Drug master files, the confidential dossiers behind generic ingredients

FDA's latest list of drug master files, current through September 30, 2026, runs to 41,672 entries, the oldest submitted in 1939, according to GxRadar's count of the agency's quarterly spreadsheet². Most of the files belong to ingredient and packaging makers whose names never appear on a pharmacy bottle.

Since October 1, the price of making one of those files usable for a generic application has been $109,899. That is the one-time fee FDA set for fiscal 2027 in a July 30, 2026, Federal Register notice¹⁷, up from $78,293 four years earlier.

A drug master file, or DMF, is how a supplier gives FDA confidential manufacturing details without handing them to its customers. For many generics, the details of how the active ingredient is made sit in a file the generic applicant may cite but does not get to read. This explainer covers the file types, how a generic application points to a DMF, the fee and completeness check that Congress attached in 2012, and what GxRadar's counts of FDA's lists show for common generics.

Five types on one list

FDA's DMF page¹ describes the files as submissions with "confidential, detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of human drug products." It says three things about them that surprise newcomers. DMFs are not required by statute or regulation. They are neither approved nor disapproved. And FDA reviews their technical contents only in connection with an application that references them.

Federal regulation 21 CFR 314.420⁴ sorts DMFs by what they describe.

Source: GxRadar analysis of FDA's DMF list, third quarter 2026 (DMFs received by September 30, 2026). Active and inactive reflect FDA's status codes.

Type II files, which cover active pharmaceutical ingredients (APIs), are the ones that matter most for generics. FDA's guidance on good manufacturing practice for ingredient makers is ICH Q7⁵, which the DMF types page lists as a resource for Type II holders. Our explainers on where generic drug ingredients come from and excipients and their supply chain cover the Type II and Type IV sides.

How a generic application points to a master file

A generic applicant cannot simply cite a supplier's DMF. Under 21 CFR 314.420(b), the holder has to authorize the reference "in writing," usually called a letter of authorization, and the application must identify the incorporated material by name, reference number, volume and page. When the holder adds, changes or deletes information, it must notify in writing everyone it has authorized to reference the file.

FDA then assesses the DMF alongside the abbreviated new drug application (ANDA), and problems in the file can hold up the generic. Under the GDUFA III commitment letter⁶ for fiscal 2023 to 2027, FDA agreed to send DMF deficiency comments to the holder at least in parallel with related comments to the ANDA applicant. Holders can ask in writing, within 30 days of a first-cycle deficiency letter, for a teleconference to clarify it, and FDA said it would strive to grant one within 30 days of the request. Once the file has no open issues for the referencing ANDA, FDA issues a "First Adequate Letter," and after the ANDA is approved or tentatively approved, a "no further comment" letter. Our pieces on how a generic gets approved, major and minor ANDA deficiencies and complete response letters cover the application side.

The fee and the completeness assessment

The Generic Drug User Fee Amendments of 2012 added two steps for Type II API files used in generics, according to FDA's completeness assessment guidance⁷. The holder pays a one-time fee, due on the earlier of the date the first generic submission references the file or the date the holder asks for an initial completeness assessment. FDA then runs that assessment, a checklist review that confirms the file contains what a full scientific review will need. It "does not replace the full scientific review," FDA's DMF types page³ notes.

A file that passes goes on FDA's public list of DMFs available for reference. One that fails gets a "GDUFA DMF Incomplete Letter" explaining why, and FDA shares that status only with the holder and, as needed, the referencing applicant, the guidance says⁸. FDA strongly encourages holders to submit and pay at least six months before a referencing ANDA. Its goal under GDUFA III is to finish 90 percent of initial completeness assessments within 60 days of the later of submission or payment.

FDA sets the fee by formula. By law, DMF fees supply 5 percent of the year's generic user fee revenue, which for fiscal 2027 meant $33,299,300 divided among the 303 fee-paying DMFs FDA projected, based on a monthly average of 25.23 paid files from fiscal 2024 through April 2026. Our explainer on GDUFA user fees covers the rest of the fee schedule.

FDA's list of DMFs available for reference⁹, run October 30, 2026, held 7,049 Type II API files. GxRadar measured the time between each file's fee payment date and its completeness assessment date.

Source: GxRadar analysis of FDA's MF User Fee Obligation Report. The list shows only files that are currently available, so counts for early years omit files later removed.

Recent medians sit well inside the 60-day goal, though the median says nothing about the slowest files.

Getting reviewed before the ANDA arrives

Normally FDA does not start a full scientific review of a DMF until an ANDA references it. GDUFA III created an exception, which FDA spelled out in final guidance in October 2024¹⁰. A holder can ask FDA to begin assessing a Type II API file six months before the planned ANDA submission if the file has not yet had a substantive assessment and the ANDA meets one of these conditions, according to the guidance¹¹:

• all patents and exclusivities will expire within 12 months of the planned submission
• fewer than four therapeutically equivalent products, including the brand, are approved, with no blocking patents or exclusivities and no carve-out
• the product could help mitigate or resolve a drug shortage, including products on FDA's shortage list
• the product could help address a declared or anticipated public health emergency
• only one approved product remains, an ANDA, with the brand discontinued, subject to further conditions

A similar early look is available for a prior approval supplement that adds a new API source, if the product is in shortage or tied to a public health emergency. FDA's GDUFA III DMF page¹² describes the program. Our piece on how FDA prioritizes generic applications explains the related ranking rules.

What the lists show for common generics

For widely used generics, a dozen or more API files often stand behind the market. GxRadar matched ingredient names against the subject lines of active Type II DMFs and of files available for reference.

Source: GxRadar analysis of FDA's DMF list (Q3 2026) and available-for-reference list (October 30, 2026). Counts match the ingredient name anywhere in the subject line and may include different salts, forms and intermediates. A listed file does not mean the holder is currently supplying the US market.

New Type II filings have also climbed. FDA's list shows 729 Type II files submitted in 2022, 917 in 2023, 1,087 in 2024 and 1,298 in 2025, with 992 more in the first nine months of 2026. The fiscal 2027 fee notice counted 753 API facilities identified in approved generic submissions, 672 of them outside the US; our piece on where FDA's registered drug factories are has that series.

Master files are also being put to new uses. FDA's PreCheck pilot¹⁸, which began taking requests on February 1, 2026, has new US plants use "a facility-specific Drug Master File" to let FDA evaluate the site before any product application arrives.

All of the fee and assessment rules described here run on GDUFA III, whose authority expires in September 2027¹⁹. FDA held a public meeting on proposed GDUFA IV enhancements on September 17, 2026, and its posted notes from reauthorization talks with industry include drug master files among the topics.