Pre and Post-Pandemic
There were a total of 1,129 cell and gene therapy companies in operation globally, operating over 2,228 active cell and gene therapy clinical trials in 2022 (1). US $23.1 billion was invested in the sector in 2021. The COVID-19 pandemic has accelerated the development of viral vector technology for vaccines and the sector is set to reap the benefits from this investment. On the flip side, the pandemic has also posed challenges to the industry's supply chain. Consideration of raw materials and supplier selection, material quality and safety assurance, current good manufacturing practice (CGMP), and other regulatory requirements have been essential to overcome pandemic-related supply chain challenges.
Clinical development is crucial to the advancement of cell and gene therapies. It allows patients to try candidate therapies and generates data to advance medicines toward commercialization. The COVID-19 pandemic stalled some advancements in clinical trials. At least 322 clinical trials conducted or sponsored by biopharma companies did not advance as originally planned by July 2020. One way it did so was the reduced access to hospitals due to pandemic protocols. (2) Despite study management guided by regulatory authorities, interruptions to clinical trials occurred. Starting in early 2020, sponsors about to launch studies had to wait for conditions to improve or for the development of new safety protocols. Now in 2022, the landscape has improved, and there is active recruitment to clinical trials, with patients able to access hospitals for treatment and candidate products can be shipped under certain conditions.
While the pandemic was disruptive, it accelerated trends in three key areas: clinical trials, cold-chain capabilities, and manufacturing capacity.
Despite these setbacks, the CGT industry may benefit in the end from technologies used in response to COVID-19. While the pandemic was disruptive, it accelerated trends in three key areas: clinical trials, cold-chain capabilities, and manufacturing capacity. (2) Additionally, there are more than 100 mRNA vaccines in development for infectious diseases (excluding COVID-19) or oncology. (3)
CGT innovators often rely on partnerships to complete development tasks within acceptable timelines. Preparing for clinical trials requires parallel workflows with modified time frames. Pandemic promoted digitally-enabled processes/enrollment/participation adoption and innovative clinical trial design. Cell and gene therapy companies can leverage new practices such as remote monitoring for long-term follow-up and develop master protocols to accelerate trials. These measures may reduce the supply chain burden.
Additionally, cell and gene therapies clinical trials have raw material needs. Supplies such as enzymes, lipids, and syringes needed to produce hundreds of millions of vaccine doses are challenging to acquire with limited time. Such challenges reflect the successes of a rapidly growing field and the need to generate high volumes. But COVID-19 mRNA vaccines improved cold-chain manufacturing, distribution, and storage capabilities. (2) Single-use assemblies and bulk media materials were particularly hard-hit by the pandemic, and the industry worked on addressing these shortages. These advancements provides a cold-chain platform that can be used for cell and gene therapy products moving forward.
Certain supply chain issues are not new. Biopharmaceutical manufacturers faced problems with changing lead times and delays before the pandemic. The industry is also experiencing shortages of certified reference materials. The variable activity of materials is difficult for manufacturers to handle. In response, suppliers must either buy reference materials or prepare them in-house. Specifically, ensuring the activity and consistency of materials such as cytokines is essential. Recently, for example, Regenxbio brought production of AAV vectors for Duchenne Muscular Dystrophy in-house due to a quality issue they had with their third-party CDMO. (4) The UK CGT workforce needs to expand from 3,000 in 2019 to 6,000 in 2024. The Advanced Therapies Skills Training Network (ATSTN) funded with £4.7 million was launched to support this objective.
COVID-19 viral vector vaccine manufacturing has drawn reagent resources away from the chimeric antigen receptor (CAR)-T cell therapy industry (5). Shortages of other important materials like plastics are common. Filling the labor gap is also difficult. For example, 83% of the UK CGT sector stated that skilled employee shortages will be a major risk that could derail forecasted expansions. (6)
Manufacturing an autologous cell therapy starts with cell collection (usually blood) from the patient in a clinical or apheresis facility, ending with the administration of the final drug product to the patient at the bedside. Dozens of transfer and processing steps take place between cell collection and administration to the patient. Patient-to-patient variability and the complexity of maintaining a live cell therapy in the supply chain differentiate cell therapy from more traditional pharmaceutical manufacturing. One-third of all cell therapy companies have reported delays or discontinuation of manufacturing activities. (2)
Mapping the entire supply chain is essential to ensure success. Risks must be fully understood, especially at critical
transfer points. Automation can lower process risk and must be brought to bear where possible. Custody and identity are maintained throughout the entire manufacturing supply chain as autologous cell therapies are personalized products with a batch size of one.
Uniquely, the starting material is different every time, a situation quite different from the typical manufacturing scenario. It is both a living starting material and a living product. Patients who typically provide the raw material have different genetic backgrounds, stages of the disease, and medical histories, all of which can introduce upstream complexity and variability into the production process.
1. Lambert J. Introduction and Industry Update. Alliance for Regenerative Medicine’s 12th Annual Cell & Gene Therapies State of the Industry Briefing. January 2022.
2. Tingting Qiu et al., The impact of COVID-19 on the cell and gene therapies industry: Disruptions, opportunities, and future prospects. Drug Discovery Today, October 2021, 26(10): 2269-2281.
3. Macdonald, Gareth. “COVID CDMO Investments to Benefit Wider Sector - Bioprocess Insider.” BioProcess International, 16 June 2021
4. Stanton, Dan. Regenxbio: ‘CDMO Issue Validates Inhouse Gene Therapy Investment,’ Bioprocess Insider, 9 May 2022,
5. Zamecnik, Adam, et al. “A Perfect Storm: COVID-19 Viral Vector Manufacturing Adds Further Burden to CAR-T Development.” Pharmaceutical Technology, GlobalData, 21 Mar. 2022,
6. Hargreaves, Ben. “UK CGT Sector Employment to Double - Bioprocess Insider.” BioProcess International, 4 Jan. 2021, .
