David Lewandowski, Business Director of Cell & Gene Therapy at Azenta Life Sciences, explains how efficient sample management can help to work efficiently and bring therapies to market faster.
The global cell and gene therapy (CGT) market reached a value of ~$4 billion in 2020 and is expected to grow to ~$34 billion by 20301. With recent approvals of several CGTs, expansive and growing pipelines, and substantial funding for CGT companies, the pace at which these therapies are commercialised is continuing to accelerate. It has been estimated that by 2025 the FDA will be approving 10 to 20 cell and gene therapy products per year2.
However, the speed at which CGT products can impact healthcare depends on how the industry will navigate novel challenges and risks from the nascent field of CGT development. Complexities arise while trying to establish a standard, cost-efficient, and expert process for research and manufacturing. The constraints are multiplied with the scarcity of subject matter experts and a fully trained workforce for an organic/in-house R&D3.
Making CGT work
Production of CGTs is complex, much more so than traditional biologics. There are several critical factors that increase the bench-to-bedside timeline, including:
- Sample lifecycle management
- Regulatory requirements
These challenges exist across the translation cycle from early research to clinical trials, manufacturing, and ultimately reimbursement. To reduce the time to market for these important life-saving therapies, CGT companies are finding partners who can help them manage their sample and logistics infrastructure so they can expend their energy doing the science.
It’s all about the infrastructure
The complexities of sample management can significantly extend the timelines for clinical trials. Clinical samples are often collected in many locations and then, transported, stored, processed, and analysed by multiple vendors. This fragmented approach to sample management can lead to spiralling sample storage costs, quality concerns, inventory documentation challenges, and poor chain of custody records.
Clinical trial sponsors need to coordinate the delivery of investigational medicinal products to clinical sites and the collection of samples from participants after they receive treatment. These processes are intertwined, and it’s advantageous to have an expert partner that can oversee both activities throughout the clinical phases and beyond. Storing and managing CGT ancillary supplies and clinical materials requires an inventory management system with various safeguards and risk mitigation protocols. For example, if a project requires a certain temperature for a group of materials, the entire logistics and supply chain system should continuously track environmental conditions and include safeguards to maintain the target temperature. From an infrastructure standpoint, everything must be done to add to the security and stability of the temperature within the storage units. For example, liquid nitrogen (LN2) freezers, whether automated or manual, should be fed by vacuum-insulated piping, which ensures immediate delivery of LN2 upon demand. Risk mitigation plans need to be in place to include a backup LN2 supply, on-call staff, and qualification services.
Regulatory requirements:the landscape is shifting
Repeatability, reproducibility, scalability, and comparability have all become very real challenges from quality and regulatory perspectives4. Regulatory barriers and regional reimbursement differences for cell and gene therapy is limiting for global expansion. As the field matures and the risks are better understood, regulators continue to streamline duplicative and burdensome oversight efforts5. Regulatory frameworks need to be established to reduce these barriers and ensure patient safety while also facilitating expeditious development of these complex and innovative products6.
In the United States, cell and gene therapies are viewed as innovative therapies by the FDA. For regulatory purposes, they may be treated more like a pharmaceutical or a blood product. A quality system that is set up to handle both is required. Obtaining state licensure to support distribution globally for both types of products is often needed. Cell and gene therapy companies may also benefit from accreditation and certifications such as ISO, CAP, EMA, and PMDA. Maintaining the quality of advanced therapies, many of which have a short shelf life and demanding storage requirements, requires a strong quality management system that meets all regulatory requirements, including Good Manufacturing Practices (GMP) and Good Tissue Practices(GTP). Also, full traceability from the moment a material is shipped all the way through to end distribution is crucial.
Logistics: Is it cold enough?
The CGT supply chain is inherently patient-centric, as patients can be both upstream and downstream of manufacturing. With autologous therapies, cells are extracted from the body, manipulated, and then injected back into the same patient, creating a supply chain that has been dubbed ‘vein-to-vein’7. A flawless CGT supply chain requires strict process control from start to finish. Supply chain partners must employ multiple tactics to protect the patient as well as the integrity of the trial. Considering each protocol requires a distinct supply chain, these tactics will vary8. Cold chain needs to be an integral part of the CGT supply chain as it must be capable of maintaining a living product in a viable state throughout storage and distribution, all the way to the patient9.
Cell and gene therapies are typically stored at ultra-low to cryogenic temperatures.These temperatures give products a longer shelf life while maintaining maximum potency. Managing these sensitive materials—including storage, transportation, and tracking—requires robust and adaptable systems to ensure safety, integrity, and regulatory compliance that are required for agency review. When storing and handling clinical-phase samples and materials, their fragility cannot be overstated. Retrieving materials manually from a liquid nitrogen freezer can quickly warm the targeted and non-targeted materials with unintended consequences. Repeated exposure over time has a compounding effect as well. For example, if a box of samples is moved from -180 ̊C to ambient conditions, there is about 90 seconds before the box starts to cross the glass transition temperature, the point at which degradation occurs. Some automated freezers are designed to keep biological materials well below their critical temperatures throughout the entire retrieval process, significantly lowering the risk of degradation.
The promise of gene therapy is substantial. There are over 7,000 genetic diseases that could potentially be cured using gene therapy10. Pharma and biotech companies clearly recognise the potential of CGTs, with 16 out of 20 of the world’s largest (by revenue) biopharma companies adding CGT assets to their product portfolios11.However, while the promise, interest, and investment have been high, the technology for manufacturing and analysing gene therapy products is still evolving. This is why this revolution in medical treatments like cell and gene therapy needs strong partners and technologies to bring rigour and reproducibility as these therapies advance toward approval. Implementing standardised operating procedures which are scalable and support the cold chain logistics of clinical trials and CGT manufacturing are critical to success.
Volume 23 – Issue 3, Summer 2022
About the author
David Lewandowski is the Business Director of Cell & Gene Therapy at Azenta Life Sciences. In his role, Lewandowski works with cell and gene therapy organisations looking to refine and add rigour to their scaling programs. As a past IBSER President, he worked with the team initiate and develop a collaboration with the Society of Cryobiology. Together they created and published the first Liquid Nitrogen-Based Storage Facility Best Practices. This consensus document includes contributions from over 20 experts from various industries depending on cryogenic material storage.\
1: TBRC Business Research PVTLTD. (2021, February 23). Gene Therapy accounts for A major portion of the cell and Gene Therapy market and it is expected to have the most growth. TBRCBusiness Research PVT LTD. https://www.globenewswire.com/news-release/2021/02/23/2180767/0/en/Gene-Therapy-Accounts-For-A-Major-Portion-Of-The-Cell-And-Gene-Therapy-Market-And-It-Is-Expected-To-Have-The-Most-Growth.html
2: Office of the Commissioner. (2019,January 15). 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.https://www.fda.gov/news-events/press-announcements/statement-fda-commissioner-scott-gottlieb-md-and-peter-marks-md-phd-director-center-biologics
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