Pain Points to Optimising Automated Manufacturing Transitions
7 February 2022
Automation & Digitisation
This Event Report assesses the challenges to be overcome when moving therapeutics development from clinical to commercial manufacturing process, including the training, facilities and talent required.
With attendees of varying specialism including manufacturing, gene therapy, machinery, and cryogenics, this working group came together to address the pursuit of process optimisation, automation, and upscaling among tool manufacturers.
Splitting into two groups for targeted discussion, the first team focused efforts on process optimisation. With an eye towards a pragmatic result, how can the tool-providing industry support therapy manufacturers as they attempt to automate and improve their processes?
For the second group, a macro perspective was the order of the day. At scale across the industry, what are the dominant gaps and blockers we can address, and what shortages such as talent present the greatest pain points?
In both instances, education emerged as a key theme. Diverse experience and in-depth discussion provided a wealth of information, resulting in a clear need to package and communicate findings. With subjects such as video education showing clear promise, accessing information and navigating IP issues to facilitate knowledge sharing will likely shape future efforts.
Education: From discovery to bedside
“By themselves, SOPs and batch records are not enough for a great transfer.”
Education is critical to a successful tech transfer, but the manner in which it is performed can vary depending on the skill and product in question. Money and time are spent excessively in attempts to replicate processes, with video training being a valuable and underutilised method for conveying and demonstrating complex instructions. A hurdle, however, lies in organisations and CDMOs having problems with IP.
By themselves, SOPs and batch records are not enough for a great transfer that is comprehensive and manageable. We see some opportunity here for early education in academia to help this, such as training on how processes work on common or industry-standard instrumentation.
Facilities and academia
“We should educate on automation as early as possible, particularly with regards to scaling up.”
With flow cytometry, core facilities in universities or even incubator sites could facilitate cell manufacturing. This could allow testing and education and demonstrate future potential beyond the discovery phase.
The use of consumables is also important. Disposable bioreactors, for instance, are too expensive to use in the discovery phase. Finding a way to get academic and early discovery users access to high-grade reagents, consumables, and bioreactors would be beneficial to the industry.
Core facilities could help to reduce costs in the early discovery phase. Frameworks for CTT production would help but this would be difficult to arrange, partly because of the variation between companies and between patients. We should educate on automation as soon as possible, particularly with regards to scaling up.
Lastly, differences in focus and mindset between industry and academic professionals presents a challenge. Bridging what is often a gap between the two has the potential to enable collaboration for which there is often a significant appetite.
Awareness and training
“Many processes have nuances that may be clear to the teacher, but not to the recipient.”
Awareness of issues that develop later in processes is a common stumbling point, particularly true for students or new professionals, cost and accessibility are key drivers that can limit interest in important equipment and refinements that enable later upscaling. An example of this is cryobiology, which includes considerations like thawing and receiving at hospitals that are often overlooked or missed when performing a tech transfer.
It’s agreed that video training is a valuable tool for facilitating good transfer and education. For example, the success of some processes can involve details such as how a vial is held. This necessitates a format like video, which can convey nuances better than other methods. Many processes have nuances that may be clear to the teacher, but not to the recipient of a transfer.
This is a great opportunity that is also potentially easier to address and resolve, but is an effort that will face difficulty when managing IP risk. Upcoming encryption technology, however, may address this issue. This discussion is also highly relevant to apheresis work – an area of work often described as an artform wherein training is improved drastically via video content.
Talent availability and first to market
“The cost of optimisation must be accessible in areas beyond manufacturing.”
We will likely see processes that are not mature enter clinical stages. The possibility to be first in a market drives companies to progress rapidly, often leading to issues in areas such as manufacturing success rates. Despite this, entering the market first still has a unique and distinct value.
Access to more experienced talent would accelerate the uptake of automation not only in manufacturing but also in product characterisation. Beyond this, the tools these professionals use must deliver data in a way that allows for automation and adjustment.
Lastly, when is the right time to automate? Many customers use off-the-shelf equipment early on, later progressing to customised tools. In these cases, companies often stick to what is familiar, expressing reluctance for the adoption of new equipment and methods. For small companies, pursuing early automation can also lead to obsolete equipment that can incur a significant initial CapEx cost. To overcome this, the cost of optimisation must be accessible in areas beyond manufacturing.
These efforts must occur in parallel to ongoing activities. As it stands, much work toward automation occurs at the end of development stages. This makes it difficult to achieve new ways of working across an entire process.
In many cases, the cost of goods becomes secondary to reductions like operator touch time; if a platform can be moved to grade C, the cost savings are enormous. This can easily offset the increase in cost of goods.
The contract and research organization (CRO) AmplifyBio has announced the acquisition of select assets from privately held biopharmaceutical company PACT Pharma Inc to advance its cell and gene therapy service offerings.
For this Article, Phacilitate Editor, Georgi Makin, explores current challenges associated with CAR-T manufacturing workflows, considering how an integrated testing approach could reduce costs and accelerate speed to market.