Why Abzena?
Our focused approach.
The discussion explores how the use of small-scale, analogous early material production from stable CHO pools can be employed to unearth potential issues in biological products allowing for better decisions during DC selection and informing process design and control strategies.
The FDA recently approved the 100th monoclonal antibody (mAb) product for
commercial use. In the 35 years since the first approval, mAb therapies have
made a significant impact on patient life expectancy and quality of life alongside
mAb fragments, bi-specifics, Fc fusion molecules and other biologics
Established platforms for expression, process development, manufacture and
analytical methods for characterization and lot release have significantly reduced
development timelines for mAb based molecules. Other biological molecules
have also benefitted from the standardization of workflows, provided they are
“well behaved” and, to at least some extent, conform to the standard.
However, many of the novel formats face specific challenges during
development and CMC. Each product is essentially unique with considerable
variability of primary amino acid sequences and post translational modifications
(PTMs) contributing to significant differences in physiochemical and biological
properties. Success during CMC development is dependent on what factors are
considered during lead drug candidate (DC) selection.
Ideally the developability of molecules and closeness of fit to a platform will be
factors in the selection process that help to de-risk development efforts and keep
timelines short. However, down-selection to a single lead may be made very
early in the process, with minimal information on characteristics such as PTM,
stability, and fit to platform. Often early work is performed in lab-scale
expression systems different to those used in manufacturing. This can result in
mis-matched characteristics when more scalable production systems are
introduced, risking complications during CMC development or worse, impacting
safety and efficacy.
In this talk we discuss strategies for maximizing the overlap of activities
during process development and manufacture, keeping DC selection options
open for longer to generate better data with the aim of minimizing risk. The
discussion will include how the use of small scale, analogous early material
production from stable CHO pools can be employed to unearth potential issues in
biological products.
Early awareness of such issues allows for better decision
during DC selection and helps inform process design and control strategies.
The early availability of greater quantities of analogous material also allows
overlap of important development activities to support a faster critical
development path, and reduced timelines to manufacture of drug substance and
product for clinical trials.