How an Agile MES as Part of a Unified Platform Can Remove Barriers to Scale and Provide Faster Paths to Approval in Precision Therapeutics

by Kevin McMahon, Precision Therapeutics Solutions Lead | posted on February 07, 2023

The precision therapeutic industry has several major challenges to overcome, to bring more consistent and cheaper treatments to a larger population of patients:

• Gaining regulatory approval for these cell and gene therapies is no trivial task, as the characterization, manufacturing, and control (CMC) process is challenging due to the variability of live cell-based products and the inherent differences in cells from one person to another. This variability makes it hard to find consistent safety, quality, efficacy, potency, and identity data for comparability from the laboratory through scale-up for tech transfer to manufacturing sites.
• Scaling production entails scaling out the process, which carries a high cost for clean room space and expensive equipment and talent to run the processes. This approach also increases the chances of cross-contamination of different patient products, which could have deadly outcomes if chain of custody and chain of identity is managed in paper and spreadsheets, as is the case in many CGT companies.
• Tech transfer of laboratory scale to production scale is not well defined due to the lack of deep understanding of the product and how variations can affect clinical data needed for BLA regulatory submission.
• Exorbitant costs of manufacturing and testing for clinical studies and commercial production inhibit the growth of the industry and usually leave the cell and gene therapy as the last line of attack after older, cheaper, and more aggressive approaches are provided to the patient first.

These challenges can be partially traced back to the industry’s heavy reliance on paper-based processes and could be greatly reduced by digitizing the entire value chain on a unified platform. Creating paper silos inhibits collaboration, reduces understanding and insight, blocks process improvement, drastically slows delivery, and ties up your talent in reviews, corrections, and investigations. An MES as part of a unified platform, can automate process and capture data where people and equipment meet the process. With a digital-first approach, you can add meaning and context to your data across the entire process and across developmental stages while adhering to CGMP practices and governance.

The Data is the Product

The CMC approach must change to incorporate learnings from the development stage through the technical transfer to the manufacturing stage, building layers of deep learning of what are critical process parameters and what critical quality attributes they affect. The earlier this process begins, the better. Notebooks and paper batch records lock the learning away and make it difficult to build a comprehensive picture of each unit operation’s effect on the intermediates and final product during the process. Data becomes the product when it leads to an understanding of how to improve the outcome by affecting a change in the upstream process. A process is then allowed to evolve and change over time to create the best outcomes and optimize based on prescriptive analytics.

When the process needs to change, or parameters need to be flexible to get the best outcomes, the data drives the models that course correct. The amount and complexity of the data the industry needs to collect to achieve this must be contextualized, curated, and ready to analyze, and MES, as part of a unified platform, can unleash this resource and drive down costs in the industry. Capturing the data at every stage on one system allows for collaboration and comparison across the entire development and implementation of the therapeutics value chain. Visibility and insight is the name of the game for optimizing CGT and generating the knowledge of how to set optimal conditions for each production run. Make the data the product that can be transferred and applied to new indications in CGT.

Scale your Process and Production

It is necessary to scale out to increase production in the CGT space, as each batch represents one patient’s therapy. Allogenic processes also start with an individual donor, although the donor is healthy, the process of selection and cell culture are mostly identical to autologous processes and have the same barriers constraining their scaling. To protect against cross-contamination and incorrect handling through this horizontal scaling, a digital solution for chain of custody (CoC) and chain of identity (CoI) must be established that builds in confidence on where a material, sample, specimen, or product is, what condition it is being stored in, how long it stays there, and ensuring it is what we expect. An MES as part of a manufacturing operations management application suite, can provide this key information and alert to any mistakes in real-time and avert costly and potentially life-threatening mistakes being made. Adding labels and scanning to these items removed another source of error, typing, and allows all the metadata associated with the item to be retrieved and used for real-time checks.

Additionally, adding in flexible, IOT-ready equipment capable of producing many products and adding robust analytical capabilities, all build into a pharma 4.0 approach.

Quality by design (QbD), digitizing and automating your process

Quality by design approach can be automated in an MES system, essentially engineering in your quality checks, where people meet process. This automation of quality checks reduces the potential for human error and streamlines the review process using “review by exception” at the end of each section or the process. Deviations are avoided during processing as the guard rails designed into the MES can detect and document any deviations as they occur, allowing course corrections and proper regulatory compliance in real-time.

Using an MES on a unified platform to build in QbD and automate the documented controls into your process supports a right-first-time, every-time manufacturing environment. Building to faster, more successful, and more robust product with positive impact for the patient and business needs.

Conclusion

Removing paper and replacing it with the right digital solution for data and process automation can supercharge the precision therapeutics industry and provide the infrastructure needed to avoid and overcome the abovementioned challenges. Connected, meaningful, contextualized data across the entire CGT value chain with process automation where people meet process is a must to bring the promise of precision therapies to the masses in a cost-effective and attractive way.