Betsy Baer is the Senior Director of Americas Contract Organizations Business at Waters Corporation.
The accelerated development of COVID-19 vaccines and subsequent manufacturing of billions of doses would not have been possible without collaboration and partnership between many different organizations, businesses, government agencies and laboratories. Several of the entities that spearheaded this monumental effort have quickly become household names, but there are also a number of unsung forces behind the historical introduction of the first mRNA vaccines to be approved for use in the United States, not least of which are contract development and manufacturing organizations (CDMOs).
CDMO laboratories, once a resource for mainly small and mid-sized pharmaceutical companies to speed and scale up their production, have seen tremendous growth and increased funding over the last decade, and many quickly jumped to the task of aiding in the development and manufacturing of the first SARS-CoV-2 mRNA vaccines. The instrumental role of these partnerships in tackling the global health crisis shows how contract organizations can offer the expertise and capacity needed when pharmaceutical solutions and innovation are in high demand.
In a recent Q&A with Labcompare Associate Editor Laura French, Betsy Baer, Senior Director of Americas Contract Organizations Business at Waters Corporation, offered an in-depth view of the capabilities of CDMOs and how they can continue to aid pharmaceutical and biotech endeavors moving forward.
Q: What are some of the main benefits of partnering with a CDMO, and in what ways have these benefits been demonstrated during the COVID-19 pandemic?
A: There are so many benefits of partnering with a CDMO, including short-term capacity needs, outsourcing development, specialization and expertise among many CDMOs, along with method cross-validation for manufacturing across many sites. These are just a few of the advantages of using CDMO partners.
There is inherent flexibility and agility in the CDMO model, with a business and infrastructure designed to develop and deploy new projects quickly, including QA teams for validation and compliance. As a manufacturer of innovative analytical technologies and software, we share many of the same customers, and our CDMO customers appreciate the expertise we bring and our keen understanding of some of the trends, requirements and challenges addressed by our enabling technologies and services.
During the pandemic, our fast and proactive efforts to support the development and manufacturing underway were paramount, as we formed a COVID-19 Innovation Response Team specifically to assist our customers, offering technical support and whatever they needed to accelerate their efforts and to ensure compliance throughout the development and production process of vaccines and critical medicines.
We also saw a very high level of collaboration and communication throughout the industry, with the common goal toward bringing effective vaccines and therapeutics to the market. Companies that may normally compete were working together to provide the expertise and capacity needed, with the flexibility to follow the science and change course as new data emerged. The CDMOs played (and still play) a very key role in adding the needed capacity and expertise to these efforts.
Q: In which areas/services across the development and manufacturing process have CDMOs had the greatest impact during the pandemic?
A: Traditionally, CDMOs were called upon for increased capacity and manufacturing based on methods developed by their sponsors. But this is no longer the case. CDMOs play a key role in all aspects of the development and manufacturing during the pandemic, they were able to react quickly to supply key components of the vaccines as well as the therapeutics, and provided the much-needed capacity that was urgently required by the pandemic.
Some of the functions and applications where they played a key role include characterization, production of APIs, fill-finish capabilities, new modalities such as mRNA-based vaccines, viral vectors and therapeutics, including mAbs and bsAbs. There were new CDMOs and CMOs that emerged based on funding from the FDA, DoD, BARDA, DARPA, NFS, etc. to ensure continued supply of critical medicines, and to lessen dependency on countries such as China and India for APIs and other raw materials.
Many CDMOs expanded their sites and built additional capacity for fill-finish facilities and flow chemistry/continuous manufacturing capabilities to produce large quantities of APIs and critical medicines. Along with therapeutics, many CDMOs supplied components of the vaccine such as the spike protein, the adjuvant, etc. These are just a few of the areas/services where CDMOs have played a critical role in accelerating the development and production of therapeutics and vaccines related to COVID-19.
Q: In what ways have CDMO partnerships helped accelerate the development of COVID-19 vaccines specifically? What strategies have CDMOs and their partners leveraged to adapt to unprecedented challenges and demand during this time?
A: You can just look at the news and the contract awards to see the key, critical role that CDMOs played in bringing vaccines and therapeutics to market. New innovative CDMOs have emerged specifically to meet this demand, some focusing on APIs and supplying critical medicines and others focusing on biologics such as vaccines, mAbs, mRNA-based vaccines and therapies and to enhance capacity and accelerate development.
There have been many expansions (new sites, as well as extended offerings) to meet the increased and urgent demand created by the pandemic. The use of technology, including automation, liquid chromatography and mass spectrometry, increased productivity and efficiency, allowing each step within the development process to move more quickly. Some of the most prominent challenges included the disruption in the supply chain and the ability to acquire critical supplies, so planning ahead and having contingency plans has become a standard practice that had to be integrated into all aspects of the development and manufacturing process.
