Advancing Cell and Gene Therapies Through Closed Aseptic Processes

Time Is of The Essence

The U.S. Food and Drug Administration has approved 25 cell and gene therapies (C&GTs) since 2017 but predicts that by 2025 it will license as many 20 new treatments per year. That prediction may be an under-estimate, as C&GTs become “industrialized” through the application of allogeneic cells and platform processes, and through the expansion of treatable disease states. With more than 800 cell or gene therapies at the IND development stage pipelines are now at full capacity but sponsors still rely on outdated production methodology borrowed from therapeutic protein processes.

No-one anticipated the speed at which C&GTs would capture our collective interest. To support this rapid growth, best-in-class CDMOs are investing in development and manufacturing technologies to meet the needs of rapidly-emerging development programs.

The industrialization of cell and gene therapies will require deep appreciation of the biological roles of key components, including advanced viral vector production technologies and adoption of allogeneic cell therapies to achieve scalability.

Viral Vectors

FUJIFILM Diosynth Biotechnologies (FDB) stays ahead of the manufacturing technology curve by collaborating with innovators on novel unit operations and by providing clients with flexible, modular manufacturing located near clinical development sites.

Viral vector production, which supports all gene therapies (including many development-stage vaccines) and most cell-based treatments, was until recently a “black box” capability based on a limited number of production platforms with poor scalability.

FDB employs a flexible, streamlined, scalable, highly-productive “triple-transfection” approach to viral vector product manufacturing that saves both time and cost, with appropriate concern for the scarcity and value of cell-based components (e.g., harvested cells). Typical projects take weeks from sequence to preclinical-grade material and several months for cGMP production.

Advanced Aseptic Processing

Lessons learned from therapeutic protein manufacturing, particularly for cell culture-based processes (which routinely achieve zero in-process bioburden), have enabled FDB to apply single-use strategies to most C&GT processes and production steps. Single-use technology avoids process bottlenecks associated with clean-in-place sterilization, while eliminating cross-contamination of infectious or patient-related materials.

But perhaps the most significant success for our company has been early adoption of closed, aseptic processing for cell-based processes at our global C&GT facilities located in College Station, Texas; Darlington, United Kingdom; and Thousand Oaks, California.

Recognizing the unique sterility requirements of cell-based therapies and their susceptibility to degradation, the FDA encourages companies to utilize closed manufacturing for these products. Unlike small molecule drugs, biologics and especially C&GTs cannot withstand terminal heat- or chemical-based sterilization.

Closed, aseptic processing assures sterility throughout the process but involves additional investments in process development, engineering, automation and equipment standards. In return, benefits include greater process scalability, robustness, flexibility and consistency with fewer batch failures. Long term these advantages lead to lower capital and operational costs, and ultimately, greatly expanded access to critical therapies for patients.

As a global CDMO, FUJIFILM Diosynth Biotechnologies currently operates at seven locations in the US, UK and Denmark, including a well-established, 90,000-square-foot cell therapy facility in Thousand Oaks, California, acquired in 2022. Through these facilities we engage with clients and technology innovators to bring the promise of C&GTs to patients worldwide.

Contact us to learn more about our cell and gene therapy CDMO services