Take a look at the past three decades in the era of pharmaceutical product evolution. It is quite evident that the importance of both the bioavailability and bioequivalence studies is growing continuously. Both BA and BE studies are playing their significant roles in seeking approvals for a particular brand-name or any generic drug.
The concept of bioequivalence relies on the fundamental application that two products under analysis are said to be bioequivalent when there is no significant difference observed in the rate and extent of drug absorption for both reference drug and test drug. Accordingly, any targeted Food & Drug Adulteration shall be therapeutically equivalent only if the generic drug product is pharmaceutically equivalent to its reference innovator product. By the term ‘pharmaceutically equivalency,’ it means that there is no significant difference in the API (active pharmaceutical product), strength, dosage form, route of their administration, and finally, the bioavailability of drugs.
FDA recommends the final bioequivalence in terms of the following endpoints –
- Pharmacokinetic endpoint
- Clinical endpoint
- Pharmacodynamic endpoint
- In vitro endpoint
- Pharmacodynamic endpoint
What are the bioequivalence studies?
A bioequivalence study comprises of three main parts –
The first part or the clinical part is where both the test generic and reference innovator products are administered to the clinical subjects. Later, the biological samples are derived from these clinical subjects to evaluate their bioequivalence. However, this part is generally not addressed in the final document.
The second part or the bioanalytical part is where the analyst records the amount or concentration of the active pharmaceutical moiety or that of its bio-transformed product.
The third part or pharmacokinetic analysis is where the analyst studies all the pharmacokinetic parameters of a drug product under investigation.
Lastly, the analyst presents his recordings about the differences between the innovator and the generic product in terms of statistical observation.
Importance of conducting bioavailability and bioequivalence studies –
For any commercial pharmaceutical product to be developed, the manufacturer needs to conduct both bioavailability and bioequivalence trials. The sole rationale behind performing these studies is the monitoring of both the pharmacokinetic and pharmacodynamic parameters. These parameters are crucial in evaluating the after-effects of an administered pharmaceutical product. The primary aim of these studies is evaluating the therapeutic equivalency of the generic formulations with that of the established innovator formulation. The reason for this therapeutic equivalency determination is simple that today, the world majorly relies on the consumption of generic medications due to their wide-scale availability and cheap prices. Besides, it also serves as an important parameter along with the pharmaceutical quality data to seek the final approval by the national regulatory authorities.
What are the general considerations that a bio-analyst should keep in mind for bioequivalence studies?
As bioanalysis majorly employees, the use of pharmacokinetic endpoints, mostly the bioequivalent studies, are performed under this consideration. Here are some crucial factors to keep in mind in this regard –
- Study design and experimental protocol for the same
- Bioanalytical method and their validation
- Appropriate selection of analyte, principle drug, metabolites, and/or prodrug
- Metrics in association with bioequivalence
- Transformation of the working data
- Approaches and analysis pattern involving biostatistics
- Establishment of the test criteria for conducting bioequivalence studies