Current State of Implementation of in-silico Tools in the
Biopharmaceutical Industry - Proceedings of the 5 th Modeling Workshop
Abstract
The fifth modeling workshop (5MW) was held in June 2023 in Favrholm,
Denmark and sponsored by Recovery of Biological Products Conference
Series. The goal of the workshop was to assemble modeling practitioners
to review and discuss the current state, progress since the last fourth
mini modeling workshop (4MMW), gaps and opportunities for development,
deployment and maintenance of models in bioprocess applications. Areas
of focus were four categories: biophysics and molecular modeling,
mechanistic modeling, computational fluid dynamics (CFD) and plant
modeling. Highlights of the workshop included significant advancements
in biophysical/molecular modeling to novel protein constructs,
mechanistic models for filtration and initial forays into modeling of
multi-phase systems using CFD for a bioreactor and mapped strategically
to cell line selection/facility fit. A significant impediment to more
fully quantitative and calibrated models for biophysics is the lack of
large, anonymized data sets. A potential solution would be the use of
specific descriptors (ex. patch sizes and types mapped to a homology
model) in a database that would allow for detailed analyses without
sharing proprietary information. Another gap identified was the lack of
a consistent framework for use of models that are included or support a
regulatory filing beyond the high-level guidance in ICHQ8-Q11. One
perspective is that modeling can be viewed as a component or precursor
of machine learning (ML) and Artificial Intelligence (AI). Recent
requests for feedback from health authorities on use of ML and AI may
provide an opportunity for more clarity regarding expectations for use
and deployment. Two specific additional outcomes of the workshop were
alignment on a key definition for “mechanistic modeling” and the
acknowledgement/realization that modeling can have a significant impact
on improving sustainability of bioprocessing through elimination of
experiments both during development and manufacturing. Feedback from the
participants was that there was progression in all of the fields of
modeling within scope of the conference. Some areas (e.g. biophysics and
molecular modeling) have opportunities for significant research
investment to realize full impact. However, the need for ongoing
research and development for all model types does not preclude the
application to support process development, manufacturing and use in
regulatory filings. Analogous to ML and AI, given the current state of
the four modeling types, a prospective investment in educating
inter-disciplinary subject matter experts (SMEs) (e.g. data science,
chromatography) is essential to advancing and maintaining the modeling
community.