For the manufacturing of recombinant protein therapeutics produced from mammalian cell culture, demonstrating the capacity of the purification process to effectively clear infectious viruses is a regulatory requirement. At least two process steps, using different mechanisms of virus removal and/or inactivation, should be validated in support of the regulatory approval process. For example, exposure of the product stream to low pH, detergents or solvent/detergent combinations is commonly incorporated in protein purification processes for the inactivation of lipid-enveloped viruses. However, some proteins have limited stability at low pH or in the presence of the detergents, and alternative techniques for achieving the inactivation of enveloped viruses would be beneficial. We present here an alternative and novel approach for the rapid inactivation of enveloped viruses using pH-neutral buffer solutions containing arginine. The implementation of this approach in a monoclonal antibody or Fc-fusion protein purification process is described and illustrated with several different therapeutic proteins. The use of the neutral pH arginine solution was able to effectively inactivate two enveloped model viruses, with no measurable effect on the product quality of the investigated proteins. Thus, the use of pH-neutral arginine containing buffer solutions provides an alternative means of virus inactivation where other forms of virus inactivation, such as low pH and/or solvent/detergent treatments are not possible or undesirable due to protein stability limitations.

Acceleration of development timelines to support material production for early‐phase clinical trials has been a continuous goal within the life sciences industry, driven largely by the need to advance an ever increasing number of novel therapeutics into the clinic. This has challenged cell culture and purification development groups to become more efficient, realized in part by leveraging a platform process in the case of mAbs, adopting high‐throughput (HT) technologies, and scaling‐up directly from the HT formats to pilot and clinical scales for toxicology and clinical production. The work presented herein focuses on a case study where a mammalian cell culture process producing mAb A was developed almost exclusively utilizing HT technology. The study describes how HT systems such as microbioreactors for cell culture development and minicolumns driven by robotics for purification development were integrated to rapidly develop a robust production process that was then directly scaled‐up nearly 17 000‐fold for cell culture and 5200‐fold for purification steps to generate material for investigational new drug‐enabling toxicology studies at the 250 L bioreactor scale, followed by another rapid scale‐up to 1000 L for clinical production. Performance comparability across scales demonstrates the effectiveness of HT process development for accelerating the time to clinic.

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