Telephone/Fax Amendments Are "Highest Priority" For ANDA Reviewers

Telephone and facsimile ANDA amendments will be designated as "highest priority" by FDA reviewers, the agency says in its recent guidance on "Major, Minor, Fax and Telephone Amendments to Original Abbreviated New Drug Applications."

"The issuance of both major and minor amendments stops the review clock while the applicant addresses the deficiencies noted by OGD, but fax and telephone amendments do not stop the clock unless the applicant does not respond within the anticipated time," the Office of Generic Drugs reports. "Therefore, fax and telephone amendments represent the reviewer's highest priority work assignment."

The guidance centralizes OGD policy on amendments into one document and outlines the office's criteria for categorizing amendments. Major, minor, fax and telephone amendments have been addressed by FDA in earlier Policy and Procedure Guides (#16-90 and #21-90); OGD policy regarding fax amendments was circulated in a 1997 letter.

An amendment will be classified as "major" if a chemistry reviewer "cannot reasonably be expected" to review requested information in less than one hour, or if requested microbiological/sterility assurance data cannot be reviewed in less than one day, the guidance instructs. An amendment addressing significant bioequivalence deficiencies also would be considered "major," FDA says.

Major amendments are reviewed within 180 days and minor amendments within 60 days if no outside consult is needed.

A "minor" amendment to an application applies if a chemistry reviewer can be expected to review requested chemistry, manufacturing and controls data in less than one hour, or microbiology reviewer requested data in less than one day. The classification also will be applied to requests for which applicants will need more than 30 days to respond. The "minor" determination will not be made if significant bioequivalence deficiencies exist, FDA notes.

Deficiencies that are primarily administrative or are clerical revisions can be addressed by fax amendments, the agency reports. In addition to meeting all criteria for a minor amendment, fax amendments apply when "all deficiencies are judged to be within the immediate control of the applicant, all revisions have been found acceptable [and] OGD expects that the applicant will be able to provide complete responses to all deficiencies within 30 calendar days."

This category of amendment applies to inconsistent statements in an ANDA that need to be clarified (but the clarification is not expected to result in further questions), or if OGD requests a specific change that will not result in additional data submission. Other examples provided by FDA include resubmission of illegible pages or correction of typographical errors, request for a postapproval commitment or if an applicant is asked to provide additional stability data accrued during the review process.

Labeling deficiencies generally can be addressed by facsimile. An amendment following a minor or fax amendment that primarily addresses administrative or minor technical issues will be classified as a telephone amendment, the guidance instructs. The classification applies if deficiencies are similar to those described for a fax amendment, and if OGD believes an applicant can provide a complete response within 10 days.

Clarification of data already submitted and requests for postapproval commitment could be classified as a telephone amendment as well, FDA says.

To expedite review, "telephone amendments may also be requested during the final office level administrative review of an ANDA, immediately prior to tentative or final approval," the guidance states.

Fax and telephone amendments can be redesignated as minor amendments if deficiencies are not satisfactorily addressed, or if a response is not received within the designated time frame, FDA says.

The agency also cites cases in which the redesignation of an amendment could alter the status of an ANDA.

"If the chemistry review is completed first and appropriate criteria are meet, OGD will issue a request for a minor amendment response to deficiencies. If the microbiology review subsequently reveals major deficiencies, these will be communicated to the applicant as a request for a major amendment response. This action will also change the chemistry response to a major amendment," the guidance says.

OGD "will not consider a request to reclassify an amendment because certain deficiencies are eliminated by an applicant's withdrawal of a portion of the application," FDA notes.