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，即上游菌株开发，中游细胞培养和下游纯化处理。生物细胞具有增强的生产所需生物产品的能力，无论是核糖体还是非核糖体，被分离或遗传构建。然后在生物反应器中培养它们进行繁殖。培养后，采用一系列下游加工步骤进行生物制品纯化。虽然生产菌株的构建通常被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资本和运营成本的很大一部分。因此，制定有效的下游处理策略成为生物工程师的一项具有挑战性的任务。Nysa Membrane Technologies, Inc.是一家加拿大公司，拥有一种新颖的、专有的基于膜的平台技术，在蛋白质纯化和其他生物和工业分离领域具有广泛的全球应用。通过建立水凝胶技术，可以弥补与纯聚合物膜相关的技术局限性，该公司迄今已开发出几种水凝胶膜产品，用于澄清（即微过滤），色谱（即阴离子/阳离子交换）和浓缩（即超滤）步骤。这些产品具有特殊的特点，如高通量，高结合力，高机械强度，在此基础上，它们能够超越许多现有的商业产品。该公司认识到实际应用于制造临床级生物产品的商用膜产品的缺乏，因此有意通过生物制药和质粒DNA制造的全球市场将其产品商业化。为此，该公司将需要建立他们的平台技术，作为传统生物产品净化技术的卓越替代品。这是Nysa和滑铁卢大学合作项目的主要目标。

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.