The promise of cell and gene therapy continues to expand, with the number of clinical trials rising by 14% in 2020 alone.1,2 Fast-track designations are helping candidates progress towards commercial approvals at an accelerated pace. Drug developers face mounting challenges linked to rapid increases in demand for the complex modalities while also accounting for the need to drive process efficiencies at scale. Working with the right integrated partner can help ease increasingly common problems with scale, access to high-demand raw material, viral vector production and quality requirements.
High Demand for Plasmid DNA
It may also be difficult for companies to obtain adequate supplies of critical raw materials, such as the plasmid DNA needed to produce viral vectors. This is especially true on a commercial scale, in part because established transient infection approaches require large amounts of plasmids. For adeno-associated viral vectors, three distinct plasmids are needed for vector production. Also contributing to plasmid demand is that the material is used for therapies that involve genetic modification of cells, such as CAR-T and in non-viral vector delivery of gene therapies. Despite the ongoing high demand for plasmids, there remains a limited number of vendors who can supply in the quantity and quality needed for later-stage studies and commercial supply.
Viral Vector Production Challenges
Many advanced therapies originate at academic labs. Their manufacturing methods typically work well for small volumes of viral vectors but scale poorly, creating a bottleneck as candidates advance into late-phase development and onto the market. For therapies developed in adherent cell culture, scaling up in a standard bioreactor used for other biologics is not possible. Some suppliers developed large adherent-based bioreactors to address the challenge of scaling. Others responded by developing suspension culture-based cell lines suitable for use in more standard bioreactors. However, both methods still rely on transient infection, meaning access to plasmids remains a constraint on manufacturing even as the scalability of viral vector production improves.
Challenges Tied to Scaling up Cell Therapies
An individualized approach for cell therapy manufacturing needs to be considered to incorporate the numerous variables involved with cell source. For example, allogeneic cells (from a donor) require different manufacturing needs than autologous (the patient’s own) cells. Additional varieties of cell types and patient/donor-specific variances need specialized care as well. Finding the right balance between standardized scale up processes while maintaining the complexity of these materials requires the right blend of scientific and manufacturing expertise.
How Integration Accelerates R&D
The pressures on developers of cell and gene therapies have intensified the need for partners with the integrated capabilities required to support each step from plasmid DNA to commercial cell therapy manufacturing.
Working with such an integrated partner across the full value chain yields multiple benefits. Timelines are shortened as a result of greater transparency across the value chain, process development and manufacturing can progress at an accelerated pace and communication across the teams supporting the value chain is more effective.
Drug developers realize benefits by partnering early with a company capable of supporting them for the long term. Picking a manufacturing partner that has an integrated workflow early on allows for a streamlined, less labor-intensive partnership as a therapeutic candidate moves into the late phase. Similarly, partners with experience across modalities and with late-phase programs are critical to jump starting early programs.
Integrated partners provide an accelerated path from gene modification to cell therapy manufacturing, as well as the benefits that come from unified teams and infrastructure. Integration provides shared quality systems, faster internal technical transfer, communication alignment and process crossover between teams, resulting in the reduction of bottlenecks and a better experience for cell and gene therapy developers.
Working with an advanced therapy leader
Catalent has the integrated capabilities and extensive experience needed to accelerate cell and gene therapy programs. With strategic customer partnerships in place within the cell and gene therapy industry, Catalent has capabilities across plasmid manufacturing, viral vector production, cell therapy manufacturing and clinical supply solutions to support a full scale program for our customers.
With more than 70 cell and gene therapy programs across all stages of development, Catalent can help companies rise to challenges posed by complex modalities by manufacturing at scale and making life-changing therapies more broadly accessible to patients.
References
1. Advancing gene, cell, & tissue-based therapies. https://alliancerm.org/sector-report/2019-annual-report/ (2020).
2. 2020: Growth & resilience in regenerative medicine. https://alliancerm.org/sector-report/2020-annual-report/ (2021).