Why cell & gene contract manufacturers must embrace digitization

The cell & gene industry is growing at a staggering 30% CAGR and is estimated to reach US$ 14bn 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 (CDMOs/CMOs) to produce them with adherence to the stringent regulatory cGMP conditions. 

Cell & 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 the batch disposition process. This complexity affects quality, compliance and accountability in the entire vein-to-vein process for the critically ill patients.

Electronic batch recording becomes vital

Cell & gene companies are emerging from years of laboratory scale development through preclinical tests and pivotal clinical trials to ultimately reaching FDA approval and product commercialization. Digital solutions such as a robust Electronic Batch Recording system (EBR) are vital. The Advanced Therapy Medicinal Products (ATMP) guidelines dictate donor and recipient identification of the cells over the complete manufacturing process to ensure treatment of the patient with the correct cells, as mistakes in this aspect can have devastating effects. EBR enables the identification of the material at any point in time and in relation to used equipment or locations, facilitating drastically the ATMP compliant procedure. Given that the raw material for these processes are actual patient cells extracted in a clinic, a failed batch is devastating and could mean the 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 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. Manufacturers who have become early adopters of digitization, automation and continuous improvement are reaping huge benefits. They have minimized the use of paper, automatized calculations and sped the design of manufacturing batch records. What’s more, they have reduced cGMP deviations and more quickly released manufacturing batches based on review by exception, which aligns with right first time initiatives. Especially the manufacturing of cells that are delivered fresh to the hospital for treatment results in time-critical batch release and supply chain prerequisites that can only be met by digital collection of all required data.

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 process and supply chain. In this vein, a CDMO/CMO that is already a fully automated facility with EBR capability can help achieve these goals.

The detrimental impact of Covid-19 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/CMOs

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 EBR 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, CDMOs/CMOs 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. 

Digital manufacturing solutions are the need of the hour

In conclusion, CDMOs/CMOs must embrace digitization! A cloud-hosted digital EBR 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 the chain of identity, chain of custody, chain of condition and the 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 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.

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