Cell and gene therapies have revolutionized the treatment of a number of diseases, offering hope to thousands of patients who previously had limited, or no, therapeutic options. Recent key advances just in this past year have included expanded approval for the first gene therapy for Duchenne muscular dystrophy and two gene-modified cell therapies for sickle cell disease (including the first-ever FDA-approved CRISPR therapeutic).

The potential of these therapies, and clinicians’ willingness to embrace cell-based treatments like CAR-T, has led demand for these innovative medicines to often outpace supply. For example, following the launch of CAR-T products Abecma and Carvykti, it has been reported that supply issues were hindering patient access.

Boom and Bust

The complexity of advanced therapies, however, means that boosting manufacturing in the face of shortages can both be costly and come with long lead times. To overcome these hurdles, businesses have adopted a variety of strategies to bolster supplies of cell and gene therapies.

Companies like Bristol Myers Squibb chose to build their own in-house manufacturing facilities. In 2021, the New Jersey-based pharma announced the construction of two state-of-the-art cell and gene facilities in the Netherlands and Massachusetts. Pfizer also announced plans to expand its manufacturing capacity in 2021 with an $85.5m investment in a plant in North Carolina. Others have outsourced the task to contract development and manufacturing organizations (CDMOs). In addition to offering specialist expertise and scalable operations, outsourcing has provided significant financial advantages by reducing investment risk.

But cell and gene therapy manufacturing has not seen consistent growth, instead mimicking the cyclical nature of other industries. The downturn in the economy between 2022-2023 caused investment in manufacturing to slow dramatically as interest rates rose. The challenges for the CDMO industry in particular were compounded by reduced capital investment in cell and gene therapy innovators, which led to fewer customers for third-party manufacturers. Uncertainty about the future – and the desire to preserve cash – led many biopharma companies to either halt or slow down major capital expenditure projects. Some contract manufacturing companies responded to the uncertainty by laying off staff. In 2023, Thermo Fisher announced the shuttering of its New Jersey cell and gene therapy facility citing changing manufacturing demands.

Out of Step

After several challenging years, confidence in the biopharma industry is now returning, helped by falling interest rates. But the 2022-2023 slowdown in expanding manufacturing capacity stood in stark contrast to the number cell and gene therapy products entering the clinic. IQVIA recently reported that 406 clinical trials of cell and gene therapy products were started in 2023 alone. This boom in clinical products has resulted in a fresh round of supply issues.

The CPHI’s Annual Industry Report also revealed that 50% of pharma execs are predicting cell and gene manufacturing capacity limitations, ‘leading to slower approvals and a potential decrease in manufacturing contract numbers’. So once again, businesses are exploring ways in which they can increase manufacturing capacity. But recent events have impacted companies’ expansion decision, particularly as they consider partnering with a CDMO.

Geopolitical Considerations

One of the world’s biggest contract manufacturers, WuXi AppTec, has found itself in the crosshairs of the Biosecure Act. Wuxi, which has been involved the development of a quarter of drugs approved in the US, has been accused of transferring US intellectual property to entities in China, an allegation it strenuously denies.

These allegations prompted the drafting of the Biosecure Act. Passed by the US House of Representatives and under consideration in the US Senate, the Act blocks any US federal funding to companies that use equipment or services from ‘foreign adversary biotech companies of US national security concern’.

In real-world terms, US biopharma companies with contracts with Wuxi would have to cut their ties to the company by 2032 to keep their products in Medicare or Medicaid. The Biosecure Act could also have implications beyond Wuxi customers, as many pharmaceutical companies rely on Chinese contract manufacturers. A survey by consultancy group LEK showed 68% of respondents were exploring precautionary actions with regard to their existing relationships with Chinese CDMOs, including: increasing legal and compliance requirements, diversifying partnerships and implementing background checks for existing partners.

This threat to a large source of outsourced manufacturing capacity is likely to lead companies to explore other options to ensure supply chain security, including pursuing M&A, building facilities closer to home, contacting with non-China based CDMOs and using advanced technologies.

Growth of Partnerships in India

For those looking for external CDMOs outside of China, attention has recently turned to India. Its large skilled workforce and the potential for lower manufacturing costs make it a highly attractive center for manufacturing. Mordor Intelligence is currently forecasting the Indian CDMO market will grow from $22.5bn in 2024 to $44.6bn by 2029, a figure that could be helped by the Biosecure Act.

But outsourcing to India is not without risk. Cell and gene therapy manufacturing is still in its nascent stages and drug quality remains a concern. More than 36% of the 400 drug manufacturing units inspected since 2023 in India were ordered to be shut down. These inspections came in the wake of the death of children in The Gambia, Cameroon and Uzbekistan due to tainted cough medicine produced in India.

Technological Solutions

In the face of challenges around outsourcing and increased competition for manufacturing assets, another avenue that cell and gene therapy manufacturers are exploring is advanced technologies. Companies are looking at how advances in automation, robotics, and AI could help not only speed up existing cell and gene therapy manufacturing processes, but also reduce costs.

Bristol Myers Squibb is one of the companies embracing automation. The group recently signed a $380m deal to reserve CAR-T manufacturing space with automation solutions company Cellares, which promises to lower cell therapy batch prices by 50%. CDMO companies are also investing in robotics and automation to speed up manufacturing processes.

In May, Ori Biotech launched their IRO platform, which they claim will shave up to 25% off processing times. Increased use of automation in cell and gene manufacturing will likely lead to the adoption of artificial intelligence to utilize the data produced by automation and apply it to process optimization, quality control, data analysis, and supply chain management.

The Future is Bright

The continued expansion of cell and gene therapies will lead to a corresponding increase merger activity, outsourcing, the use of advanced technologies, and companies building manufacturing capacity. Each approach offers distinct advantages, from expanding capacity to enhancing efficiency. To successfully scale production, a balanced integration of these strategies is essential, coupled with ongoing collaboration and innovation. By effectively leveraging these tools, the industry can overcome current supply challenges and accelerate the delivery of these transformative therapies to patients.