Single-column (batch) preparative chromatography is the technique of choice for purification of biotherapeutics but it is often characterized by an intrinsic limitation in terms of yield-purity trade-off, especially for separations containing a larger number of product-related impurities. This drawback can be alleviated by employing multicolumn continuous chromatography. Among the different methods working in continuous mode, in this paper we will focus in particular on Multicolumn Countercurrent Solvent Gradient Purification (MCSGP) which has been specifically designed for challenging separations of target biomolecules from their product-related impurities. The improvements come from the automatic internal recycling of the impure fractions inside the chromatographic system, which results in an increased yield without compromising the purity of the pool. In this article, steps of the manufacturing process of biopharmaceuticals will be described, as well as the advantages of continuous chromatography over batch processes, by particularly focusing on MCSGP.

单柱（批次）制备色谱是生物治疗药物纯化的首选技术，但它通常在产量-纯度权衡方面具有内在局限性，特别是对于含有大量产品相关杂质的分离。这个缺点可以通过使用多柱连续色谱来缓解。在以连续模式工作的不同方法中，在本文中，我们将特别关注多柱逆流溶剂梯度纯化 (MCSGP)，该方法专为具有挑战性的目标生物分子与其产品相关杂质的分离而设计​​。这些改进来自色谱系统内部不纯馏分的自动内部回收，从而在不影响池纯度的情况下提高产量。在本文中，将通过特别关注 MCSGP 来描述生物制药的制造过程的步骤，以及连续色谱相对于批处理过程的优势。