GLP Perspectives of Bioequivalence Studies

Bioequivalence is a term in pharmacokinetics used to access the expected in vivo biological equivalence of two proprietary preparations of a drug. Bioequivalence studies are usually performed for generic drugs. Two pharmaceutical products are bioequivalent if they are pharmaceutically equivalent and their bioavailabilioes after administration in the same molar dose are similar. Bioequivalence is usually accessed by single dose in vivo studies in healthy volunteers and the reference product is usually the innovator product that is marketed. Regulatory definition of bioequivalence is based on the statistical analysis of thebioavailability of the reference and test product. In general, two products are evaluated as bioequivalent if the 90% confidence interval of the relative mean Cmaxand AUC of the test to reference product are within 80.00% to 125.00% in the fasting state. Key process in bioequivalence study is development and validation of bioanalytical method, determination of the drug concentration in the biosamples (usually plasma or serum) obtained from volunteers, calculation of the pharmacokinetic parameters and statistical analysis of the pharmacokinetic parameters. Although current guidelines and regulations do not require the bioequivalence studies to be done under good laboratory practice (CLP), the issues to perform the bioequivalence studies under GLP environment is emerged both from the regulatory and industry side. GLP perspectives of bioequivalence studiesare needed to be discussed in respect to achieve quality assurance in bioequivalence studies.