{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T05:12:04Z","timestamp":1778044324795,"version":"3.51.4"},"reference-count":108,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008990","name":"Zhejiang Provincial Department of Science and Technology","doi-asserted-by":"crossref","award":["2024C03123"],"award-info":[{"award-number":["2024C03123"]}],"id":[{"id":"10.13039\/501100008990","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>The activated sludge process serves as the core barrier in pharmaceutical wastewater treatment, yet its stability is inherently challenged by the extreme complexity of influent composition and the unpredictability of toxic shocks, particularly under contract development and manufacturing organization (CDMO) operations. Current biotoxicity assessment methods face inherent trade-offs among timeliness, specificity, and matrix robustness, resulting in fragmented, reactive management that lacks predictive capacity. In response, this review critically synthesizes evidence on toxicity pathways and monitoring technologies, systematically evaluating their mechanistic basis and engineering applicability. Building on these findings, we propose a conceptual perception\u2013cognition\u2013response architecture that structures decision-making across three adaptive tiers: (i) a perception layer that tolerates false positives for rapid anomaly detection; (ii) a cognition layer that requires effect-based biological verification; and (iii) a response layer that authorizes resilience-oriented interventions. Rather than a linear pipeline, the three tiers form an adaptive feedback cycle that dynamically aligns monitoring intensity, verification depth, and response authority with real-time risk gradients and site-specific constraints. By explicitly linking biological mechanisms to assessment limitations and tiered decision rules, this review provides a hypothesis-generating roadmap that orients biotoxicity management from episodic, composition-based assessment toward adaptive, effect-driven control. The proposed framework is intended to guide future pilot validation, multi-sensor integration, and context-specific calibration, offering a unified narrative for advancing proactive biotoxicity control in complex pharmaceutical wastewater systems.<\/jats:p>","DOI":"10.3390\/toxics14050395","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T07:57:29Z","timestamp":1777967849000},"page":"395","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From Static Assessment to Dynamic Management: A Paradigm Shift in Biotoxicity Evaluation of Activated Sludge for Pharmaceutical Wastewater Treatment"],"prefix":"10.3390","volume":"14","author":[{"given":"Zhicheng","family":"Zhang","sequence":"first","affiliation":[{"name":"Zhejiang Key Laboratory for Restoration of Damaged Coastal Ecosystems, Zhejiang International Science and Technology Cooperation Base for Biomass Resources Development and Utilization, School of Life Sciences, Taizhou University, Taizhou 318000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenyan","family":"Huang","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory for Restoration of Damaged Coastal Ecosystems, Zhejiang International Science and Technology Cooperation Base for Biomass Resources Development and Utilization, School of Life Sciences, Taizhou University, Taizhou 318000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinfeng","family":"Ding","sequence":"additional","affiliation":[{"name":"Taizhou Environmental Science Design and Research Institute Co., Ltd., Taizhou 318000, China"},{"name":"Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenli","family":"Liu","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory for Restoration of Damaged Coastal Ecosystems, Zhejiang International Science and Technology Cooperation Base for Biomass Resources Development and Utilization, School of Life Sciences, Taizhou University, Taizhou 318000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruoxuan","family":"Xia","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory for Restoration of Damaged Coastal Ecosystems, Zhejiang International Science and Technology Cooperation Base for Biomass Resources Development and Utilization, School of Life Sciences, Taizhou University, Taizhou 318000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1231-072X","authenticated-orcid":false,"given":"Worou","family":"Chabi Noel","sequence":"additional","affiliation":[{"name":"Water Science and Technology Laboratory, National Water Institute, University of Abomey-Calavi, Abomey-Calavi 01 BP 526, Benin"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongjian","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Biomass Chemical Engineering of Ministry of Education, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Chen","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory for Restoration of Damaged Coastal Ecosystems, Zhejiang International Science and Technology Cooperation Base for Biomass Resources Development and Utilization, School of Life Sciences, Taizhou University, Taizhou 318000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Yao","sequence":"additional","affiliation":[{"name":"Zhejiang Key Laboratory for Restoration of Damaged Coastal Ecosystems, Zhejiang International Science and Technology Cooperation Base for Biomass Resources Development and Utilization, School of Life Sciences, Taizhou University, Taizhou 318000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"131826","DOI":"10.1016\/j.jclepro.2022.131826","article-title":"A review on conventional and advanced hybrid technologies for pharmaceutical wastewater treatment","volume":"356","author":"Eniola","year":"2022","journal-title":"J. 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