Bioanalytical methods validation: A critique of the proposed FDA guidance

The criteria generally applied to the validation of bioanalytical methods are largely based on the Consensus meeting held in Washington in 1990 in a number of Journals. In December 1998, the FDA published Draft Guidelines for Human Bioanalytical Studies, based on the 1990 Consensus report. Subsequently a meeting Bioval99 was held in June 1999 in London and a workshop jointly organised by the FDA and MPS was held in Crystal City. Points emerging from the latter meeting appear in an Addendum (p. S-67). The present article was written in advance of it [as was Muirhead's art., p. S-72-Ed.]. Bioanalysis, in this context, is a term that has been applied for over 30 years to the quantitation of drugs (therapeutic agents) in biological matrices, usually plasma, serum or blood for the purposes of defining their pharmacokinetics. More recently with the ascendancy of biotechnology, this term has been adopted by protein chemists to define the analytical methods used for characterising proteins. This article amplifies a previous article in-this series [1]1) following the publication of the recent FDA guidance and incorporates recent thought as discussed in Bioval 99. Recently the FDA published 'Guidance for Industry; Bioanalytical Methods Validation for Human Studies', in January 1999, with a requirement for comments to be provided within sixty days. These guidelines were based on the consensus meeting held in December 1990, at Crystal City, Arlington, Washington DC (organised by AAPS, FIPS, HPB, AOAC and the FDA). These Crystal City Guidelines, or Shah (the senior author) guidelines as they have become variously known, were published in a variety of journals in 1992 [2], and since that time have gained universal acceptance throughout the pharmaceutical industry. The MPS and FDA have organised a further meeting, Crystal City (revisited) 2000 to be held in Crystal City in January 2000. As such the proposed FDA Guidance for industry are in abeyance until a further consensus is reached. As part of this consensus process the RSC and RPS (GB) in the form of JPAG and the PSG, together with EUFEPS organised a European based meeting in June lastyear in London (Bioval 99) in order to provide a European perspective.