FDA DRUG MASTER FILE FINAL GUIDELINE

Executive Summary

FDA DRUG MASTER FILE FINAL GUIDELINE discourages applicants from establishing a drug master file (DMF) when the material to be referenced is contained in the applicant's own IND, NDA or ANDA. The just-released guideline states: "When an applicant references its own material, the applicant should reference the information contained in its own IND, NDA, or ANDA directly rather than establishing a new DMF." Like the draft guideline published in October 1987, the final document instructs applicants to include in their annual updates any changes to the list of persons authorized to reference the file. The "DMF holder should also submit a statement that the list is current . . . if the list is unchanged on the anniversary date," FDA noted. The guideline incorporates proposed revisions to the definitions of the five types of DMFs. The revised definitions are also issued separately as a proposed rule. Both guideline and proposed rule are published in the Oct. 17 Federal Register. The proposed rule and final guideline amend the description of a Type I DMF (manufacturing site, facilities, operating procedures, and personnel) to make clear that the DMF will not generally be necessary for domestic firms. The revised description in the proposed rule states: "Because an FDA on-site inspection of a foreign drug manufacturing facility presents unique problems of planning and travel not presented by an inspection of a domestic facility, this information is only recommended for foreign manufacturing establishments." The proposed rule and guideline also revise the title of Type V DMFs from "preclinical or clinical data" to "FDA-accepted reference information." The proposed rule explains that "the agency has found that the Type V DMF is sometimes used to submit information that is either inappropriate or should be submitted with other documentation. For example, FDA has received clinical data in Type V DMFs that properly should be part of investigational and marketing applications. Therefore, the proposed change is intended to discourage the submission of Type V DMFs for miscellaneous information, duplicate information, or information that should be included in one of the other types of DMFs." The final guideline instructs DMF holders to submit a letter of intent to FDA's DMF staff before submitting information not covered by DMF types I through IV. FDA is accepting comments on the proposed rule and final guideline until Dec. 18. Copies of the guideline may be obtained from FDA's Legislative, Professional, and Consumer Affairs Branch (HFD-365), 5600 Fishers Lane, Rockville, MD 20857.