Objectives/Goals: The number of FDA-approved cellular and gene therapy products has doubled from 23 in 2022 to 46 in 2025. For allogeneic cell therapies, cell banks are essential both during preclinical development and manufacturing clinical products. The objective of this study is to establish a cell bank system for preclinical research of a cartilage repair biologic. Methods/Study Population: To conduct large animal preclinical studies required by the FDA for load-bearing cartilage repair products, the FDA has described in its guidance documents for Investigational New Drug (IND) applications the use of an animal-based “analogous cellular product” (ACP). Here, costal chondrocytes from 6 minipigs (3 male, 3 female) were isolated and expanded to create master cell banks (MCBs) at passage 2. ACPs (i.e., tissue-engineered neocartilage) were generated from each MCB, and the critical quality attributes, properties such as morphology and mechanics, were assessed. By comparing functional properties of the ACPs to those of the native cartilage tissue they intend to replace, donors were selected for inclusion in working cell banks (WCBs) to support both academic research and ongoing IND-enabling research. Results/Anticipated Results: All six donors produced tissue-engineered cartilage that passed morphologic release criteria (i.e., round, flat). However, ACPs showed distinct donor-based variability in terms of mechanical release criteria (e.g., tensile Young’s modulus and compressive aggregate modulus). Based on release criteria data, two types of WCBs were created at passage 5: 1) a pooled donor WCB for academic studies that require multiple donors and 2) multiple single-donor WCBs for manufacturing ACPs tested in ongoing IND-enabling dose-response and pivotal long-term studies. It is estimated that between 160k-400k, ACP constructs can be produced from each of the six MCBs, analogous to clinical-scale manufacturing. Discussion/Significance of Impact: Overall, this study illustrates a cell bank system that can be used to support IND-enabling research. This cell bank produced preclinical neocartilage analogous to the intended clinical product, and it is currently being used in dose-response and pivotal long-term large animal studies for temporomandibular joint disc repair.
Nordberg et al. (Wed,) studied this question.