Why and How – Health Canada Master Files

The Master File (MF), formerly Drug Master File (DMF), is a regulatory filing used to provide supporting submission information to Health Canada, without revealing the contents to the sponsor of the drug submission. Health Canada is bound to protect the confidential business information (CBI) in the MF in compliance with the Food and Drugs Act and the Access to Information Act. There are certain circumstances under which Health Canada can disclose CBI, which are described in Section 21.1 of the Food and Drugs Act.

The following five key topics should be considered when filing of an MF with Health Canada:

1. MF Types and Structure:

The types of MFs are clearly defined by Health Canada and can be submitted to support a drug substance, drug product, excipient, container closure system or facility. An MF will contain an “Applicant part”, which consists of information to be shared with the submission sponsor, and a “Restricted part”, which contains CBI to be kept confidential by Health Canada.

2. Processing and Timelines:

When a new MF transaction is received at Health Canada, the MF administration unit verifies that the MF is in the appropriate format and contains the required administrative documents and that fees are paid. The MF unit aims to process the MF transaction within 30 calendar days of receiving a complete package. MF holders are encouraged to submit MFs at least 2 months ahead of a sponsor’s cross-referencing submission, in case there are any issues during MF processing.

It is the responsibility of the MF holder or their designated MF agent to ensure that fees are promptly settled upon receipt of Health Canada’s acknowledgments and invoices. Failure to pay fees in a timely manner for an MF amendment or the Letter of Access (LoA) is a common deficiency observed in cross-referencing applications, often resulting in Screening Deficiency Notices (SDNs) issued to the submission sponsor.

3. Review Process by Health Canada:

Health Canada reviews the quality information in initial MFs or subsequent amendments only when cross-referenced by a sponsor’s drug submission. Once the cross-referencing submission (Clinical Trial Applications, New Drug Submissions and supplements etc.) is received by Health Canada, the standard review process and timelines will apply. Any relevant comments about the Restricted part of the MF are sent directly to the MF holder in the form of an MF letter of deficiency or a clarification request. Comments on the Applicant part of the MF may be sent to the sponsor or the MF holder.

4. MF Amendment Process and Communication Between MF Holder and Sponsor:

Any subsequent update to an MF with Health Canada is filed through an amendment. When changes are proposed to the MF content, the change is communicated to the sponsor of a cross-referencing submission, so that they can determine the required post-approval submission level. An amendment filing to the MF is required when the change would be classified as a Level I (Supplement) or Level II (Notifiable Change) for the cross-referencing submission.

Health Canada does not expect timely updates to the MF for minor (Level III or IV) changes. All minor changes to the MF are kept on file and submitted in the next amendment filing. However, MF holders are permitted to file an MF amendment at any time, even for minor changes. They sometimes choose to do this for purposes of life-cycle management. Even if the MF is not updated, Level III and IV changes must be reported, as required, by the cross-referencing sponsor to their submissions.

5. Transition to eCTD Format:

Although the agency is still accepting amendments to existing MFs in non-eCTD (electronic Common Technical Document) format, all new MF submissions are required to be filed in the eCTD format. Intrinsik has supported many of its clients for the conversion from non-eCTD to eCTD format.

Intrinsik Services: Intrinsik provides support for MF filings with a range of services, including MF content plans and authoring for initial filings and amendments. Intrinsik can act as the agent and regulatory contact as well as support MF submission publishing. For MF publishing, Intrinsik has experience filing in the Applicant part and Restricted part format as well as providing eCTD structure advice for filing a compliant MF. Intrinsik can also support DMF submissions to the United States (US) Food and Drug Administration (FDA).

For more information on how Intrinsik can help your company, please contact .

Intrinsik Blogger: Meenu Aggarwal