Rapidly accelerated development of neutralizing COVID-19 antibodies by reducing cell line and CMC development timelines.

Since the Coronavirus Disease 2019 (COVID-19) outbreak, unconventional cell line development (CLD) strategies have been taken to enable development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-neutralizing antibodies at expedited speed. We previously reported a novel chemistry, manufacturing, and control (CMC) workflow and demonstrated a much-shortened timeline of 3-6 months from DNA to investigational new drug (IND) application. Hereafter, we have incorporated this CMC strategy for many SARS-CoV-2-neutralizing antibody programs at WuXi Biologics. In this paper, we summarize the accelerated development of a total of seven antibody programs, some of which have received emergency use authorization  approval in less than 2 years. Stable pools generated under good manufacturing practice (GMP) conditions consistently exhibited similar productivity and product quality at different scales and batches, enabling rapid initiation of phase I clinical trials. Clones with comparable product quality as parental pools were subsequently screened and selected for late-stage development and manufacturing. Moreover, a preliminary stability study plan was devised to greatly reduce the time required for final clone determination and next-generation sequencing-based viral testing was implemented to support rapid conditional release of the master cell bank for GMP production. The successful execution of these COVID-19 programs relies on our robust, fit for purpose, and continuously improving CLD platform. The speed achieved for pandemic-related biologics development may innovate typical biologics development timelines and become a new standard in the industry.

Reshaping cell line development and CMC strategy for fast responses to pandemic outbreak.

The global pandemic outbreak COVID-19 (SARS-COV-2), has prompted many pharmaceutical companies to develop vaccines and therapeutic biologics for its prevention and treatment. Most of the therapeutic biologics are common human IgG antibodies, which were identified by next-generation sequencing (NGS) with the B cells from the convalescent patients. To fight against pandemic outbreaks like COVID-19, biologics development strategies need to be optimized to speed up the timeline. Since the advent of therapeutic biologics, strategies of transfection and cell line selection have been continuously improved for greater productivity and efficiency. NGS has also been implemented for accelerated cell bank testing. These recent advances enable us to rethink and reshape the chemistry, manufacturing, and controls (CMC) strategy in order to start supplying Good Manufacturing Practices (GMP) materials for clinical trials as soon as possible. We elucidated an accelerated CMC workflow for biologics, including using GMP-compliant pool materials for phase I clinical trials, selecting the final clone with product quality similar to that of phase I materials for late-stage development and commercial production.