The Inactive Ingredient Guide (IIG) is a regulatory database published and maintained by the United States Food and Drug Administration (USFDA). It serves as a critical reference for pharmaceutical scientists, formulation developers, and regulatory affairs professionals engaged in the development and approval of drug products—particularly generic drugs submitted through the Abbreviated New Drug Application (ANDA) pathway.
Purpose and Scope of the IIG
The IIG provides a comprehensive listing of excipients, also known as inactive ingredients, that have been previously approved by the FDA for use in marketed drug products. Each listing includes the maximum potency or quantity of an excipient as found in approved products, categorized by route of administration (e.g., oral, injectable, ophthalmic, topical) and dosage form (e.g., tablet, capsule, suspension, ointment). The guide is limited to excipients used in approved NDA and ANDA submissions in the United States.
How the IIG Supports Formulation Development
During drug product development, especially for generics, formulators must justify the selection and quantity of each excipient. The IIG helps developers determine if an excipient has been previously used and at what level, reducing the need for additional safety or toxicology studies. If an excipient is used within the IIG-listed maximum level for the same route and dosage form, it is generally considered safe and acceptable by the FDA without requiring further justification. This simplifies the regulatory review process and improves the efficiency of drug development.
Limitations and Considerations
While the IIG is a valuable tool, it is not exhaustive. It only includes excipients that have been approved in existing NDAs or ANDAs, meaning newer excipients or those used in novel drug delivery systems may not be listed. Inclusion in the IIG also does not guarantee automatic approval, especially if the excipient is used beyond the listed level, in a different dosage form, or via an unlisted route of administration. In such cases, sponsors must provide additional scientific or safety justification, such as toxicology reports, literature references, or published safety data.
Regulatory Importance in ANDA Submissions
In ANDA filings, the use of excipients at levels consistent with the IIG can support a bioequivalence waiver and minimize review queries from the FDA. It helps applicants demonstrate that the proposed formulation does not pose new safety risks, thereby expediting the review process. For drugs submitted under 505(b)(2) or new dosage forms, the IIG can still serve as a useful reference but may require supplemental justification.
Read also:
- 20 Essential Databases for Industrial Pharmacists
- Critical Material Attributes (CMAs) of Excipients
- How to Calculate Maximum Daily Intake Using IIG Database?
Resource Person: Moinuddin Syed. Ph.D, PMP®