‘Under GDUFA II, FDA has committed to clean up inaccurate, inconsistent and missing information and verify data integrity’

DuPont Nutrition & Health’s regulatory team, from direct participation on joint IPEC and FDA working groups, has the expertise to assist its customers with understanding the FDA requirements for using the IID and developing bridging justifications, informs Priscilla Zawislak, Global Regulatory Affairs Advocacy Manager & Tejas Gunjikar, South Asia Technical Application Leader at DuPont Nutrition & Health, in conversation with Usha Sharma

Tell us about the complexities and challenges associated with the US FDA Inactive Ingredient Database (IID).

The change in 2011 to list each excipient grade and UNII code with information from the GSRS has created a lot of confusion in the industry. The current database is incomplete and has missing information. Under GDUFA II FDA has committed to clean up inaccurate, inconsistent and missing information and verify the data integrity. FDA has been updating the IID on a quarterly basis. Users are recommended to check items of interest each time since information can change. Maximum potency is a source of confusion, it is not a MDI. FDA has also committed under GDUFA II to adding a column in the database for MDI and will eventually populate it. Nomenclature in the IID comes from the GSRS which is the ‘preferred name’ and may not be the compendial name. Tradenames, sometimes referenced in the IID are being removed. The GSRS has a listing of synonyms for the preferred name which may include the compendial name and trademarks.

US FDA has revised Refuse-to-Receive Guidance for ANDAs submission, tell us about the revised guidelines and their impact on the pharma industry?

If the excipient being used is not listed in the IID based on the route of administration and dosage form it is considered a novel excipient by FDA and a bridging justification is needed in the ANDA to use the information in the IID to support other grades, route of administration, dosage form or level of use. The bridging justification must include the context of use in the specific formulation and this information must come from the drug product manufacturer.  The excipient supplier usually can only provide safety and toxicology information for the excipient. FDA requires that the bridging justification ‘tell the story’ which includes the context of use of the excipient in the specific drug product formulation. It is recommended to submit a Controlled Correspondence to request information about MDI. The CC must include details of the specific formulation, excipient, route of administration, dosage form and level of use.

Providing the bridging justification in the CC is often recommended before submitting the ANDA. FDA has been asking for toxicology studies for each grade of excipient but toxicology is typically the same within a polymeric excipient family. Studies are not conducted in individual grades. Rather, a ‘bracketing’ approach is used that is representative of all grades within the family. This is one of the reasons a bridging justification must be provided to ‘bridge’ the information between grades.

How does DuPont Nutrition & Health support customers on the use of excipients in oral solid dosages?

DuPont N&H has toxicology summaries for many of our excipient products that can be used to support bridging justifications. Our regulatory team, from direct participation on joint IPEC and FDA working groups, has the expertise to assist our customers with understanding the FDA requirements for using the IID and developing bridging justifications.