There is a critical shortage of experienced biomanufacturing staff for advanced cell and gene therapies today. This, in turn, is creating a high demand for contract manufacturers with proven cell and gene therapy (CGT) platforms. Now, companies have no alternative but to use outsourced services. In BioPlan Associate’s 20th Annual Report and Survey of Biopharmaceutical Manufacturing¹ we found that 51.3% of the industry is experiencing critical manufacturing staff shortages. A figure that has more than doubled in only three years, from just 21.2%. This jump highlights just how serve the problem of staff shortages has become in the cell and gene therapy contract manufacturing industry over the last three years.

A major contributor to the problem is the fundamental growth of the cell and gene therapy contract development and manufacturing organizations (CDMO) segment. Of the approximately 365 global BioCDMOs of any size or platform, around 30% claim either cell or gene therapy platform capabilities. However, according to our Top1000bio.com database of global biologics facilities, only a handful of these have the capability to produce either late-stage clinical, or commercial scale therapies.²

The cell and gene therapy manufacturing landscape has changed over the past 5 years. This shift toward more sophisticated platforms that permit scale-up, more automation, and more quality systems has also shaped the contract manufacturing industry. And because the number of approved cell and gene therapy products on the market is increasing every year, the need to improve processes is becoming more urgent.

Generally, the industry has shown a near doubling over the past 5 years of the number of cell and gene therapy candidates. There is now increased pressure on the contract manufacturing sector to alleviate bottle necks. With this increased international production comes new opportunities in contract manufacturing. In response, contract pharmaceutical manufacturing has seen an increase in funding. New organizations are popping up around the world (discussed in later sections) to provide cell and gene therapy manufacturing services.

Inevitable staff storages

This international growth has led to an increased demand for highly skilled employees. Over the 20 years BioPlan has assessed industry capacity, we have long highlighted a continued worsening of staffing shortages in biologics manufacturing. However, in the field of gene and cellular therapies, which are such cutting-edge segments that there is limited staff available who have the industry knowledge required to meet the growing demand. The shortage of experienced staff has become one of the major bottlenecks of many cell and gene therapy contract manufacturing organizations (CMOs), with waiting times for trained new staff expected to take 6-12 months.

The shortage of staff in the industry is not expected to be alleviated anytime soon. Especially as cell therapies move through the pipeline, more GMP-competent organizations and individuals will be required to meet the need. This will ultimately lead to greater demand for GMP-educated and highly skilled employees. The competition for trained staff at such organizations will likely continue to spike before an equilibrium is reached. The most successful cell and gene therapy CDMOs may have to focus more on staff retention. Keeping already trained, high functioning staff will be critical as opportunities for workers rise, making it easier for existing staff to seek employment at competing organizations. This may represent a generally positive trend for CDMO staff who now have more opportunities for career growth, and international advancement. Some may be attracted to regions not traditionally known as a pharmaceutical contract manufacturing hub, such as India and China.

CGT industry continues to grow and mature

In our Annual Report, we found that process control and automation was another important point that has grown significantly (by 93%) over the past three years (Figure 1). This trend is likely due to the shortage of experienced personnel in the industry. With the lack of available employees, companies are increasingly turning to the potential future benefits of automation to help offset this deficiency.


Another clear indicator of the need for growth on the cell and gene therapy segment is the 48% increase in industry decision makers (from ~21% to ~31% over the past three years) considering modular manufacturing facilities to be a critical area in need of improvement. Companies can’t grow rapidly enough through traditional manufacturing facilities. This is an indication of the time pressures being felt by the industry. If these decision makers don’t see a solution in contract manufacturing of their cell and gene therapy products, they may be looking to modular manufacturing as a potential alternative solution. 

Contract manufacturing options for R&D also grew to 27.3% of respondents indicating the need for improvements in 2022 for clinical production, and to 24.2% for commercial production. This shows that interest in contract manufacturing organizations to aid in production has increased since 2021. Though the figures represent a drop from the peak of interest seen at the height of the pandemic in 2020, industry disruption during COVID makes the data difficult to assess.

Companies are outsourcing because of staff shortages and because they are having trouble with a few key issues. GMP-compliant commercial-scale manufacturing was a key issue for 38.8% of respondents, highlighting a lack of expertise in the industry (Figure 2). Decision makers are also focused on the manufacturing capabilities of key therapy areas such as the manufacturing of cell therapies, gene modification and viral vectors/gene therapies.

