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To resolve this time dependency, intra\u2010experimental parameter shifts as part of design of dynamic experiments (DoDE) can be performed to study mammalian growth and production kinetics in fed\u2010batch processes. This enables growth phase\u2010dependent optimization, aligned with cellular requirements. Here, we provide a comprehensive, head\u2010to\u2010head comparison of our phase\u2010dependent optimization approach with intra\u2010experimental shifts of process parameters to a static optimization that retains parameter settings through the entire bioprocess. Showcasing a monoclonal antibody production process development scenario, the study examines growth phase\u2010dependent effects of temperature (T) and dissolved oxygen (DO) together with time\u2010invariant parameters for feed and seeding cell density. While the static optimization suggests settings near the center of the design space, phase\u2010dependent optimization finds an optimum by shifting T and DO between the exponential growth, transition, and production phases. Overall, the phase\u2010wise optimized process gives an experimentally validated ~30% increase in product titer while maintaining comparable product quality. Furthermore, the approach breaks the correlation between product titer and acidic charged variants: both depend on T but at different timeframes. Additionally, DoDE uncovers a crucial interaction between T and DO, with low T and high DO during the exponential growth phase, leading to strong lactate accumulation. The data demonstrate the advantages of phase\u2010dependent optimization enabled by DoDE. The results may serve as a good practice example for follow\u2010up research.<\/jats:p>","DOI":"10.1002\/btpr.88508","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T06:05:41Z","timestamp":1779084341000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multivariate phase\u2010dependent optimization of bioprocesses boosts performance and quality\u2014Why timing (of exposure) matters"],"prefix":"10.1002","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6816-0401","authenticated-orcid":false,"given":"Samuel","family":"Kienzle","sequence":"first","affiliation":[{"name":"Global Development CMC Biologicals Boehringer Ingelheim Pharma GmbH &amp; Co. 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