Management of Bioanalytical Samples in BA/BE Studies: Challenges Faced.

Abstract The design, performance and evaluation of bioavailability and bioequivalence have evolved over the last few years substantially. The bioavailability (BA) and bioequivalence (BE) study findings are crucial to know the safety and tolerability of generics against corresponding innovator drugs; to ensure they are comparable and safe for consumption by human subjects. The BA/BE study process is streamlined by applicable regulatory guidelines or requirements worldwide. In this regard a gold standard has already been established by global agencies like USFDA, EMA, CDSCO etc., who have produced extensive and detailed guidance documents adhering to GCP guidelines. This study aims to examine the practical on-the-field issues and challenges in processing the bioanalytical samples collected in BA/BE studies. The issues or drawbacks in the existing practices and their impact on the quality and consistency of pharmacokinetic data shall be explored in this study. Following that, we will try to understand the perspective and opinions to make improvements in the process, from the experts in the field of BA/BE studies who are currently working in the industry and who have faced and overcame the bottlenecks. While sponsors are required to submit the BA/BE data before any further clinical research and/or drug development process, it is crucial to understand the importance of the accuracy of these data. The reason being, that those values are the basis to assess the rate and extent of absorption of a particular active pharmaceutical ingredient in a drug, be it a NCE or generic one. In this study, special attention has been attributed to instrumentation adopted during BA/BE studies. Calibration of the instrument is crucial to maintain accuracy and precision throughout the analysis, while ionization efficiency affects the sensitivity and detection limits of the method. The importance of accurate mass measurements is emphasized, as it impacts the identification and quantification of analytes. In conclusion, the quality of BA/BE data that will be used in clinical research is influenced by multiple factors, including sample preparation, chromatographic separation, instrumental considerations, data acquisition parameters, and data processing. A comprehensive understanding of the impacting factors is essential for optimizing the safe and appropriate conduct of BA/BE study, ensuring robust and reliable results in clinical research applications.