Andrew Bulpin, Head of Process Solutions Strategic, Marketing & Innovation, MilliporeSigma
A: Biosimilar market growth is heightening the pressure to improve cost and quality. To lower manufacturing costs, biosimilar developers are looking to new technologies with higher productivity and reduced costs that can be achieved through process intensification. The intensification of individual unit operations can deliver significant cost savings in manufacturing, with reductions in CapEx, labor, utilities, manufacturing space and process time. Additionally, novel technologies may offer improvements in product quality, such as new chromatography media with higher selectivity for charge variant removal, enabling target-product profile matching.
Michael Murray, Downstream Process Development, FUJIFILM Diosynth Biotechnologies U.S.A., Inc.
A: For processes operating on a platform or well-defined processes, fully automated chromatography systems are increasing throughput and reducing effort in downstream process development. These systems integrate multiple chromatography steps and run continuously over one to two days to generate grams of purified material using preprogrammed recipes. With a platform approach, these systems can be coupled with automated buffer preparation systems to even further reduce time and effort.
Timothy Hill, Director, Upstream Process Development, FUJIFILM Diosynth Biotechnologies U.S.A., Inc.
A: Lab analytical instrumentation technology is advancing rapidly to meet process development demands for protein characterization in real time. CMO customer expectations for biosimilars are that they will have shorter process development and clinical trial timelines, especially if the biosimilar is a monoclonal antibody. To address this expectation, use of high-throughput process equipment, including mini-bioreactors (below 1L working volume) and scaled-down integrated chromatography steps, enables rapid process optimization and earlier advancement to GMP manufacturing. Essential for rapid process optimization is having a strong analytical capability. Key process and protein attributes must be monitored throughout development runs to ensure the final product quality matches originator standards. Lab analytical instrumentation technology is advancing rapidly to meet process development demands for protein characterization in real time. This analytical feedback loop provides data for process development scientists to modify or lock-in process steps and controls to achieve desired PQ using only a few experiments. This approach also provides good confidence in process performance with scale-up and eliminates the need for engineering batches, in many cases.
Abel Hastings, Director, Process Sciences, FUJIFILM Diosynth Biotechnologies U.S.A., Inc.
A: Effective biosimilar development focuses heavily on shortened timelines and efficiency. In standard projects the selection and establishment of specifications and quality attributes can be effort consuming, can require late-breaking large-scale data and can be of great regulatory consequence. Because critical quality attributes are known well in advance, we advocate early mapping of the critical quality attributes (CQAs) to unit operations and to specific parameters in order to expedite and de-risk early large-scale runs. In addition, developing clarity regarding the process control strategy can jump-start the PPQ activities to ensure paperwork is never the rate-limiting factor. We have developed a suite of tools aimed at rapidly mapping the process control strategy and evaluating process noise and capability. In addition, we developed template process validation protocols and documents to greatly reduce cycle time and improve reliability. The increasing market of biosimilars, and especially monoclonal antibodies, has allowed us to leverage lessons learned into systematic approaches, which ultimately increases value for our clients.