Samsung Biologics’ Senior Vice President, James Park, explores the opportunities emerging for CDMOs to support mRNA developers as they explore new therapeutic areas for patients.
Prior to the pandemic, messenger RNA (mRNA) drug development was niche and predominantly pointed at different disease targets, including infectious diseases and cancers. However, as pharma sought solutions, the Emergency Use Authorization (EUA) of the Moderna and Pfizer-BioNTech vaccines emerged as the fastest, most efficient way to create a vaccination safe enough to inoculate over 11 billion patients1,2. Both vaccines, offering 94% efficacy for fully vaccinated adults, rely on mRNA technology, which deliver instructions to human cells on how to fight the coronavirus through a ‘biological Trojan horse’3.
mRNA technology is proving to be the rising star of nucleic acid therapies and a practical, versatile route offering developers opportunities to innovate therapies beyond vaccines. Still somewhat niche, post pandemic, mRNA technology’s commercial capabilities and therapeutic effectiveness are still being explored by pharma. However, this discovery is being accomplished with help from contract development and manufacturing organisations (CDMOs) – compelled by the vaccine’s developers to expand capability to support vaccine development during pandemics.
Despite the challenges involved in commercially manufacturing mRNA therapeutics successfully, CDMOs are investing in the capabilities to manufacture emerging mRNA product modalities to help stay ahead of pharma’s renewed mRNA development curve.
Why mRNA has potential
One aspect that makes mRNA technology popular with drug developers is that its proteins can be easily edited. mRNA presents versatility plus flexibility to target a broader range of diseases.
The value of that versatility is reflected by the number of mRNA-based therapeutics in clinical trials. Up to July 2021, there were 17 mRNA therapeutics in clinical pipelines globally. More candidates are now in early development, many targeting cancers, ischaemic heart disease, and rare and viral diseases including rabies and HIV7.
As with mRNA technologies, lipid nanoparticle carriers, have seen similar development, advancing the potential of mRNA and enabling efficient in vivo delivery and potentially prolonged antigen expression4. These improvements facilitated the success of mRNA-based Covid-19 vaccines and highlighted the expansive abilities of mRNA technologies.
The rise of global demand
The surge in popularity of mRNA therapeutics in such a short time frame is prompting CDMOs, supporting development and manufacturing, to develop and adapt processes and operations. The investment in mRNA’s potential is significant. At the end of 2019, the combined market capitalisation of the top five public companies listed and focused on mRNA platforms was $15 billion. As of August 2021, the figure exceeded $300 billion5.
Fortunately, as mRNA synthesis relies on in vitro transcription reactions, vaccines based on it can be produced (relatively) cost-effectively, in a way that is easily scalable. Their subsequent cost-efficient production means that mRNA technologies are often payer- friendly, with their flexibility being leveraged to increase yields within an increasingly smaller facility footprint.
As with many biologics, mRNA molecules are fragile and require extensive cold chain capabilities to prevent degradation and other negative impacts throughout their journey to patients. At the onset of the Covid-19 pandemic this had manufacturers scrambling to align and expand cold chain capabilities. The speed at which the CDMO industry and its logistics partners aligned cold-chain capabilities to support the distribution of mRNA-based vaccines contributed materially to one of the fastest commercialisation timelines in pharmaceutical history. Unfamiliar formulation techniques, including the application of lipid nanoparticles, also had an impact on production timelines.
A key aim for most biopharma companies is to achieve commercialisation in the shortest time while maintaining high quality. This is a primary reason why so much of biologic drug development and manufacturing has been assigned to external partners. The urgency stemming from the pandemic meant that mRNA-based products had to demonstrate safety and efficacy in an even shorter timeframe. Even with regulatory agencies’ fast-track approval procedures, many CDMOs still needed to employ extraordinary measures to achieve production efficiencies with existing capabilities – and do this while meeting the accelerated timelines and capacity requirements that pharma and society were demanding. That accelerated innovation and investment in optimising most aspects of development and manufacturing to reduce risk, while assuring product quality, patient safety and therapeutic value.
Supply chain vulnerability
Much of the industry agrees that the pandemic’s impact exacerbated supply chain problems. The focus on developing mRNA vaccines had a gravitational effect on pharmaceutical development and its incumbent global supply chains. The pull from companies aiming to support Covid-19 vaccine development, production and distribution had an impact. Some biomanufacturers reported waiting up to a year for single-use equipment critical to core
In particular, mRNA technology is proving to be the rising star of nucleic acid therapies processes. The pandemic also highlighted how reliant biopharma’s manufacturers were on certain countries. For example, manufacturers using sterile bags for cell cultivation were dependent on a handful of companies globally6.
Supply disruptions and shortages have always had the potential to delay pharmaceutical development and patient access and mRNA-based projects are no exception. Pharma is beginning to understand how critical managing supply chain integrity is to sustaining business continuity. With or without robust supply chain management processes in place, the CDMOs that organised their supply chains for resiliency and reliability were able to minimise the impact of Covid-19 disruptions while supporting company growth under challenging conditions.
Embracing the challenges and successfully delivering mRNA- based vaccines during an unprecedented time of need has placed CDMOs in a good place for all impending mRNA-based projects. Expanding cold chain and fill-finish capabilities and capacity with new-era enabling technologies is one operational area receiving intensive focus by both CDMOs and equipment suppliers to accelerate therapeutics safely to markets.
All of biopharma understands that aseptic, controlled environments are required for the safe, sterile production of mRNA-based products. To deliver the capacity to meet the expected growth in the development of parenteral biologics, CDMOs are equipping production lines with enabling digital automation and control technologies. Investment in sterile injectable capacity across the CDMO industry has laid a solid foundation for producing biologics, including mRNA based therapies capable of treating myriad disease targets, especially cancers.
CDMOs adapting fast
It is unlikely the demand for the development and manufacture of mRNA-based therapeutics will abate soon. Now that the pull of Covid-19 vaccine production has left the sector, it’s clear CDMOs that adapted their capabilities to support this previously unfamiliar niche of biologic development have the expertise to work with and scale the new wave of mRNA technologies on the horizon.
Beyond mRNA technologies, the industry has also become more capable of supporting the development and manufacture of the coming new era of cell and gene therapies (C>s). According to a report in The American Society of Gene and Cell Therapy’s Gene, Cell, and RNA Therapy Landscape Quarterly Data Report (Q3 2021), some 3,366 C>s are currently in development globally8.
Reflecting this, the global C> manufacturing services market is predicted to grow at a compound annual growth rate (CAGR) of 12.4% in the next five years, with the market predicted to be valued at $13.8 billion by 20269. The number of therapies in development and the expected increase in the market demand for C>s demonstrate the need for the capabilities to meet the potential for opportunities within this growing area.
In wake of the pandemic, the importance of being prepared and staying ahead of any challenge that occurs is the challenge. Agility is important and the positive patient outcomes from the industry’s concerted mRNA vaccine delivery effort demonstrates many biopharma CDMOs were fit for the task. Responding quickly and accurately to the shift in market dynamics, CDMOs that optimised manufacturing capabilities with enabling technologies are now more capable than ever to produce new-era biologics of all kinds safely and efficiently.
Volume 23 – Issue 4, Fall 2022
About the author
James Park is a Senior Vice President and Chief Business Officer at Samsung Biologics. With over 25 years of organisational leadership experience in the biopharmaceutical and pharmaceutical industries, Park has held various technical and operational positions, as well as business development management leadership positions in biopharmaceutical companies in the US.