries) [3,23]. 

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