Digital solutions advance your mRNA manufacturing workflow

Some have predicted that digital technologies will increasingly impact the biomanufacturing industry, ushering in even more advances to the way therapeutics are made (1, 2). When it comes to leveraging these digital solutions, the question remains, is biopharma ready to embrace the changes?

Whether implementing more advanced automation, building out smart plants, or moving toward paperless manufacturing, improving the level of digital maturity within drug manufacturing processes can reduce costs, save time, and mitigate risk. For emerging mRNA-based drugs that can sometimes require small, intensified batches, paperless manufacturing—using automated, digital data management instead of paper-based recordkeeping—offers even more competitive advantages. In this article, we address the benefits of paperless manufacturing to both small and emerging companies alike, why it’s essential to incorporate a digital strategy early in the manufacturing process, and how a digital solution for mRNA manufacturing can help small batch manufacturers more effectively produce these soon-to-be essential medicines.

mRNA therapeutics continue to find their way

Due to the rapid development of mRNA-based COVID-19 vaccines during the coronavirus pandemic, messenger RNAs (mRNAs) have become an emerging class of therapeutic that are poised to play a large role in the future of targeted treatments—going beyond vaccines to include cell and gene therapies. In fact, the mRNA landscape is rapidly evolving, with nearly 900 drugs belonging to eight application areas currently being developed across the industry according to a recent Beacon report (3). In addition to the sheer number of drug products being explored as development candidates, the demand for diversity in therapeutic indication is also growing, including for applications such as immunology (vaccines), oncology, protein replacement, and ex vivo and in vivo cell therapy. The area of oncology includes both personalized and medium batch size drug products with a high likelihood of regulatory approval within next 24 to 36 months.

By the same report, the “mRNA field is growing faster than any other RNA modality, and even though a higher number of oligonucleotides have reached late-clinical stages, mRNA therapeutics are indeed catching up.”

Key challenges to manufacturing mRNA-based therapeutics

It is important to note that the majority of mRNA drugs are in preclinical stage, and their development to regulatory stage presents many key challenges to drug developers, including delivery of payload to key cell types, cell-specific expression, immunogenicity, stability, and expression period.

mRNA-based drugs and other advanced therapy medicinal products (ATMPs) are poised to benefit as much or more from digitalized, automated biomanufacturing processes than more traditional modalities. mRNA production for personalized medicines is on a small batch scale, requiring processes designed not only for smaller scale but also for flexibility and efficiency (4, 5). mRNA manufacturing also requires adapting to changing needs and timelines. Making sure processes, including setup and monitoring, meet cGMP standards is new for mRNA-based molecules, and this introduces its own set of challenges.

According to our latest Global Biopharma Resilience Index (6), “manufacturing for cell and gene therapies continues to suffer from a lack of streamlining and limited standardization.” Getting it right the first time will avoid last minute changes that can negatively impact timelines.

Employing digital solutions at the start

With intensification, digitalization is essential. This is especially true for personalized cancer therapies where these therapies require many small batches instead of one large batch. Even though smaller, intensified batches can de-risk manufacturing, they shift the burden to quality control and paperwork.

For early stage or small-scale manufacturers, a common misconception is that paper is cheaper and faster than adopting a digital solution. Moreover, they believe that a paperless solution is only for larger or more advanced companies. However, the reality is that a paperless approach streamlines data management, reduces contamination risk, and improves upon manual entry—for large and small manufacturers alike—accelerating development and cutting costs.

Using a digital solution, manufacturers can streamline data management by shortening processing time, allowing for many batches. The chain of custody, identity, and batch release are challenging at a personalized scale.

Going digital also lowers the risk of contamination. By its nature, mRNA is sensitive to contamination. In going digital, manufacturers can save time and avoid the risk of autoclaving paper records in and out of the manufacturing suites, which is currently a step in some processes.

Not only does entering data manually hold up process steps, manual entries or transcription of paper-based data need 4-eye verification when being made digital. For example, if one batch of mRNA-based therapeutic could have 200 consumables that need to be logged in the batch record, that presents a large burden of verification. Ultimately, the US Food and Drug Administration requires electronic submissions, making going digital at the outset much more valuable and cost effective.

For academia, a digital approach is even more important. A tech transfer process could include hundreds of documents, and it might occur multiple times during the development of a product. With distributed manufacturing, there will be even more, additional transfers to ensure that it is the same product regardless of site. A paperless approach will save time and labor while lessening time for tech transfer.

Paperless manufacturing: reducing the burden of documentation

While smaller batches can reduce risk, they also tend to put more emphasis on paperwork, which can be addressed with new ways of manufacturing. In fact, documentation burden can be greatly reduced by implementing automated solutions that provide real-time data management, electronic batch records, and electronic standard operating procedures (eSOPs).

Electronic batch records trace every manufacturing step with automation to increase productivity, reinforce GMP compliance, and improve the security of patients’ samples through increased traceability. eSOPs are designed for specific processes to manage deviations, promote adherence to protocol, and provide guidance to ensure sensitive patient cells are handled appropriately.

For example, one of our customers reported that one deviation took 45 additional hours of work. Improved management of deviations provides incentive to move away from a paper-based model.

In conclusion, the earlier a manufacturer adopts a paperless solution, the greater impact this digital approach will have on the entire manufacturing process. Commercial maturity shouldn’t deter an organization from adopting a digital solution. Organizations that are mindful of the hidden costs of paper at every phase of manufacturing can more effectively implement and maintain their digital transformation.

Read more about how Cytiva is leading the charge to improve the discovery and manufacture of mRNA therapeutics with its FlexFactory™ biomanufacturing platform and Chronicle™ automation software.