Release by exception is an aspiration that could significantly reduce therapeutic release time and cost. Currently, quality compliance (QC) cost of autologous products can comprise up to 32% of cost of goods sold (COGS) per dose, while making up to 23% of COGS per dose for allogeneic products.[i]
Why do cell and gene therapy QC costs run so high?
In both autologous and allogeneic cases, QC cost is the second highest cost factor, second to only the cost of consumables. For small lot sizes of 50 doses per lot, QC costs can run even higher, at more than 50%.[ii] These high costs are due in large part to the significant manpower needed to review hundreds of pages of batch information before the batch can be released.
This lengthy review must be done for every batch at each individual unit process, regardless of whether deviations and/or errors are suspected or not. This conventional release process is cumbersome, open to human error, and requires a large (and expensive) labor force.
The role of manufacturing automation in reducing QC costs
Adopting manufacturing automation technologies would allow quality teams to implement a release by exception process which would drastically reduce the number of costly reviews required, saving on both the time and money needed to produce cell and gene therapies (CGT).
Release by exception is a review approach where quality teams would review information only when pre-established targets are not met, or certain alarms are triggered. This means that products can be released automatically unless pre-defined metrics are not met.
The release by exception method does require that a manufacturing process is well-characterized and well-defined enough so that clear trigger metrics and events requiring review can be established. It has the potential to cut down on the cost and time that current standard release processes accepted in the CGT industry demand.
Because of the process consistency that closed and automated platforms can provide, automation technology makes release by exception a possibility, along with all the benefits that it brings.
Assuring patient safety
One of the questions that release by exception raises is safety. How can CGT manufacturers be certain that all released batches are safe for patients? CGT manufacturers and automation technology providers would need to validate the equipment first – not a trivial activity, but one that can unlock key long-term manufacturing benefits.
In many cases, cell therapies are a patient’s final chance at survival. Reducing the time needed to produce a high quality, safe, and efficacious dose is important. Based on published information for αCD19 CART-T therapies for example, up to 10% of manufacturing runs routinely fail.[iii]
By employing release by exception methods afforded by automation platforms, CGT manufacturers could set up alarms and predefined triggers to alert when manufacturing runs are not meeting specified standards. In this way, the industry could move away from lengthy and costly reviews of every single batch, while still upholding high quality standards.
In our new guide, we dive further into release by exception, finding the right manufacturing automation inflection point, automation strategies for CGT manufacturers, building a robust supply chain and more.
[i] Chimerica antigen receptor-T cell therapy manufacturing: modelling the effect of offshore production on aggregate cost of goods. Cytotherapy. https://pubmed.ncbi.nlm.nih.gov/30770285/ Accessed May 10, 2021.
Jon is the San Diego Cell Therapy Manager, responsible for the Invetech applications science team. He has almost 20 years cell therapy experience, initially in cord blood banking and transplantation in the UK National Health Service, before moving into industry in the U.S. and developing novel cell isolation and selection technologies.