RegMedNet explains how COVID-19 has affected CAR-T therapy supply chains, from transporting raw materials to manufacturing and delivering therapies.
COVID-19 has profoundly disrupted many industries, including the life sciences sector. One of the biggest disruptions that the life sciences sector has seen is longer supply chain delays for CAR-T therapy (chimeric antigen receptor T cell therapy), the immunotherapy that involves using patients’ immune cells to treat their conditions. The already complex supply chain and production processes for CAR-T therapy have placed additional strains on many manufacturers, who have worked to deliver raw materials and therapies throughout the pandemic.
Here, RegMedNet explores how COVID-19 has affected the supply and manufacture of CAR-T therapy, how cell therapies are enabling researchers to develop COVID-19 research, and the good practices and safety concerns that surround manufacturing CAR-T therapies.
The Impact of COVID-19 on CAR-T Therapy Supply and Manufacture
COVID-19 has highlighted the fragility of the CAR-T therapy supply chain and the obstacles that often stem from inefficiencies and mismanagement. Supply chains in the cell therapy space rely heavily on strong coordination to ensure effective timing. However, many manufacturers have faced capacity issues and delays in their supply chains during the pandemic, both of which have hindered manufacturing.
On top of this, transportation limitations (like reduced flights) have made it difficult for many supply chain parties to move products during the pandemic. For example, COVID-related transport limitations have seen some vendors only make stem cell collections in areas with low COVID-19 infection rates. Other vendors have broadened the number of couriers that they work with to avoid relying on one carrier during such a turbulent time. Some researchers have also tried to minimize variability from site to site during stem cell collections and note that new regulations could standardize stem cell collections across multiple regions.
Furthermore, during the pandemic, many manufacturers who collect starting materials have been reassigned to work on emergency tasks or have had to work remotely, leaving some supply chains undermanaged. The spread of COVID-19 has also left many staff members self-isolating. To overcome these workforce challenges, some manufacturers have used software that allows them to monitor workflows and authenticate processes remotely.
Another obstacle has arisen from the fact that different manufacturers tend to ask the same suppliers to work using different protocols. Such a request can drain resources for suppliers, who are trying to keep up with the demand for clinical delivery. As a result, there is a need for commonality across manufacturers so suppliers can automate their processes and streamline supply chains.
Safety and Quality Assurance in Raw Materials
Ensuring that the starting material, whether from a healthy donor or a patient, is of high quality can make the overall supply chain process particularly complicated. This is primarily because researchers must adhere to various policies and regulations to ensure the safety of both donors and patients.
Manufacturers must also check that materials arriving from all over the world are correct and will meet patients’ needs. This pressure can make it difficult for manufacturers to know how much inventory to carry. Some manufacturers may also need to preserve stem cells, which they may not have the infrastructure to do.
Meanwhile, some manufacturers order their materials from only one source, which can cause supply chain issues if that one source faces a blockage. This can be especially time-consuming when manufacturers need to validate new processes with new suppliers.
Raw materials aside, the quality of disposables and packaging containers is also important, and many manufacturers have struggled to source disposable kits throughout the pandemic.
Cell Therapy in COVID-19 Research
Many researchers who analyze potential therapeutics have pivoted their studies to focus on COVID-19 during the pandemic, which became a new priority for many. This gear shift has been bolstered by funding for COVID-19 research projects from agencies like the Department of Defense and the National Institutes of Health. However, although cell therapy has come to the forefront of many COVID-19 research projects, the rush to conduct this research has undermined quality in some places.
Meanwhile, some illicit stem cell clinics have offered unproven COVID-19 therapies, many of which focus on stem cell administration. Stem cell medical tourism was a problem before COVID-19, and this problem has unfortunately grown with the pandemic. Therefore, before using a clinical study, it’s important to check that the study:
- Is regulated by an appropriate authority like the FDA in the U.S. or the EMA in the EU.
- Has been conducted transparently; researchers should make the source and biological attributes of cells they are utilizing clear.
- Involves a control group of participants who have received a placebo in a randomized, double-blind fashion (alongside the participants who have tested the new medication or therapy).
Good Practices for Manufacturing CAR-T Therapies
These are some of the most important practices in manufacturing CAR-T and other cell therapies.
1. Ongoing Training and Collaboration
As the cell therapy field rapidly grows, so does the need for ongoing training and collaboration among stakeholders. This is especially important as training gaps can lead to quality and safety issues: Clusters of expertise have emerged as cell-based therapies have advanced over the past four decades, but these pockets of know-how have created silos to protect intellectual property. This owes to funding constraints and limited knowledge mobilization activities. As a result, gaps in the standardization of training have arisen.
