In particular, Tam spoke of the exciting developments in AI and ML for improved clinical observations and management, which she deemed “a rapidly growing field”. The opening overview also touched on the prospect of real-time release testing to optimise the evaluation of and ensure the quality of final biotherapeutics drug products.
After Amy’s introduction concluded, the debate began. Rachel Chen opened the floor to discuss the current high interest and industry trend of accelerating timelines during analytical development. Chen spoke about the various technologies available to streamline analytical workflow, such as digitising platforms and implementing post-translational modification procedures. She stated the importance of “early engagement via conducting research analytics during or even before RTD transition to ensure methodical transfer and significantly shorten the development timeline”. An interesting point raised was the cost and financial burden of accelerating the analytical development of biotherapeutics. A vital concern includes the possibility of wear-out behaviour whereby certain acceleration measures result in different elements of the drug candidate possibly ageing or becoming fatigued. This consequence inevitably undermines the efficiency of acceleration and leads to increased costs.
The panel continued with debate over in vitro and in vivo correlation and the extent to which the latter requires monitoring. Whilst some agreed that the importance and value of such correlations had been proven with specific Fc fusion proteins, where their circulation level is critical for clearance and PharmaKinetics, others disagreed. Chen pointed out how currently, for other modifications such as thymine oxidation and deamidation, there is little understanding about the value of in vitro and in vivo correlation. Fellow panellist Galahad Deperalta identified this as a particular interest and commented on how several members of his team at Genentech are working on in-vivo CQA mapping as a strategy to declassify the relationship. Deperalta described the need for CQA mapping as trying “to make the case that it isn’t critical due to the certainty of how post-translational modifications are affected by the human body”. He continued by arguing that this prior knowledge undermines the necessity of monitoring the in vitro and in vivo correlation. Deperalta also pointed out that “the question about whether the regulatory and health authorities accept this case is, however, another issue altogether”.
In response to the various hurdles posed by biotherapeutics optimisation, the discussion turned to future outlooks on automation technologies. For audience member Thomas Halder, R&D Manager Biopharma at Blau Farmaceutica, intuitive technologies are the way forward for ensuring both the efficiency and efficacy of biotherapeutic manufacturing. For Halder, “doing fewer things manually is a good idea if you want to end up with a working multi-attribute method solution”. He continued, by saying “to increase automation is to reduce the human error, and in doing so decrease the level of difference, you’re detecting”. Current trends include AI-based strategies to process large databases and screening programs to usher in quicker, cheaper, and more reliable drug discovery and development methods. Amy Tam attested to the promise of automated and computational technology, deeming them a “powerful vehicle in improving method development and validation of biotherapeutics”.
The discussion group concluded with some final thoughts on the future outlook of analytical development methods for biotherapeutics. With ongoing research and development and numerous exciting pipelines emerging in the field, the future looks bright for the biotherapeutics industry. At Oxford Global, we couldn’t have been more pleased with the turnout for our October biologics discussion group. The conversation was engaging, the debate stimulating, and the industry insights invaluable. We will continue our discussion group series this November to address Bispecific & Multi Specific Antibodies and Therapeutics. Learn more about the Oxford Global discussion group series at our Biologics Portal.