February 19, 2019
This is prime requirement in world of generic medicines.
The general definition of bioequivalence is expressed in terms of rate and extent of absorption of the active ingredient or moiety at the site of action, underline the use of pharmacokinetic measures in an available biological matrix such as blood, plasma, or serum and/or urine to show the release of the drug substance from the drug product into the systemic circulation. This approach resets on the understanding that measuring the active moiety or ingredient at the site of action is not generally possible and, furthermore, that some relationship exists between the efficacy/safety and concentration of the active moiety and / or its important metabolite or metabolites in the systemic circulation.
Bioequivalence studies are intended to compare the in-vivo performance of Absorption, Distribution, Biotransformation and Elimination of a test pharmaceutical product (generic product developed by sponsor) compared to a reference pharmaceutical product (standard drug which is already available in market). Prior to start of the study sufficient number of subjects will be enrolled into the study to ensure adequate statistical results. A general screening including physical examination, medical history, routine blood chemistry, serology, hematology tests and urinalysis should be performed to ensure normal hepatic, hematological and renal functions is performed for all the volunteers who are willing to participate in the study. Apart from general screenings study specific laboratory tests will be performed for all the subjects prior to enrollment into the study.
Subjects should be free of any history of serious gastrointestinal, renal, hepatic, cardiovascular or hematological disorders and should have no history of adverse reactions to the study drug (or its class). All subjects who are going to be enrolled into the study are checked initially for exclusion and inclusion criteria which is already stated in the study protocol. Subjects will be selected for study participation, if they meet inclusion criteria and subjects will be excluded from the study, if they meet any of the exclusion criteria. The subjects are not permitted to take any prescription or over-the-counter drug products within two weeks of the start of the study. Ingestion of alcohol or caffeine or related xanthine containing food or beverages is not allowed within 48 hours prior to first drug administration and during the course of washout period. Each subject is enrolled after signing study specific Informed Consent Form (ICF) which is approved by Independent/Institutional Ethics Committee (IEC) or Institutional Review Board (IRB). Both the study protocol and ICF are approved by an appropriate IEC or IRB prior to the start of the study. A prior provision is made for the replacement of dropout subjects by enrolling additional subjects into the study.
A most common design for a bioequivalence study involves administration of the test and reference products with standard amount of water in case of solid dosage forms on two occasions to subjects who are enrolled in the study and each administration is separated by a washout period. The washout period is chosen in such way that to ensure the study drug given in one treatment is entirely eliminated prior to administration of the next treatment with study drug. Just prior to administration, and for a suitable period afterwards, blood and/or urine samples are collected and assayed for the concentration of the drug substance and/or one or more metabolites. The rise and fall of these concentrations over time in each subject in the study provide an estimate of how the drug substance is released from the test and reference products and absorbed into the body. To allow comparisons between the two products, these blood (to include plasma or serum) and/or urine concentration time curves are used to calculate certain bioequivalence metrics of interest. These metrics are calculated for each subject in the study and the resulting values are compared statistically.
