Vince Paolizzi, Peli BioThermal

A quick look at the history of cell and gene therapy (CGT) shows an industry with decades of incremental growth followed by more recent acceleration. With fast growth comes a pattern of progress through trial and error. A peek into recent headlines shows this in real time, with conversation around improving accessibility, managing costs through research and development, and perfecting a just-in-time (JIT) manufacturing and delivery model.

Unlike many pharmaceutical products, CGTs are a one-to-one treatment. Starting materials most often originate from the patient, and the final therapy is infused back into the same patient. There’s no room for delay or temperature excursions. The supply chain must operate flawlessly.

Though the words "cell and gene therapy" are used in combination, they are different fields of biomedical research and treatment. Both treat, prevent, and cure genetic and acquired diseases. However, they work differently.

According to FDA, gene therapy is used to modify a person’s genes with the intent to treat or cure a disease.

 By contrast, cellular therapy uses healthy transplanted human cells to grow, replace, or repair damaged tissue that causes disease.

 These cells either originate from the patient (autologous) or a donor (allogeneic).

Hematopoietic blood stem cell transplantation—a cell therapy—was first explored in humans in the 1950s and is currently a well-established treatment for blood diseases. Gene therapy was first introduced in the late 1970s, and the first trial in humans began in 1990 when colleagues at the National Institutes of Health (NIH) performed the first-approved gene therapy procedure on a 4-year-old with severe combined immunodeficiency (SCID).

Growth for the CGT market is exponential and expected to continue a rapid climb for the foreseeable future. Currently, most of the therapies use products derived from blood samples. But with growing momentum to develop treatments for solid tumors and other tissues, more products with different requirements are likely to emerge. In 2021, the CGT market size was $5.9 billion. The market is expected to reach $42.56 billion by 2030—a compound annual growth rate (CAGR) of 39.42%. Additionally, there are currently seven approved CGT drugs in the US with 1,200 in the pipeline.

Though becoming increasingly complex as pharmaceutical manufacturers expand globally, a typical pharma supply chain is straightforward. A product is manufactured, it’s distributed to retail pharmacies and hospitals, and it’s provided to patients. On a commercial scale, these products are delivered in large quantities and not unique to a specific patient.

CGTs, on the other hand, are unique to a specific patient and not currently manufactured at scale. Starting materials most often originate from the patient, are sent to a manufacturing site to create the therapy, delivered back to the same patient’s bedside, and infused into the patient. Key touchpoints in the supply chain are handled at medical facilities that vary in infrastructure, available equipment, technologies, and staff trained in processes, such as temperature control.

Since CGTs are generally a treatment of last resort, patients are often very sick. Many would not be able to donate a second blood sample if the first sample or therapy experienced damage. The supply chain leaves no room for error. One delay or a temperature excursion that renders a therapy obsolete can mean life or death for a patient.

Foolproof temperature control is necessary, especially when shipping a patient’s cells to a biotech organization. Yet medical facilities may not have equipment to refrigerate or freeze cells, space to store bulky temperature-controlled packaging, or appropriate freezers to condition packaging components.

Staff familiarity with and training on temperature-controlled packaging could also introduce risk in the form of temperature excursions.

Companies that specialize in temperature-controlled packaging now make single-use and reusable shippers to help overcome many of these challenges. New refrigerated shippers require no conditioning, are more compact and lightweight than traditional shippers, and require only the touch of a button to activate the cooling process for refrigerated materials.

These systems use evaporative, reactive cooling technology that responds and adjusts to varying ambient temperatures. This ensures the payload remains between 2-8°C and is protected from external temperature fluctuations throughout the duration of the shipping process. Therapies shipped back to a patient’s bedside often ship frozen using vaporized liquid nitrogen (LN2). This requires special training, since LN2 can cause frostbite or skin burn if touched, and its gases can damage delicate eye tissue.

Maintaining supply chain integrity is critical to mitigating risks and ensuring the safe and secure transportation of health-giving and life-saving cells and therapies. And stakeholders in pharmaceutical shipments are demanding increasing levels of transparency regarding the status of shipments, including location information and temperature history.

Cold chain and courier companies can use advanced asset management software to monitor temperatures and validate location information. Real-time temperature monitoring using smart loggers and devices connected to the internet of things (IoT) makes it possible to understand what happens to a payload in transit. This real-time information is especially helpful when a payload is hand couriered to a final destination, allowing preventive or corrective supply chain actions as they’re needed.

GPS and cellular are current technologies that provide real-time location tracking, though they are not widely used. GPS technology tends to be heavy, expensive, and takes up a fair amount of payload space. Additionally, when loaded on an airplane, the tracking signals must be turned off so that they do not interfere with airplane navigation. This technology is most often used with individualized chimeric antigen receptor T-cell (CAR-T) therapies, where the loss of a product could mean life or death for the patient. When exact location and condition is not needed, JIT devices offer the ability to review historical information about a shipment.

The CGT industry is at a pivotal point as it transitions out of early development and into rapid growth. Its long-term success will depend on managing costs with innovative strategies to create more “off-the-shelf” therapies, or proving the cost and benefit of current therapies align, scaling manufacturing while keeping costs low, and optimizing the supply chain.

CGT companies face several complex challenges, including protecting the integrity of temperature-sensitive, high-value payloads during transportation. As the market continues its evolution, CGT manufacturers, cold chain companies, and other stakeholders will need to work closely to standardize the supply chain. The future of CGTs depends on this coordination.

https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/what-gene-therapy

https://alliancerm.org/technologies/cell-therapy/

3. Scheller, E.L.; Krebsbach, P.H. Gene Therapay: Design and Prospects for Craniofacial Regeneration. 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2907101/#:~:text=On%20September%2014%2C%201990%2C%20W,)%20(Anderson%2C%201990)

4. Cell and Gene Therapy Market Size, Growth, Trends, Forecast Report 2022-2030. Vision Research Reports, August 11, 2022. 

https://www.biospace.com/article/cell-and-gene-therapy-market-size-growth-trends-forecast-report-2022-2030/

Vince Paolizzi is the Director of NanoCool Sales, Peli BioThermal.

Articles

How cell and gene therapies can be safely protected as they move along the supply chain, even when temperature-related challenges present themselves.