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Potency assays are key to the development, registration, and quality control of biological products. Although previously preferred for clinical relevance, in vivo bioassays have greatly diminished with the advent of dependent cell lines as well as due to ethical concerns. However, for some products, the development of in vitro cell-based assay is challenging, or existing method has limitations such as tedious procedure or low sensitivity. The generation of genetically modified (GM) cell line with improved response to the analyte provides a scientific and promising solution. Potency assays based on GM cell lines are currently used for the quality control of biological products including cytokines, hormones, therapeutic antibodies, vaccines and gene therapy products. In this review, we have discussed the general principles of designing and developing GM cells-based potency assays, including identification of cellular signaling pathways and detectable biological effects, generation of responsive cell lines and constitution of test systems, based on the current research progress. In addition, the applications of some novel technologies and the common concerns regarding GM cells have also been discussed. The research presented in this review provides insights for the development and application of novel GM cells-based potency assays for biological products., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yu Lei reports financial support was provided by Chinese Pharmacopoeia Commission., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Enterovirus 71 (EV71) is a major cause of hand, foot, and mouth disease in children and may be fatal. A vaccine against EV71 is needed., Methods: We conducted a randomized, double-blind, placebo-controlled phase 3 trial involving healthy children 6 to 71 months of age in Guangxi Zhuang Autonomous Region, China. Two doses of an inactivated EV71 vaccine or placebo were administered intramuscularly, with a 4-week interval between doses, and children were monitored for up to 11 months. The primary end point was protection against hand, foot, and mouth disease caused by EV71., Results: A total of 12,000 children were randomly assigned to receive vaccine or placebo. Serum neutralizing antibodies were assessed in 549 children who received the vaccine. The seroconversion rate was 100% 4 weeks after the two vaccinations, with a geometric mean titer of 170.6. Over the course of two epidemic seasons, the vaccine efficacy was 97.4% (95% confidence interval [CI], 92.9 to 99.0) according to the intention-to-treat analysis and 97.3% (95% CI, 92.6 to 99.0) according to the per-protocol analysis. Adverse events, such as fever (which occurred in 41.6% of the participants who received vaccine vs. 35.2% of those who received placebo), were significantly more common in the week after vaccination among children who received the vaccine than among those who received placebo., Conclusions: The inactivated EV71 vaccine elicited EV71-specific immune responses and protection against EV71-associated hand, foot, and mouth disease. (Funded by the National Basic Research Program and others; ClinicalTrials.gov number, NCT01569581.).