A record level of investments across the biopharma industry have created a wide range of new opportunities in global healthcare. According to the Drug, Chemical & Associated Technologies Association, data from investment firm Jefferies Financial Group Inc. shows “venture-capital funding, initial public offerings, and secondary offerings by already-public companies led to $88 billion in new equity in 2020, with most going toward emerging biopharma companies.”1 This will likely result in a flurry of collaborations with contract development and manufacturing organizations (CDMOs) in order to help fill the resource and expertise gaps within these nascent companies.
Regardless of whether you are just entering the field or simply responding to the influx of competition, you must know how to vet potential providers, especially for process development services. This critical step is a key factor in determining your drug program’s overall success. A panel of experts with experienced and diverse perspectives discussed this topic during an online event titled Best Practices for Outsourcing Process Development, where four themes surfaced that may help drive the best outcomes with your process development service provider.
1. Determine your process development needs.
Before selecting a CDMO for your outsourced process development needs, first determine what you need and what outcomes you expect to achieve. Your current product life cycle phase may help you determine your needs. If you are in Phase I, the process has not been locked in yet, so there is still room for process development optimization. Conversely, if you are already in Phase III, any process changes would be hard to implement due to compatibility studies and other regulatory hurdles.
Determining your process development needs also depends on your existing resources, such as in-house expertise and capacity. However, don’t let “perfect” get in the way of “good enough.” Ask yourself, does my current process provide sufficient quantity and quality of product in the time required at the given scale and capacity? This requires an understanding of the quantity of product required at each phase of the process, which will increase as you progress. This exercise would also factor in scale, batch size, and run capacity with respect to time. The definition of success can change over time, especially as you move through each clinical phase, so avoid getting tied down by a certain outcome if you have already achieved the quantity and quality of product required at the scale and capacity needed.
2. Look for providers with experience and flexibility.
By the time you collaborate with a CDMO, you probably already have a process development and technology roadmap that outlines the most appropriate tools for your project’s needs. Therefore, the best process development organizations are those that are most flexible when it comes to technology. This is because, typically, you do not go to a CDMO and let them do everything from start to finish. You usually have already done some process development (often in academic labs where the original product or molecule came from) and know what the process should look like. It would not make sense to bring your product to a CDMO that is fixed on one technology and is going to tell you how to make your product. As the industry adage goes, the process is the product, so it’s important you maintain control of it. In addition, you must ensure the CDMO has the equipment that you need for your process to facilitate a technology transfer (along with documentation, process details, successful and failed run data, as well as all other relevant information). One-stop-shop CDMOs tout expertise in all areas of development and manufacturing; do your due diligence to ensure they can walk the talk. While some CDMOs may be able to do it all, it may be necessary to bring certain steps to more qualified providers.
Overall, experience and adaptability are two significant characteristics to have in a CDMO. The industry has many established molecules and processes, but it also has various emerging technologies. Understanding how to expedite the development or manufacturing of any of the diverse spectrum of molecules—and the flexibility to do it—is critical. Platform processes can help in this effort, but speed, quality, and reliable resources will always be fundamental characteristics for a CDMO. Also, look for a provider that has a successful outsourcing history. With a ripening market for CDMOs, some drug manufacturers with underutilized infrastructure and expertise are offering their own resources and capacity. Although this could be beneficial in certain situations, working with a CDMO that knows how to be a CDMO is likely going to be the best path forward.
3. Set safeguards to manage supply of critical raw materials.
The impact of the COVID-19 pandemic has been far-reaching, especially on the pharmaceutical supply chain, where it impeded production of critical raw materials and exposed existing weaknesses that further emphasized the need to focus on security of supply. Whether you rely on a CDMO or your own process development and/or manufacturing capabilities, advanced planning, an adequate general inventory both on and off-site, and an inventory of the materials with the longest lead time are all vital safeguards for combatting global supply chain issues. This should include not only raw materials and consumables but also other supplies and items that can sometimes be taken for granted, such as pipettes, gowning, and gloves. Platform processes can also allow early design-in of critical raw materials and, therefore, enable a consistent inventory or placement of orders for these materials far in advance.
It’s also important to confirm if your CDMO has control over or ownership of the supply chain that produces the supplies, raw materials, or consumables needed for process development and manufacturing. For example, imagine you have multiple vendors funneling into the supply chain for your GMP materials. One of these suppliers should, in theory, be able to back integrate into the starting materials that you need. If there is a fundamental global supply disruption, such as those seen as a result of the COVID-19 pandemic, the CDMO retains the ability to manufacture and supply the critical raw materials that you will need to further process your material to meet your goals. This upfront planning can occur without any change in expenses or timing.
4. Focus on quality from the start.
Effective quality management is, of course, a primary focus and essential function throughout the drug development and manufacturing life cycle. Therefore, it only makes sense that careful scrutiny of a CDMO’s quality department and its processes sits high on the list of considerations. This can begin as early as the request for proposal (RFP) process. Often, the RFP template that the sponsor uses to provide their project’s requirements and expectations is designed by the CDMO. Although the information requested is important, it is biased toward their needs. Instead, design your own template that outlines the information necessary to help you vet quality from the start.
For example, if the CDMO is going to be progressing work into the GMP or compliance portion of a project, information about their interactions with regulators, history of success (or failures), and even audits should be included in the template. Make sure they share raw data about project campaigns, batch history, and audit findings, and be specific about what details you want. It is also important to find out their ratio of quality to manufacturing personnel. Ideally, the ratio should sit somewhere around one quality person for every five in manufacturing. If there is an overwhelming number of people in manufacturing and only a couple in quality, then you will want to inquire about the turnaround time for batch release and batch release data once production is finished, as this ratio could indicate potential delays.
The right RFP template can also help streamline the work that goes into getting a project started, reducing the wait time to get up and running. Indicating early on that you want to negotiate master service and quality agreements, as well as requesting specifics about communication channels, can facilitate later steps such as documentation review cycles by the respective legal and management teams. The faster all of this is completed, the sooner you can move on to readying key components of your project such as raw materials and consumables.
While these considerations cover some of the most critical areas in the path to market—quality, supply, and expertise—there are many factors you must take into account when finding the right CDMO for your process development needs. Designing a plan of action on how to vet your future CDMO is an early but vital step toward securing a collaboration that lasts the entire product life cycle.
The last several years brought important lessons to our industry and will continue to do so. Stakeholders across the biopharmaceutical industry today have a greater responsibility to ensure the choices we make continue to advance our cause.
Interested in outsourcing your process development? Get in touch and learn more about Cytiva’s Fast Trak™ process development services.