Good API development and manufacturing leads to safe and effective drugs and the control of critical illnesses and diseases in patients. So, it’s no wonder that large amounts of time and money go into their discovery and production. Getting a new drug from discovery through clinical trials to approval can take at least ten years, with the average cost estimated at $2.6 billion.
Adding to the complexity, each new molecule is completely different. So scaling up, manufacturing and commercializing each new one is a quest into the unknown with twists and curves along the way.
Most of the costs of API manufacturing are unpredictable, but inevitable. Here are eight considerations that a sponsor can address that can go a long way to helping to avoid some of the cost over-runs that quite often occur.
- Become closely aligned from the beginning. The familiarization and optimization phases can take eight to 16 weeks, and set the tone for the entire project. Starting with a kickoff meeting, the sponsor and the CDMO team should meet to share all the technical information available, including an overview of already-conducted work and relevant reports and documents. This is also when the quantity and types of raw materials, chemistry and analytical requirements are established.To ensure that work is not duplicated or valuable time is not spent playing detective, information sharing by the sponsor is crucial. Time really is money; the more knowledge, information, concerns and history that can be imparted by the sponsor to the CDMO, the better. Likewise, at a kick-off meeting, it’s important for the sponsor to articulate the regulatory strategy, which will dictate how much analytical work needs to be done and how it needs to be done.
- Have regular synch-ups. Some start-up sponsors 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.
- Plan on problems. Even with the most experienced CDMO, problems can happen — from raw material impurities to lower-than-expected yields. Things beyond the control of anyone can upset the apple cart. When this happens, however, the key is to not get sidetracked. If a yield is not good, that may not be the best time to go into lengthy development to analyze why, but to simply go back and redo it or add additional starting material.
- Don’t skimp in the kilo Lab. Since the real rewards come when an API is commercialized, everyone wants to get there as quickly as possible. To do this, they often want to skip kilo scale-up and move right into GMP manufacturing. But, this can easily wind up costing significantly more, since many surprises are uncovered in the kilo lab. Immature processes, other technical issues and unexplained high impurities, are always better addressed on a smaller scale, when project costs are lower.We recommend running 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 manufacturing larger quantities will go smoothly.
- Stick with the same CDMO throughout the project. Having a CDMO that can perform both R&D and manufacturing puts you at a distinct advantage. 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.The recent acquisition of PCI Synthesis by global Novacap helps us to put this benefit into overdrive. Employing more than 3,000 people at 28 industrial plants around the world, including 11 cGMP facilities, customers don’t need to look elsewhere to fulfill specific phases of the project, but can be assured of seamless and continuous operations without the delays caused by technology transfer.
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- Check into prior experience. Related to the consideration above, the closer the match between the CDMO’s experience and the nature of the chemistry to be developed, the greater the chance is for success. Much of API manufacturing can be trial and error. It’s to your advantage to work with a CDMO that has experienced something similar to your project and can put their lessons learned to bear on it.
- Look for a strong FDA track record. Any time a CDMO is inspected by the FDA, issues that are raised can seriously delay project schedules. Working with a CDMO with a strong track record of smooth inspections can ensure that projects are not impacted by lengthy inspections that take time away from your project. Typically, the FDA conducts routine inspections at a minimum of every two years, yet lately, for those CDMOs that have positive inspections, this often is moved to a four-year basis.
- Work with companies with strong sourcing. Many times the problems that can raise costs, include problems with raw materials, or simply not being able to source enough of the raw material required – especially when procuring 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.
Essentially, in API manufacturing the biggest costs are in three key areas: the cost for chemistry, scale-up and GMP plant time. Working with a CDMO that can understand your regulatory strategy up front and what may be required for GMP release, can go a long way to easing the cost overruns that can plague an industry often dealing with the unknown.
For more articles on how to save costs in API manufacturing, read: “Four Ways the Kilo Lab Development Phase of Drug Manufacturing Can Save Time and Money,” “Three Ways to Save Money when Managing Impurities During API Scale-Up How can you minimize their impact on cost-over-runs?,” and “How to Keep CMO Costs Down During the Process Optimization Stage of Drug Development.” If you have a question or want to speak to one of our experts, please call us at (978) 462-5555 or email us at email@example.com.
About the Author
Ed is the President and CEO of PCI Synthesis (PCI), he serves as a co-chair of the New England CRO/CMO Council and sits on the Industrial Advisory Board for the Department of Chemical Engineering at UMass, Amherst. Ed is also a long standing member of the American Chemical Society and advises the Bulk Pharmaceutical Task Force of the Society of Chemical Manufacturer’s and Affiliates (SOCMA).
Do you have questions? Talk to Ed.