While the draft guidance retains much of the substance from the 1989 guidance, the newly released draft document restructures the 1989 guidance and expands on many of its components.

For the first time since September 1989, federal agencies have issued draft guidance concerning drug master files (DMFs), submissions to the FDA that may be used to provide confidential, detailed information concerning the manufacturing, processing, packaging and storing of human drug products. Notably, the release of this draft guidance comes on the heels of a recent executive order by President Trump aiming to curb the use of agency guidance documents to avoid the formal rule-making process.

Among other things, the October 9, 2019, executive order explained that while agencies are permitted to clarify federal requirements through nonbinding guidance, many agencies have acted inappropriately by “attempt[ing] to regulate the public without following the rulemaking procedures of the APA [Administrative Procedure Act].” As such, the White House announced a policy requiring “that agencies treat guidance documents as non-binding both in law and in practice, except as incorporated into a contract, take public input into account when appropriate in formulating guidance documents, and make guidance documents readily available to the public.”

FDA regulations, at 21 CFR § 314.420, explain that a DMF may be used to incorporate certain information by reference in an investigational new drug application (INDA), a new drug application (NDA), an abbreviated NDA (ANDA), or an amendment or supplement thereto―or to permit the person who submitted and holds the DMF to authorize others to rely on the information to support a submission to the FDA, without the DMF holder being required to disclose the information to the third party.

There are currently four types of DMFs (Type I having been discontinued in 2000):

  • Type II: Drug substance, drug substance intermediate and materials used in their preparation, or drug product;
  • Type III: packaging material
  • Type IV: excipient, colorant, flavor, essence or material used in their preparation; and
  • Type V: FDA-accepted reference information.

Critically, utilization of the DMF process is voluntary; that is, it is not required by federal law or regulations or guidance from federal agencies, as explained in both the existing and draft versions of the DMF guidance.

While the draft guidance retains much of the substance from the 1989 guidance, the newly released draft document restructures the 1989 guidance and expands on many of its components. Among other things, the draft guidance contains a fairly comprehensive overview of the requirements governing a letter of authorization (LOA):

A letter from a DMF holder that authorizes an applicant or another DMF holder to incorporate by reference all or part of the DMF’s contents to support an application, supplement, or another DMF or an amendment to any of these documents.

Further, an LOA authorizes the “FDA to review applicable portions of the DMF.”

Also detailed in the draft guidance is the FDA’s “current thinking” on DMF format and delivery; how subsequent submissions are to be made; and on specific recommendations for submission of particular types of DMFs (described above). For example, with respect to the latter, the draft guidance recommends that Type III DMF packaging materials “be identified by type (e.g., bottle) and material of construction (MOC) (e.g., high-density polyethylene).” The draft guidance also requires the submission of English translations for each part of a NDA, ANDA or DMF that is not in English.

Although agency guidance documents do not carry the force of law, guidance issued by federal regulatory agencies—concerning their perspectives as to implementation of the federal laws and regulations they are tasked with enforcing—can be invaluable for manufacturers and developers striving for regulatory compliance. In line with the policy espoused in the October 9 executive order, the FDA is currently soliciting comments and suggestions on the draft guidance from industry participants, who have until December 20, 2019, to provide feedback.