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April 16, 2020

Is not using a CDMO slowing down your process development?

By Patrick Guertin, Global Technical Manager, and Ed Hines, Global Technical Manager, Cytiva

In today’s biomanufacturing industry, drug manufacturers must navigate a changing landscape that is more diverse than ever before. Advances in science to address previously unmet needs are paving a new course in patient treatment while also challenging how drugs have traditionally been developed and manufactured. New technologies to increase efficiency and flexibility in small batch production, such as high-throughput technologies, modular equipment and single-use technology (SUT), combined with automated solutions create novel ways to produce drugs faster with better quality and safety oversight.

As a result, many companies are considering creative ways to expedite not only their timelines but also their knowledge and technical capabilities. And while adding capacity and expertise can help you remain competitive, so too can partnering with a CDMO to create and optimize biomanufacturing processes that can improve yield and reduce production costs. Doing so also allows you to delay any major financial decisions on your molecule until you see how it performs in the clinic. So, as you think about your internal strategies and what your next best step is, consider what process development capabilities you have versus what you could possibly gain from working with a CDMO to not only be successful but also improve your chances of getting to market sooner.

What You Can Gain From A CDMO

Infrastructure, experience, and expertise are key variables in achieving the time-saving efficiencies needed to get ahead. If your facility is still equipped with traditional or older technologies, you are already at a disadvantage. A CDMO can offer automated systems, such as those that can execute either the designs of experiment (DoE) or create the design space, allowing you to save time by generating meaningful process data using a scientific approach rather than guesswork. It is also important to establish a platform approach, whether it is bench scale, high throughput, or large-scale manufacturing, as well as the analytical capabilities that will not just support where you are now but also where you want to be in the future. If you do not already have these resources, you will need to increase your capital expenditures to obtain them, as well as the skilled staff to run them.

Using a CDMO with the capacity and advanced equipment you need and the large-scale experience necessary to utilize them properly and efficiently helps make the process more economical. Experience, in general, is important for a CDMO but having experience with a wide range of cell types and molecules is also beneficial, as working on various types of projects may help them anticipate what problems you might encounter and which solutions to use to address them quickly. Another benefit of working with an experienced CDMO is the knowledge and experience your staff will gain by working with a seasoned partner. This includes process development and cGMP manufacturing. For example, relative to cGMP manufacturing, each phase of clinical trials brings new demands for your product and your team. Knowing what information to provide to regulators and when can help expedite your clinical trial process, facilitating product approval and market entry. And as you continue through each phase, scale-up needs increase, particularly when you get into human clinical trials. Many companies lack the large-scale capabilities in-house, so having a CDMO on hand to help as the demands of your clinical trials change helps avoid major delays.

Finally, you not only benefit from expedited work and support along with a broad background of experience, but you are also strengthening your internal team through this experience. This support is especially important for companies working on multiple initiatives where prioritization becomes important. As your staff improves their base of knowledge and transfers some of their work to a CDMO, they also free up some time, which can then be dedicated to the areas where they are more skilled or focused, such as upstream or downstream. This creates more flexibility in decision making and where they ultimately dedicate their time. A company may even decide to outsource only those areas for which they lack the necessary resources, rather than the entire process development process, which is an option you can explore with the CDMO you choose.

What Are The Risks of Working with a CDMO?

There are many benefits you can gain from partnering for process development, but it can be intimidating to share your product and your knowledge about it with a company that is offering the same services to your competitors. One of the biggest perceived risks of doing so is the loss of intellectual property (IP) rights when working with a CDMO. Companies want to know how their IP will be protected by their partner, which includes key components such as equipment, resins, etc. A nondisclosure agreement is also always implemented at the earliest stages and helps to ease the mind of the customer. At Cytiva (formerly GE Healthcare Life Sciences), the goal is to build long-term relationships with customers rather than one and done transactions. That is why, if something is developed jointly with Cytiva, a customer is given a royalty-free license for that in perpetuity.

Another concern of many customers considering outsourcing as an option is that they will lose their decision-making capabilities. While some organizations may be rigid and uncompromising in their ability to collaborate with customers, it is important that a CDMO is flexible and operates in a collaborative way. The communication style and transparency of a partner are important factors when selecting your future CDMO. Look for one that has worked with a wide spectrum of customers, from large pharma companies to small virtual companies and even startups. This shows they have the willingness and ability to adjust to the needs of different customers, regardless of size and/or experience.

It is difficult to know in early stages what path you eventually want to take with your product (whether you manufacture it yourself, transfer to a different manufacturer, or eventually sell it to someone else), so you want a partner that empowers and enables you by developing a process that can be easily transferred to other organizations. They should maintain open lines of communication with you throughout the duration of the project, such as regular meetings to discuss the most recent data and the status of the development process compared to timelines and expectations. This allows the customer to stay in the loop and retain their decision-making ability and, if necessary, change the direction of the project or provide input that might be helpful.

How To Evaluate Your CDMO Options

Determining the right CDMO for your project is often dependent on the scope of capabilities of your service provider. Do they perform process development through cGMP manufacturing and, if so, to what stage? Another very important consideration are your end goal(s). For example, if you do not want to invest in manufacturing capacity, then you will want to look at what the CDMO’s capabilities are in terms of commercial supply. Do they have what you will need to meet your commercial needs? Will they be able to fit you into their schedule? Look for a CDMO that has flexible manufacturing solutions to fit your end goal. If you want to have your own manufacturing capabilities, choose a CDMO that can perform a reliable technology transfer of the process back to you as well as offer you solutions that fit your future capacity needs, such as a modular facility.

Use a high-level checklist with input from all relevant team members/departments to evaluate your partnering options. A site visit is also an important activity as you can not only view the site but also review the facility infrastructure, including equipment and building. This will give you a chance to interact face to face with the scientific and managerial team members who will be assigned to your project. When doing so, make sure there will be a dedicated project manager who will act as the main point of contact but allow direct communication between the respective subject matter experts from each team. Look for any red flags that may indicate potential issues down the road, such as a history of failed FDA audits or a refusal to let customers onsite during process steps.

Overall, find a CDMO that aligns with your desired outcomes for each stage and the milestones you need to achieve your end goal. Process development is an iterative stepwise process striving for process reliability and product safety, ideally resulting in robust cGMP manufacturing. If you struggle with buy-in from others within your company, help them understand this is a multifaceted initiative, ultimately allowing you to save time and money while also achieving the highest level of product quality.