Cell-Line Engineering Should Be Evaluated by Product Quality Robustness Rather Than Yield Alone

Chinese hamster ovary cell-line engineering is often judged through productivity-centered endpoints because titer is easy to rank, economically visible, and strongly coupled to development timelines. Yet a high-producing clone is not necessarily the clone whose product attributes remain fit for purpose as genetic state, culture age, metabolic load, media composition, or bioreactor conditions change. This Perspective argues that cell-line evaluation should therefore shift from yield maximization alone to product-quality robustness: the capacity of an engineered production system to preserve predefined quality attributes and acceptable process performance across a relevant, explicitly bounded set of perturbations. The argument integrates evidence on genomic integration, epigenetic state, secretory and metabolic burden, glycosylation engineering, process-dependent quality variation, scale-down perturbations, and analytical forecasting. A proposed quality-robustness logic is developed without treating molecular change as failure, analytical prediction as mechanism, or a single perturbation study as proof of manufacturing generalizability. The practical implication is not that productivity becomes secondary, but that yield should be interpreted jointly with product quality, stability, perturbation response, and evidence strength when selecting engineered cell lines.