Rate is notably emphasized from the quick purification development timelines, indicated from the hatched package, conducted in a matter of days, and the overlap of the timelines for the upstream toxicology batch, which also served while the final process verification, and the initial clinical production batch that followed by approximately one week. This rapid development led to consistent product quality (data not shown) while optimizing the yields that transferred across scales ( Figure 4). Open in a separate window Figure 4 Purification yields by unit operation. production at Genentech inside a first-time process transfer under compressed timelines between the companies. Graphical Abstract Open in a separate windows Current Opinion in Biotechnology 2022, 76:102715 This review comes from a themed issue on Pharmaceutical Biotechnology Edited by Brigatinib (AP26113) Sarah Harcum and Robert Kiss For total overview of the section, please refer to the article collection, Pharmaceutical Biotechnology Available on-line 15th March 2022 https://doi.org/10.1016/j.copbio.2022.102715 0958-1669/? 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Intro Neutralizing antibodies have been used successfully in the treatment of infectious diseases [1]. The COVID-19 pandemic offers specifically demonstrated the necessity to both accelerate the antibody development process (rate) and increase the demand for antibody treatments (need). Regenerons platform approach to the expedited development of neutralizing antibodies to treat infectious diseases, previously demonstrated during the Western Africa Ebola outbreak [2] and now incorporated into the first-time collaboration Brigatinib (AP26113) with Genentech to increase production capacity, has resolved speed and need requirements. The result has been the REGEN-COV? cocktail consisting of the casirivimab and imdevimab monoclonal antibodies currently with emergency use authorization (EUA) or commercial approval in various countries. The Regeneron platform using VelociSuite? systems allowed the recognition of candidate antibodies in an accelerated fashion. As a historic example [2], these systems were used to generate the now authorized treatment for Ebola (Inmazeb?, a cocktail of three monoclonal antibodies). In the case of the COVID-19 pandemic, monoclonal antibody candidates against the spike protein of severe acute respiratory syndrome coronavirus 2 also used a cocktail approach [3] and resulted in obtaining an EUA for casirivimab and imdevimab in less than 10 weeks ( Number 1). More specifically, candidate antibodies were derived both from your VelocImmune? platform through immunization of VelocImmune? mice and by cloning from cells of previously infected human being individuals [4]. The VelociMab? technology platform has an considerable history and brings these candidates into a platform allowing accelerated screening and production of these antibodies with high-level Chinese hamster ovary manifestation systems. Open in a separate window Number 1 Milestone event timelines. Timeline of important events in the generation of casirivimab and imdevimab from the time of initiation of monoclonal antibody generation using the VelocImmune? platform or cloning of antibody genes from previously infected individuals through EUA. Figures in the Brigatinib (AP26113) circles represent the antibody candidates available at the indicated stage in the process. Four candidates were taken into process development and Good Manufacturing Methods (GMP) Manufacturing. Casirivimab and imdevimab represent the final two antibodies that came into clinical tests and were produced at the largest Mouse monoclonal to KSHV ORF45 scales available at Regeneron and Genentech. The reddish package emphasizes development and developing activities that are further detailed in Number 3. Process development and technology transfer, the focus of the current review, emphasized accelerated timelines (rate) and were performed on four candidate monoclonal antibodies, which included casirivimab and imdevimab that went from lead selection to initiation of medical tests in 56 days. To accommodate potential demand (need), the platform process was simultaneously Brigatinib (AP26113) transferred to both the standard intermediate-scale single-use bioreactor platform (2000?L) and, for casirivimab and imdevimab, the larger stainless-steel manufacturing level (10?000?L) available at Regeneron. These transfers were the 1st instance in which the current version of the production platform was used at 10?000?L level. After successful process performance qualification Brigatinib (AP26113) (PPQ) of the batches at the two scales at Regeneron, the process was rapidly transferred to an even larger stainless-steel manufacturing level (25?000?L) at Genentechs Vacaville manufacturing facility as part of the Genentech collaboration. The process transfer for these antibodies was the 1st between the two companies. This transfer required building process transfer teams and understanding different developing systems while operating.