With the advent of novel biotherapeutics in indications such as oncology, the attention has moved to making these therapies patient centric, potentially available for self-administration. Given the volume limitations of the other convenient routes of administration such a subcutaneous, intramuscular, there is a need for high concentration drug products. Along with the concerns of inherent protein instability at high concentration, there are other practical challenges during the development of these drug products. This review focuses on the considerations in formulation screening, process development, manufacturing, analytical methods and stability for high concentration liquid drug product. For the scenarios where, high concentration liquid drug product is not feasible, alternate approaches can be undertaken to obtain high concentration drug product during administration. The discussion on the current available alternate technologies with an overview of their advantages and disadvantages are covered here. The scope of the overall discussions is introductory and limited to cautionary notes and experiences as opposed to prescriptive recommendations and detailed literature reviews: our primary goal is to provide a compiled set of considerations that can guide a detailed literature research and a to-do list for high concentration development and manufacturing activities. This manuscript aims to highlight the motivations to develop high concentration parenteral protein drug products, a wide range of -commonly known or sometimes overlooked- challenges associated with their development and manufacturing, as well as some approaches towards mitigation of said challenges.

中文翻译：

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高浓度生物药物产品开发与生产中的挑战与思考

随着诸如肿瘤学等适应症的新型生物疗法的出现，人们的注意力已转移到使这些疗法以患者为中心，并有可能用于自我管理。考虑到其他方便的给药途径如皮下，肌内给药的体积限制，需要高浓度的药物产品。除了担心高浓度蛋白质固有的不稳定性外，在开发这些药物产品期间还面临其他实际挑战。这篇综述重点关注高浓度液体药物产品的制剂筛选，工艺开发，制造，分析方法和稳定性方面的考虑。对于高浓度液体药物产品不可行的情况，可以采用其他方法在给药过程中获得高浓度的药物产品。本文涵盖了有关当前可用替代技术的讨论，并概述了它们的优缺点。总体讨论的范围是介绍性的，仅限于警告性说明和经验，而不是说明性建议和详细的文献综述：我们的主要目标是提供一套综合考虑因素，可以指导详细的文献研究和工作清单。高集中度的开发和制造活动。本手稿旨在强调开发高浓度肠胃外蛋白质药物产品的动机，以及与产品开发和制造相关的一系列（众所周知的或有时被忽视的）挑战，