Why cell and gene contract manufacturers must embrace digitization

The cell and gene industry is growing at a staggering 30% CAGR and is estimated to reach $14B by 2025. A number of cell, gene and stem cell therapy sponsors currently have novel drug substances and products and many rely on Contract Development Manufacturing Organizations (CDMO) to produce them with adherence to stringent regulatory cGMP conditions. 

Cell and gene manufacturing for both autologous (one to one) and allogenic (one to many) treatments face difficult issues such as: a complex supply chain, variability on patient and cellular level, cell expansion count and a tight scheduling of lot disposition process. This complexity affects quality, compliance and accountability in the entire vein-to-vein process for critically ill patients.

Electronic batch recording becomes vital

Cell and gene companies are emerging from years of laboratory scale development through preclinical tests and pivotal clinical trials to ultimately reaching FDA approval and commercialization. Digital solutions such as a robust Electronic Batch Recording system (EBR) are vital. Given that the raw material for these processes are actual patient cells extracted in a clinic, a failed batch is devastating and could mean loss of a patient’s life. A failed batch due to poor paper record handling must be avoided at all costs.

A crucial component in reducing Cost of Goods Sold (COGS) in developing cell, gene and stem cell therapies is through increased efficiency of the manufacturing process. Automation provides a suitable option to address this challenge. Those manufacturers who have become early adopters of digitization, automation and continuous improvement are reaping huge benefits. They have minimized the use of paper, automatized the calculations, sped the design of manufacturing batch records, reduced cGMP deviations and more quickly released manufacturing lots based on review by exception, which align with right first time initiatives.

Automated processes are a good starting point

Cell therapy manufacturers rate manufacturing process stability and scalability as their top two considerations throughout clinical trials. They equally rank process variability, scale-up ease and reduced cycle time as motivation for automating both their manufacturing processes and supply chain. In this vein, a CDMO that is already a fully automated facility with EBR capability can help achieve these goals.

The detrimental impact of Sars-Cov-2 has challenged cell therapy sponsors with a stoppage of clinical trials and supply chain hurdles. In the manufacturing domain, both in-house and contract manufacturers have implemented strict guidelines to ensure employee safety. Manufacturers, who had embraced automation, quickly rebounded to get systems back online to meet delivery deadlines. In addition, they had a reduced risk of contamination as fewer hands touch paper or the final product, thereby drastically reducing the four-eyes-principle steps.

Cell therapy sponsors select CDMOs

Cell therapy sponsors have two options for how to manufacture: build an internal manufacturing capability or employ a CDMO/CMO. Investing in their own manufacturing facility would develop internal expertise, optimize processes, control manufacturing capacity, and potentially save money in the long run, if the drug commercializes. 

However, utilizing CDMOs/CMOs can help provide flexibility in capacity planning, reduce commitments to evolving technology platforms, and reduce initial investments. CDMOs/CMOs have existing cGMP facilities designed to comply with regulatory authorities. More importantly, they have a skilled workforce who can execute the process, manufacture the product and deliver it to hospitals and clinics. Some cell therapy sponsors employ a regional manufacturing model and use CDMOs/CMOs to manufacture their products in various geographical regions. Concurrently, smaller scale sponsors are utilizing co-working or collaborative spaces such as The Center for Breakthrough Innovation (King of Prussia, PA, USA) and the Cell and Gene Catapult (Stevenage, UK) for meeting their development and manufacturing needs.

Paper-based processes are inefficient and error-prone

Sponsors’ demands are growing and complex, which have many CDMOs/CMOs pushing to become leaner and digital. To be agile enough to meet sponsor requirements of patient delivery deadlines and frequent schedule changes, an Electronic Batch Record solution should be a minimum prerequisite. Paper-based manufacturing systems are too slow and cumbersome in the cell therapy world. They lack the ease for tracking of data and continuous improvement. 

For instance, given the volume of different manufacturing processes in the cell, gene and stem cell space, contract manufacturers must continuously manage customers’ work instructions and standard operating procedures (SOPs) which change regularly. Operator training, manufacturing recipes and product specifications also vary and need to be updated frequently. Accurately and safely managing all of these changing documents via paper-based records is incredibly challenging and inefficient, with significant risk for harmful errors, delays and a lack of transparency.

In conclusion, CDMOs/CMOs must embrace digitization. A cloud-hosted digital electronic batch records solution coupled with a flexible scheduling solution and integration to other supply chain and IT systems is the “need of the hour” today. With an EBR, cell therapy sponsors can monitor the CDMO/CMO process right from their desk. The most important compliance parameters of chain of identity, chain of custody, chain of condition and limited time horizon for critically ill patients can be monitored right at one’s fingertips. Any events, delays or changes can be addressed immediately.

With some upfront initial effort, CDMOs/CMOs will save a lot of effort downstream when data is integrated across the enterprise and quality and production teams are relieved of an enormous documentation burden. Companies who have adopted EBR have reported an 83% decrease in data input errors and more than 87% decrease in review time after production completes by embracing the review by exception paradigm.