Ensuring Timely, Secure Delivery of Therapies for Rare Diseases

Clinical Researcher—October 2023 (Volume 37, Issue 5)


Dea Belazi, PharmD, MPH




Clinical trial research teams are increasingly focused on the development of specialty drugs and cell and gene therapies (CGTs) to provide an estimated 300 million people worldwide with potentially lifesaving, curative treatment for the 7,000 known rare diseases. Today, there are more than 2,000 clinical trials under way{1} with 200 in Phase III targeting patients with rare, complex diseases who often face death, disability, or poor quality of life from lack of effective treatments. As specialty drugs continue to be the main category in the U.S. Food and Drug Administration’s (FDA’s) pipeline for new approvals as of mid-2023 and it has been projected that 13 new cell or gene therapies could be approved in the U.S., Europe, or both by the end of 2023,{1} optimizing the supply chain must a priority throughout the pre-commercialization phase of drug development.

Among the myriad challenges to researchers are the unique requirements of these new, innovative therapies and the burdens tied to establishing protocols for flexible, agile supply chain logistics in support of their research and development. A focus on cold chain design, which begins when the cell-based raw material leaves the cell bank or transplant center and ends with arrival at the transplant center for transfusion, often requires engaging a logistics partner with deep experience in rare diseases early enough in the planning stage. All designs require effective response to the distinct, just-in-time demand requests that account for delivery interruptions, shortages of resources, dosing site storage flexibility, and warehousing capacity.

The need for risk management is paramount, given the multiple stakeholders involved in the supply chain. Contingency plans should be in place to safeguard a zero-error environment. By implementing best practices and leveraging advanced technologies, research teams can help to ensure a supply chain that is robust, efficient, and compliant. The process to identify efficiencies that could speed up therapy for small patient populations is highly relevant to CGTs, in particular, where complex and multifaceted delivery routes necessitate close coordination and collaboration between stakeholders to ensure product integrity and security all the way to the administration site.

In cases of specialty/orphan drugs under development, there is heightened need for temperature controls to maintain stability and drug efficacy for these products, which are largely biologics. A reliable distribution partner with deep experience and expertise with rare disease can provide fully compliant cold chain logistics support for all temperature, shock, vibration, and atmospheric pressure-sensitive orphan drug therapies. This level of support will maintain product availability and efficacy from the manufacturer to the site of care—even in the most challenging climates.

Monitoring temperature and location, as well as unique logistics-related challenges, is increasingly important in these complex formulations where the loss of product can be costly and time-consuming to both the supply chain and the patient.

Spotlight on CAR-T Cell Therapies

There are currently six FDA-approved CAR-T cell therapies available to patients in both the U.S. and Europe to treat various blood cancers.{2} The supply chain of cellular therapy is unique and distinct from that of other medical therapies. Cells are harvested from a living donor, typically in a clinical location, and then sent to a processing facility for selection, expansion, and genetic modification before they arrive at a clinical location for administration. Experience shows that the cells must remain viable and functional along this complex supply chain, and that ineffective methods of preservation limit growth in the use of cell therapies. Effective methods of cryopreservation permit coordination of the therapy with patient care and completion of safety and quality control testing.

Many factors in cryopreservation affect the outcome of a cell therapy, including formulation and introduction of a freezing medium, cooling rate, storage conditions, thawing conditions, and post-thaw processing.{3} Industry experts report that post-thaw processing of cryopreserved cells varies greatly, with some studies infusing the cells immediately upon thawing, some diluting the cells in a carrier solution of varying formulation before infusion, some washing cells to remove cryoprotective agents, and others reculturing cells to recover any viability or functionality lost due to cryopreservation. To address these variables, many clinical trial researchers depend upon a third-party resource to advise on these decisions and augment in-house expertise.

Demand Forecasting and Supply Chain Logistics

While it is often difficult to accurately predict the manufacturing capacity that will be needed when a new, innovative product is finally launched, the advent of CGTs requires demand forecasting unencumbered by the uncertainties of the CGT supply chain or the absence of long-term historical data. Despite these issues, manufacturing capacity should be matched carefully with demand so that patient-specific doses are delivered just in time to sites of care,{4} including independent facilities, hospital-based centers, clinical trial sites, and the home setting. Experts advise that beginning dynamic demand forecasting as early as three years before the actual launch optimizes the supply chain design.{5}

Accurate forecasting should establish a digital supply chain thread that includes real-time track-and-trace data on critical information such as the location and quality of cells extracted from patients for autologous cell therapies, reports that follow the patient journey, and market intelligence that captures payer reimbursement levels. Precise forecasting also requires specific data on the size of the eligible patient population, including real-world evidence of treatment outcomes and quality-of-life scores for patients.

All providers in the supply chain should be part of the chain of identity and chain of custody, capable of tracing and recording every step of the product’s journey and every person/container involved, from the sourcing of raw materials to final delivery to the patient.


  1. Hunt T. 2023. The Cell and Gene Therapy Sector in 2023: A Wave is Coming – Are We Ready? IN VIVO. https://invivo.pharmaintelligence.informa.com/IV146781/The-Cell-And-Gene-Therapy-Sector-In-2023-A-Wave-Is-Coming–Are-We-Ready
  2. Li R, et al. 2019. Preservation of cell-based immunotherapies for clinical trials. Cytotherapy 21(9):943–57. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6746578/
  3. Mogilyanskiy L. 2019. What factors can impact your cryopreservation quality? Eurofins Bio/Pharmaceutical NEWS. https://www.eurofins.com/biopharma-services/product-testing/news-events/newsletters/winter-2019/what-factors-can-impact-your-cryopreservation-quality/#:~:text=The%20quality%20of%20cryopreservation%20depends,freeze%20profile%20that%20are%20used
  4. McKinsey & Company. 2022. https://www.mckinsey.com/industries/life-sciences/our-insights/viral-vector-therapies-at-scale-todays-challenges-and-future-opportunities
  5. McKinsey & Company. 2022. https://www.mckinsey.com/industries/life-sciences/our-insights/eight-imperatives-for-launching-cell-and-gene-therapies

Dea Belazi

Dea Belazi, PharmD, MPH, is President and CEO of AscellaHealth.