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  1. Development & Approval Process

Veterinary Master Files

A Veterinary Master File (VMF) is a submission to the Food and Drug Administration’s (FDA) Center for Veterinary Medicine (CVM) that provides confidential detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of veterinary drugs and drug substances.

Effective October 1, 2018, CVM will not accept paper submissions. VMFs should be submitted electronically using CVM’s eSubmitter tool. For information about submitting electronically to CVM, see CVM’s Electronic Submissions page. If you have any questions regarding electronic submissions, email CVM’s Electronic Submissions Support Team at cvmesubmitter@fda.hhs.gov.

Types II-V Veterinary Master Files Lists
Types of VMFs and Their Content
Opening a New VMF
Agents/Contacts
Authorization for Referencing a VMF
Change of Ownership or Company Name
Closure of a VMF
Master File and Drug Substance Guidances
Inspection Classification Database Search

Types of VMFs and Their Content

Type I VMF’s are obsolete, and we no longer accept them.  Type II through Type VI VMFs are considered manufacturing VMFs; information concerning post-approval manufacturing changes for both the VMF holder and the authorized users can be found in CVM Guidance for Industry #83 Chemistry, Manufacturing and Controls Changes to Approved NADA/ANADA.

Type II: Manufacturing Information for Drug Substances and Intermediates includes manufacturing information used to support the production of the drug substance intermediates, bulk drug substance, medicated articles, medicated feeds, or finished dosage forms. These VMFs should be limited to a single drug intermediate or drug substance. This information may include general information on the molecule, information on the manufacturing facility, details of the manufacturing or fermentation process used, and controls such as release and stability tests and methods.

Type III: Packaging Material includes information to support the intended use, components, composition, and controls of packaging materials (i.e., vials, bottles, stoppers, syringes), information about the suppliers/fabricators of the components, and data supporting acceptability of the packaging material for its intended use. Such data may include evidence of compliance with USP <660> Containers – Glass or <661> Plastic Packaging Systems and Their Materials of Construction and 21 CFR Parts 175 through 178, Indirect Food Additives.

Type IV: Excipient, Colorant, Flavor, Essence, or Material Used in Their Preparation includes identification and characterization data such as method of manufacture, release specifications, and testing methods may be submitted in a Type IV VMF for materials intended for use in veterinary pharmaceuticals but not intended to be active ingredients. Toxicological data for these substances may be included under this type of VMF if the data are not otherwise available by cross-reference to another document. Type IV VMFs should include any other supporting information and data that are not available by cross reference to another document.

Type V: FDA Accepted Reference Information includes non-product-specific information to support the manufacturing site, facilities, personnel, environmental safety studies, operating procedures and controls for finished dosage forms or medicated articles, and sterilization process validation for producing sterile dosage forms and sterile bulk drugs. Type V VMFs may also include animal effectiveness, safety, residue chemistry and metabolism, or toxicity information and data that may be applicable to more than one animal drug application.

Type VI: Free-Choice Medicated Feeds and Medicated Feed Assay Methods includes information about free-choice medicated feeds and medicated feed assay methods, including effectiveness/consumption data for a free-choice feed as described in CVM Guidance for Industry #13--Evaluation of Effectiveness of New Animal Drugs for Use in Free-Choice Feeds-Medicated Block

Type VII: Information to support the Division of Animal Bioengineering and Cellular Therapies (DABCT) project information and Tech Team Working Process includes information to support the Division of Animal Bioengineering and Cellular Therapies (DABCT) project information and Tech Team Working Process. Type VII master files are not considered manufacturing VMFs.

Type VIII: Import Tolerance Requests will be reviewed by the Division of Human Food Safety and Environmental Safety Team with the Office of Surveillance and Compliance. Type VIII master files are not considered manufacturing VMFs. See Import Tolerances for more information.

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Opening a New VMF

We first recommend that you register with our Electronic Submission System and download our eSubmitter software as detailed here: CVM Guidance for Industry #108 Registering with CVM’s Electronic Submission System if you do not have an account. To establish a new VMF, use eSubmitter and attach a letter requesting establishment of a VMF as part of the initial submission through eSubmitter. A response e-mail should arrive within a few minutes that signals successful transmission through eSubmitter and contains the new VMF number. CVM recommends that one VMF per facility per drug substance be opened. If a VMF holder manufactures a drug substance at another site, even with similar processes, each facility should have its own VMF.

