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.
Rosuvastatin cocrystals: an attempt to modulate physicochemical parameters