To demonstrate that a dose-determining assay is fit for purpose, the measurement uncertainty associated with a reported release test result must be suitably small. The establishment of a corresponding product specification is inextricably linked to the tolerance for error in assigning a dose value for a vector lot. By adopting an equivalence-based lot release model which includes a total error approach to assay qualification, specific testing strategies can be evaluated quantitatively for dose error and lot release decision risks throughout the drug development process. This article aims to reinforce how the concepts tied to an equivalence-based lot release model are interrelated and applied in practice. It provides in-depth explanations of fundamental concepts and clarifies common misunderstandings for quality control, quality assurance, and regulatory affairs personnel held accountable for decisions made in vector dose assignment and product lot release.
Tag: <span>lot release</span>
The approval of several gene therapy products and gene-modified cell therapies over the last five years has led to increasing numbers of investigational new drug applications (INDs) using adeno-associated and lentiviral vectors. However, these successes have been tempered by the risks of dose-related toxicities. The therapeutic window for a product is derived from pre-clinical and clinical dose response models, which assume statistically that measurements of dose are exact. Whether vector is administered directly or used as a critical reagent to prepare a gene-modified cellular product, the assignment of a label concentration to a vector batch is critical for establishing consistency of product used in preclinical and clinical development.