Temperature-Controlled Needs for Advanced Therapies
Emerging cell and gene therapies (CGTs) are showing enormous potential for treating cancer, neurodegenerative diseases, and a wide range of other conditions. The CGT industry is expected to grow 30% between 2019 and 2025, and the transition from clinical trials to commercial-scale production is now seen as inevitable.¹
Pharmaceutical companies are addressing the challenges that CGTs present for temperature-controlled logistics. Unlike traditional biological therapies requiring temperature control, CGTs (as well as some biological samples) require ultra-cold temperatures, ranging from –4 °C and –20 °C to –80 °C, –120 °C, –150 °C, and beyond.
Despite this, investment in the CGT market is strong. Between January and June 2020, CGT developers raised $10.7 billion from IPOs, venture capital, and other sources.² This is a 120% increase from the first half of 2019. Noting the upswing, the U.S. Food and Drug Administration (FDA) released a statement in January 2019 stating that it expects more than 200 investigational new drug (IND) applications a year through 2025.³
Because of their potential to cure disease, CGTs are seen as potentially disruptive to traditional therapies. Thus, pharmaceutical companies are making CGT an important part of their growth strategy. Amid the continued growth of these markets, temperature-controlled logistics account for nearly 18% of all biopharma logistics spending, according to the 2020 Biopharma Cold Chain Sourcebook published by Pharmaceutical Commerce.⁴
The ultra-cold storage requirements of these products, their personalized nature, their direct patient involvement in a circular supply chain ("vein-to-vein"), and limited industrial capacity are challenges to achieving an efficient supply chain. Pharmaceutical companies are having to outsource ultra-cold-chain services to third-party companies, including outsourcing temperature-controlled storage to biorepositories. Biorepositories are primarily collections of human specimens and associated data, but their functions have expanded to include specimen processing, information management system, storage, and preparation for distribution.
This article will focus on the current purposes of biorepositories for CGT and outsourcing to biorepositories as one solution to transitioning to commercial-scale production.
Biorepositories Maintain the Chain of Identity
With today's CGT products, other biologic therapies, and several COVID-19 vaccine candidates currently in clinical trials, there is increasing demand for storing product at deep frozen temperatures (on the order of –40 °C to –80 °C), and cryogenic for living cells (requiring liquid nitrogen; –160 °C to –196 °C).²
In contrast to traditional medications, the patient is part of the manufacturing process in the CGT supply chain, donating and/or receiving a live therapy. This vein-to-vein supply chain means that biorepositories need to create logistics platforms that will connect therapies to the correct patients.
As a result, CGT biorepositories have become not just storage facilities but information management systems that coordinate closely with manufacturers, providers, and distributors to ensure that therapies are in good shape and are delivered to the right patients. The chain of identity must be maintained and verified throughout the entire supply chain.
All the relevant information, as well as data concerning the study participant and laboratory analyses, must be properly stored in a biorepository's interoperable information management system. With this patient identity information also comes the responsibility of protecting personal health information.⁵ A biorepository must be compliant with Health Insurance Portability and Accountability Act (HIPAA) and General Data Protection Regulation (GDPR) health privacy regulations in the United States and the European Union, respectively.⁶ ⁷
Unlike conventional, large-batch drugs, each CGT patient requires his/her own manufacturing batch. The patient is literally the first step of the supply chain. Few manufacturers have the systems in place to track the condition of the cells from the moment of apheresis until re-infusion of the therapy. Data tracking and verification capabilities must preserve the chain of identity. This is more complex and nuanced than simply tracking a consumer. This demands an infrastructure that can track and verify that CGTs get to patients efficiently and compliantly to drive the best possible outcomes and potentially save lives.
Multiple Storage Sites
Multiple storage sites at dispersed locations becomes an expensive but often necessary reality. This is partly due to the ongoing impacts of the COVID-19 pandemic, which has led to even further decentralization of the vein-to-vein supply chain. Fear of infection forced apheresis centers and facilities to close or decentralize and collect specimens closer to or at patients' homes.
Biorepositories –– and integrated outsourced providers that provide such services –– must now coordinate with a wider network of apheresis centers, clinical sites, patients, logistics vendors like distributors, and biopharmaceutical partners. This decentralization will likely last after the pandemic. Patients have come to enjoy less commute time to collection sites, and the added comfort associated with the increased patent-centric practices resulted from the decentralization of clinical services.
Multiple storage sites become even more important when one considers remote locations or developing countries. It is not always possible to have access to liquid nitrogen, ultra-cold freezers, or even electricity in some situations. In situations where freezer systems may not be available, lower-cost options include saliva filter cards, certain branded collection tubes, and tissues fixed in formalin and embedded in paraffin blocks.⁸ Biorepositories can work with pharma companies to assess the best collection and storage options.
Experiences in the industry with spoiled product have led biorepositories to rely heavily on the use of data-collection tools, such as advanced monitoring systems and telemetry, to reduce the frequency and likelihood of delays and temperature excursions.
