ABSTRACT
Methods ............................................................. 286 8.4 Methods Used for Product Characterization,
Release, and Stability Testing.................................... 286 8.4.1 QC Release Tests — Thumbs Up or
Thumbs Down? ................................................. 289
8.4.2 Stability Tests — Looking for Ghosts with Metal Detectors?............................................... 290
8.4.3 Product Potency Assays — Why the Ends Do Not Justify the Means................................ 293
8.5 Methods Used for Comparability Assessment .......... 293 8.6 Development, Qualification, and Validation of an
Analytical Method ....................................................... 295 8.7 Typical Assay Development Strategy ........................ 296 8.8 Conclusion.................................................................... 317 References............................................................................. 319
8.1 ANALYTICAL CHARACTERIZATION OF BIOMOLECULAR PRODUCTS
Historically, as technologies were developed that allowed biological or biotechnological materials to be produced in large quantities for pharmaceutical use, the statement was frequently heard in both industry and regulatory circles that “the process is the product.” This perspective was based on the understanding that the main production agents — living organisms — produce large quantities of chemically similar material (e.g., proteins) that must undergo a variety of separation steps that can (hopefully) select the greatest yield of the highest purity of a desired molecular entity from the cellular-derived milieu. The separation processes used to sort out the one or more target proteins from other, often copurifying, proteins are optimized, scaled, and validated to reliably achieve the same population of molecular entities from each batch of biologically produced material. The nature of these separation processes is such that even subtle changes in some steps can impart significant variations in the resulting population of proteins. It has been shown repeatedly that successfully defining and controlling the process can define and control the product, hence the rationale for the phrase [1].