COVID-19 has underlined the need for more capacity in biotherapeutics manufacturing. This rise in capacity will rely on a sufficient talent pool, effective training modalities, and reduced person-to-person contact. If cell therapy researchers apply the same level of collaboration to cell therapy as they have to the race for a COVID-19 vaccine, the cell therapy field could see huge growth. For example, sharing sequencing data on SARS-CoV-2 strains facilitated candidate vaccine production and clinical testing. Taking a similar approach to CAR-T therapy could expedite sector growth.
2. Common Standards
The cell therapy field needs common standards to ensure high-quality, safe manufacturing and keep collaborative manufacturing processes consistent. A harmonized training approach is key here. There are many cell therapy platforms under development, so the challenge is to identify the common underlying skills and tasks that apply to each and ensure training reflects these. This way, researchers can improve participant capacity and enrollment while streamlining the time required to reach training goals.
3. Government-Led Initiatives
The cell therapy space also needs government-led initiatives to advance the sector. Such initiatives could include financial investments and a mandate to trigger economic developments around the field’s expansion. This way, researchers can standardize innovative CAR-T and other cell therapy practices. A reform of the regulatory framework could also lay the groundwork for advanced clinical studies and the commercialization of cell therapy technologies.
Additionally, a greater network of advanced therapy centers would enable the growth of expertise in supply chains, manufacturing, clinical delivery of therapeutics, and patient follow-ups. Such growth in resources would increase manufacturing capacity and enable a higher level of delivery to patients.
ISCT Safety Considerations for CAR-T Therapy
These are some of the safety considerations that researchers can uphold to ensure quality in CAR-T and other cell therapies.
1. Transparency
Transparency in CAR-T therapy is essential to safe communication with patients. In the cell therapy field, many treatments offered aren’t yet consolidated. This is acceptable, but only when patients and clinicians know the therapies are experimental, not routine, procedures. Therefore, it’s important to have surveys or registries that transparently capture different studies. This transparency enables the eventual standardization of methods and contributes to patient safety.
That said, no single organization can take full responsibility for transparency. That’s why the International Society for Cell and Gene Therapy (ISCT) enables various international societies and working groups that are active in the domains of cell and gene therapy to communicate and collaborate on such matters.
2. Real-World Data
Researchers can use real-world data in regenerative medicine testing to improve transparency. In any study, researchers should disclose the number of patients, the types of cells tested, the indications, and the groups tested. Real-world data can refer to the number and modalities of treatments performed and doesn’t have to refer to an outcome. Such data can capture trends and track changes in the sector. This information could be invaluable to clinicians and patients.
3. Developing Therapies for Small Patient Cohorts
As researchers develop and hone cell therapies for rare diseases with small patient cohorts, developing and using registries risks studies remaining anecdotal in nature. But converging the efforts of multiple societies across different geographical regions could enable researchers to transform anecdotes into accessible data. In this case, globalization could open opportunities to develop cell therapies for rare diseases.
4. Point-of-Care Manufacturing for Cell Therapies
The pandemic has triggered a rise in point-of-care manufacturing, which could become a valid model for delivering cell therapy products like CAR-T therapy. In this case, manufacturers would need to produce therapies in a decentralized fashion, much like manufacturers of transfusion products, to bypass logistics challenges.
That said, this approach would lead to challenges surrounding the monitoring of production through in-process controls and microbiological analyses. These must be properly transferred while upholding rigorous standardization. Technological advances in the availability of closed and automated bioreactor systems for graft manufacturing and cell culture could facilitate this kind of manufacturing in future.
The Future of the Cell Therapy Supply Chain
COVID-19 has highlighted the gaps in the supply and manufacture of CAR-T therapy and other cell therapies, spotlighting areas that need development. The pandemic has also made the need for robustness in supply chains clearer. These insights from the pandemic could help researchers plot a sturdier future for the supply and manufacture of CAR-T and other cell therapies.
A Community for Scientists and Researchers
RegMedNet is a community site for research professionals and scientists across the regenerative medicine sector. The site provides the digital resources that these professionals need to keep up with this fast-moving field. These resources include free webinars, peer-reviewed journal articles, and news pieces. Users can access a host of resources about cell therapies’ development, manufacture, regulation, and commercialization.
RegMedNet’s sister journal Regenerative Medicine published its first issue in 2006. Since then, the peer-reviewed, open-access journal has consistently published high-quality papers and reviews that cover the whole regenerative medicine sector. Users can catch up on matters concerning small molecule drugs, biomaterials, biologics, cell and gene therapies, and tissue engineering.
Together, RegMedNet and Regenerative Medicine serve a fast-growing, multidisciplinary community with information on advances in regenerative medicines and a specialist forum for experts to address challenges and advances in their fields.
