Abstract
The demand on biologics has been constantly rising over the past decades and has become crucial in modern medicine. Promising approaches to cope with widespread diseases like cancer and diabetes are gene therapy, plasmid DNA, virus-like particles, and exosomes. Due to progress that has been made in upstream processing (USP), difficulties arise in downstream processing and demand for innovative solutions. This work focuses on the integration of precipitation using a quality by design (QbD) approach for process development. Selective precipitation is achieved with PEG 4000 resulting in an HCP depletion of ≥80% respectively to IgG. Dissolution was executed with a sodium phosphate buffer (pH = 5/50 mM) reaching an IgG recovery of ≥95%. However, the central challenge in process development is still an optimal process design, which is transferable for a broad molecular variety of new products. This is where rigorous modeling becomes vital in order to generate digital twins to support early-stage process development and reduce the experimental overhead. Therefore, a model development and validation concept for construction of a process model for precipitation is also presented.
Highlights
Due to the rising demand of biopharmaceuticals and the progress that has been made in upstream processing (USP) over the past decades, downstream processing (DSP) has to overcome bottlenecks in purification to handle constantly increasing titers and process volumes [1,2]
Temperature has an effect on precipitation, due to a decrease of solubility of proteins while temperature reduction occurs
In the context of process development using a quality by design (QbD) approach and the evaluation of all influencing factors in relation to purity and recovery, there is a shift in apprehension
Summary
Due to the rising demand of biopharmaceuticals and the progress that has been made in upstream processing (USP) over the past decades, downstream processing (DSP) has to overcome bottlenecks in purification to handle constantly increasing titers and process volumes [1,2]. Protein A resins are not tolerant towards cleaning agents, on account of fragility of the immobilized Protein A. All of this results in a limited lifecycle and a demand on finding new solutions for unit operations or the reactivation of already existing ones [4,5,6,7,8]. Precipitation might have all it takes to overcome the disadvantages mentioned above [9] It is a relatively simple unit, which can be used for volume and impurity reduction. It is easy scalable and various working groups have already proven the feasibility of continuous operation [10,11,12,13]
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