Significance of ‘post bioanalysis phase’ in bioanalysis: is GMP creeping into GLP?
“In the year 2011, during a vendor (CRO) qualification audit, I asked the analyst what is the reason for the failure of an analytical run? He responded “the root cause of analytical run failure is the non-compliance of QC samples to pre-defined acceptance criteria” ... Can this be a root cause? I thought. Although I was not convinced with the analyst’s response, but at the same time realized the significance of correct bioanalytical practices especially with regard to post bioanalysis phase.” Rationale interpretation of regulated bioanalysis implies intrinsic use of bioanalytical science, ‘quality’ aspects, regulatory requirements and good practices (GxP). With an increasing demand for reconstruction of bioanalysis using available documents on-site, laboratory data on accuracy and reproducibility, time-bound performance and continuous efforts to improve method efficiency, signify the importance of controlling quality and thoughtful human intervene using a robust quality management system (QMS). In addition to bioanalysis, this system also applies to drug substance and drug product analysis. As per current understanding, regulated bioanalysis can be categorized into four key phases: method development, method validation, bioanalysis (study sample analysis) and post bioanalysis, which includes reviews, hypothesis creation, reinvestigations and corrective actions and preventive actions (CAPA). Although these phases have evolved significantly in the last two decades, post bioanalysis phase has been a subject of intense scientific discussions at different forums. The issues related to the failure of analytical batches, pharmacokinetic repeats, conduct, failure and reporting of incurred sample reanalysis (ISR) have indeed highlighted the importance of this crucial phase. The expertise of rationale interpretation of regulated bioanalysis not only emphasizes the adequate use of an error-proof QMS but also implies prudent use of good quality practices (GxP; good laboratory practice [GLP]; good clinical practice [GCP]; good documentation practice [GDP] and good manufacturing practice [GMP]) for various bioanalytical phases by taking into account the scientific, quality or regulatory calls rationally based on the type and intensity of the analytical problems. The bioanalytical method validation and application phase of a validated method are well established, and are accepted as process-driven phases (standard operating procedures [SOPs], protocols, instructions and training, among others). On the contrary, similar method development phase, post bioanalysis phase demands a high degree of thinking and innovative approaches to hypothesize, investigate and resolve problems encountered by bioscientists in their day to day regimen. At the same time, it poses different level of challenges as most of the problems encountered in this phase are required to be resolved through detailed investigation, conclusion, CAPA and documentation within a stipulated time frame. From the historical front, the preregulations era in mid to late 1990s, bioanalysis was characterized by basically two phases, Significance of ‘post bioanalysis phase’ in bioanalysis: is GMP creeping into GLP?