Bioequivalence evaluation

M. Bialer, L. Arcavi, S. Sussan, A. Volosov, A. Yacobi, D. Morus, B. Levitt, and A. Laor, Existing and new criteria for bioequivalence evaluation of new controlled release products of carbamazipine, Epilepsy Res., 32, 371 (1998). 

C. T. Rhodes, Bioequivalence evaluation, possible future developments, Clin. Res. Drug Reg. Affairs, 11, 181 (1996). 

A. Kayali, Bioequivalency evaluation by the comparison of in vitro dissolution and in vivo absorption using reference equations, Eur. J. Drug Metab. Pharmacoki-net., 19, 271 (1994). 

For the dissolution test to be used as an effective drug product characterization and quality control tool, the method must be developed with the various end uses in mind. In some cases, the method used in the early phase of product and formulation development could be different from the final test procedure utilized for control of the product quality. Methods used for formulation screening or BA and/or bioequivalency evaluations may simply be impractical for a quality control environment. It is essential that with the accumulation of experience, the early method be critically re-evaluated and potentially simplified, giving preference to compendial apparatus and media. Hence, the final dissolution method submitted for product registration may not necessarily closely imitate the in vivo environment but should still test the key performance indicators of the formulation. 

Therefore, the development and validation of a scientifically sound dissolution method requires the selection of key method parameters that provide accurate, reproducible data that are appropriate for the intended application of the methodology. It is important to note that while more extensive dissolution methodologies may be required for bioequivalency evaluations or biowaivers (i.e., multiple media, more complex dissolution media additives, and multiple sampling time points), it is also essential for the simplified, routine quality control dissolution method to discriminate batch-to-batch differences that might affect the product s in vivo performance. 

Establishing in vitro in vivo correlation (IVIVC) for modified release dosage form provides a justification for waiving in vivo bioequivalence evaluation only for certain specified post approval changes. Since a correlation is dependent on the mechanism of drug release, it is not used in situations that could potentially alter its mechanism (16). 

Boroujerdi M. (2002b) Bioavailabihty and Bioequivalence Evaluation. In Pharmacokinetics Principles and Applications. McCh-aw-Hill, New York, NY, pp. 315-329. 

Our first stereospedfic bioequivalence evaluation using verapamil formulations was a pilot study conducted in 24 healthy male volunteers. The study compared the bioavailability of two sustained-release dosage forms and an immediate release formulation of racemic verapamil in a three-way cross-over study. Table 2 summarizes the results observed for verapamil. Table 3 the results for norverapamil. First, pharmacokinetic... 

In general, bioequivalence evaluations involve comparisons of dosage forms that are pharmaceutical equivalents. Such dosage forms are defined as drug... 

The SPEC works in contact with mcmy organizations participating in the review and approval of clinical trials and drug products, but mainly with the SIPCDE. In order to carry out its tasks the SPEC may utilize employees of other healthcare departments, establish provisional expert commissions and task forces. Thus a provisional task force consisting of members of the SPEC and SIPCDE has drafted the regulations on bioequivalence evaluation, which later were adopted by the SPEC as standard operating procedures. 

European Medicines Evaluation Agency, Committee for Medicinal Products for Human Use (CHMP). Concept paper for an addendum to the note for guidance on the investigation of bioavailability and bioequivalence Evaluation of bioequivalence of highly variable drags and drug products. Doc. Ref. EMEA/CHMP/EWP/147231/2006, April 2006. 

Rhodes C (1994) Bioequivalence evaluation - possible future development. Clinical Research and Regulatory Affairs 11 181-192. 

I. Bashir, A. Sethi, M. Zaman, J. Qureshi, R.M. Sarfraz, A. Mahmood, M.I. Sajid, T. Jamshaid, and M.A. Akram, Formulation and in-vitro bioequivalence evaluation of verapamil hydrochloride matrix tablets with Calan SR, Int. Curr. Pharmaceut. /, 3, 286-290, 2014. 

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... 

The topic of what standards should be applied in the evaluation of development bioequivalency seems to have received relatively little specific attention in the pharmaceutical literature. It seems that some scientists and regulators assume that no distinction need be made between these two types of bioequivalency. This is unfortunate since there are clearly occasions when it is quite inappropriate to require generic bioequivalency standards when development bioequivalency is being considered. 

The new millenium professional pharmacist with rigorous training in the scientific and clinical properties of drug substances and pharmaceutical formulations should be well able to dispassionately evaluate bioe-quivaleny data and give an objective, professional opinion as to validity of data purported to demonstrate generic bioequivalence. 

OTCs) are used as subjects in bioequivalency studies. Such persons, often, university students, have been regarded as human test tubes in whom bioequivalency is evaluated. However, with the emergence of a school of thought that believes that bioequivalency should be a clinical mirror for the behavior of the test and reference products, this situation may change. Pregnant and nursing females are normally excluded from all bioequivalency studies. 

Some commentators on bioequivalency have voiced concerns as to whether it is appropriate for states to second-guess the FDA on matters concerning bioequivalency. Once FDA has carefully evaluated an ANDA and decided that the generic product should be approved and given a rating that allows for substitution, it seems hard to conceive any likely circumstances under which an individual state should be able to opt... 

Even the most superficial evaluation of bioequivalency requirements for controlled-release products will indicate that for some of these products, at least, the conventional AUC, Tmax, and Cmax measures of bioequivalency may well be insufficient. Thus, for a non-pulsatile sustained-release product with a dosing interval of 24 hours (as compared to 4 hours for the noncontrolled product), the time period during which plasma concentrations are maintained at essentially a plateau level might well be regarded as of critical... 

For development of bioequivalence studies (in which different formulations have been used in clinical trials), it would seem that normally there would be no need to conduct bioequivalency studies using a stereoselective assay for the evaluation of the concentrations of drug in the plasma samples. We would not usually expect any noticeable difference in the ratio of R to S isomer exiting in plasma samples derived at the same postdosing time point from different... 

The general principles of bioequivalence as used by the FDA Center for Veterinary Medicine are essentially the same as those used by the Center for Drug Evaluation and Research when the products are designed for use by companion animals [44]. 

L. Endrenyi and L. Tothfalusi, Truncated AUC evaluates effectively the bioequivalence of drugs with long half lives, Int. J. Clin. Phrmacol. Ther., 35, 42 (1997). 

P. Sathe, J. Venitz, and L. Lesko, Evaluation of truncated areas in the assessment of bioequivalence of immediate release formulations of drugs with long half lives and CMax with different dissolution rates, Pharm. Res, 16, 939 (1999). 

CPMP Note for Guidance on the Investigation of Bioavailability and bioequivalence (CPMP/EWP/QWP/ 1401/98) The European Agency for the Evaluation of Medicinal Products, 2001. 

U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER). Guidance for Industry Waiver of In Vivo Bioavailability and Bioequivalence Studies for Immediate Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System. 2000. 

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