Making the Decision to Engage a CDMO
There is no one-size-fits-all answer for cell and gene therapy developers seeking to determine why, and more importantly when, to outsource manufacturing or process development to a CDMO. Each developer will have unique needs depending largely on the stage of their technology. For instance, a pre-clinical company will have vastly different needs from a company in Phase III clinical trials. For every developer, however, the substantial risks associated with changing a process later in development should drive early engagement. In general, a good time to start talking to a CDMO is prior to moving from the pre-clinical stage into manufacturing for clinical trials.
Common Product and Process Development Services Provided by CDMOs
Transferring processes from research-grade to industrial manufacture:
Processes designed in an academic lab will primarily use research-grade materials. To ensure products are suitable for clinical use, it is recommended that reagents, facilities and documentation practices be compliant with current Good Manufacturing Practices (cGMP). Through relationships with government bodies and commercial entities, CDMOs have access to cGMP grade materials (e.g. cell lines, media, cytokines, and other raw materials) that can be used in the development process. CDMOs can either acquire cGMP-grade materials, facilitate conversations with key vendors, or link companies with the appropriate licensors.
Guidance on regulatory strategy:
Before investing significant resources into process development, it is critical to have insight into how to meet relevant regulatory requirements. CDMOs provide regulatory advice through in-house regulatory experts and can help clients make connections with the right professionals. CDMOs also facilitate preparation of documents and arrange pre-submission meetings, such as pre-CTA or pre-IND meetings, with regulatory bodies such as Health Canada and the FDA. Engaging in regulatory conversations early on will inform critical aspects of experimental design including cell sourcing, data integrity, pre-clinical animal studies, analytics requirements, and safety testing and avoid costly changes down the road.
Companies who wish to perform their own process development require a baseline amount of equipment (e.g. bioreactors, biosafety cabinets, incubators). Further, these companies will need to engage people with the appropriate expertise. Taken together, this is a potential resource burden that may be prohibitive to some companies. When budgets do not allow for these types of expenditures, a CDMO can be the perfect partner. Outsourcing process development to a CDMO allows a company to maintain a very small footprint or even operate virtually.
Development and optimization can happen at every step of a process and may include: bioreactor testing, reagent testing, cryoprotectant testing, process scale-up or intensification, increasing the efficiency of a process to obtain higher yields, custom media development, analytics development, and process closure, among others.
An experienced CDMO will ask the right questions to determine a customer’s key needs and tailor their efforts toward delivering a cost-effective and customized process that is suitable for industrial manufacture.
Benefits of Working with a CDMO
CDMOs have the specialized expertise and infrastructure to create custom manufacturing solutions for their customers. In partnering with a CDMO, companies can benefit by not having to invest heavily in building these capabilities in-house. Furthermore, CDMOs have the experience to determine the optimal pathway to industrial manufacture. While a developer may be an expert in their specific technology, they may not have insight into all aspects that contribute to the successful manufacture of a cell and gene therapy product. Working with a CDMO to optimize critical aspects of your process at an early stage ultimately leads to cost savings, and safer products for patients.