Tim Tressel

Basic concepts in Q membrane chromatography for large-scale antibody production.

The large‐scale production of recombinant human monoclonal antibodies demands economical purification processes with high throughputs. In this article we briefly describe a common antibody process and evaluate the Q membrane adsorber for process‐scale antibody production as an alternative to a Q‐packed‐bed column in a flow‐through mode. The scientific concepts underlining Q membrane technology and its application are reviewed. The disadvantages and advantages of using Q membrane chromatography as a purification unit in large‐scale production are discussed, including problems initially seen with the Q membrane scale‐down model but solved with the invention of a new scale‐down model. The new Q‐membrane unit operation has a process capacity greater than 3000 g/m2 or 10.7 kg/L with a LRV over 5 for four model viruses. In this Review, a cost analysis illustrates that Q membrane chromatography is a viable alternative to Q column chromatography as a polishing step in a flow‐through mode for process‐scale antibody production.

Implementation of advanced technologies in commercial monoclonal antibody production.

Process advancements driven through innovations have been key factors that enabled successful commercialization of several human therapeutic antibodies in recent years. The production costs of these molecules are higher in comparison to traditional medicines. In order to lower the development and later manufacturing costs, recent advances in antibody production technologies target higher throughput processes with increased clinical and commercial economics. In this review, essential considerations and trends for commercial process development and optimization are described, followed by the challenges to obtain a high titer cell culture process and its subsequent impact on the purification process. One of these recent technical advances is the development and implementation of a disposable Q membrane adsorber as an alternative to a Q‐packed‐bed column in a flow‐through mode. The scientific concept and principles underlining Q membrane technology and its application are also reviewed.

Risk–benefit evaluation of on-line high-performance liquid chromatography analysis for pooling decisions in large-scale chromatography☆

In the production of a human therapeutic protein from inclusion bodies, product related impurities of very similar size and charge to the product are created as byproducts of the refold process. Their removal is usually challenging even when using chromatography with high performance resins and elution by shallow linear gradients. Additionally, performing this type of separation for commercial production adds increased complexity. To maximize productivity, columns are loaded so high that product elution profiles are not well separated from the impurities and pooling decisions are challenging. In this paper, conventional UV pooling based on fractionation or predefined absorbance based criteria will be compared to pooling based on fast on-line HPLC analytic. The development and implementation in a GMP process will be shown for a specific challenging separation by hydrophobic interaction chromatography. The different approaches have their unique complexities, timelines, uncertainties, and risks during development and implementation as well as during manufacturing. This study presents a probabilistic framework for quantitative comparison of two processes with unequal variability and uncertainty to evaluate the potential benefits of a PAT technology for its routine use in GMP Bioprocess manufacturing.