If your start-up company has developed a biological product and is planning to file an investigational new drug (IND) application with the FDA or register the product with another federal agency, and you don’t have the physical infrastructure to perform manufacturing in-house, you are probably in the process of evaluating contract development and manufacturing organizations (CDMOs) that can conduct process development, scale-up and manufacturing of your product.
Selecting a CDMO is a very important decision, as you aren’t just entering a transactional relationship – you are forming a long-term partnership that can not only impact the success of your current product, but also benefit the manufacturing of future products in your pipeline.
What stage are you in?
One of the first things to think about when evaluating different CDMOs is to consider what stage of the manufacturing process you are in and what your needs are. Typically, your project will fall into one of these categories:
You have a product concept and have done discovery and/or academic research, but you have performed little or no process development or evaluated the scalability of your process. For example, you may currently be working in pre-clinical trials with animal models.
For early stage projects, it is essential that your CDMO offer process and assay development in addition to manufacturing. Their process development equipment and capabilities must provide a smooth scale-up to their manufacturing-level counterparts. Additionally, considering how long the lead times can be for manufacturing, conducting process development earlier will mean your product is well positioned to transition to manufacturing when slots become available, reducing time losses.
You have done internal process development (i.e. bioreactor and purification process work) and are looking to transition to a larger scale production and/or to GMP-grade manufacturing. Having a CDMO with process development capabilities will facilitate the testing and scale-up of your developed process, but the availability of large-scale/GMP production becomes a more important factor.
You have developed a complete process that has been tested at the desired scale and you aim to transition or expand to a new CDMO. The availability of large-scale/GMP production is likely to be the most important criterion once you have established compatibility between the CDMO’s capabilities and your process requirements.
Evaluate the top 10 “intangibles”
Once you have established what your needs are and what type of CDMO you should work with, the harder part begins: how to choose between the organizations that fit your criteria. While some factors, like CDMO size, available equipment, or process development capabilities, may be easily assessed over the internet or in a short conversation, there are other criteria that, in my experience, can have a deeper, longer-lasting impact on the success of the project and can influence whether or not the relationship will become a strong, long-lasting partnership.
We can refer to these factors as “intangibles”, since they have more to do with the nature of the organization, the way in which communication flows, and the compatibility between your company and the CDMO. Below, I describe some of these intangibles, how they can shape your CDMO search, and what types of questions you can ask to assess them:
How quickly can the CDMO sign a non-disclosure agreement (NDA) so that you can start a more detailed conversation? This process can be as fast as days or a slow as weeks or even a few months. Additionally, how quickly can they produce a quote or a statement of work? It is very important, at the very least, for them to keep the conversation going, even if there are delays in the writing and signing of the documents. If they aren’t moving fast during the scoping and proposal phase, what does that say about their delivery timelines?
You have already established whether they offer process development according to your needs. Now, it is time to ask whether they have the adequate capabilities and expertise to work on your process, especially if your system is not the most widely used platform in the field. For example, some CDMOs may have extensive experience with lentiviral vectors but very little work with adenoviral vectors, or a CDMO may have limited experience with fermentations in hosts other than E. coli.
How communicative are they during the project scoping stage? In my experience, a high level of responsiveness during early stages generally translates into good communication throughout the relationship.
How soon can they start working on your project? Can they start working on tech transfer and process development to minimize time losses? This is particularly important when there are long delays for manufacturing space.
Do they require you to utilize their process, and if so, are there are IP repercussions? Ideally, the CDMO can adapt to your process, unless they provide a strong justification (e.g. scalability, availability of reagents); this can mean bringing in new pieces of equipment, new reagents, new in-process measurement methods, etc. How do they respond to special requests?
Do they allow you to visit and inspect their facilities prior to signing an agreement and once the project has started? Are they open to external audits? How do they respond to conflicts of interest?
7. Willingness to Collaborate
Are they willing to work with you as the process is being developed and optimized, and once manufacturing begins? Can the client visit and troubleshoot things together with the CDMO? This is, in my opinion, one of the strongest indicators of a good and healthy partnership, as it can be a measure of how well you will work together and how much the CDMO cares about the success of your project.
How much do they value client confidentiality? How do they act during phone calls and video conferences? For example, do they casually mention other clients by name? Are they careless when sharing screens such that client names are visible in files and folders? When you visit their facilities, do you see papers, notebooks, and other exposed materials that could reveal the names of other clients, or the nature of other processes (i.e. I.P.)?
How would you evaluate the quality mindset of the CDMO? What quality system do they use? How strong is their quality team, and how much experience do they have? How many audits have they had? This is a good opportunity for you to ask the CDMO to describe how they have dealt with quality issues in the past.
How compatible is your company with the CDMO? The aspiration is that the relationship will become a long-term partnership and that you may work on more projects together in the future if everything is successful. Therefore, you would ideally want interactions with the CDMO to be cordial, easygoing, and welcoming, particularly during visits.
You should expect any future partner to be responsive and demonstrate understanding when problems arise during process development or manufacture. The bottom line is that you want to look forward to talking to and working with them.
Consider intangibles to create a long-lasting partnership
As more organizations enter the space, making a final decision on which CDMO will handle the scale-up and manufacturing of your product can seem like a daunting task. However, once you identify your needs and potential organizations you can work with, you can research the criteria that will most strongly influence your relationship with the CDMO so that you can make a well-informed decision.
In addition to standard factors like cost and availability, make sure to consider these intangibles, as they can help you assess the level of compatibility between the two organizations and give you an indication of whether your relationship with the CDMO will be well positioned to blossom into a strong, long-lasting partnership and not a transactional relationship.