Developing a product with multiple strengths? How do you go about filing multiple strengths in an IND? How and when do you draft one CMC section covering multiple drug strengths for the same dosage form?
Long-term drug development goals may include multiple strengths of a drug product to support the market needs. Even so, early in the drug development, the IND stage for example, only one strength would be studied in the clinic for proof of concept. Therefore at the IND stage only one strength would be supported in the CMC section of the application. As the development program evolves additional strengths can be added to the application.
There may however be situations when multiple strengths of a drug product formulation will be studied in Phase 1. Two distinct Chemistry, Manufacturing and Controls sections for each drug concentration are not required; clarity that two drug strengths are included in the application is recommended. The CMC section should point to the differences and similarities in the formulations and describe how the drug product is or is not impacted as a result.
As an example, when describing the formulation you may have one table with the formulation components listed and one column heading for each strength. The pharmaceutical development section would include a discussion of the experience obtained with each concentration of drug product and whether there are any manufacturing, analytical, handling or stability differences between the two drug products. If there are differences, when possible, an explanation of the source of the difference helps the reviewer and demonstrates the sponsor’s expertise. This should be reflected in the narrative as it applies to each of the CMC sections. If all the components are the same, then the excipient section should state that fact. In the analytical section, the sample preparation might be the only difference as a result of the different drug strengths. Batch analysis and stability data to support the multiple strengths of product to be studied in the clinic should be provided or an explanation of why the data provided are sufficient to demonstrate suitable shelf-life.