Strategies and Best Practices to Ensure You’re Getting the Most Value from Your CDMO
Active Pharmaceutical Ingredients (APIs) are the lifeblood of critical drug treatments and can make or break the sponsoring organization marketing them. But, getting a new drug from discovery through clinical trials to approval can take a minimum of ten years, with costs upwards of billions of dollars. For such an expensive endeavor, with a lot riding on its success, sponsoring organizations work diligently to select the right Contract Development & Manufacturing Organization (CDMO) for the job.
Yet, while a CDMO can meet all of the required criteria, nature can waylay the best-laid plans. Molecules can be very unpredictable and are often a quest into the unknown. A CDMO can never predict exactly how one will respond, if it will contain too many impurities or how it will scale up.
This unpredictable nature can cause fixed costs to become unpredictable as well, but there are a few things that can be controlled, and they can go a long way to reigning in costs and paving the way for better outcomes. Consider the following best practices.
Focus on Comprehensive Knowledge Transfer
Starting with the first kickoff meeting, the sponsor should share all of the technical information available with the CDMO, including an overview of project history and relevant reports and documents. Make sure that everyone in the sponsor’s organization who was involved in the project has an opportunity to weigh in with their particular area of expertise. There is no such thing as too much technical information. This is also important when the quantity and types of raw materials, chemistry and analytical requirements are established, so it’s important to share as much as possible to ensure that work is not duplicated or valuable time is not spent playing detective. Likewise, at a kick-off meeting, it’s important for the sponsor to articulate a well-thought-out regulatory strategy, which will dictate how much analytical work needs to be done and how it needs to be done.
Establish Regular Sync-Ups
Especially with smaller sponsors, they often don’t realize the depth of work that goes into their projects – and steps that need to be taken to address changing FDA requirements. Getting into the habit of regular, weekly meetings are important and can be eye-opening, helping to raise concerns, demonstrate progress and provide a realistic touchpoint for estimated time and resources required. This is also when project delays and issues should be openly discussed and unexpected costs can be properly explained to corporate boards or investors.
Plan on Problems
Even with the most experienced CDMO, problems can be expected to occur - from raw material impurities, to lower-than-expected yields, to scale-up issues. When this happens, however, the key is to not get sidetracked. If a yield is not good, this may not be the best time to go into lengthy forensics to analyze why, but to simply go back and redo it or add additional starting material. It’s important that your CDMO is on the same page on this approach so that the most straight-forward path is followed.
Don’t Skip Steps to Get to the Finish Line
It’s tempting to race to current Good Manufacturing Practices (cGMP) manufacturing if certain steps, like kilo scale-up can be eliminated, but it’s not a good idea. Skipping the kilo lab can add costs to the project in the long run, since many issues can be uncovered in the kilo lab, such as specific technical issues or unexplained new impurities. It’s easier and much less expensive to discard batches in a non-GMP environment instead of wiping out much larger ones, or perhaps scrapping projects altogether, when they are realized in the GMP plant.
A good CDMO should run processes at least three times at kilo scale. Once everything works as expected – in quantities from 1 Kg to 20 Kg, it is far more likely that GMP manufacturing for larger quantities will go smoothly as well.
Choose Your CDMO Wisely and Plan for a Long-Term Relationship
Since a major cost in API development is the time involved in technology transfer, having the same organization develop the API and also manufacture it can save hundreds of thousands of dollars not to mention valuable time. Often, information can be missing when transferring from one CDMO to another – especially when working with overseas CDMOs that may not follow the same reporting or process-control protocols. For this reason, using one CDMO can provide a more seamless experience and less costly project delays if things go sideways.
Look for Matching Skills
It also pays to select your CDMO carefully to make sure it’s the right fit for the job. The closer the match between the CDMO’s experience and the nature of the chemistry to be developed, the greater the chance for success. Problems that the CDMO may have encountered in the past can work to your favor, making sure that the issue is proactively addressed this time around.
Consider the Sourcing Partnerships
One of the biggest culprits to project delays is problems with raw materials – namely too many impurities. This issue can cause severe and costly project set-backs. In addition, CDMOs with a lack of adequate sources for raw materials can experience a shortage of the needed raw material to even begin the project on time. This can be especially challenging if you need to procure only small and infrequent batches for smaller or specialized projects. Yet, CDMOs with strong suppliers, as well as alternative suppliers for back-up measures, can help to ensure that projects are not stalled because of a lack of raw materials.
Avoid the Blame Game
You’ve spent a lot of time vetting your CDMO. Most likely they have a good reputation and have been in this business for a long time. At the same time the CDMO is running a business and it has other projects and customers. Drug substance development and manufacturing can be a difficult and messy endeavor. Problems arise, but the best CDMOs will work with you collaboratively in a professional and respectful manner and you should approach problem solving in the same way. It’s individuals that get the work done and you want them to be as invested in your program as you are. Accountability for both sides needs to be understood and as long as all players are expending their best efforts the eventual outcome is usually a positive one.
There are many things out of your control in API manufacturing, but there are some key ways to either avert or manage them. Selecting the right partners, trusting them with your most critical projects and collaborating with them each step of the way can go a long way to easing the cost overruns that can derail the most promising of projects.
Author Biography
Ed Price is President and CEO of Seqens North America (formerly PCI Synthesis), an integrated global provider of pharmaceutical synthesis and specialty ingredients. From the company’s Newburyport, Mass. operations, Seqens N.A. provides emerging and mid-sized pharmaceutical companies access to the expertise needed to develop and manufacture complex small molecules. Seqens is part of Seqens CDMO, an integrated global leader in pharmaceutical synthesis and specialty ingredients, delivering custom-made products and solutions to its customers that operates 24 industrial plants and 3 R&D centers in Europe, North America and Asia.