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CDMOs need to consistently demonstrate agility as demand increases for newly developed therapeutic modalities.
The COVID-19 pandemic highlighted the potential of an array of modalities within the biopharmaceutical industry. In particular, the success of messenger RNA (mRNA)-based COVID-19 vaccines has encouraged biopharmaceutical companies to explore and utilize these technologies for other diseases and look to rapidly expand their capacity and capabilities in response to an upsurge in demand.
At the end of 2019, the combined market capitalization of the five publicly listed companies focusing on mRNA platforms was $15 billion, and as of August 2021, that value of capitalization reached more than $300 billion (1). This significant boost in market valuation reflects the optimism that mRNA technology can deliver much more and go beyond the current prophylactic COVID-19 vaccines.
Preparation for this new wave of technology brought new challenges. The continued growth of biologics pipelines magnified limitations in internal manufacturing capacity, driving drug developers to partner with contract development and manufacturing organizations (CDMOs) to enlarge the manufacturing network.
CDMOs needed to expand capacities and facilities to serve the dynamic market changes. More robust technologies and cold chain capabilities had to be offered to meet the demand too.
By increasing capacity and preparing for the multi-modalities of new technologies, CDMOs have put themselves in good stead for new therapeutics on the horizon, such as mRNA treatments targeting advanced cancers and heart disease. Preparing for these advancements will ease transitions into supporting the production of cell and gene therapies (C>s), another key growth area for the industry in the future.
Prior to the past decade, mRNA technologies were slow to advance and there was little investment into the area. With gradual innovations, mRNA began to be considered a safe and efficient therapeutic tool in vaccine development. However, it was not until recently, with the onset of the COVID-19 pandemic, that the mRNA vaccine field quickly expanded. The need for a rapid response drove the swift adoption of these new technologies in vaccine and treatment development.
CDMOs were increasingly becoming more heavily relied upon to support the development and manufacturing of these new drug technologies. This necessitated CDMOs to rapidly prepare for improvements to accommodate mRNA manufacturing and overcome any challenges they faced in an unprecedented amount of time.
Adapting existing capabilities quickly. With an upsurge in demand for this new wave of technology, manufacturers needed to make necessary changes to their facilities and processes for them to be optimized to the product characteristics.
Cold chain capabilities had to be expanded and optimized to suit the temperature-sensitive nature of mRNA molecules. This has been achieved by investing in different types of capabilities, from blast rate freezers to control rate freezers, and offering a wide range of container storage types to best fit the needs of the product. The necessary standard operating procedures (SOPs) have also had to be put in place for each new storage capability.
The lipid nanoparticles used to encapsulate the mRNA were also unfamiliar to many manufacturers that predominantly worked with water-like solutions. Time was needed to determine how the nanoparticles would behave and how processing conditions could impact the characteristics of the mRNA products.
Balancing new and existing projects. Not only did CDMOs need to accommodate and support COVID-19-based projects, including vaccines, but they also needed to maintain the production of other medications requiring similar facilities. Ensuring sufficient capacity was, therefore, one of the greatest challenges to CDMOs during the COVID-19 pandemic.
Careful management was needed to avoid delays due to bottleneck processes and ensure sufficient capacity for the increased level of demand. Balancing these requirements also necessitated both flexibility and scalability to successfully support the development of a wide variety of essential products.
Accelerating speed to market was essential. Speed was essential in the delivery of products to patients in a short time frame, especially during the COVID-19 pandemic, and presented another challenge to manufacturers. To facilitate speed to market, regulatory approaches to accelerate the availability of vaccines and treatments were heavily relied upon. These included FDA’s Emergency Use Authorization (2) and Priority Review (3) approaches and emergency conditional market authorization in the European Union (4).
To successfully shorten timelines and meet capacity demand, CDMOs needed to expand facilities to offer improved scalability and increase efficiency of existing processes. This required all aspects of development and manufacturing to be highly optimized. Throughout this process, the high quality had to be balanced with delivering at an unprecedented speed.
