As the saying goes, “The best-laid plans of mice and men often go awry.” Yet, while API manufacturing projects may not often go awry, there are times when projects can fall behind schedule. Problems can arise in the lab or plant that may be completely out of the control of the Contract Development & Manufacturing Organization (CDMO), but which can still throw project timelines out the window.
Here at Seqens NA, we work hard to keep projects on schedule, and we’re proud of the fact that 90 percent of our projects come in on schedule. Yet, when problems do occur, it’s important to get right back on track, by understanding what those problems are, cutting them off at the pass if possible, and if that doesn’t work, working to lessen the blow.
What Causes Project Delays?
Since API manufacturing is never predictable, and chemistry is constantly changing, some of the problems that can occur and cause project delays, include:
- Issues with raw materials. On average a dozen raw materials must be procured for each project, and they often come from overseas. It can be impossible to predict how these materials will interact and behave. If problems are identified early in the synthesis, it isn’t as much of a problem; but when scaling up, the loss of batches of material can be a major and costly issue.
- Equipment malfunctions. Despite having the most advanced technology and equipment, there can be problems with dryers, filters, reactors, vessels and other critical tools that can put projects behind schedule.
- Scale-up problems. Once the raw materials pass muster, the chemical process itself can cause the molecules to undergo a chemical reaction which can alter the composition. Despite low levels of impurities and quality output in the Kilo lab, new impurities can crop up when scaling up batches.
- Project pipeline backlog. Any problem that sets back one project can have a rippling affect across the pipeline. Since many projects must be completed in cGMP suites, they usually follow a tight schedule. So when a project hits a roadblock, it can delay projects behind it as well.
- Analytical challenges. As issues crop up in a molecule as it goes through various stages of manufacture, changes must also be made to the analytical method to understand its chemical state. This can cause delays and require significant collaboration among the scientific team.
While problems happen, there are procedures, processes and best practices that can be implemented to make sure projects get off on the right foot. Consider five of the following:
- Let the CDMO do its work. It’s important to maintain a regular schedule of communication between sponsor and CDMO and also update the sponsor immediately when issues arise. Aside from that, a sponsor that has complete trust in its CDMO – not requiring review and approval of every batch record, analytical method and other activity – can experience faster delivery schedules and efficiency.
- Share as much history as possible. At the outset of a project, a sponsor should share as much information about prior project history and challenges, including prior batch records and documentation, to ensure no one is spending time reinventing the wheel. For example, if the sponsor previously contracted with an overseas firm for batch processing, any information on the duration of time it took to run the chemistry would be helpful in providing a more accurate estimate of timeframes. Also, any abnormalities that were noted in the plant previously would help in anticipating possible issues going forward.
- Set realistic timelines. Since the cost and time of using cGMP suites and equipment can be a big investment, it’s important to set realistic timelines that factor in the possibility of problems occurring. By providing some gaps in between projects, you can make sure that projects remain on schedule and business smoothly flows along.
- Plan for overages in proposals. It’s important to estimate the cost of project overruns when developing the initial proposal and let sponsors know that they should plan for 25-percent overage costs. While the additional fees usually are not required, it’s a good way to make sure the sponsor does not get caught off-guard and has the necessary funds in the event problems occur.
- Vet your raw materials suppliers. Since most setbacks occur because of impurities in raw materials, or a lack of adequate supply, it pays to make sure you develop a trusting relationship with your raw material provider. You should feel confident that not only are you getting adequate supplies, but they are of the highest quality possible.
API manufacturing can be a messy business, filled with many unknowns and curveballs that can derail project timelines. Increasing your chances of keeping projects on schedule and problems at a minimum requires a concerted approach between sponsors, CDMOs and suppliers to maintain communication, collaboration and a strong foundation of mutual trust.
For additional insights and observations, please check out: API Manufacturing Technology Transfer; Shattering 5 Myths About CDMOS; or Best Ways to Keep GMP Polymer Projects on Schedule.
About the Author
Ed is President & CEO of SEQENS North America (formerly PCI Synthesis). 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.