In submitting stability data in a NDA, there is the primary data which are generated on the drug substance and drug product prepared by the proposed commercial synthesis/process and proposed commercial formulation/manufacturing process, respectively. In addition, there is supportive stability data.

For drug substance and drug product, at least 3 batches of each are required. The scale should be at least 1/10 of the proposed commercial scale for drug substance and at least 100,000 units for drug product or 1/10 commercial scale, whichever is larger. A minimum of 12 months stability data on these batches are required.

All materials, e.g. starting materials, reagents, solvents, excipients, used to manufacture these primary stability batches of drug substance and drug product, should be tested and released according to their proposed commercial specification with their proposed commercial analytical methods.

Supportive Data

At least 3 batches of primary and supportive data are required

Supportive stability data for drug substance may include material made with synthetic or process variations, tested by similar methods and released to similar specifications. For drug product, supportive stability data may include drug product that is qualitatively and/or quantitatively similar, and/or manufactured by the same or a different process .It may also include drug product packaged in similar pack configurations.

FDA generally relies on the primary data for its review and approval decisions. However, supportive data could figure in as part of the decision process as it feels it is applicable to the demonstration of formulation and/or process understanding, and/or risk understanding and mitigation.

More than One Site of Manufacture

Primary stability data supporting more than one site of manufacture for drug substance and/or drug product can be included in the NDA submission. However, very detailed comparative information for any changes in equipment, process, process parameters, etc. as a consequence of the sites will need to be fully described and justified.  These data should demonstrate the site and any associated differences do not impact drug substance and/or drug product quality, including specifications, stability, impurity profiles, etc.

For additional information on NDA stability requirements for drug substance and drug product, please contact us.