Biotherapeutics validation

Validation of Ligand-Binding Assays to Support Pharmacokinetic Assessments of Biotherapeutics... 

Because LBAs are conceptually simple and operationally easy to perform, there is often a perception among scientists that LBA method development and validation should be fairly straightforward and simple to conduct. In reality, establishment of LBAs for GLP-compliant bioanalysis to support PK/TK assessments of biotherapeutics is often a challenging task. Successful LBA establishment involves a systematic... 

A full validation assessing all of the performance characteristics discussed above should be performed for a new method. Unlike for small molecules, for biotherapeutics it is recommended that a full validation be conducted when there is a change in species (e.g., rat to mouse) and a change in matrix within a species (e.g., rat serum to rat urine). In all the situations discussed in detail below, it is necessary to have a validation plan with a priori established acceptance criteria. 

The ideal PK immunoassay standard curve, which is nonlinear and heteroscedastic, is derived from solutions of well-characterized macromolecules added to a relatively nonreactive sample matrix. However, rarely does one encounter an ideal situation when describing bioanalytical methodology, thus developing and validating analytical methods for macromolecules, and analyzing samples from preclinical or clinical trials must include an evaluation of these variables and possibly many others. Careful consideration must be given to the topics described in this chapter to achieve the goal of accurate and reproducible quantification of biotherapeutics necessary for pharmacokinetic analysis. 

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