ABSTRACT
Therapeutic proteins, including
monoclonal antibodies, are typically manufactured using
clonally-derived, stable host cell lines, since consistent and
predictable cell culture performance is highly desirable. However,
selecting and preparing banks of stable clones takes considerable time,
which inevitably extends overall development timelines for new
therapeutics by delaying the start of subsequent activities, such as the
scale-up of manufacturing processes. In the context of the COVID-19
pandemic, with its intense pressure for accelerated development
strategies, we used a novel
transposon-based Leap-In
Transposase® system to rapidly generate high-titer
stable pools and then used them directly for large scale-manufacturing
of an anti-SARS-CoV2 monoclonal antibody under cGMP. We performed the
safety testing of our non-clonal cell bank, then used it to produce
material at a 200L-scale for pre-clinical safety studies and formulation
development work, and thereafter at 2000L scale for supply of material
for a Phase 1 clinical trial. Testing demonstrated the comparability of
critical product qualities between the two scales and, more importantly,
that our final clinical trial product
met all pre-set product quality
specifications. The above expediated approach provided clinically-ready
material within 4.5 months, in comparison to 12-14 months for production
of clinical trial material via the conventional approach.