Monoclonal antibody (mAb) is the fastest growing segment of therapeutic proteins today and in the foreseeable future. The ability to use antibody-based therapies to treat serious life-changing conditions with minimal side-effects necessitates the need to produce these products quickly and cost-effectively throughout the entire drug candidate life-cycle. At the heart of the solution to rapid and cost-effective mAb manufacturing is a platform approach to cell culture, purification, and fill-and-finish unit operations. On the purification side of this strategy, Protein A chromatography is the cornerstone of mAb process platforming. The ability to carry out this capture step with high contaminant removal efficiency and degree of consistency determines how uniform the purification platform design is across a portfolio of mAb candidates. Elevated levels of contaminants and chromatography interfering species present in the ever increasing high density production cell cultures are a challenge to the goal of maintaining both the efficiency of contaminant removal and consistency of product purity of the Protein A capture step. This is a serious barrier to creating fully standard approaches for mAb manufacturing and impacts discovery-to-clinic time frames as well as overall productivity of commercial manufacturing. We previously reported (BPI West Conference 2016) that removing DNA and associated protein complexes ahead of Protein A column significantly improves Protein A pool product purity, eliminates post viral inactivation turbidity, produces tighter product elution peak, and results in a more concentrated product pool. Even more significant is that the new approach utilizes industrially scalable chromatographic clarification technology, and works in tandem with traditional commercial grade HCCF clarification and Protein A unit operation. In this presentation we present further evaluation the effect of DNA removal, using chromatographic clarification, on the Protein A column performance. The goal is to deliver a smaller, simpler, and more robust Protein A unit operation and, thus, the entire mAb purification process. Our approach maintains direct industrial relevance by seeking strategies and using technologies that are deployable and scalable in today’s commercial biopharmaceutical manufacturing.

Improving protein A performance using chromatographic clarification strategy

253rd National Meeting (2017)

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