Q: As with any other lab, CDMO labs need equipment. Have you seen any trends in how CDMOs are leveraging instrumentation to increase efficiency and throughput?
A: Yes, absolutely. With the high growth in biologics (biotherapeutics, ADCs, vaccines, etc.) the need for technology advancements and analytical capacities becomes more pronounced. Biologics and complex molecules require characterization to assure consistency, and to assess quality attributes which can include impurity profiles, peptide mapping, glycan analysis, intact protein analysis, excipients, aggregation, among other analyses to ensure quality, safety, efficacy and consistency. The use of mass spectrometry and compliant software such as UNIFI and Empower are key to many of these analyses, so we are seeing many CDMOs adopt MS as an important tool to assess their biologics and for small molecules as well.
With the importance of compliance, data integrity and data security, combined with the increase in capacity and analytical workflows, results management can be a challenge. The use of LMS systems such as NuGenesis is increasing in adoption to allow these CDMOs to efficiently aggregate and re-purpose the data in a compliant environment, reducing manual processes and transcription errors and also enabling customized reports for their sponsors.
We are also having many discussions about tools for automation, fit-for-use applications kits and automated workflows (e.g. glycan analysis, peptide mapping, MAM workflows, high throughout purification and online/at-line testing for real-time release testing). Our cloud-based Andrew+ robot is another great example of increasing efficiency and productivity by moving manual (and often tedious) tasks to an automated workflow for many applications with a series of automated liquid handling steps. Innovation and new enabling technologies are key to the CDMO to ensure they are competitive and aligned with their sponsors in applying these technologies and their expertise to some of the new emerging modalities.
Q: What factors are most important to pharmaceutical companies when selecting a CDMO to work with?
A: In speaking with many of the pharmaceutical sponsors, some of the important factors include:
- Agility – The ability to scale up quickly to the needed capacity and to meet the project deadlines, including all the resources and expertise needed for the entire project
- Quality – Quality systems in place, proactive measures in place to assure quality during all stages of the development and manufacturing process; SOPs in place for consistency across all sites that will be working on a given project
- Compliance – Data integrity, ensuring a GLP and cGMP testing environment with controls and regulatory expertise and support. This is critical for FDA audits and analytical systems as well as enterprise software for technologies such as LC and MS. How are the results managed, archived, and reported in a compliant and secure format with so many different tests and numerous sponsors to support? With the increasing number of cyberattacks, Data and Digital Security are challenges that many CDMOs are addressing with the assistance of their software and network architecture suppliers.
- Expertise – Some CDMOs offer end-to-end services, while others have more specific and unique expertise, so ensuring there is inherent knowledge and experience within the CDMO for a given project and to ensure successful tech transfer to the CDMO.
- Training of their employees – How are the employees trained? Do they have the experience and expertise to take on the project, and what other resources may be needed to ensure success?
- Innovation – Can the given methods be improved? For discovery and methods development, are the latest technologies being used to generate the highest quality results?
- Scaling and tech transfer – Is there ample capacity to scale up to larger quantities, and how is tech transfer seamlessly implemented and validated across different sites of the CDMO?
- Value and prior history – the cost, Return on Investment, value-adds and prior history with a given CDMO will always be considered in the final decision of selecting a CDMO.
Q: Following the massive growth of the CDMO sector over the last year and a half, in what ways do you see these services influencing areas other than vaccines and COVID-19 therapeutics?
A: I would say that the pandemic highlighted the need for less dependency on other countries for our pharmaceutical supply chain – including drug substances and drug products. So we have seen a trend toward onshoring to assure continued supply of critical medicines (especially APIs) with several new startup CDMOs (many with government contracts) to accelerate production of critical medicines – both small molecule and biologics. CDMOs will continue to support the pharmaceutical industry with tremendous growth in areas such as bioprocessing, cell and gene therapy, mAbs, bsAbs, therapeutic peptides and oligonucleotides, continuous manufacturing, and many applications outside of COVID-19 vaccines and therapeutics.
The pandemic highlighted the agility, expertise and capacity the CDMO’s could offer to the pharmaceutical market, but the scope and value they bring go well beyond their response and key role during the pandemic with vaccine and therapeutic development and production. Partnerships and collaborations (including innovative technology providers such as Waters) were front and center during the pandemic to accelerate bringing new vaccines and therapeutics to market, and these trends and best practices will likely continue for everyone’s benefit, especially the patients receiving these critical medicines.
About the Expert: Betsy Baer is the Senior Director of the Contract Organizations Business for Waters, leading the sales and business development efforts for the Americas. Betsy has initiated and facilitated many customer collaborations and has played a key role in the continued growth of the CO business for Waters. Prior to this position, Betsy was the General Manager for the East US Business Operations for Waters, driving growth and innovation within the field sales and service teams. Betsy’s background is in analytical chemistry, with an extensive background in business development and creating and leading high performing, creative teams.