'Global' Review of Drug Master Files Hits Packaging Manufacturers

Date: Sep 01, 2002

The U.S. Food and Drug Administration (FDA) has initiated "global" reviews of Drug Master Files (DMFs). FDA's Center for Drug Evaluation and Research (CDER) began this new practice to achieve consistency in the information in DMFs.

It is, however, causing consternation for DMF holders of packaging materials.

The DMF system provides relevant information to FDA about facilities, processes or articles used in the manufacture, processing, packaging and storage of human drug products, when such information is considered confidential by its owner. Many packaging materials suppliers use DMFs to provide information to FDA about the safety and suitability of their materials for use in drug packaging. FDA refers to these as Type III DMFs.

Thus, Type III DMFs let a packaging material supplier provide proprietary information directly to FDA without sharing the information with its customers. The DMF holder may then authorize FDA to reference the DMF in support of the Agency's review of a specific new drug application (NDA). FDA then reviews the DMF to determine whether the packaging material is suitable for its intended use.

FDA suggests that DMFs be updated at least annually - and whenever product changes are made. Failure to do so may result in FDA classifying the file as "inactive," and in need of updating before the Agency reviews the contents in support of an NDA.

Historically, FDA has conducted a substantive review of the contents of a particular DMF only if the Agency is reviewing a pending drug submission that references that specific DMF.

Over the last two years, FDA has been quietly implementing a low-level project to conduct complete reviews of Type III packaging DMFs. These so-called "global" reviews are unrelated to any specific drug submission that might reference a DMF. FDA apparently is targeting those DMFs that generate the most confusion among drug reviewers and give rise to the most deficiency letters. To date, approximately 20 DMFs have undergone global reviews.

Once the global review is complete, a memorandum is sent to the file indicating the status of the DMF. If deficiencies are noted during the global review, a letter is sent to the DMF holder indicating the problem areas.

Once a packaging DMF has been the subject of a global review, any reviewer who is directed to the DMF by a specific drug submission can use the global review memorandum, and supposedly will not have to review the contents of the file.

The intent of the new system is to make the DMF review process more efficient by limiting the number of independent DMF reviews required and eliminating the potential for inconsistent reviews performed on a particular file.

However, since many drugs are unique and require a full-fledged review in any case, some reviewers are not likely to rely on this independent review alone.

Global reviews can be avoided. Ask your packaging material suppliers to make sure that their DMF is in proper order - that amendments and additions over the years are not so numerous that the DMF is unwieldy or difficult to follow. It's better to have a DMF in good shape when FDA goes to review it for real, then to delay review of your NDA while your packaging material supplier answers the Agency's questions.

Used with permission. Copyright FOOD & DRUG PACKAGING, September, 2002.

For further information about this article, please contact George G. Misko at 202-434-4170 or by e-mail at misko@khlaw.com.