8.3  Sourcing Issues

8.3.1  Severe disruptions to supply chains due to the COVID-19 pandemic have eased and, for the most part, manufacturers are reporting that they are able to get consumables and reagents within reasonable time frames. The specialized enzymes, capping technologies, modified nucleotides, and lipids required for mRNA–LNP production, however, contribute to the high cost of mRNA products, and manufacturers are always conscious of these supply chains. There are generally only a few suppliers of these materials (^{Table 8}), and they must be selected with care to ensure appropriate quality.^[117] One of the biggest challenges is accessing GMP-compliant versions of these specialty materials for use in the clinical and commercial manufacturing of mRNA vaccines and therapeutics.^[118]

8.3.2  Although pDNA supply isn’t in the scope of logistical hurdles the manufacturer must manage, it is often the time-limiting reagent because it is custom-manufactured in an E. coli fermentation process, often at a different manufacturer. The developer, therefore, must coordinate production of the pDNA with the mRNA.

8.4  Moving Toward End-to-End Contract Manufacturing

8.4.1  Some in the industry believe that the highly fragmented nature of CDMO services in the mRNA field is one off the biggest challenges for advancement of pipeline candidates. Having to manage multiple CDMOs for pDNA, mRNA drug substance, and mRNA–LNP drug product manufacturing, as well as fill/finish activities, adds not only time and cost but complexity and significant risk of product loss.^{[117][118][119]} It is anticipated that mRNA therapeutic and vaccine developers will wish to partner with CDMOs that have the ability to produce plasmids, develop cell lines, and manufacture mRNA active ingredients and final formulated products using internal platform technologies.^[120]

8.4.2  Larger CDMOs have attempted to address this issue by acquiring smaller CDMOs that specialize in different unit operations. Others have formed collaborations to establish “end-to-end” capabilities. A few CDMOs have made specific efforts to establish integrated capabilities at one location — even under one roof. For a list of recent capacity expansions, see ^{Table 12}. The belief is that this level of integration will allow for greater efficiency, lower costs, higher product quality, and accelerated development and manufacturing.^[116]

8.5  Modularity Essential for Future Success

8.5.1  Personalized medicines are a growing percentage of the drug pipeline, and mRNA has significant potential for this type of application as well as for global vaccines. As mentioned above, this is creating a need for versatile manufacturing facilities that can accommodate many different types of RNA-based candidates and approved products produced at different scales. The set of digital tools, including not just PAT but digitalization of the entire production plant, will be crucial to enabling sufficient flexibility and agility.

8.6  CDMO Market Summary

8.6.1  In the post-COVID-19 pandemic world, however, demand for COVID-19 mRNA vaccines has declined dramatically. Both Pfizer and Moderna project demand in the fall of 2023 in the United States to be 50–100 million doses, which is much lower than the over 150 million doses administered in the fall of 2022.^[123] Moderna announced in September 2023 that it was planning to downsize its use of fill/finish outsourcing services^[124] and reduce its reliance on Lonza for drug substance production.^[123]

8.6.2  After the pandemic, projections for mRNA vaccines declined. For example, Roots Analysis estimated in February 2024 the value of the global mRNA manufacturing and mRNA synthesis services market to be $1.95 billion and declining at a CAGR of -1.7% through 2035.^[99] Projections have bounced back, however. The combined global market for mRNA vaccines and therapeutics is currently forecast to grow from approximately $63.3 billion in 2025 to over $253.8 billion by 2034, representing a compound annual growth rate (CAGR) of 16.7%.^[95] Within this broader market, the mRNA therapeutics segment alone is expected to more than double, from $20.8 billion to $42.6 billion during the same period.^[2][92] The mRNA vaccines market, while maturing after the pandemic surge, is still anticipated to expand at a robust pace, with projected growth from $10.4 billion in 2025 to $18.3 billion by 2030.^[94]

8.6.3  The global market for CDMO services related to mRNA is estimated at $4.17 billion in 2024 and is projected to grow to $6.91 billion by 2031, reflecting a compound annual growth rate of approximately 7.5%.^[1][148] While this growth is slower than the boom years of COVID-19, it reflects a steady expansion of the underlying infrastructure needed to support mRNA therapeutics and next-generation vaccines. The market is increasingly shaped by strategic partnerships between biopharma companies and CDMOs, designed to expedite development timelines, ensure regulatory compliance, and derisk manufacturing scale-up.

