This is Olga Peycheva overview of FDA CMC Pilot webinar which was held on 10 Sep 2025 and was recorded for the Solutions OP Clinical Trials podcast. You can listen to the original recording here. Please note that discussions points below are adapted and not a transcript. This was done to improve readability.
I attended on 10th of Sep a webinar organised by US FDA regarding their Chemistry, Manufacturing and Controls (CMC) Development and Readiness Pilot Program which has been ongoing for some years now. During the 4 hour meeting they shared information on the purpose of the program and also gave opportunities to participants from the pilot to provide feedback on their experiences.
What are the main issues with Chemistry, Manufacturing and Controls (CMC)?
Pharma companies always set aggressive timelines for their clinical development in attempt to reach the market as soon as they can, but their manufacturing is lagging behind. And often the issues with manufacturing are the reason for marketing authorisation applications to be rejected and products not reaching patients. It is important for pharma companies to understand that the product needs to meet the safety, purity and potency requirements.
To support this FDA started in 2023 CMC Development and Readiness Pilot which will be ongoing until 2027. The idea behind this project is to improve the communication between pharma companies looking for expedited approval and FDA which will help improve the drug manufacturing and discuss options for flexible product development. The final result should be products to each the patients faster.
Who can qualify for that pilot?
The detailed criteria are listed on the FDA website but here I can mention that pharma companies need to have an active commercial Investigational New Drug Application. Some of the products that would qualify for this pilot are cell therapies, gene therapies, radiopharmaceuticals, vaccines, small molecules and other biological products. The company must have Breakthrough or other fast track designation.
What does it mean accelerated clinical development?
The standard development process goes through pre-clinical phase, phase 1, phase 2, phase 3 and then marketing authorisation application. However, in accelerated drug development there is a pre-clinical phase and then phase 1 and 2 which is followed by marketing authorisation application. This means that the companies have a lot shorter timelines to scale up their manufacturing.
What are the common challenges that companies face with manufacturing?
Due to the acceleration of drug development, there are some unique manufacturing challenges:
- Manufacturing changes and comparability – During the discussion with the participants from pharma companies in the pilot program they mentioned that often there are changes in suppliers or shortages of Active Pharmaceutical Ingredient (API); or sometimes the product has a short life which brings additional challenged in manufacturing. Sometimes the companies have to change the manufacturing facilities, or they have limited experience with scaling up manufacturing.
- Process validation, Assay validation – For example, in cell therapies you have a lot of variability of the biological product which could be a significant challenge when you try to validate your assay.
- Potency assays – When you have a new product from new class and you are looking to fast track it to the market you will have significant challenges with establishing your potency assays simply because it is a new product and developing such reliable assays take time.
- Stability – For example, in radiopharmaceuticals you work with isotopes which have a short life, and they need to be handled in a completely different manner than other products. Often, they are released before all the testing is completed to speed up delivering them to the patients while in parallel there is an ongoing additional testing.
- Readiness of manufacturing facilities – It is normal for products to be manufactured initially in small amounts and scaled up during the drug development. However, in accelerated drug development this time for scale up is very short.
- Extractables and Leachables – Have any sort of contamination due to interaction of the product with the packaging or equipment is a well-known issue in drug manufacturing. Handling that in accelerated drug development could be a significant challenge especially for new classes of products which are not so well studies yet.
What are the main challenges of this program?
As always, the challenges are lack of time and lack of resources. What made an impression to me was that all the participants in the pilot who were on the meeting represent big pharma companies or work in collaboration with big pharma companies. This pilot will not be accessible to start-ups and small companies which do not have the resources for that. Even FDA admitted that they have not included some companies in the pilot because they are not advanced enough in their development program. My best guess is that these are likely smaller companies.
While such pilots are very helpful for the companies, we need to be realistic on how much resources they can invest in developing their product while having ongoing discussions with the regulators.
Another significant challenge is lack of harmonisation. Even the FDA admitted that they are not always aware what other regulators have advised the companies. This means that if the company plans to obtain marketing authorisations in several regions around the world they need to coordinate with all different regulators, and this becomes almost impossible mission for smaller companies.
Is this pilot helpful? Yes, definitely! Is it going to help small companies? I doubt that. Again, I would say that we need something tailored for small companies and startups.
