Enabling Scalability of Cell & Gene Medicines with Connected Lab Cold Storage

Contributed Commentary by Scott Masiella

September 17, 2021 | The life sciences industry is getting closer to delivering the promise of precision medicine to the mainstream as scientific innovation continues to improve. Researchers have known for many years that the personalized nature of these treatments has made them highly effective in treating rare and fatal conditions. Most recently, the National Institutes of Health released research detailing an investigational gene therapy trial that successfully and permanently treated 48 of 50 children born with an inherited rare and deadly immune disorder.

The global cell and gene therapy market reached a value of nearly $4.39 billion in 2020 and the market is expected to grow to $15.48 billion in 2025. However, despite its success, ability to scale and standardize remains a top bottleneck holding cell and gene research back from the mainstream, as the manufacturing quality necessary to produce successful treatments is often difficult for regulators to evaluate and companies to commercialize en masse. In the past year, the Food and Drug Administration (FDA) has demonstrated greater scrutiny around cell and gene treatments and called for more consistency in their development.

As a result, many cell and gene researchers are turning to technology to assist in scaling their operations. Multiply Labs recently announced the development of a new robotic manufacturing platform to ease bottlenecks in cell therapy development. Connected and intelligent equipment is also becoming crucial for developers to meet research goals and maintain compliance, including connected ultra-low temperature (ULT) and cryogenic freezers capable of communicating temperature changes, product safety, and more.

Challenges on the Road to Cell & Gene Therapies

Cell and gene therapies have been subject to human inefficiencies and errors that make them challenging to scale. Biological materials must be stored at ULT or even cryogenic temperatures to remain viable for effective bioprocessing and downstream treatment. Furthermore, these treatments face the added challenge of being bidirectional in the supply chain, from vein to vein.

In personalized treatment, a biological specimen is harvested from the patient, transported to a lab before undergoing the development process, and then transported back in a modified or derivative form for patient therapy. Temperatures must be monitored and controlled constantly throughout this journey, and any failure could be severely costly and dangerous to patients. The fact that every individual treatment is also personalized and may come with varying requirements creates a whole new level of complexity.

The biggest challenge to scale these treatments in the mainstream for more widespread conditions will be around infrastructure implementation in research labs, supply chains, and long-term storage facilities for quality assurance purposes. Fortunately, the development of mRNA COVID-19 vaccines has already contributed to the rapid expansion of necessary infrastructure, as major logistics providers implemented ultracold chain distribution processes to roll them out. However, traceability of these products will become all the more critical as these treatments are custom developed and delivered to specific patients.

Regulators and industry leaders are still working together to establish standards for the development of these treatments, but also the assurance that the conditions they are tested under can be adequately maintained at scale in the real world. Developers must be able to guarantee that the right product is delivered to the right person, stored properly at every step, and that is viable and effective to use at the point of administration. Ultimately, the final piece of the puzzle will be to standardize as many elements of the process as possible despite the nuances of each treatment. This puts the onus on developers to ensure their infrastructure is as flexible and reliable as possible and a clear audit trail can be produced to validate their success.

The Rise of Connected Technology

Monitoring technology in biopharma has progressively evolved from a “nice to have” asset to a critical enabler, as it has become essential to meet growing regulatory reporting requirements. Governing bodies require developers to ensure their products are stored and handled as they were designed to be throughout clinical trials as well as in post-market environments. The realities of these validation requirements are tenfold for cell and gene developers due to the high cost and fragility of the final product.

Integrated data management is becoming a vital process for monitoring, tracking and preserving the integrity of cell and gene therapies throughout clinical trials, downstream manufacturing, cold chain distribution and administration. As a result, digital and cloud-based data management systems are gaining traction in all phases of bringing advanced therapies to market and delivering them to patients in the clinical environment. This can range from enabling more streamlined development to monitoring their temperature and condition throughout the chain of custody.

The advent of robotics for the cell & gene development space is also automating repetitive processes to support greater scale, while also improving safety and efficacy via digital tracking and monitoring and reduced opportunity for human error. Linking these technologies to data management platforms then contributes to better traceability by automating data capture. This information becomes essential to give regulators what they need to confidently make decisions about treatment approvals.

While the potential of robotics in the development and delivery space is great, there are functions that simply will not be logical or cost effective to automate. A machine will never compare to the expertise of a scientist to properly formulate and mix a treatment. Furthermore, the individualized nature of each treatment would demand many machines and highly specific programming that would be cost prohibitive to implement and maintain. Instead, these technologies can support a balance between humans and machines.

For example, by integrating ULT freezers with information and sample management systems, developers can enable guided access and retrieval of ULT-stored therapies and doses. This ensures that the right samples are being retrieved and returned to cold storage before their quality is impacted. Human error is mitigated, development and distribution are streamlined, and focus can stay on the final product. All the while, that data is captured and maintained in a virtual audit trail.

Though hurdles remain, the industry has come remarkably far on cell and gene therapies in the past decade. The tools and technologies to address these challenges exist today and are continuing to improve. The increased downstream reliability and traceability of ULT and cryogenic infrastructure will become the foundation for developers to deliver highly effective treatments that will improve and save the lives of patients around the world.

Scott Masiella is Director of Product Management at Stirling Ultracold. Scott has extensive experience in engineering, market segmentation and product management. He has worked at Stirling Ultracold for the last three years defining the product roadmap and working on continuous freezer improvement initiatives. He is very knowledgeable on ultra-low temperature storage and uses his strong customer relationships to continue to sharpen the company’s ability to exceed customer demands.  His prior experience is with several large nationally recognized manufacturing companies, such as, General Electric (GE) and Thermo Fisher Scientific, where he most recently worked in the chemical analysis division as the Senior Global Market Segment Manager. He can be reached at smasiella@stirlingultracold.com.