By the time an active pharmaceutical ingredient (API) is ready to be introduced into preclinical or cGMP manufacturing, a significant investment in both time and money has been expended. It has undergone synthesis, analysis, quality control, stability studies and much, much more – and that’s just a broad categorical view. Within each of the categories, there are the numerous steps and problems to be solved that are inherent to creating new chemistry that is slated to become a safe, effective therapeutic. As anyone in the industry knows, creating an API is a challenging endeavor every step of the way.
No less challenging is preparation for API manufacturing. Whether producing critical material for Phase 1, 2 or 3 clinical trials, or for commercial launch of a new drug, or to provide on-going API supply for a commercial product, a great deal must be done to prepare for a successful drug product, and to do so as quickly and efficiently as possible.
The jump from the R&D labs to the cGMP manufacturing suites is never simple or easy. In most instances, today’s active pharmaceutical ingredients have increased in complexity. Chemistry issues often arise when producing the larger quantities of these materials needed as the project progresses. Keeping the molecules within specifications to meet FDA, EMA and ICH guidelines can break down at any step along the way.
Although speed and efficiency are prized, stellar R&D is more than just a matter of expediting research. It’s a must-have in today’s competitive pharmaceutical industry where first-to-market advantages can only be realized if the R&D program is reproducible, well-documented, and garners regulatory approval without undue delays.
This article will focus on what’s involved in R&D for development of APIs.
Learnings from an experienced CDMO
Every year, Seqens CDMO North America, one of the most awarded cGMP API manufacturing companies, produces custom NCEs, controlled substances (Schedule II-V), generic APIs and custom manufactured fine chemicals for sponsors. We create new molecules, put them into clinical trials and produce commercial supplies of APIs for numerous major generic and pharmaceutical firms. Whether large or small volumes are required, we help our partner companies succeed first with the FDA or EMA, then in the marketplace, more than any other CDMO in North America.
The 10 best practices for API development
Here’s what we have learned over the years. As a CDMO that develops APIs in our labs and also manufactures them in our cGMP suites, we are attuned to the numerous reasons for API failures, and we are skilled at avoiding them. The more complex the molecule, the more need to adhere to these best practices:
- Maintain complete API records.
- Perform appropriate testing to assure conformance to specifications.
- Assure that each chemical step is problem-free before moving to the next step.
- Maintain thorough, complete data from laboratory tests and also include any failed attempts.
- Ensure that all equipment is reliably cleaned.
- Investigate critical deviations adequately.
- Document each step diligently and thoroughly as required by regulators.
- Have all measurement instruments on-site as now required by regulatory bodies.
- Maintain frequent and open communication between the CDMO and sponsor teams – this is critically important.
- Choose a CDMO with highly experienced project managers.
Look ahead and choose an integrated CDMO
Whether embarking on an early or mid-stage R&D for API development project, many sponsors find it wise to look ahead and be prepared for cGMP manufacturing after successful FDA or EMA approval. One good reason is that one never knows with certainty whether the chemistry will behave in the same way when scaled up to larger quantities. It doesn’t necessarily follow that the chemistry developed when working with small quantities will be problem-free when preparing the first GMP batch or larger quantities of material for later-stage clinical trials. The scale up process sometimes unearths new impurities or temperature sensitivity or a myriad of other issues that require processes to be tweaked.
Who better to do that most efficiently than the CDMO that developed the chemistry and is intimately familiar with its behavior?
There are at least four other good reasons for sponsors to choose an integrated CDMO:
- It’s the surest way to adhere to timelines, as it eliminates the considerable time spent in technology transfer from one organization to another.
- Although the billing rate at an integrated CDMO may be somewhat higher to reflect large investments in plant and equipment, the total project cost will most likely be lower, since processes will not need to be validated again and again every time a new organization works on the project.
- A CDMO experienced in both API development and manufacturing can often anticipate and circumvent potential issues, saving time and money.
- Integration eliminates any lag time in sourcing quality raw materials and intermediates for the project.
The significant time and money spent on API development is best invested in a CDMO that can get the complex job expertly done, from beginning to end — and one you can count on to provide reliable information and communicate openly every step of the way.
To assure the smoothest possible process, Seqens CDMO NA has built a seamless development solution that enables you to begin your active pharmaceutical ingredient development in our Devens R&D lab and then migrate it directly into our nearby cGMP Newburyport API manufacturing plant, where we offer up to 20,000 gallons of manufacturing capacity. Because of our closely aligned R&D API synthesis and scale-up capabilities, you can feel confident in knowing that we’ll be with you all the way, from discovery to commercialization.
We’ve written a lot about API manufacturing. If you’re interested, please check out articles that include: “10 Factors to Consider When Picking a Partner for Commercial Scale API Manufacturing,” “5 Best Ways to Save Money in API Development: 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,” “The Art of Reducing API Failures. Five questions to ask to de-risk development of complex molecules,” and “Eight Considerations to Reduce the Cost of Success in API Manufacturing.” Please consider signing up for our newsletter or if you have specific questions, email us at firstname.lastname@example.org or call us at (978) 462-5555.