Therapeutics
Figure 1 A variety of anti-idiotypic
reagents have been developed to specifically function within pharmacokinetic assays. Ranging from standard monoclonal antibodies to antibody alternative protein
scaffolds, they offer a range of different benefits
sensitivity achieved from screens of naïve recombi- nant antibodies is often insufficient, requiring an additional affinity maturation step which adds to
reagent costs and extends development timelines9, 10. Rapid development times are a key considera- tion for anti-ID reagents, as the drug development process relies on the availability of suitable bioan- alytical reagents to develop and validate PK assays. With any anti-ID reagent, ensuring consistent performance and supply involves one of two options: obtaining small batches of the reagent and carrying out multiple batch-to-batch standardisa- tion processes over the course of drug develop- ment; or obtaining larger reagent batches, requir- ing fewer batch-to-batch standardisation process- es, but with consideration of the shelf-life and sta- bility of the reagent5. Having a reliable source of critical reagents that can be produced consistently at scale is therefore a benefit. In addition to shelf-life stability, selected PK assay reagents must also show functional stability across a range of critical ligand binding assay con- ditions. Many biological molecules are sensitive to variations in assay conditions, such as pH and tem- perature, causing variability in performance and potentially resulting in erroneous assay results. It is
10
essential that any selected PK assay reagent shows consistent high target affinity, specificity and sensi- tivity across the desired assay range in the presence of biological components from patient samples when used within the specific assay containers, without showing matrix effects5-8.
Regulatory background for critical reagents
From a regulatory perspective, it is clear that anti- ID reagents must fulfil high quality standards for use in clinical settings5-7. In addition to consistent batch-to-batch control, high specificity, sensitivity, and reproducibility in assay performance are key attributes as they may be used for several years over the lifetime of the drug evaluation process. It is therefore crucial that a reagent continues to per- form to the same standards throughout the drug development lifecycle8,11,12.
There has been recognition from the industry that all ligand-binding assays are dependent upon the critical reagents used within the assays, with the essential assay features of specificity, selectivi- ty and sensitivity all being determined by the affin- ity reagent used5. Extensive established methods exist for the analytical validation of critical
Drug Discovery World Winter 2017/18
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