Data verification and sensitivity analysis of statistical analysis in bioequivalence studies / 药学实践杂志

Objective To sort out the key points, problems and countermeasures of data verification through data verification of statistical analysis in 18 bioequivalence studies, and provide reference for improving the statistical analysis reports of related research. Methods SAS and WinNonlin software was used to illustrate that whether the random number tables, main pharmacokinetic parameters and bioequivalence data could reproduce the corresponding results in the original statistical analysis reports. Results Among the 18 studies, sensitivity analysis was supplemented or re-performed for 5 studies due to sampling time deviation of individual subjects or adjustment of sensitivity data sets, resulting in differences in pharmacokinetic parameters from the original statistical analysis report, but same for the bioequivalence evaluation. Other verified data was consistent with the original statistical analysis reports. Conclusions The verification of statistical analysis data of bioequivalence studies is extremely important, and the problems found in this paper should be fully considered when writing such statistical analysis reports.

General considerations for bioequivalence studies with pharmacokinetic methods for anti-schizophrenic drugs / 中国临床药理学与治疗学

On account of the characteristics of anti-schizophrenic drugs, combined with the technical guidelines for bioequivalence studies of anti-schizophrenic generic drugs in different regulatory institutions at home and abroad, taking some drugs as examples, this paper discusses the key points to be considered in carrying out bioequivalence studies from the perspective of experimental design, so as to provide certain reference for the research and development and evaluation of related products.

Bioequivalence regulation in emerging countries: Example of Moroccan regulations on immediate release formulations and comparison with international guidelines

The purpose of this study was to analyze Moroccan regulations on bioequivalence studies and compare them with someinternational guidelines. It emerged that, as most common guidelines, Moroccan regulations treated essential questionsrelating to the conduct of bioequivalence studies while remaining general. An effort to harmonize the Moroccanregulations as closely as possible with international guidelines such as European Medicines Agency and World HealthOrganization was made. The decree 2-12-198 on bioequivalence studies includes worldwide gold standards such asinclusion and exclusion criteria, study design, choice and number of subjects, conduct of the study, pharmacokineticparameters, BE acceptance criteria, and biowaiver requirements. It specifically addresses issues such as pro-drug,metabolites, urinary samples, and endogenous substances. Specific precisions such as the case of the modified releaseforms, the replacement of subjects on the withdrawal, or drop-out of a volunteer are not covered by this general decreeand should be part of new directives, in the future. For an emerging country, the integration of BiopharmaceuticsClassification System biowaivers within the decree confirms the efforts being made by the Moroccan regulations tojoin the most advanced guidelines on the investigation of bioequivalence and to prepare the International Council onHarmonisation M9 adoption

Study of regulatory requirements for the conduct of bioequivalence studies in US, Europe, Canada, India, ASEAN and SADC countries: Impact on generic drug substitution.

In the last one decade, due to expiry of patented products as well as their exclusivity period, a drastic decline of branded pharmaceutical products and up streaming of generic drug market has been observed in developed as well as developing nations. This up rise in generic drug market is expected to rise in future till the arrival of new brand in market. This prevailing conditions could result in proliferation of generic drug manufacturing companies. The fact that generics do not undergo thorough extensive trials like innovator drugs, fuels further fears regarding their inferiority. Moreover, due to the hard competition amongst various companies to market their generics, the frequency of fraud and corruption have embarked doubts in consumers mind to reality. In order to blow away the doubts and re-establishing the credibility of generics in market, bioequivalence (BE) guidelines with stricter regulation should be the demand. The present study highlights the relevant regulatory guidelines for the conduct of bioequivalence studies in US, Europe, Canada, India, South Africa and South East Asian Nations. A comparative study of the differences in study design and specifications have also been addressed.

Design of dissolution media for in-vitro bioequivalence testing of Lamivudine.

The present investigation is aimed at developing the stability indicating dissolution media for the determination of lamivudine (3TC) in pharmaceutical dosage forms. The stability of 3TC was tested in various dissolution media maintained at ambient temperature and 37 oC for 48 hrs. Stability studies of 3TC in various media indicated that the drug was stable in 0.1M HCl, pH 1.2 KCl-HCl buffer, pH 6.2 and pH 7.0 phosphate buffers. The λmax were found to be 280.0, 278.8, 273.0 and 271.5nm for 0.1M HCl, pH 1.2 KCl-HCl buffer, pH 6.2 and pH 7.0 phosphate buffers respectively with low CV of <4.44%. The linearity of standard plots in optimized media was 0.5-40 μg/ml for 0.1M HCl and pH 1.2 KCl-HCl buffer. Similarly it was 0.5-60 μg/ml in pH 6.2 buffer and 0.2-40 μg/ml in pH 7.0 phosphate buffer. The validated methods were applied to determine 3TC concentration in formulations. In-vitro dissolution testing indicated that the 3TC was stable and drug release is uniform from tablet dosage forms. The optimized media could be employed to study the dissolution profiles of 3TC in bioequivalence studies.