Introduction: The development of novel complex biotherapeutics led to new challenges in biopharmaceutical industry. The potential of these particles has been demonstrated by the approval of several products, in the different fields of gene therapy, oncolytic therapy, and tumor vaccines. However, their manufacturing still presents challenges related to the high dosages and purity required.Areas covered: The main challenges that biopharmaceutical industry faces today and the most recent developments in the manufacturing of different biotherapeutic particles are reported here. Several unit operations and downstream trains to purify virus, virus-like particles and extracellular vesicles are described. Innovations on the different purification steps are also highlighted with an eye on the implementation of continuous and integrated processes.Expert opinion: Manufacturing platforms that consist of a low number of unit operations, with higher-yielding processes and reduced costs will be highly appreciated by the industry. The pipeline of complex therapeutic particles is expanding and there is a clear need for advanced tools and manufacturing capacity. The use of single-use technologies, as well as continuous integrated operations, are gaining ground in the biopharmaceutical industry and should be supported by more accurate and faster analytical methods.

中文翻译：

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生物治疗颗粒制造中的当前挑战。

简介：新型复杂生物疗法的发展给生物制药行业带来了新的挑战。这些颗粒的潜力已在基因治疗，溶瘤治疗和肿瘤疫苗的不同领域中通过多种产品的认可得到证明。然而，它们的制造仍然带来与所需的高剂量和高纯度有关的挑战。涉及的领域：这里报道了生物制药行业当今面临的主要挑战以及不同生物治疗颗粒制造的最新进展。描述了纯化病毒，病毒样颗粒和细胞外囊泡的几个单元操作和下游流程。还着眼于连续和集成过程的实施，突出了不同纯化步骤的创新。专家意见：由少量单元操作，更高产量的流程和降低的成本组成的制造平台将受到业界的高度赞赏。复杂的治疗颗粒的流水线正在扩大，显然需要先进的工具和制造能力。一次性技术的使用以及连续的集成操作在生物制药行业中日益普及，应以更准确，更快速的分析方法予以支持。