Bioavailability and bioequivalence studies provide useful information about the availability of safe and effective pharmaceutical drugs to patients and medical practitioners. The bioequivalence studies help in the assessment of the bioavailability of two closely related pharmaceutical entities. The main focus of the bioequivalence studies is establishing a comparative drug product performance.
The bioavailability and the bioequivalence documentation help establish supporting links between early-stage and late-stage clinical trials, useful formulations to be employed both in the clinical and stability studies, and the to be marketed, pharmaceutical drug candidate.
Basic Principles for accomplishing the Bioequivalence Studies –
When two medical products indicate pharmaceutical equivalency or function as pharmaceutical alternatives, they are said to be bioequivalent. For two products to be labeled as bioequivalent, they need to be bioavailable in the same molar dose lying within acceptable pre-defined limits after their administration.
In bioequivalence studies, the rate and extent of the drug absorption are assessed through the plasma concentration-time curve.
Critical criteria for accomplishing BE studies –
FDA recommends the following essential measures for achieving the bioavailability and bioequivalence studies –
The total count of the bioequivalence studies and the study design are dependent on the physico-chemical parameters, pharmacokinetic properties, and the composition proportionality of the given pharmaceutical drug candidate.
The number of subjects participating in the bioequivalence studies should be selected per an appropriate calculation of the sample size. The subjects should be cleaned in accordance with different parameters such as their medical history, clinical laboratory tests, and, finally, their physical examination.
The sampling time to be described in the plasma concentration-time profile should consist of frequent sampling around the predicted value of Tmax. This helps in obtaining a reliable estimation of peak drug exposure.
The bioequivalence studies are usually conducted under fasting conditions. This is one of the most painful conditions employed in detecting the potential difference between two pharmaceutical formulations.
The pharmaceutical compound’s evaluation should be worked according to the measurement of the concentration of the parent ingredient in your pharmaceutical entity under consideration.
Baseline correction should be employed in the determination of pharmacokinetic parameters if the substance being tested is endogenous.
If the pharmaceutical entity under consideration has several different strengths, it becomes inevitable to accomplish bioequivalence studies using only one or two different concentrations.
Bioanalytical Methodology in Bioequivalence –
The bioanalytical content of your bioequivalence studies should be accomplished according to the GLP principles. Such methods should be well characterized, validated, and fully documented to facilitate the yielding of reliable results. The performance and the reliability of the bioequivalence studies are assessed through the application of parameters such as lower quantitation limit, selectivity, accuracy, precision, response function, and stability.
Bioequivalence Study Report –
The bioequivalence study report should supplement the bio-analyst with complete documentation highlighting its protocol, conduct, and final evaluation. It is mandatory to write the bioequivalence study report according to the ICH E3 guidelines and the investigator’s signature. The study report should also include the name and affiliation of the study investigator, study location, execution period, and audit certification. The study investigator should provide the name and composition of the test pharmaceutical product under evaluation, batch size, number, manufacturing date, and expiry date of the test pharmaceutical product.