API development is a highly complex process, which makes it an expensive undertaking. That’s mainly because developing new chemistry is often full of surprises. There is no clear, predefined path, no GPS to guide us precisely along the route, although previous travel in that direction is enormously helpful. There are no road signs that tell us we’re definitely on the right path. Rather, we’re engaged in a stepwise progression of molecule-building, one step at a time.
Despite the lack of a road map, more than 20 years in the CDMO business has given us a pretty good idea of what it will cost to develop an API. Always, we make every effort to choose the path that minimizes costs whenever we can, without cutting corners.
This article will focus on five top ways to save money in API development.
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 result in savings of hundreds of thousands of dollars.
Technology transfer requires extensive interaction between scientists, whether in the initial stages of handoff from sponsor to CDMO, or in Phase I and Phase 2 of drug development, when transfer is undertaken to determine whether the laboratory-scale process can be successfully scaled up to a development scale process.
In both cases, a comprehensive Process Transfer Protocol (PTP) can make all the difference between an efficient transfer and one that gets bogged down with rework and repeated calls for more information.
We previously developed a technology transfer checklist for early stage technology transfer to a CRO or CDMO detailing what the API developer needs to make the process as smooth and fast as is reasonably possible. But once the API is developed and ready to be manufactured, having the same CDMO organization take it from lab to manufacturing suite is the straightest, most direct route to a final product. It avoids the high cost of yet another complex technology transfer from a CRO to a different CMO, no matter how comprehensively documented the analytical methods.
A single source for API development and manufacturing is a major cost and time saver.
There’s no substitute for experience in API development. The closer the match between the CDMO’s experience and the nature of the chemistry to be developed, the less tinkering in the lab it will take to create the molecules that will comprise the desired drug candidate.
Practically speaking, experience with similar chemistry could mean the difference between 8 weeks and 12 weeks of project time. At $7,500 a week for R&D, it adds up quickly.
Everyone is always in a hurry to get projects done. Sponsors occasionally ask us to skip the interim kilo scale-up step and move right into the manufacturing suite to save time. We suggest that is a terrible idea. It can easily wind up costing significantly more, not less, and take more time.
The reason is that if unpleasant surprises crop up when scaling up, they can be caught early and processes reworked in the kilo lab at a cost of $10,000 to $20,000 a week compared to the $75,000 price for a week in the GMP manufacturing suite.
Kilo lab scale-up entails running the manufacturing process in a non-GMP environment and tweaking the process as necessary to assure that the desired product and yield are obtained. Kilo scale-up identifies many technical issues, immature processes and impurities that if not found until already in the GMP manufacturing suite could cause costly delays. It gives scientists the chance to fix a problem better encountered before manufacturing begins.
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.
We are all aware that process automation can save customers time and money. At Starbucks you can have the machine-made coffee, or a cup of pour-over coffee made by a barista that will cost you twice as much because it’s less efficient. From our point of view as a busy CDMO, we prefer to automate where we can to get projects done as quickly and efficiently as possible for our customers.
That’s why as new technologies that speed processes come to market, we evaluate them carefully. If we determine that they will make our work more efficient without compromising quality, we purchase them and train our scientists to use them.
For example, in the old days if an intermediate step in API development required freeze drying, we would take the material and place it in glass flask in the lab. Then we would chill the flask using acetone and dry ice to remove water molecules from the material under vacuum. That method works, but it’s neither efficient nor scalable. As the need for lyophilization within projects began to increase, we invested in the most up-to-date freeze-drying equipment.
We’ve done the same for other processes including using automated rota vaps in order to complete projects as rapidly and efficiently as possible, saving our sponsors a great deal of time and money.
To reduce costs, processes need to be performed as efficiently as possible. A CDMO’s experience, equipment and ability to do both R&D and manufacturing are enormously helpful, as stated above. However, there’s more to efficiency than that. There’s also great value to be realized with a top-notch project manager.
At PCI Synthesis we truly respect and admire our project managers. We rely on them from the beginning to the end of each project. Issues are bound to come up in the complicated business of active pharmaceutical ingredient development. The best project managers can handle the pressure. They are problem solvers. They rework things if they are not going as well as they could. They make sure everyone on their project team has what they need when they need it. Consummate multitaskers and communicators, they pursue all options with one goal in mind: keeping projects on time and on budget.
In addition to working with a project manager who has these skills, another important factor in determining a project’s efficiency is whether project managers have the authority to make decisions.
If you’ve been working with us you know what I mean – we believe our project managers are among the best in the business. If you’re still in the process of selecting a CDMO, take a close look at the project managers—and the tools at their disposal. They are as vital to project efficiency and cost as GPS has become in getting us to where we need to go.
Ultimately, to lower costs consider a CDMO’s efficiency. It is a far more important and reliable variable than the initial project cost estimate. That’s because as in all aspects of drug development, even when automating some processes, nothing is easy or routine. Each new chemical entity (NCE) has different characteristics, and numerous other factors come into play during development and manufacturing that are unique to that NCE.
The key to minimizing API development costs are these: finding a CDMO whose R&D and manufacturing teams have experience with similar compounds. Reducing the need for time and resource-consuming technology transfer. Including kilo-lab scale-up prior to starting manufacturing. And having a seasoned project manager focused on efficiency who has the tools and authority to make decisions.
Figuring out how to save money is an important topic for outsourcers. We’ve written a lot on the topic, including: “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.