A Survey of the Regulatory Requirements for the Waiver of In Vivo Bioequivalence Studies of Generic Products in Certain Dosage Forms by Participating Regulators and Organisations of the International Pharmaceutical Regulators Programme (original) (raw)
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Journal of Pharmacy and Pharmaceutical Sciences, 2021
This article describes an overview of waivers of in vivo bioequivalence studies for additional strengths in the context of the registration of modified release generic products and is a follow-up to the recent publication for the immediate release solid oral dosage forms. The current paper is based on a survey among the participating members of the Bioequivalence Working Group for Generics (BEWGG) of the International Pharmaceutical Regulators Program (IPRP) regarding this topic. Most jurisdictions consider the extrapolation of bioequivalence results obtained with one (most sensitive) strength of a product series as less straightforward for modified release products than for immediate release products. There is consensus that modified release products should demonstrate bioequivalence not only in the fasted state but also in the fed state, but differences exist regarding the necessity of additional multiple dose studies. Fundamental differences between jurisdictions are revealed regarding requirements on the quantitative composition of different strengths and the differentiation of single and multiple unit dosage forms. Differences in terms of in vitro dissolution requirements are obvious, though these are mostly related to possible additional comparative investigations rather than regarding the need for product-specific methods. As with the requirements for immediate release products, harmonization of the various regulations for modified release products is highly desirable to conduct the appropriate studies from a scientific point of view, thus ensuring therapeutic equivalence.
Journal of Pharmacy & Pharmaceutical Sciences, 2019
In relation to the registration of generic products, waivers of in vivo bioequivalence studies (biowaivers) are considered in three main cases: certain dosage forms for which bioequivalence is self-evident (e.g. intravenous solutions), biowaivers based on the Biopharmaceutics Classification System and biowaivers for additional strengths with respect to the strength for which in vivo bioequivalence has been shown. The objective of this article is to describe the differences and commonalities in biowaivers for additional strengths of immediate release solid oral dosage forms between the participating members of the International Pharmaceutical Regulators Program (IPRP). The requirements are based on five main aspects; the pharmacokinetics of the drug substance, the manufacturing process, the qualitative and quantitative composition of the different strengths, and the comparative dissolution profiles. For the pharmacokinetic aspects, many regulators/agencies have the same requirements....
Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques, 2018
The Biopharmaceutics Classification System (BCS) based biowaiver is a scientific model which enables the substitution of in vivo bioequivalence studies with in vitro data as evidence of therapeutic equivalence subject to certain conditions. Despite being based on the same principles, BCS-based biowaivers are interpreted and regulated differently among international regulatory agencies. In this survey, the Bioequivalence Working Group (BEWG) of the International Generic Drug Regulators Programme (IGDRP) compared the criteria for BCS-based biowaivers applied by the participating regulators and organisations. Differences and similarities regarding solubility, permeability, dissolution, excipients and fixed-dose combination products, were identified and compared in a detailed survey of each participant's criteria for BCS-based biowaivers. These criteria were determined based upon the participants' respective regulatory guidance documents, policies and practices. This review h...
International Journal of Pharmaceutics, 2012
In the European Union multiple dose bioequivalence studies are required for the approval of generic prolonged-release products, but they are not required by the US-FDA. In order to investigate if the multiple dose bioequivalence studies are necessary, the bioequivalence studies assessed in the Spanish Agency for Medicines and Health Care Products in the last 10 years were searched to find all reasons for rejection and identify those cases where the multiple dose study had failed to show bioequivalence and the single dose study had shown bioequivalence. In these latter cases, the plasma concentration at the end of the dosing interval (C) in the single dose study was assessed to investigate its sensitivity to predict non-bioequivalence in the steady state. The search identified six cases where the non-equivalence in the multiple dose study was not detected by the corresponding single dose study. C was not able to detect the difference in five cases and in general it was more variable than conventional metrics. In conclusion, the multiple dose bioequivalence study is necessary to ensure therapeutic equivalence and the use of C would be counterproductive, increasing the sample size of the studies without enough sensitivity to detect differences in the steady state.
Texila International Journal of Academic Research, 2019
Generic pharmaceutical products need to comply the same standards of quality, efficacy and safety as required of the innovator product. Generic drug market is expected to rise in coming future. Specifically, the Generic product should be therapeutically equivalent and interchangeable with the reference product. Present study highlights the regulatory guidelines for conduct of bioequivalence in India and the Gulf Cooperation Council States. There is no international harmonization of regulatory requirements for bioequivalence, however, bioequivalence range and statistical analysis are to some extent harmonized, but there are differences in selection of subjects, food effect, application of multiple dose study, in vitro dissolution study, reference product etc. In bioequivalence studies, the plasma concentration time curve is generally to assess the rate and extent of absorption. Selected pharmacokinetic parameters and preset acceptance limits allow the final decision on bioequivalence of the tested products. (AUC) the area under the concentration time curve reflects the extent of exposure. (C max) the maximum plasma concentration or peak exposure, and the time to maximum plasma concentration, (t max) are parameters that are influenced by absorption rate. Bioequivalence study is one of the main requirements for generic drug approval process. This review provides an easy and quick overview for regulatory consideration required for bioequivalence study in those regions. In this paper includes information about important aspects of bioequivalence study design and specifications guidelines of each parameters also have been addressed. Keywords: Bioequivalence, Bioavailability, Pharmacokinetics, GCC (Gulf Cooperation Council).
Clinical Pharmacology & Therapeutics, 2011
The demonstration of bioequivalence (BE) is an essential requirement for ensuring that patients receive a product that performs as indicated by the label. The BE standard for a particular product is set by its innovator, and this standard must subsequently be matched by generic drug products. The Biopharmaceutics Classification System (BCS) sets a scientific basis for an improved BE standard for immediate-release solid oral dosage forms. In this paper, we discuss BE and the BCS, as well as the issues that are currently relevant to BE as a pharmaceutical product standard.