8.6.4  To support the unique demands of mRNA-based product development, CDMOs provide a comprehensive suite of services that span the full product life cycle. These typically include synthesis of RNA templates via enzymatic transcription, as well as downstream steps, such as 5' capping, 3' polyadenylation, purification, and quality control testing. LNP formulation — a critical component for intracellular delivery — is a core competency for many advanced CDMOs. Fill/finish, sterile packaging, and analytical and stability testing round out the offering, particularly for organizations aiming to serve as end-to-end partners.

8.6.5  Several CDMOs have emerged as leaders in the mRNA space, each bringing different capabilities and geographic footprints. Catalent, BioNTech, Samsung Biologics, and Exothera are among those with established mRNA manufacturing platforms. Quantoom Biosciences has drawn attention for its efforts to decentralize mRNA production, particularly through a pan-African initiative involving Eva Pharma and DNA Script aimed at building regional autonomy in vaccine manufacturing.^[149] These examples illustrate how CDMOs are positioning themselves not only as service providers but also as strategic actors in global health infrastructure.

8.6.6  The CDMO landscape for mRNA is also being reshaped by evolving market dynamics. A notable contraction in post-COVID demand has led some players to scale back or cancel contracts, as illustrated by Moderna’s announcement of program cuts and a $238 million cancellation charge related to contract manufacturing.^[150][151] At the same time, CDMOs are adapting by investing in dual-use capacity that can accommodate newer RNA formats, such as circular (circRNA), self-amplifying RNA (saRNA), and RNA editing–based modalities. These next-generation technologies offer longer durability, lower dosing, or more precise gene modulation and are expected to underpin future growth.^[8][98]

8.6.7  As mRNA continues to evolve beyond its initial applications, CDMOs are playing a critical role in supporting scalability, innovation, and timely market entry. Their ability to offer specialized capabilities in synthesis, formulation, and fill/finish — often on accelerated timelines — has become a key strategic enabler for both emerging biotech companies and large pharmaceutical players. With the shift toward next-generation mRNA platforms and RNA modalities such as saRNA, circRNA, and RNA editing, the market for mRNA-related CDMO services is expected to become increasingly competitive and differentiated.

8.7  Challenges and Constraints

8.7.1  Despite its promise, the RNA therapeutics and manufacturing sector faces persistent challenges that could temper growth trajectories and introduce uncertainty into commercial planning. Among the most pressing is the issue of scalability. While many companies rapidly built RNA production capacity during the COVID-19 pandemic, much of that infrastructure was oriented around emergency vaccine production and may not be readily transferable to new therapeutic modalities or non-pandemic use cases. CDMOs that expanded to meet pandemic demand are now contending with underutilized facilities and uncertain long-term demand patterns.

8.7.2  Supply chain volatility also remains a major constraint. The RNA manufacturing process depends on a range of specialized inputs, including enzymes, nucleotides, and lipid components, many of which are sourced from a small number of suppliers. Any disruption in these supply chains — whether due to geopolitical tensions, regulatory shifts, or manufacturing issues — can delay production timelines and increase costs, especially for smaller developers who lack purchasing leverage.

8.7.3  Another structural limitation is the cold chain. Many mRNA-based products, particularly vaccines, require ultra-cold storage conditions to maintain stability. This requirement complicates global distribution and increases the logistical burden for both developers and healthcare systems. While formulation advances are underway to improve thermal stability, cold-chain demands remain a significant barrier to wider adoption, particularly in low- and middle-income countries.

8.7.4  CDMO capacity, though expanded during the pandemic, remains constrained when it comes to large-scale production of newer RNA modalities. Producing saRNA, circRNA, or RNA-editing components requires not only physical infrastructure but also highly specialized technical know-how and regulatory experience. As a result, capacity gaps may emerge just as the clinical pipeline begins to diversify, creating potential bottlenecks for developers pursuing these next-generation formats.

8.7.5  Regulatory uncertainty is another challenge, especially for novel constructs that do not fit neatly into existing frameworks. While regulators have shown a willingness to engage and adapt during the pandemic, questions remain about how emerging RNA modalities will be evaluated in terms of safety, efficacy, and long-term durability. Developers may face unpredictable approval timelines and evolving data expectations as agencies calibrate their oversight.