Managing supply chains to avoid disruptions. Manufacturers had to also ensure they maintained a reliable supply of raw materials and consumables. Many projects, both COVID-related and not, relied on much of the same equipment, processes, and raw materials. However, with the onset of the COVID-19 pandemic, biomanufacturers were waiting up to a year for supplies and equipment. Despite vendors responding to increased demand by expanding capacity, projects still took months to come online (5).
Essential materials for making vaccines were in short supply—exposing how the supply chain is reliant on only a handful of countries, and even companies when it came to the sterile bags used for cell cultivation in bioreactors (6). Despite the rise of globalized supply chains in the past decade, the COVID-19 pandemic has highlighted the need to proactively monitor and quickly react to potential delays.
Manufacturers had to identify several potential sources of equipment and consumables to have alternative options in the event of delays from their primary source. Identifying alternative suppliers close to the production facility for localization of materials helped to minimize risks associated with delays. Additional time also had to be taken to ensure that the alternative equipment and consumables identified were suitable and optimized for the manufacturing needs.
The growing interest in mRNA technology is in part because of its ability to be easily edited, providing the potential for it to be used in the treatment of countless possible diseases. In this way, mRNA technologies have the ability to be used as a “plug-and-play” platform, offering unprecedented versatility. Recent advances in mRNA vaccine technologies have further improved translatability. Carriers have also been developed to prolong antigen expression in vivo, further increasing its potential.
Additionally, vaccines that rely on mRNA technologies provide the added benefit of having the potential for inexpensive, rapid, and cost-effective scalable manufacturing. As mRNA can be synthesized using relatively simple in vitro transcription reactions, high yields can be achieved with a small, good manufacturing practice (GMP) facility footprint.
As a result, mRNA technologies are being used in abundance in drugs currently at clinical trial. As of July 2021, there were more than 70 mRNA therapeutics in clinical pipelines globally and many more assets in early development (7). The therapies in development are to be used in an array of therapeutic areas. These include drugs for cancers (ovarian, lymphomas, melanomas, and glioblastomas), ischemic heart disease, rare diseases (caused by Zika virus, Chikungunya virus), and more common diseases (caused by Rabies virus, HIV) (8).
It is likely that demand for manufacturing support will persist for years to come, especially with the immediate need for COVID-19 booster vaccinations. CDMOs will need to keep adapting to solve the challenges associated with the storage of mRNA technologies, as well as develop their services to provide end-to-end mRNA capabilities. Overcoming these issues may in turn position the manufacturers in a stronger position to support other therapeutic modalities such as C>s further on the horizon.
With an increased demand for drugs based on new technologies, CDMOs will need to consistently demonstrate their agility while ensuring quality and safety in all stages of a product cycle. This is essential to respond to other new technologies and shifting market dynamics. To achieve this, processes will need to be highly optimized to reduce timelines and provide speed to market.
The pandemic has highlighted that foresight, careful preparation, and agility continue to be essential traits for CDMOs and will prevent them from mismanaging their priorities. Client satisfaction and the lives of patients are, and always should remain, the highest priorities.
1. W. Xie, B. Chen, and J. Wong, Nat. Rev. Drug Discov., 20, 735–736 (2021).
2. FDA, Emergency Use Authorization, Policy Framework [content current as of Jan. 25, 2022].
3. FDA, Priority Review information available from fda.gov [content current as of Jan. 4, 2018].
4. EMA, Conditional Marketing Authorization information available from ema.europa.eu [accessed Jan. 25, 2022].
5. D. Stanton, “Single-Use Lead Times up to 12 Months as COVID Takes its Toll,” BioProcess International, May 3, 2021.
6. J. Feinmann, BMJ, 375 (8312) n2375 (2021).
7. Statista, “Number of mRNA Therapeutics in Clinical Pipelines Worldwide as of July 2021, by Therapy Area,” Statistics (July 2021).
8. NIH, ClinicalTrials.gov, Database [accessed Nov. 15, 2021].
James Park is executive vice-president and managing director of the Global Sales Center at Samsung Biologics.
Supplement: Biopharma Outsourcing Innovation 2022
When referring to this article, please cite it as J. Park, “Preparing for the Future: Expanding Capacity and Facilitating Multi-modalities,” Biopharma Outsourcing Innovation 2022(February 2022).