Bioavailability bioequivalence

Bioavailability, Bioequivalence, and Pharmacokinetics. Bioavailabihty can be defined as the amount and rate of absorption of a dmg into the body from an adrninistered dmg product. It is affected by the excipient ingredients in the product, the manufacturing technologies employed, and physical and chemical properties of the dmg itself, eg, particle size and polymorphic form. Two dmg products of the same type, eg, compressed tablets, that contain the same amount of the same dmg are pharmaceutical equivalents, but may have different degrees of bioavailabihty. These are chemical equivalents but are not necessarily bioequivalents. For two pharmaceutically equivalent dmg products to be bioequivalent, they must achieve the same plasma concentration in the same amount of time, ie, have equivalent bioavadabihties. 

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... 

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... 

JR Crison, GL Amidon. Expected variation in bioavailability for water insoluble drugs. In HH Blume, KK Midha, eds. Bio-International 2, Bioavailability, Bioequivalence, and Pharmacokinetic Studies. Stuttgart, Germany Medpharm, 1995, pp 301-310. 

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. 

Tam KY. Potential of Using Cell Based Technology for Predicting Bioavailability. Amsterdam Dissolution, Bioavailability Bioequivalence, 2003. 

Kramer J. In Role of in Vitro Dissolution Test. Tokyo Bioavailability, Bioequivalence and Pharmacokinetic Studies, 1996. 

During the 1990 Washington Conference on Analytical Methods Validation Bioavailability, Bioequivalence and Pharmacokinetic Studies [1], parameters that should be used for method validation were defined. The final report of this conference is considered the most comprehensive document on the validation of bioanalytical methods. Many multinational pharmaceutical companies and contract research organizations contributed to its final draft. This scientific meeting was sponsored by the American Association of Pharmaceutical Scientists (AAPS), the Association of Official Analytical Chemists (AOAC), and the U.S. Food and Drug Administration (FDA). The conference report has been used as a reference by bioanalytical laboratories and regulatory agencies worldwide. 

Measurement of Metabolites. The elimination of drug usually happens through metabolites that are more polar than the drug itself to enhance their excretion via urine or bile. Some special situations exist in bioavailability/bioequivalence that require the determination of metabolites ... 

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]. 

Biobatch manufacturing Inspection to determine the establishment s compliance with cGMP requirements, including a data audit of the specific batches on which the application is based (e.g., pivotal clinical, bioavailability, bioequivalence, and stability) is a field office responsibility. CDER scientists are responsible for the review and evaluation of the records and data submitted in the application, including the components, composition, batch instructions, in-process and finished product test points, and... 

Lobenberg R, Amidon GL. Modern bioavailability, bioequivalence and biophannaceutics classification system. New scientific approaches to international regulatory system. Eur J Pharm Biopharm 2000 50 5-12. 

Phannaceutical products must demonstrate and maintain established public standards for attributes that relate to their safety or effectiveness. In the United States these attributes are expressed as identity (e.g., chemical structure), strength (e.g., assay, content uniformity), quality (e.g., combination of certain physical, chemical, and biological attributes), purity (e.g., limits on impurities and degradation products), and potency (e.g., biological activity, bioavailability, bioequivalence) [10]. Public standards serve as one of several mechanisms for minimizing the risk of product-related injuries. In principle these standards should reflect the current state of scientific understanding and ensure and promote the development of high-quality products. 

In regulatory assessment of bioavailability/bioequivalence, increased emphasis is being directed toward in vitro methods. 

Biobatch A lot of drug product fonnulated for purposes of pharmacokinetic evaluation in a bioavailability/bioequivalency study. This lot should be 10% or greater than the proposed commercial production batch or at least 100,000 units, whichever is greater. 

Kalantzi, L. et al., Characterization of the human upper gastrointestinal contents under conditions simulating bioavailability/bioequivalence studiiSiarm. Res., 23, 165, 2006. 

Shah VP, Midha KK, Dighe SV, et ah Analytical methods validation bioavailability, bioequivalence, and pharmacokinetic studies./. Pharm. Sci. (1992) 81 309-312. 

Kringle RO An assessment of the 4-6-20 rule for acceptance of analytical runs in bioavailability, bioequivalence, and pharmacokinetic studies. Pharm. Res. (1994)... 

Bioavailability/Bioequivalence Financial Certification (Form FDA 3454) Disclosure Statement (Form FDA 3455, submit copy to Regulatory Branch Chief)... 

Tabs. The contents of the submission should be organized by sections, and each section should be identified by a tab that corresponds to the section set forth in the table of contents. The tab shows the number and brief descriptive name of the section it identifies (e.g., Appendix B, Section VI—Bioavailability/Bioequivalence ). 

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