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What Went Wrong? Make Sure Your Bridge Stays Intact, CMC and Dissolution

Make Sure Your Bridge Stays Intact: CMC and Dissolution in 505(b)(2) Development

One of the most common reasons for a company developing a drug to receive a Refuse to File letter from the FDA is for problems with Chemistry, Manufacturing, and Controls (CMC). Camargo has a robust in-house CMC team to help address and prevent those problems before they start.

For our third episode in our video blog / podcast series called What Went Wrong? Dr. Ruth Stevens, Exec VP and Chief Scientific Officer of Camargo Pharmaceutical Services, discusses important CMC and Dissolution considerations with Dr. Lynn Gold, VP of Scientific and Regulatory Affairs at Camargo.

To watch the 2-minute dialogue, press play below.

Make Sure Your Bridge Stays Intact: CMC and Dissolution in 505(b)(2) Development


Dr. Stevens: A number of clients come to us already understanding that with 505(b)(2), they have to be prepared with a commercial quality product. How do they maintain that quality product from the bridging study or their opening protocol throughout all of their studies for NDA registration?

Dr. Gold: That is a great question. A good example might be an extended release product where your pharmacokinetic (PK) bridging study which is pivotal to your NDA application has a specific dissolution profile and you have human data which correlates to that profile. If you make a scale change in your process that affects the extended release profile, you need to connect that back to your original data. Typically you would, Number 1, do that with the Controls and the Manufacturing Process. You need to know your manufacturing process well enough to know what will impact that dissolution profile. Second, you need to have a dissolution method that can detect those differences.

Dr. Stevens: Do you find that often with our sponsors coming to us?

Dr. Gold: What we find is that people don’t understand how critical that is. Often, for instance, the dissolution method would be an evolution from a USP methodology and not have all of the critical boundaries established. They don’t have a robust dissolution method development report that establishes how well they can detect change and the impact of change.

Dr. Stevens: Maintaining the quality of the product, even though changes do occur. I hear that there are ways to ensure that you are able to bridge to the quality of the product for registration trials.

Dr. Gold: That is correct.

Camargo CMC

Camargo’s early involvement in the drug development process saves a program substantial time and monetary investment, and reduces the regulatory risk by ensuring proper bridging. From API and formulation sourcing, to manufacturing, scale-up, and packaging, experts at Camargo provide valuable strategic guidance and management services.  Contact us to learn more.