The rise of international CGT CMOs

With this increased international production comes new opportunities in contract manufacturing. In response to COVID-19 and the number of new biopharmaceutical products seeking approval, contract biopharmaceutical manufacturing has seen an increase in funding both public and private as new organizations pop up around the world to provide cell and gene therapy manufacturing services and established industry players work to maintain their lead and status. Having the capacity to manufacture pharmaceutical (small molecule) products of all kinds has become a point of national interest and healthcare policy for many regions.  And many regions have moved into more complex biologics, recombinant therapies, and other large molecule biomanufacturing. 

However, moving into advanced therapy segments such as cell and gene therapy manufacturing will require time and substantial investment in training, GMP systems, and infrastructure.

Although most of the growth in clinical and commercial scale advanced therapies will continue to be in the U.S. and Europe, powerhouses in generics and biosimilars, such as India, China and other Asia-Pacific countries do have R&D programs in these advanced therapies.

An example of such cell and gene therapy manufacturing investment in Southeast Asia is Thermo Fisher Scientific’s announcement in February that it has launched a new Cell Therapy Collaboration Center Program in Singapore. The purpose of this center is specifically to develop and accelerate cell therapy across the Asia-Pacific region, with Singapore poised to become a hub of cell and gene therapy contract manufacturing within the region.

This international expansion in the gene and cell therapy contract manufacturing is also being supported by an increasing number of large pharmaceutical companies.

Indian and Chinese markets mature

India and China have been investing in cell and gene therapy manufacturing capabilities over the past few years. China has more than 400 cell therapies in clinical trials with two cell therapies commercially approved. Although these will likely remain limited to their domestic markets, in the future, some technologies and innovations may find global interest. As pipeline products come closer to approval, the need for CDMOs in China could also increase. At present, the seven CDMOs in China involved with cell or gene therapies tend to have very small operations. However, it is possible that they will be called upon in the future to put these products into production.

India is a behind China in its production of cell and gene therapies but a group of new biotech startups in the industry are starting to tackle this problem. Organizations such as Immuneel Therapeutics and ImmunoACT are currently in the process of developing CAR-T cell therapies. While other organizations such as Stempeutics Research are in Phase III clinical trials of the cell therapy stempeucel, a treatment for osteoarthritis and diabetic foot ulcers.

Perhaps most importantly, India soon will be the most populous country in the world; along with China they represent over a third of the world’s population. Further, their consumer classes represent over 1 billion people capable of affording these lifesaving therapies. Today, there is a lack of availability of cell and gene therapy treatments in India and China. However, their domestic innovators are working to change this. As these products gain approval, local CDMOs, especially for cell therapies will be needed to bring these products to market.

Conclusion: Demand grows, staff shortages remain

The promise of cell and gene therapies are slowly being realized as more therapies enter the biologics pipeline, and more are approved. Demand for cell and gene therapy CDMO services is on the rise. Investor groups and analysts have recently expressed concern that with the interest and investment in this area, there may be an oversupply of capacity. However, physical capacity to produce a biologic is only a part of the challenge. And as these advanced therapies move through the early-stage clinical pipeline, the demand for quality systems capable of meeting GMP requirements becomes increasingly critical. 

Those quality systems demand skilled and trained staff capable of doing the work necessary to meet GMP requirements. The alternative will be to see rationing and delays in production of these life-saving therapies if they are to be commercialized.

Global expansion has also contributed to a shortage of experienced and highly skilled employees in biologics in general, but with cell and gene therapy in particular. Despite these hiring difficulties the industry has remained bullish, expecting that the economic potential of inventing not just a treatment, but a cure for many devastating diseases will resolve manufacturing hurdles. 

References
1. 20th Annual Report and Survey of Biopharmaceutical Manufacturing Capacity and Production, BioPlan Associates, Inc. Preliminary Data, Publication Date April 2023, Rockville, MD 
2. Top1000bio.com Database of Global Biologics Facilities, Accessed April 15, 2023, see: www.top1000bio.com, BioPlan Associates, Inc. Rockville, MD

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Arvind Deol is Sr. Director Strategic Research, at BioPlan Associates. His background in research, publishing, and analytics within the biotechnology industry brings strategy development, market research, competitive analysis, and business intelligence with an international perspective. He has experience with global scientific thought leader organizations, such as Springer Nature, an MSc in Biotechnology, Bioprocessing & Business Management, University of Warwick, UK and a degree in Microbiology from the University of Georgia.

Eric Langer is President and Managing Partner at BioPlan Associates. He has over 30 years of experience in biotechnology and life sciences international marketing, management, market assessment, and publishing. He has held senior management and marketing positions at biopharmaceutical supply companies. He is an experienced biotechnology strategist, marketing practitioner, publisher, and researcher. He lectures extensively on marketing, pricing, and channel management topics, and teaches at Johns Hopkins University and American University.