As of 2020, coinciding with the outbreak of COVID-19, there has been a steady increase in demand for new technologies such as messenger RNA (mRNA). Contract Development and Manufacturing Organizations (CDMOs) are being forced to rapidly expand their capabilities to respond to this upsurge. Let’s see how CDMOs have prepared for the new wave of technologies on the horizon and the challenges they have faced to welcome a new era of these technologies.
The COVID-19 pandemic has highlighted the successful development and use of mRNA vaccines. This has encouraged biopharmaceutical companies to explore and use these technologies for other diseases. There are a significant number of new therapeutic programs based on mRNA and lipids, which encourages CDMOs to invest in new expertise to provide end-to-end solutions.
CDMOs have been building new capabilities, while developing capabilities, to better prepare for the new wave of technologies. Many CDMOs have invested in new processes and resources to preserve product integrity, minimize waste, enable safe and efficient supply to patients without delay.
“In mRNA technology, we’ve seen CDMOs make almost exclusive in-house builds, while others make strategic acquisitions to expand their mRNA capabilities. Many CDMOs, such as the Center for Breakthrough Medicines, are expanding to include this dedicated and separate capability. This is an extraordinarily complex process and different from other processes that CDMOs currently perform, so you need to make sure to separate these operations from your existing manufacturing as much as possible,” said Joerg Ahlgrimm, President and CEO, Center for Breakthrough Medicines, USA.
With mRNA-based drugs surging in popularity in such a short time, companies supporting their development and manufacturing had to adapt quickly because mRNA-based vaccines required cold chain capabilities and technologies. more robust aseptic fill-finish.
weather the storm
Even though COVID-19 has fueled the growth of the CDMO market, it has also brought its fair share of challenges. Supply chain management was perhaps the biggest challenge, as the pandemic had a sudden and extreme impact on the supplier/distributor network.
“This challenge required the rapid, yet precise, expansion of clinical supply chains, which should be informed by data and expertise and underpinned by global infrastructure and network,” said Kevin Cheong, Director, Clinical Operations-Asia, Almac Clinical Services, UK. Kevin is based in Singapore.
As mRNA-based technology is a newer modality in the industry, few CDMOs have extensive experience and track record to point to. However, CDMOs with teams of scientists who have the expertise in the field could meet the challenges and address the growing mRNA market much faster.
“The technological challenges based on mRNA are not necessarily unique. All technologies for making cells and genes have encountered obstacles that had to be overcome. That said, for mRNA, I see both of these challenges. The first is to create or acquire the ability to increase manufacturing, as well as being able to provide high quality mRNA synthesis. The other is mastery and the ability to replicate the technology process, which is key to being a successful CDMO,” Joerg said.
During the pandemic, production capacity and yields had to be significantly increased, which came with obvious challenges. “Capacity is another barrier to DNA and plasmid production, a process that uses fermentation alongside E. coli. Suite dedication is a key issue, as performing a fermentation process in a suite that is also running mammalian cell culture would pose a risk of cross-contamination. As a result, alternative manufacturing platforms such as synthetic plasmid DNA (doggy bone) could gain prominence,” said Lawrence Yap, Global Head, Technical Operations, Hilleman Laboratories, Singapore.
The unique nature of mRNA also creates analytical challenges in drug development. It is important to remember that mRNA technology itself is rapidly advancing and continuously evolving. Developers of analytical methods for mRNA-based therapies and vaccines are therefore faced not only with the complexity of these biomolecules and their delivery vehicles, but also with the need to develop flexible methods capable of adapting to ongoing changes in mRNA structures and final formulations.
“There is also the analytical challenge of identifying appropriate tests that can monitor the quality of each intermediate. This requires highly specialized testing and analytical testing to properly characterize the molecule and select the most appropriate formulation, which may include manufacturing lipid nanoparticles,” Lawrence added.
The shortage of skilled labor is another bottleneck. CDMOs need highly technically skilled talent to develop, produce and test each mRNA-based entity. “It has been difficult to find talent that can support rapid development in manufacturing, analytics, manufacturing science and technology (MST), technology transfer and chemistry, and manufacturing and controls (CMC). We are seeing a growing demand for talent with skills and in-depth knowledge of microbial fermentation as well as the biocatalytic enzyme synthesis process,” said Lawrence.
The pandemic and the resulting rapid vaccine approvals have highlighted the industry’s ability to move much faster through the drug development process than ever thought possible. It also shows the importance and power of strategic collaborations.
“One of the most important lessons we have learned about preparing for the future stems from our experience with COVID-19 vaccines. It is clear that both innovative companies and CDMOs, with the right public support, can develop a product and bring it to market extremely quickly. That said, all the stars were aligned. Every government and health agency wanted a quick fix – a product that worked and worked safely, so the normal barriers to getting a product to market faster were eliminated.,said Joerg.
Another important lesson is having strong supply chain management processes in place. “One of the lessons learned relates to managing the supply chain to avoid disruptions. Manufacturers need to ensure that there is always a reliable supply of raw materials and consumables. At the same time, we need to identify potential sources of equipment and consumables as alternate options in the event their primary source is delayed,” Lawrence said.
Contract manufacturers are now moving into the contract research and manufacturing services (CRAMS) space, becoming valuable partners for pharmaceutical players in every sense of the word. “The model involves working with contract research organizations (CROs) to generate data supporting the pathway into the clinic, followed by partnering with an innovator to provide the resources for further drug development. The small biotech-innovator relationship will ideally evolve into a three-way deal where the execution component continues to come from an integrated service provider (CRO-CDMO) with end-to-end capabilities,” said Dr Mahesh Bhalgat, COO, Syngene International, India.
Much of what CDMO could achieve during this crisis is also due to technology and the digitalization of the development and manufacturing process, and advancing technology will play an even greater role in the operation of CDMOs.
The challenges the industry has faced throughout the pandemic have highlighted how important it is to be nimble and flexible to ensure consistent and cost-effective delivery. CDMOs that have demonstrated agility and ability to respond to changing market dynamics, as well as adapt their manufacturing capabilities to new technologies, are best suited for the future.