Institute for Organic Chemistry and Biochemistry, Technische Universität Darmstadt, Alarich-Weiss-Strasse 4, D-64287 Darmstadt, Germany; Ferring Darmstadt Laboratory, Alarich-Weiss-Strasse 4, D-64287 Darmstadt, Germany.
Ferring Darmstadt Laboratory, Alarich-Weiss-Strasse 4, D-64287 Darmstadt, Germany.
Int J Pharm. 2021 Feb 1;594:120164. doi: 10.1016/j.ijpharm.2020.120164. Epub 2020 Dec 10.
Therapeutic monoclonal antibodies and related products have steadily grown to become the dominant product class within the biopharmaceutical market. Production of antibodies requires special precautions to ensure safety and efficacy of the product. In particular, minimizing antibody product heterogeneity is crucial as drug substance variants may impair the activity, efficacy, safety, and pharmacokinetic properties of an antibody, consequently resulting in the failure of a product in pre-clinical and clinical development. This review will cover the manufacturing and formulation challenges and advances of therapeutic monoclonal antibodies, focusing on improved processes to minimize variants and ensure batch-to-batch consistency. Processes put in place by regulatory agencies, such as Quality-by-Design (QbD) and current Good Manufacturing Practices (cGMP), and how their implementation has aided drug development in pharmaceutical companies will be reviewed. Advances in formulation and considerations on the intended use of a therapeutic antibody, including the route of administration and patient compliance, will be discussed.
治疗性单克隆抗体及相关产品稳步发展，成为生物制药市场的主导产品类别。生产抗体需要特别注意确保产品的安全性和有效性。特别是，最大限度地减少抗体产品的异质性至关重要，因为药物物质变体可能会影响抗体的活性、功效、安全性和药代动力学特性，从而导致产品在临床前和临床开发中失败。本综述将涵盖治疗性单克隆抗体的制造和配方挑战和进展，重点是改进工艺以最大限度地减少变体并确保批次间的一致性。监管机构（如质量源于设计（QbD）和现行良好生产规范（cGMP））所采用的流程，以及它们在制药公司药物开发中的实施情况，将进行回顾。还将讨论制剂方面的进展以及治疗性抗体的预期用途的考虑因素，包括给药途径和患者顺应性。