Temperature-sensitive packaging is essential for the preservation of CGT products. Along their journeys through production, storage, and shipping, specimens are exposed to extreme temperature that can fluctuate anywhere from –190 °C to 37 °C. Biorepositories need to supply appropriate packaging for storage (primary) and shipping (secondary).
Packaging also needs compliant chain-of-identity labelling, unique National Drug Code codes for various dosing kits, and additional labeling text statements, which may impact label size and placement. Adding country-specific requirements in multiple languages can further complicate the development of product labeling. Biorepositories and integrated logistics providers must have excellent information management systems and knowledge of country regulations to make sure no labeling errors are made.
Outsourcing Temperature-Controlled Storage
With so many variables to consider, it's no surprise that pharmaceutical companies are increasingly outsourcing their temperature-controlled ––including ultra-cold –– storage needs to providers with biorepository capabilities. Outsourcing to third party temperature-controlled services occurs at every development phase, especially phase II.⁹
Pharma companies would rather focus on research and development. They know that logistics companies tend to be more experienced at engineering solutions that reduce costs, such as creating warehouse space by building giant freezer farms, holding temperature-controlled inventory, providing CGT on a just-in-time basis, expanding use of preconditioned shippers, reducing the multi-step process to just two or three steps, and tightening process integration.²
As the number of approved CGT products continues to grow, there is more demand for cryogenic storage systems that can maintain internal temperatures between –150 °C and –180 °C for extended periods of time. Biotech companies need to grow their cryogenic storage infrastructure, especially liquid nitrogen cryogenic storage (–180 °C).
This is especially difficult for small biotech companies that lack hard assets like cryostorage but are conducting clinical trials. They need CGT-experienced biorepositories that use a logistics-by-design approach to tackle temperature-controlled storage and provide other services.¹⁰ For example, some biorepositories can go beyond informatics, storage, and packaging by taking on tasks like aliquoting (dividing) specimens for further analysis.
Yourway Biopharma Services offers the storage needed to service the CGT temperature-controlled chain no matter how complex a project and its needs may be. With a robust and advanced temperature-controlled global GMP deport network, Yourway provides storage at 21 depots around the world, as well as integrated primary and secondary packaging services. Yourway can store material within hours or even minutes of its destination.
Yourway also provides clients with the ability to seamlessly manage inventory through our easy-to-use customer portal. Our warehousing and logistics services are fully automated, allowing you to monitor your inventory 24 hours a day, seven days a week. Simply call in your orders and they will be immediately dispatched by next-flight-out (NFO) or ground transport. Partnering with Yourway means minimized overhead, field inventory levels, and — most importantly — faster turnaround time, enhanced quality/compliance, and reduced costs.
- Biggins, Jay. "The Rise Of Gene & Cell Therapy And The Resulting Need For In-House Production Facilities: A Guide." Cell & Gene. 9 Sep. 2020. https://www.cellandgene.com/doc/the-rise-of-gene-cell-therapy-and-the-resulting-need-for-in-house-production-facilities-a-guide-0001, 9/29/2020.
- Shelley, Suzanne. "Today's pharma cold chain is going cryogenic." Pharmaceutical Commerce. 9 Sep. 2020. https://www.pharmaceuticalcommerce.com/view/todays-pharma-cold-chain-is-going-cryogenic.
- Statement from FDA Commissioner Scott Gottlieb, M.D. and Peter Marks, M.D., Ph.D., Director of the Center for Biologics Evaluation and Research on new policies to advance development of safe and effective cell and gene therapies. U.S. Food and Drug Administration. 15 Jan. 2019. https://www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-and-peter-marks-md-phd-director-center-biologics
- Basta, Nicholas and Mark Lipowicz. "2020 Biopharma Cold Chain Sourcebook, 11th Edition." Pharmaceutical Commerce. 2021. https://www.pharmaceuticalcommerce.com/view/sourcebook
- "Best Practices." National Cancer Institute. 17 Dec. 2018., https://biospecimens.cancer.gov/bestpractices/
- Health Insurance Portability and Accountability Act (HIPAA). 1996. https://www.hhs.gov/hipaa/index.html.
- General Data Protection Regulation (GDPR), https://gdpr-info.eu/
- Vaught, J.B. and M. Henderson. "Biological sample collection, processing, storage and information management." IARC Sci. Publ. 23–42 (2011).
- Branch, Emilie, Steve Kuehn, Carrie Cao, and Cynthia Challener. "Keeping the Chain Going," Pharma's Almanac. 8 Mar. 2017. https://www.pharmasalmanac.com/articles/keeping-the-chain-going
- Harris, Erin. "Sneak Peek: The Unique Challenges Of Cell And Gene Supply Chains." Cell and Gene. 22 Jan. 2019. https://www.cellandgene.com/doc/sneak-peek-the-unique-challenges-of-cell-and-gene-supply-chains-0001
Note: This article was originally published on PharmasAlmanac.com.