Biopharmaceutics bioequivalence

Waiver of in vivo bioavailability and bioequivalence studies for immediate release solid oral dosage forms based on a biopharmaceutics classification system. Center for Drug Evaluation and Research, Food and Drug Administration, issued 8/2000, posted 8/31/2000. http //www.fda.gov/cder/guidance/ index, htm... 

Biopharmaceutical issues to be addressed will include a discussion of the pharmaceutical development process as it relates to in vivo and in vitro performance and the general approach taken concerning bioavailability, bioequivalence, and in vitro dissolution profiles. There should be a comparative analysis of relevant studies—objectives, study design, conduct, outcome, and data analyses. The effects of formulation changes (including different strengths of product and... 

FDA Guidance for Industry Waiver of in vivo Bioavailability and Bioequivalence Studies for Immediate Release Solid Oral Dosage Forms Containing Certain Active Moieties/ Active Ingredients Based on a Biopharmaceutics Classification System, CDER-GUID 2062dft.wpd Draft, Jan. 1999. 

AC ADME ANS AUC BA/BE BBB BBM BBLM BCS BLM BSA CE CHO CMC CPC CPZ CTAB CV DA DOPC DPPC DPPH aminocoumarin absorption, distribution, metabolism, excretion anilinonaphthalenesulfonic acid area under the curve bioavailability-bioequivalence blood-brain barrier brush-border membrane brush-border lipid membrane biopharmaceutics classification system black lipid membrane bovine serum albumin capillary electrophoresis caroboxaldehyde critical micelle concentration centrifugal partition chromatography chlorpromazine cetyltrimethylammonium bromide cyclic votammetry dodecylcarboxylic acid dioleylphosphatidylcholine dipalmitoylphosphatidylcholine diphenylpicrylhydrazyl... 

CDER Waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a biopharmaceutics classification system Food and Drug Administration, 2000. 

Bioavailability and bioequivalence are also usually assessed in animals. Such studies are undertaken as part of pharmacokinetic and/or pharmacodynamic studies. Bioavailability relates to the proportion of a drug that actually reaches its site of action after administration. As most biopharmaceuticals are delivered parenterally (e.g. by injection), their bioavailability is virtually 100 per cent. On the other hand, administration of biopharmaceuticals by mouth would, in most instances, yield a bioavailability at or near 0 per cent. Bioavailability studies would be rendered more complex if, for example, a therapeutic peptide was being administered intranasally. 

Note that a choice of pH 6.8 test conditions for quality control assures that at least one of these three criteria will be met by the product, thus harmonizing quality control measures with biopharmaceutical tests for bioequivalence. 

Kramer J. The biopharmaceutics classification system—an overview of the current status in relation to IR and MR dosage forms. 1st International Conference on Bioavailability, Bioequivalence and Dissolution Testing, London, 2002. 

Centre for Drug Evaluation FDA (2000). Waiver of In Vivo Bio availability and Bioequivalence Studies for Immediate Release Solid Oral Dosage Forms Based on a Biopharmaceutical Classification System. Guidance for industry. 2000. 

The publication of the U.S. FDA Guidelines allowing the waiver of bioequivalence study for compounds classified as Class I based on the Biopharmaceutics Classification System... 

Food and Drug Administration (FDA). Guidance for Industry. Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate-release Solid Dosage Forms Based on a Biopharmaceutics Classification System. RockviUe, MD FDA, 2000. 

Schellekens FI. Bioequivalence and the immuno-genicity of biopharmaceuticals. Nat Rev Drug Disc 2002 1 457-62. 

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). 

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