FDA Issues Guidance Revision 2: ANDA Submissions – Refuse-to-Receive Standards

According to FDAnews Drug Daily Bulletin, “The FDA has again updated guidance on its criteria for refusing to receive an ANDA, providing a broader definition for major deficiencies and downgrading four major deficiencies to minor ones in order to make requirements less burdensome for industry.

In a second revision to the final guidance since last year, the FDA says a major deficiency is one that, in its judgment, is significant in nature, whereas before the agency defined a major deficiency as one that cannot easily be remedied.

The document reclassified four major deficiencies as minor, including the failure to:

·         Contain an environmental assessment or claim of categorical exclusion;

·         Provide English translations of each part of the application that is not in English;

·         Provide daily elemental iron calculation for products that contain iron; and

·         Provide the Pharmacy Bulk Package Sterility Assurance Table.

The changes are intended to clarify the scope of what FDA considers a major deficiency and better align with its current practice‎. The guidance also relaxes the standards for refuse-to-receive notifications to give industry some flexibility, the FDA said.”

Click here for the revised guidance or here for help with your ANDA submission, including PK study design.

Note that for drugs that are not intended to be absorbed into the bloodstream, “FDA may establish alternative methods to show bioequivalence that may be expected to detect a significant difference between the drug and the listed drug in safety and therapeutic effect (21 U.S.C. 355(j)(8)(C); 21 CFR 320.24)”. In June 2010, FDA published a guidance describing their processes for publishing product-by-product guidance on design of BE studies in support of support ANDAs. This guidance and subsequent product-specific guidances marked the end of the previous approach of individual applicant requests for such information.  FDA now adds to, and updates these guidances periodically.  As of November 2016, there were a total of 1573 bioequivalence recommendations for specific products. Click here to learn more.