Proceedings of the 2017 Viral Clearance Symposium—

Introduction

Viral clearance and inactivation by the bulk protein purification process are critical components of the overall strategy to ensure the safety of therapeutic proteins derived from mammalian cell culture. A mechanistic understanding of the factors that influence viral clearance and inactivation is essential for ensuring that adventitious agent control is conserved as downstream unit operations are refined and implemented.

A recognition of the critical nature of viral clearance and opportunities for improvement led to the initiation of the Viral Clearance Symposia Series in 2009. Since then, five meetings were held and brought together industry and regulatory agency representatives for a critical evaluation of viral clearance practices. Proceedings of the previous four meetings have been published (1⇓⇓–4).

The 5th Viral Clearance Symposium in Penzberg, Germany, opened with regulatory perspectives presented by officials from Health Canada (Omar Tounekti), the US Food and Drug Administration (FDA; Sarah Johnson), and Paul-Ehrlich-Institut (PEI; Johannes Bluemel).

The following sessions addressed upstream risk mitigation, downstream unit operations including resin lifetime, submission strategies, as well as facility risk mitigation and continuous processing.

The upstream risk mitigation session focused on cell bank and bulk harvest testing as well as virus barrier filtration of media components.

Downstream unit operations were addressed in individual sessions on (i) unit operations dedicated to viral clearance (i.e., virus inactivation and virus-retentive filtration) and (ii) chromatography including recently established unit operations, such as multimodal and membrane chromatography.

During the resin lifetime session, an extended data set on virus clearance capacity of used chromatography resin was the starting point to continue the exchange across the community regarding challenges and best practices in validation of used chromatography resin, as well as potential surrogates for these time- and material-consuming studies.

The session on submission strategies combined recent approaches to support projects ranging from standard antibodies with standard timelines to novel molecule formats and accelerated scenarios across clinical and commercial stages. Process understanding is a key component in these approaches to reduce the effort for product-specific viral clearance studies, thus enabling early access to new medicines while ensuring patient safety at the same time.

In the facility risk mitigation session, updates on sanitization and disinfection methods were presented. In addition, the Consortium on Adventitious Agent Contamination in Biomanufacturing (CAACB) proposals for a quantitative risk assessment of potential virus carryover and a definition of “functionally closed” were discussed to support the alignment of industry and regulatory perspective.

Reflecting the large number of contributions, the last session was dedicated to viral clearance considerations for continuous processing. Concepts were presented to study virus inactivation, weak ion exchange chromatography, and virus-retentive filtration, each operated in continuous mode. The discussion concluded that unit operations that are well understood and show robust viral clearance capacity in classical batch mode will likely remain effective in continuous mode. At the same time, it is challenging to demonstrate the viral clearance capacity. Health authority representatives recommend the development of strategies for continuous unit operations and viral clearance studies on the industry end and collection of health authority feedback prior to filing submission.

In this issue of the PDA Journal, the summarized findings and next steps from the 2017 Viral Clearance Symposium are presented.