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>consistency</span>
Growth performance testing in cell culture is an effective approach to making serum suitability and purchase decisions. An independent commercial testing lab conducted two separate and sequential growth promotion studies to underscore the need for pre-purchase lot performance testing with: (1) FBS; and (2) FBS alternatives. Results from both studies are presented here to compare and contrast:
• FBS lots to each other
• FBS alternatives lots to each other
• FBS alternatives lots to FBS
FBS alternatives are included because they are often overlooked as a cost-effective substitute for FBS, providing, in many cases, equivalent performance. It is advisable to avoid preconceived notions concerning the quality or performance of a serum product without considering the culture system, culture conditions, and the subject cells, which can all have a material impact on its performance in cell culture.
Test – then decide…
The approval of a new biological drug for therapeutic use requires supporting data from a variety of studies, including those that demonstrate the suitability of the manufacturing process. The regulatory guidance advocates that one of these studies address the issue of cell substrate stability by testing for consistent production of the product of interest by a characterised cell bank, generally the working cell bank (WCB). The study should evaluate stability during cultivation for production by examining a minimum of two time points — at a minimal number of population doublings and at or beyond the limit of in vitro cell age for production. The guidelines state that, “Evaluation of the cell substrate with respect to the consistent production of the intended product of interest should be the primary subject of concern”…
On January 31, 2003, FDA under the leadership of Commissioner Dr. Mark McClellan, issued a report entitled “Improving Innovation in Medical Technology: Beyond 2002.” One of the goals described in this report is to “speed potentially important emerging technologies to the market by reducing regulatory uncertainty and increasing the predictability of product development.” The technology areas of cell therapy and gene therapy were specifically identified. This article highlights some of the challenges for manufacturers and regulators of these products and describes ongoing efforts at FDA — as well as opportunities to partner with FDA — to improve the product development process for cell therapy and gene therapy products…