Guidance on procedures and administrative requirements for master files: Overview

Document change log:

Date adopted: 2008/08/08
Effective date: 2024/01/02

Date	Nature of and/or reason for change	Location
2023/06/26	The revised guidance document is administrative in nature. It was revised to include the change to an online web-based XML application process.	Ottawa
2024/01/02	The revised guidance document is administrative in nature and was revised to include changes related to the onboarding of Master Files for products for veterinary use. In addition, revisions have been made throughout the document for the purpose of increasing clarity.	Ottawa

On this page

• Introduction
• Policy objective
• Policy statements
• Scope and application
• Background
• Note about guidance documents in general

Introduction

A master file (MF) is a reference that provides information about specific processes or components used to manufacture, process or package a drug. The MF is a useful vehicle for providing information to Health Canada, where that information is confidential business information (CBI) and is not available to the:

• manufacturer of the dosage form
• sponsors of a drug submission
• applicants of a drug identification number (DIN) application or clinical trial application (CTA)

Health Canada must protect CBI in accordance with the law.

This guidance document provides MF-related definitions, information on filing requirements, processing and assessment procedures for Type I to V MFs. It also outlines the registration requirements for new MFs, as well as other MF transactions including administrative changes, updates, withdrawals and closures.

Policy objective

The policy objective is to provide direction on the procedures that allow MF holders, authorized MF agents and authorized third parties filing on behalf of MF holders to file CBI directly with Health Canada. The CBI referenced is in support of an applicant’s drug submission (including DIN applications) or CTA with respect to quality information.

Note: ‘MF holder’ includes authorized MF agents and authorized third parties filing on behalf of the MF holder. This term is used throughout this guidance document.

Policy statements

MFs are categorized as regulatory transactions.

For more information, consult:

• Guidance document: Preparation of regulatory activities in non-eCTD format
• Guidance document: Preparation of regulatory activities in the electronic common technical document (eCTD) format

MFs are voluntary registrations filed with Health Canada. They can be referenced by applicants seeking drug marketing authorizations or clinical trial authorizations involving pharmaceuticals and biologics for human and/or veterinary use.

Applicants are responsible for submitting non-CBI provided by the MF holder. This information is public and/or developed by the applicant in the drug submission, DIN application or CTA.

The information included in the MF should be up-to-date. Applicants should also contact the MF holder to confirm that Health Canada has received this information before filing their submission, DIN application or CTA with us.

The restricted part of the MF will be held in strict confidence. Health Canada will use it in support of the drug submission or CTA only when we have received a written letter of access (LoA) from the MF holder.

The LoA is signed by the MF holder. It indicates to Health Canada that the applicant and MF holder have agreed that the MF can be referred to during Health Canada’s assessment of the drug submission or CTA.

Scope and application

This guidance document applies to all MF holders intending to file MFs that support drug submissions and DIN applications for products for human and/or veterinary use or CTAs. In addition, this guidance document applies to applicants that use an MF to support their drug submissions and DIN applications for products for human and/or veterinary use or CTAs. Finally, this guidance document also applies to Health Canada employees involved in MF processes.

Submissions and applications that can be supported by MFs include the following:

• extraordinary use new drug submission (EUNDS)
• new drug submission (NDS)
• new drug submission with flexibilities for designated COVID-19 drug (NDS CV)
• abbreviated new drug submission (ANDS)
• abbreviated EUNDS (AEUNDS)
• supplements (SNDS, SANDS, EUSNDS, EUSANDS)
• applications for DINs (DINA and DINB)
• post-authorization Division 1 changes (PDC and PDC-B)
• notifiable changes (NC)
• yearly biologic product reports (YBPR)
• CTAs, CTA-notifications (CTA-N) and CTA-amendments (CTA-A)
• investigational new drug (IND) submission and IND amendments
• experimental studies certificate (ESC) application and ESC amendments

This guidance document does not apply to MFs used in support of natural health products (NHPs) subject to the Natural Health Products Regulations. For NHP MFs, contact the Natural and Non-prescription Health Products Directorate (NNHPD) at nnhpd.consultation-dpsnso@hc-sc.gc.ca.

MFs may be referenced by more than 1 applicant and are classified according to the types listed in Table 1.

Table 1. Master file classifications

Type of master file	Description
Type I Active substance master files (ASMFs)	For pharmaceuticals: Active pharmaceutical ingredients (API) (drug substances), starting materials or intermediates used to manufacture a drug substance. For biologics: Drug substances can include bulk process intermediates, vaccine antigens, adjuvants (except for alum), albumin (except when used as an excipient) and critical raw materials for radiopharmaceuticals or vectors for gene therapy.
Type II Container closure system master files (CCS MFs)	Container closure systems (CCS) or CCS components
Type III Excipient master files	All excipients including those of biological origin (such as albumin), capsule shells, coating ingredients, colourants, flavours and other additives (such as gelatin, alum and growth media)
Type IV Dosage form master files (dosage form MFs)	Dosage forms and drug product intermediates
Type V Facilities and equipment master files (FMFs)	Diagrams illustrating manufacturing flows (including movement of raw materials, personnel, waste and intermediate(s) in and out of the manufacturing areas, for example) Information on all developmental or approved products manufactured or manipulated in the same areas as the applicant's product Information on procedures (such as cleaning and production scheduling) and design features of the facility (such as area classifications) to prevent contamination or cross-contamination of areas and equipment, where operations for preparing cell banks and product manufacturing take place

Background

The principles outlined in this guidance document are intended to create greater alignment with the procedures used internationally for the management of MFs. Extensive knowledge has been gained through international regulatory initiatives such as the International Generic Drug Regulators Programme (IGDRP).

This guidance document also incorporates procedures and terminology from the International Council for Harmonisation (ICH) guidelines and the use of certificates of suitability to the monographs of the European Pharmacopeia (CEPs).

In keeping with international best practices, the term ‘master file’ (MF) is used. This term was previously known as drug master file (DMF).

Note about guidance documents in general

Guidance documents provide assistance to industry and health care professionals on how to comply with governing statutes and regulations. They also provide guidance to Health Canada staff on how mandates and objectives should be met fairly, consistently and effectively.

Guidance documents are administrative, not legal, instruments. This means that flexibility can be applied. However, to be acceptable, alternate approaches to the principles and practices described in this document must be supported by adequate justification. They should be discussed in advance with the relevant program area to avoid the possible finding that applicable statutory or regulatory requirements have not been met.

As always, Health Canada reserves the right to request information or material, or define conditions not specifically described in this document, in help us adequately assess the safety, efficacy or quality of a therapeutic product. We are committed to ensuring that such requests are justifiable and that decisions are clearly documented.

This document should be read along with the accompanying notice and the relevant sections of other applicable guidance documents.