Introduction to the proposals from the global bioanalysis consortium harmonization team.

Abstract

Bioanalysis in Pharmaceutical Research & Development has been at the crossroad of science, technology, and regulations from its onset [1]. The first American Association of Pharmaceutical Scientists (AAPS)/Food and Drug Administration (FDA) Bioanalytical Workshop in 1990 in Crystal City, USA (CCI) was a major landmark for the industry to agree on execution and documentation of bioanalytical experiments. And although the resulting conference report was not a regulatory guidance, it was a roadmap for bioanalysts around the world for a decade on how to validate and apply bioanalytical methods [2]. In early 1999, the FDA promoted bioanalysis in support of pharmacokinetic evaluation in clinical and preclinical studies more formally into the regulated space by issuing a draft guidance. After broad industry consultation during an AAPS/FDA meeting again in Crystal City (CC-II) in early 2000 [3], FDA issued a guidance for Industry on Bioanalytical Method Validation in May 2001 [4]. This guidance provided the bioanalytical community the regulatory framework for bioanalytical method validation and the application of these methods. Although the guidance set clear expectations in many areas, the lack of detail on expectations in some paragraphs resulted in different interpretations in industry or by the inspectors. This, in combination with the rapid technological advancements in separation sciences, mass spectrometry, and ligand binding assay (LBA) or cell-based assay formats, resulted in individual views on how to validate bioanalytical methods and apply them to routine sample analysis. In trying to provide assistance in the interpretation of this guidance, the FDA continued to reach out to industry at conferences. In addition, some inspection findings documented in Form 483s provided a way forward. The 2001 guidance only referred to LBAs that enabled small molecule analysis and did not address the bioanalysis of macromolecules. In support of the rapidly growing ligand binding assay scientific community, two additional white papers were published to cover LBA aspects of macromolecule bioanalysis [5, 6]. To further discuss and clarify the 2001 FDA Guidance, FDA/AAPS organized a next meeting in Crystal City (CC-III), from which a comprehensive conference report was issued [7]. Crystal City III also put Incurred Sample Reanalysis (ISR) back on the foreground, a controversial topic which was further discussed during Crystal City IV [8]. Next, as mentioned in the Kudoh paper [1], multiple other guidelines or best practices on GLPs, GCPs, computer/software, or analytical instrument validation increasingly impacted the bioanalytical laboratory. Last but not least, other regions/countries besides the USA issued their own guidelines on regulated bioanalysis [9–11]. Building the Global Bioanalytical Consortium At the initiative of four regional professional organizations from Europe (European Bioanalysis Forum (EBF)) and North America (AAPS, Applied Pharmaceutical Analysis (APA) APA and Calibration & validation group (CVG—currently represented in GBC by Canadian Forum for Analytical and Bioanalytical Sciences CFABS), a letter was sent to the FDA and the European Medicine Agency (EMA)), formally requesting the health authorities and bioanalytical community to join hands and harmonize global bioanalysis scientific best practices. The need for global harmonization of the bioanalytical guidance was also supported by publishing this letter as an open letter [12], an initiative which was supported by many [13–15]. At the same time, the authors from aforementioned open letter together with additional representatives from these organizations (currently referred to as founding members), proposed to form an organization which brings together experts from the global bioanalytical community to discuss, share, and finally propose a harmonized view on bioanalytical best practices that could lead to a guidance: the Global Bioanalysis Consortium (GBC). A consensus was reached among around 280 delegates, including five Regulatory Agencies, during the 5th Workshop on Recent Issues in Bioanalysis (5th WRIB) in April 2010 on the main characteristic of what a “harmonization and Global Bioanalytical Guidance” should be based upon the following: science driven with inclusion of a rationale behind each requirement to prevent “box checking”. In addition, it should have a global perspective (not local issues), should not be prescriptive, and finally must get buy-in from all the countries [16]. From there, the GBC founding members proposed the mission of the organization [17] and reached out into the global bioanalytical community to build the GBC ensuring balanced representation from North America, Latin America, Europe/Middle East/Africa and Asia-Pacific.