8.7.6  Finally, the market is undergoing a period of correction and reprioritization in the post-pandemic era. Some companies have scaled back R&D portfolios or canceled CDMO contracts in response to profitability pressures, as seen in Moderna’s recent strategic shift and manufacturing cancellations.^[150] This recalibration phase reflects a more measured approach to portfolio development and capacity utilization and may impact the pace at which new RNA products reach the market. While the long-term outlook remains strong, these short-term headwinds are reshaping investment decisions, partnership strategies, and operational models across the ecosystem.

8.8  Regional Analysis

8.8.1  The global RNA therapeutics and manufacturing landscape is marked by distinct regional strengths, shaped by differences in regulatory environments, industrial capacity, and public health priorities. While North America continues to lead in innovation and commercial activity, Europe and Asia–Pacific are playing increasingly important roles in the advancement and democratization of RNA technologies.

8.8.2  North America remains the dominant force in the RNA therapeutics and mRNA CDMO markets, driven by its concentration of biotech innovation hubs, robust venture capital ecosystems, and established regulatory infrastructure. The United States is home to many of the leading mRNA developers — including Moderna and Pfizer/BioNTech’s U.S. operations — as well as CDMOs like Catalent and Thermo Fisher Scientific. The region benefits from strong translational research networks and a deep bench of clinical trial infrastructure, making it an attractive environment for early- and late-stage development. Public–private initiatives supporting pandemic preparedness and biodefense have further solidified North America’s role in advancing RNA-based platforms.

8.8.3  Europe also plays a critical role, with a combination of regulatory leadership and strategic investment in RNA technologies. The European Medicines Agency (EMA) has been proactive in creating pathways for RNA-based drug approvals, and several European governments have backed RNA manufacturing initiatives in response to the COVID-19 pandemic. Companies like BioNTech and CureVac anchor a growing ecosystem of RNA research and production. In addition, European firms such as Quantoom Biosciences are working to extend mRNA manufacturing capacity beyond the continent.

8.8.4  Asia–Pacific is rapidly emerging as both a manufacturing base and a center for RNA vaccine development. Countries including South Korea, China, India, and Singapore have invested heavily in biologics and nucleic acid infrastructure, often as part of national health security strategies. South Korea’s Samsung Biologics, for instance, has made significant investments in RNA production capacity and is positioning itself as a global CDMO leader. In parallel, regional players are advancing their own mRNA vaccine candidates, including for regionally endemic diseases. This expansion is helping to localize RNA supply chains and reduce global dependency on North American and European production hubs.

8.8.5  Together, these regional efforts reflect a global realignment of RNA innovation and manufacturing capacity. While disparities in access, technical expertise, and regulatory harmonization remain, the landscape is increasingly collaborative and interconnected, laying the foundation for a more distributed and resilient RNA ecosystem.

8.9  Competitive Landscape

8.9.1  The RNA therapeutics sector is characterized by a diverse and evolving competitive landscape, where established pharmaceutical companies, emerging biotechs, and contract development and manufacturing organizations each play distinct but increasingly interdependent roles. The current market is defined not only by the number of players involved but also by the variety of approaches they are taking to platform development, delivery optimization, and strategic partnering.

8.9.2  Among the big pharmaceutical companies, Moderna, Pfizer/BioNTech, CureVac, and Sanofi remain dominant forces. These companies led the charge during the COVID-19 pandemic, rapidly deploying mRNA vaccines at unprecedented speed and scale. Since then, they have moved aggressively into new areas, including oncology, cardiovascular disease, and infectious disease prevention beyond SARS-CoV-2. Their continued investment in mRNA and adjacent RNA technologies reflects a long-term commitment to platform-based R&D, with many also developing in-house manufacturing capacity to reduce dependency on third-party partners.

8.9.3  In parallel, a new generation of emerging biotech companies is helping to drive innovation, particularly in underdeveloped RNA modalities and novel disease areas. Companies such as Aera, Skyhawk Therapeutics, and Airna are developing advanced RNA-based therapeutics for indications including neurological disease, rare genetic disorders, and respiratory conditions. These biotechs are often at the cutting edge of RNA science, pioneering approaches that go beyond protein replacement or antigen expression to modulate RNA splicing, repair, or editing.

