mRNA Synthesis

Overview

The applications of RNA, in both basic research and clinical R&D, have increased after advances in the field of molecular biology have significantly improved the in vitro stability of such molecules. Presently, there are more than 150 therapeutics and vaccines, either based on mRNA molecules, or involve the use of mRNA in their respective production processes, which are being evaluated for the treatment of a wide variety of indications. It is worth highlighting that most of the aforementioned product candidates are in the preclinical stages of development. Prominent examples include dendritic cell vaccines, T cell therapies, other anti-cancer therapies / vaccines, and stem cell therapies, which are modified in vitro using transgenes encoded into mRNA vectors; on the other hand, there are certain novel therapeutic paradigms that are exploring the in vivo transformation of cells using stable mRNAs (carrying therapeutic gene segments) that are delivered via viable nanocarriers. In fact, the first two of the vaccines to be approved (Pfizer / BioNTech’s BNT-162 and Moderna’s mRNA-1273) against the SARS-CoV-2 viral pathogen, were based on mRNA and have recently been approved for use across various global regions. According to the CDC, more than 374 million doses of vaccines have been delivered in the US alone. 

The success of the anti-COVID-19 vaccines has created an enormous need for consistent supply of these new vaccines; for instance, Pfizer needs to deliver 1.6 billion doses and Moderna needs to produce between 800 million to 1 billion doses of their respective products by the end of 2021. As a result, there is an evident increase in demand for mRNA manufacturing capacity. Fundamentally, the production of this biomolecule is complex, cost intensive and requires specialized expertise. In addition, scaling up the manufacturing of RNA is also associated with a number of challenges, mostly related to process development, and maintaining purity and stability. Referring to scaling up of manufacturing activities to meet pandemic level requirements, Tanya Alcorn, Vice President of Pfizer’s biopharmaceutical global supply chain, recently identified the need for harmony in the efforts of the various stakeholders (suppliers and manufacturing teams) in order to adequately amplify production output. Moreover, some of the processes associated with mRNA production, such as the purification step, involve the use of hazardous solvents / materials. Once manufactured, mRNA therapeutics need to be stored in conditions that do not compromise their stability (thereby, requiring specialized facilities and cold chain transportation); they also require appropriate drug delivery systems to efficiently administer the intervention (in a manner that they can avoid degradation by cellular endonucleases). Given such technical and operational challenges associated with the production of RNA-based products, innovators in the biopharmaceutical industry are increasingly leaning on contract service providers. Moreover, the COVID-19 pandemic has caused a notable surge in outsourcing activity, with vaccines developers entering into strategic deals with contract service providers to cater to the urgent global demand. The services landscape features a mix of large, mid-sized and small companies, which claim to have mRNA-related capabilities. Recent developments in this segment of the biopharmaceutical industry indicate that service providers are upgrading their capabilities and infrastructure to accommodate the current and anticipated demand for this novel class of biologics. In the foreseen future, as more of such RNA-based leads mature and move into the clinic and / or the market, we anticipate the mRNA synthesis service providers market to witness healthy growth.

Scope of the Report

The “mRNA Synthesis and Manufacturing Market, 2021-2030” report features an extensive study of the current market landscape and future opportunity for the players involved in the synthesis of research- and GMP-grade mRNA for use in development of therapeutics and vaccines. The study presents an in-depth analysis, highlighting the capabilities of various stakeholders engaged in this domain, across different geographies. Amongst other elements, the report includes:

• A review of the overall market landscape of mRNA synthesis service providers  (custom synthesis service providers and cGMP service providers), including analysis based on the services offered (custom synthesis, modification, purification, process development, scale-up / manufacturing, formulation and fill / finish), type of modification (3’ modification, 5’ modification, base modification), types of purification techniques (precipitation, chromatography, electrophoresis and others ), input data for synthesis (plasmid DNA, mRNA sequence, PCR fragments and others), scale of operation (research / preclinical, clinical and commercial), GMP compliance, and mRNA specifications (length  and quantity). In addition, the chapter provides the list of companies involved in the development of custom mRNA synthesis kits along with information on kit type, number of reactions, type of enzyme, incubation time, cap included, modified bases included, yield and price.
• Elaborate profiles of key players engaged in the synthesis of mRNA (shortlisted based on strength of service portfolio). Each profile includes a brief overview of the company, mRNA synthesis service highlights, information on additional services offered, recent developments and an informed future outlook (if any). Additionally, the chapter also includes profiles of the key mRNA synthesis kits providers (shortlisted based on strength of product portfolio).
• An insightful company competitiveness analysis, highlighting prominent custom mRNA service providers, based on supplier strength (based on the company’s employee count), service portfolio strength (which takes into account the number of services offered by the company), scale of operation and geographical location of the company.
• An analysis of the partnerships and collaborations that have been established since 2014, covering manufacturing agreements, supply agreements, acquisitions, technology development agreements, and other relevant deals. The chapter includes analysis based on various parameters, such as year of partnership, type of partnership model, geographical distribution of partnering activity and most active players (in terms of number of partnerships inked) in this domain. 
• An analysis of the initiatives related to mRNA, undertaken by big pharma players, based on parameters, including number of initiatives, year of initiative and the type of initiative.
• A detailed analysis of completed, ongoing and planned clinical trials of mRNA-based therapeutics and vaccines taking into consideration several relevant parameters, such as trial registration year, number of patients enrolled, gender of patients enrolled, trial phase, recruitment status, and study design, highlighting the leading players (in terms of number of trials conducted), type of organization, key therapeutic areas and regional distribution of trials.
• An informed estimate of the current annual demand of the marketed mRNA-based  products (in grams); the analysis takes into consideration the number of doses ordered, dosing frequency and dose strength of the products. The annual clinical demand of mRNA-based drug products was also estimated based on parameters, such as ongoing and planned clinical trials, enrolled number of participants (if available), quantity of mRNA used in each dose and number of doses.

One of the key objectives of the report was to estimate the future growth potential of mRNA synthesis services market, over the coming decade. Based on multiple parameters, such as mRNA products market, cost of goods sold, manufacturing cost and share of outsourcing, we have provided an informed estimate on the evolution of the market for the period 2021-2030.  The report features the likely distribution of the current and forecasted opportunity across [A] Type of Products (API and drug products) [B] Application Areas (Infectious Disease Vaccines, Other Vaccines, Therapeutics and Others), [C] Scale of Operation (Research / Preclinical, Clinical and Commercial), [D] Key Geographical Regions (North America, Europe, Asia-Pacific and Rest of the World). In order to account for uncertainties and to add robustness to our model, we have provided three market forecast scenarios, portraying the conservative, base and optimistic tracks of the anticipated industry’s growth.

Key Questions Answered

• Who are the key service providers engaged in the custom synthesis of research-grade mRNA?
• Who are the key service providers engaged in the manufacturing, formulation and fill/finish of GMP-grade mRNA?
• Which regions are current hubs for GMP grade production of mRNA?
• Which companies are actively involved in conducting clinical trials for their mRNA-based therapeutics and vaccines? 
• Which regions are leading the enrollment of patients in mRNA-based therapeutics and vaccines clinical trials?
• Which partnership models are commonly adopted by stakeholders engaged in this domain?
• Which factors are likely to influence the evolution of this market?
• How is the current and future market opportunity likely to be distributed across key market segments?