Developing membrane platform technology for manufacturing of clinical-grade bioproducts

生物制造过程通常包含三个主要组成部分，即上游菌种开发、中游细胞培养和下游纯化处理。分离或基因构建具有生产所需生物产品的能力增强的生物细胞，无论是核糖体还是非核糖体。然后在生物反应器中培养它们进行繁殖。在培养后，采用一系列下游加工步骤进行生物制品提纯。虽然生产菌株的构建被普遍认为是成功开发生物工艺的关键先决条件，但下游加工可能占整个生物工艺的资本和运营成本的很大一部分。因此，开发有效的下游加工策略成为生物工程师的一项具有挑战性的任务。NYSA膜技术公司是一家加拿大公司，拥有一种新颖的、基于膜的专有平台技术，在蛋白质纯化以及其他生物和工业分离方面具有广泛的全球应用。通过建立可弥补与纯聚合物膜相关的技术限制的水凝胶技术，该公司迄今已开发出几种用于澄清(即微滤)、层析(即阴离子/阳离子交换)和浓缩(即超滤)步骤的水凝胶膜产品。这些产品具有高熔剂、高结合能力和高机械强度等特殊特性，在此基础上它们能够超越许多现有的商业产品。认识到缺乏实际用于生产临床级生物制品的商用膜产品，该公司有兴趣通过瞄准生物制药和质粒DNA制造的全球市场来将其产品商业化。为此，该公司将需要建立他们的平台技术，作为传统生物产品纯化技术的优越替代方案。这是Nysa和滑铁卢大学合作开展的拟议项目的主要目标。

Biomanufacturing processes often contain three major components, namely upstream strain development, midstream cell cultivation, and downstream purification processing. Biological cells with an enhanced ability for the production of desired bioproducts, either ribosomal or non-ribosomal, are isolated or genetically constructed. They are then cultivated in bioreactors for multiplication. Following cultivation, a series of downstream processing steps are adopted for bioproduct purification. While construction of production strains is generally recognized as a key prerequisite for successful bioprocess development, downstream processing could account for a big portion of the capital and operation costs of the overall bioprocess. Hence, developing strategies for effective downstream processing becomes a challenging task for bioengineers. Nysa Membrane Technologies, Inc. is a Canadian company in possession of a novel, proprietary membrane-based platform technology with broad global applications in protein purification and other biological and industrial separations. By establishing the hydrogel technologies which can complement technical limitations associated with pure polymeric membranes, the company has so far developed several hydrogel membrane products for clarification (i.e. microfiltration), chromatography (i.e. anion/cation exchange), and concentration (i.e. ultrafiltration) steps. These products have special features, such as high flux, high binding capacity, and high mechanical strength, based on which they are able to outperform many existing commercial products. Recognizing the lack of commercial membrane products practically applied for manufacturing of clinical-grade bioproducts, the company is interested in commercializing their products by targeting the global market in biopharmaceutical and plasmid DNA manufacturing. To this end, the company will need to establish their platform technology as a superior alternative to the conventional one for bioproduct purification. This is the primary goal of the proposed project, a collaborative work between Nysa and University of Waterloo.