8.9.4  CDMOs are also playing an increasingly competitive and strategic role. The landscape includes both focused providers that specialize in particular aspects of RNA manufacturing — such as LNP formulation or in vitro transcription — and full-service organizations offering end-to-end solutions, including regulatory support and fill/finish capabilities. Strategic partnerships between CDMOs and biopharma companies have grown in prominence, as the complexity of RNA products demands specialized technical expertise and reliable scale-up capabilities. Players like Samsung Biologics and Exothera have positioned themselves as go-to partners for both mRNA and broader nucleic acid programs, with new entrants also targeting niche areas of the value chain.^[149]

8.9.5  Technological innovation remains a key differentiator across the competitive spectrum. Next-generation RNA platforms are drawing significant investment and partnership interest.^[8] Similarly, non-coding RNA therapies, including those that target microRNAs or long non-coding RNAs for gene regulation, are expanding the functional scope of RNA therapeutics beyond traditional protein expression paradigms.^[20]

8.9.6  In this competitive environment, success will increasingly hinge on scientific differentiation, manufacturing agility, and the ability to forge strategic collaborations that span the full development life cycle. As the RNA space matures, companies that can integrate platform innovation with executional excellence will be best positioned to lead the next wave of therapeutic breakthroughs.

8.10  Strategic Implications for CDMOs

8.10.1  As the RNA therapeutics sector expands and diversifies, CDMOs are being called upon to play an increasingly strategic role — not merely as service providers, but as enablers of innovation, scale, and speed. Meeting the evolving needs of both large pharmaceutical companies and smaller biotech innovators requires a high degree of platform flexibility, particularly in core capabilities such as RNA synthesis, LNP formulation, and GMP-compliant fill/finish. The ability to accommodate different RNA modalities has become a key competitive differentiator.

8.10.2  One of the clearest opportunities for CDMOs is their ability to differentiate through execution. Speed to clinic, scalability of operations, and familiarity with complex regulatory requirements are increasingly cited by sponsors as critical decision-making factors when selecting manufacturing partners. CDMOs with a proven track record in navigating evolving regulatory pathways, especially those involving novel RNA formats, are well positioned to capture a growing share of development programs. Equally important is the ability to provide flexibility in batch size and production scale, enabling both early-phase testing and commercial ramp-up within the same operational ecosystem.

8.10.3  The expansion into adjacent RNA modalities is also reshaping the CDMO value proposition. As sponsors move beyond mRNA into RNA interference, antisense oligonucleotides, and more structurally complex nucleic acid constructs, CDMOs must build or acquire new capabilities across synthesis, purification, and formulation. This includes adapting to different delivery requirements, such as conjugates or viral vectors, in addition to LNPs. Those that can serve as multi-modality RNA partners will stand out in a crowded and rapidly evolving supplier landscape.

8.10.4  Finally, partnerships with small biotech firms and academic institutions have emerged as a key growth strategy. These early innovators often bring cutting-edge science but lack the infrastructure to scale or navigate regulatory complexity on their own. By aligning early with these partners — sometimes through integrated development programs or co-investment models — CDMOs can embed themselves into the trajectory of promising new platforms and expand their influence across the RNA innovation life cycle. In this way, CDMOs are not just responding to market demand but actively helping to shape the next generation of RNA-based therapeutics.

8.11  Market Bifurcation Around Scale

8.11.1  By our analysis (^{Table 11}), there are 224 trials ongoing or pending for all RNA modalities but only 51 for mRNA modalities. The majority of these trials are for infectious diseases, but, surprisingly, non-COVID-19 indications will continue to require nearly as many patients and will drive IVT CDMO demand.

8.11.2  The noninfectious disease indications are a much smaller total patient requirement but still require many trials, which means more individual projects. Because these clients require vastly different scales per trial, the operational mode that a manufacturer may build might be quite different if they are catering to the noninfectious (mostly rare disease) indications. Although many CDMOs prefer clients that request large GMP batches, there is value to be created by catering to clients (23 trials total, nearly the same as infectious trials) with specialized logistical and scale requirements.

8.11.3  Taken together, we view the mRNA landscape as a tale of two operational systems: large scale (vaccines) and small scale (rare diseases). The large-scale operational systems will follow a batch-and-release process similar to traditional protein biologics, but the rare disease trials may require an operational workflow and corresponding quality management system (QMS) similar to that of CAR-T therapeutics and other precision medicines.

8.12  Numerous Investments in Capacity

8.12.1  CDMOs, both those offering integrated services and those focused on one or two aspects of the overall mRNA production process, are responding to expected demand growth with significant investments in capacity, including expansions of existing plants/sites and construction of greenfield facilities. Listed below are some of the announced projects.