The Relationship Between Cold Chain Logistics and Cell & Gene Therapies

Wilfredo Marin

Cell & gene therapies—often referred to as CGTs—are continuing to serve as gamechangers within our industry, due to their ability to treat complex diseases. Pharmaceutical Commerce sat down with Wilfredo Marin, senior product application scientist at Thermo Fisher Scientific, to discuss the ultra-low temperature (ULT) storage requirements surrounding CGTs, along with the flexibility for customization.

Pharmaceutical Commerce: Could you describe the importance of ultra-low temperature storage? Given the sensitivity of some of these medications/CGTs, what are the potential repercussions of not adhering to these requirements?

Wilfredo Marin: ULT storage serves the cell and gene therapy manufacturing process by providing a secure and reliable cold environment for valuable products. Labs and facilities are prioritizing both the short and long-term stability of their products at varying temperatures but emphasizing ultra-low temperature freezers because of their wide availability and validated mapping. As we continue learning about the vitality of novel delivery mechanisms including nanocarrier compositions for therapeutics, so too are requirements for optimal storage temperatures. This process helps ensure that those medications maintain their potency to direct an immune response while also avoiding expiration or excessive medical waste.

The genuine consequences include potentially upsetting regimented treatment cycles that mean life or death for many patients. The requirements for maintaining a properly recorded temperature-controlled environment truly help avoid contamination and the loss of a medication’s effectiveness. Proper storage at specific ultra-low temperatures gives researchers more time to gather and genetically engineer the treatment coming from a patient or cohort. Similarly, using ULTs all along the cold chain can maximize therapeutic results by extending the use-by date for manufacturers. The greatest risk for cold chain logistics is unknowingly operating within a process susceptible to audits. These events can be mitigated by managing qualified cold storage equipment.

PC: Having said that, why do you believe cold chain logistics should be flexible with the ability to customize support and resources along the supply chain?

Marin: One of the greatest advantages in CGT is the ability to remain flexible along the supply chain, allowing for quick pivots that ensure critical patient timelines can be realized. This may sound in stark contrast to the increasing demand for regulation along the cold chain, but both compliance and customization are complementary approaches. The key to making these improvements is carefully coordinated monitoring that can be used to make informed decisions. Consistent temperature monitoring also permits a more accurate transfer of cold-chain custody creating the audit trail. In my opinion, this activity adds value for the manufacturer and confidence for the patient.

In reference to optimal temperature storage, different types of therapeutic products may require cryopreservation as a sample preparation method, which then permits specialized equipment for transport. Increased support to understand the key customizable steps while sharing resources for better overall planning are examples where agility can differentiate success for cold chain logistics. Along these lines, it is very possible to maintain a compliant workflow that emphasizes quality without sacrificing performance.

PC: How specifically can this be accomplished?

Marin: There is much to offer in the form of manufacturing sites partnering with facilities using fit-for-purpose cold storage equipment in strategic locations. The relationship that industry can share with providers is to reliably supply critical materials thereby avoiding shortage risks and higher associated costs. Achieving a collaborative environment where experts across different fields (cell engineering, temperature-controlled warehousing and shipping, or transport) can work together will improve the cold chain logistics process.

Another very crucial factor in cold chain logistics is traceability. All stakeholders should be able to identify, historically track, and locate their products in a facility or during transport. Specifically, users are asking for more early warning features during storage or advanced real-time queries of their shipments. This is all intended to avoid temperature overruns or excursions that can result from information lags where every minute matters. Accomplishing greater traceability will require embracing innovative connected solutions and versatility of storage options permitting multi-modal transportation. The increasing implementation of sensors to gather data pertaining to time and temperature—even humidity and shock indicators—will help safeguard vital therapies.

PC: What is Thermo Fisher doing to help simplify these processes?

Marin: In my experience, working with customers in CGT and understanding the numerous product solutions, Thermo Fisher Scientific has done very well to improve cold storage technologies alongside greater connectivity options. When therapies are being transported, a customer needs to know that storage products adhere to best practices and guidelines. The TSX Universal ultra-low temperature freezers are considered high-performing models capable of supporting heavy entry/reentry activity while maintaining low energy consumption. These freezers can be quickly qualified and now purchased as medical device models across all four cabinet sizes.

The ability to utilize suitable sizes and configurations for cold storage equipment is essential to horizontal and geographic scaling for businesses. Most importantly, in line with traceability to ensure repeatable results and quality therapeutics, more products should be able to acquire and communicate status information along with performance data. The entire Thermo Scientific cryogenic transport and storage family also offers different capacities across its product lines. In this manner, the options are clear when choosing to transport vials in canes or boxes versus bags in canisters. These aluminum dewars can provide longer cold temperature hold times, which can lower the cost or need to use refrigerated shipments.

PC: Looking ahead, what can be done in order for these cold chain logistics processes to become even more efficient over the next decade?

Marin: Part of what makes many of the recent CGT approvals exciting is the potential for greater access to patients. New front-line therapeutic options as well as existing products used during regular treatment cycles can all be helped by leveraging expertise within the cold chain. It will be very interesting to see how much more cold chain logistics with temperature-controlled spaces can be integrated into the highly regulated cell manufacturing and management process. The maturation of IoT and deep integration of artificial intelligence with cold chain technology standards will certainly provide new solutions to overcome regulatory challenges.

The various supply chain services benefit most from speed of distribution but can also adopt new technologies. A recent regional international cell & gene therapy society meeting suggested a rapidly changing landscape from tailor-made autologous therapies to larger capacity allogenic therapies partially driven by better guidance from the FDA. In practical terms, this means the total volumes one expects to be transported via the cold chain will be higher. This will hopefully improve accessibility of the therapies but also efficiency of storage and delivery highlighted with increased market growth.