VMFs are not subject to the same user fees as Drug Master Files (DMFs) that are used to support human drugs. CVM does not charge a fee to establish, amend, or reference a VMF under its current user fee agreements. VMFs do not undergo completeness assessments before review as do DMFs submitted to FDA’s Center for Drug Evaluation and Research (CDER). CVM has access to and can review DMFs in support of animal drug applications. If a master file is referenced in support of both animal and human drugs, then only a single DMF (and no VMF) should be maintained. For DMF information and lists, see Drug Master Files (DMFs). Send inquiries concerning DMFs to dmfquestion@fda.hhs.gov.

Agents/Contacts

To facilitate communication, CVM strongly encourages foreign VMF holders to appoint an agent who is familiar with FDA regulations, guidances, and procedures. However, there is no requirement for an agent for any VMF, foreign or domestic. An agent for a VMF is not the same as an agent for FDA’s Drug Listing and Registration System (DRLS), which is required. We do not require agents or contact persons for a VMF be located in the United States, although this is recommended. VMF holders should provide the name, telephone and fax numbers, email address, and specific responsibilities of the contact person and the responsible official (if different from the contact person).

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Authorization for Referencing a VMF

CVM will not review a VMF until the VMF holders submits a letter of authorization (LOA) to the VMF regarding a specific application or another VMF. The LOA permits CVM to review the VMF and permits the authorized party (the company or individual who submits an application or another VMF) to incorporate information into an application or another VMF by reference. The VMF holder should send a copy of the LOA to an authorized party. The authorized party should include a copy of the LOA in its application or VMF. An LOA does not give an authorized party permission to view or access a VMF. The VMF holder should submit each LOA to the VMF. The LOA should include the following:

  • Date of letter
  • Name of VMF holder
  • VMF number
  • Name of persons authorized to incorporate information in the VMF by reference
  • Specific products covered by the VMF
  • Sections, volumes and page numbers to be referenced
  • Statement of commitment that the VMF is current and that the holder will abide with the statements made in it
  • Signature of the authorizing official/agent
  • Typed name and title of the official authorizing reference to the file.

The VMF holder should keep an updated list of authorized users in the master file. It is not necessary to reissue LOAs if there are no changes in the holder, authorized party, subject of the VMF or items referenced if this list is maintained in the VMF. If the VMF holder or authorized party changes its name, the VMF holder should submit a new LOA. LOAs should include the VMF number and therefore should not be provided in the first submission to the VMF.

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Change of Ownership or Company Name

When a VMF holder changes its name, whether through sale of the company or change in the company’s name, the original VMF holder should notify CVM within 30 days. A change in the name of a company for registration purposes will not change the VMF holder name. When transferring a VMF from one company to another, the original holder should submit:

  • An administrative amendment stating that they are transferring the VMF to the new holder
  • Contact name and address for receipt of correspondence from FDA for new holder
  • Effective date of transfer
  • A statement that all rights to the files have been transferred to the new holder
  • A list of all third parties authorized to reference the file
  • A statement that a copy of the notification letter was provided to the new holder
  • Signature of the responsible transferring official
  • Typewritten name and title of the signer.

The new holder should then submit an administrative amendment stating that they are accepting the VMF from the former holder. A statement of commitment signed by the new VMF holder should be included in name change and acceptance notifications stating that the VMF is current and that the holder will comply with the statements made in the VMF. CVM will not provide an acknowledgment notification for transfers of ownership or changes in holder name.

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Closure of a VMF

A request to close a VMF should be submitted as a general correspondence (G submission) to the file. The request should include a statement that all authorized parties have been notified of the closure. All holder obligations, including completion of any stability commitments, should be fulfilled before the VMF is closed.

Master File and Drug Substance Guidances

FDA and International Guidances for Industry (GFIs) that may be useful for submitting and updating master files may be found at Chemistry Manufacturing and Controls (CMC) Guidances for Industry (GFIs).

Inspection Classification Database Search

For information regarding FDA inspections of regulated facilities, please read about the FDA Inspection Classification Database and search the database.

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