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Guidance on procedures and administrative requirements for master files: Implementing, processing, assessing and updating master files

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Health Canada Master Files

The MF holder submits an MF when the company does not wish to disclose CBI to the applicant of the drug submission, the DIN application or the CTA.

Type I and Type IV MFs are divided into 2 parts:

The LoA is signed by the MF holder. It indicates to Health Canada that the MF holder has agreed that the MF can be referred to during the assessment of the applicant's drug submission, DIN application or CTA.

Confidentiality

Health Canada keeps the restricted part of the MF confidential. We must protect the information in accordance with applicable law, which includes the Access to Information Act and the Food and Drugs Act.

The Access to Information Act applies where an access request is made under that Act for records under the control of a government institution. Section 20 of the Act is a mandatory exemption. This exemption protects:

CBI contained in an MF could also be subject to the disclosure authorities in the Food and Drugs Act. Section 21.1(2) authorizes the disclosure of CBI about a therapeutic product where the Minister believes the product may present a serious risk of injury to human health. Section 21.1(3) of this Act authorizes the disclosure of CBI about a therapeutic product to a government, a person from whom the Minister seeks advice or eligible persons for the purpose of protecting or promoting human health or safety.

Consult the following guidance document:

Registration Requirements

The web-based Extensible Markup Language (XML) Master File Application Form (MF application form) must be provided with every electronic common technical document (eCTD) and non-eCTD transaction that is sent through the Common Electronic Submissions Gateway (CESG).

MFs should be filed no more than 1 year, but no less than 2 months before a drug submission, DIN application or CTA that refers to those MFs is filed. All MFs must include at least 1 LoA at the time of filing.

An MF number is assigned at the end of the registration process. Thus, any LoAs submitted at the time of registration should include "MF number unassigned" on the LoA. The LoA should not be re-filed at a later date to include the MF number.

Learn more about the filing requirements for LoAs.

Any LoAs re-filed to include the MF number will be subject to fees.

The following documents are required for all new MF registration transactions:

Note: MF transactions will be placed on "process hold" until the transaction MF is considered to be administratively complete.

The MF application form should include the MF holder's business address or headquarters address. The address provided on the form will be considered the MF holder's billing address. All invoices and account statements will be sent to this address.

Manufacturing site addresses should not be provided on the MF application form unless the manufacturing site address is the same as the business or headquarters address.

The address must be the same for all MFs held by the MF holder, including subsequent transactions for such MFs. It is not possible to provide MF application forms with different addresses for different MFs or for different transactions. If the address that the MF holder enters on the MF application form is not the same as what was previously provided for other transactions for MFs held by the MF holder, the MF Administration Unit will issue a process hold letter to resolve any discrepancies.

Type I and IV MFs should include the following:

For Type II and Type III MFs, multiple components or formulations may be included in a single MF provided they are similar (for example, a complete CCS, different stopper formulations, multiple flavours). A limit of 50 components or formulations will be enforced for each MF. A numbered index listing all components or formulations should be included with the MF in Module 1, Section 1.0.7 Note to Reviewer. Additional components or formulations should be filed in a new MF.

An MF filed in support of a CTA may include a QOS in place of the applicant part and restricted part. As well, a single MF covering both an active substance (Type I MF) and dosage form (Type IV MF) can be filed in support of a CTA.

Of note, MFs will only be reviewed with an applicant's drug submission, DIN application or CTA for which an LoA has been provided. Health Canada does not authorize the MF unless a DIN, notice of compliance (NOC) or no objection letter (NOL) is issued for the associated drug product. Health Canada does not have a database that lists all MFs registered in Canada.

A single MF may contain information on different products or a family of products. Type I MFs may contain information on different products in accordance with "when to file a new MF registration".

Type II and III MFs may contain information on different products within a family of products (for example, for stoppers manufactured using the same formulation).

Type IV MFs may have more than 1 product strength with the same formulation except for changes necessary to accommodate the different strengths. In such cases, the information for each product should be clearly differentiated within the Type IV MF.

Type V MFs may contain information on different processes (for example, sterilization, cleaning) for products, or a family of products, manufactured at the same facility. Information for each process should be clearly differentiated within the Type V MF.

If the MF holder has more than 1 MF for a similar product, the cover letter should state this. A table comparing the different products should be created and placed in Module 1.0.7, General Note to Reviewer. The MF holder should provide a name that distinguishes the MF from any previously registered MFs.

Naming a Master File

For Type I MFs, the preferred name of the MF should be the generic name (for example, the international non-proprietary name (INN) for an API) followed by any manufacturer's internal API brand names, processes or codes to identify a particular product. If applicable, any counterions or solvated states of the API should be clearly identified.

Format and Structure of the Master File

All MF transactions must be filed using the CESG in the non-eCTD or eCTD format as appropriate.

For more information on submitting MF transactions using the CESG, please refer to:

MFs in the eCTD format:

Since January 1, 2020, all new MF registration transactions are required to be filed in the eCTD format.

Consult the following guidance document for more information:

Existing MFs can also be converted to the eCTD format (refer to next section on converting).

First-time MF holders: Contact eReview at eReview@hc-sc.gc.ca before filing any type of MF in eCTD format.

MFs in the non-eCTD format:

Regulatory transactions for existing MFs previously filed in the non-eCTD format (for example, updating a registered MF, LoAs, administrative changes), where an MF number and dossier ID have already been assigned, may continue to be filed in the non-eCTD format.

For structure and formatting requirements for MF transactions in the non-eCTD format, consult the following guidance document:

Converting MFs from non-eCTD Format to eCTD Format

MF holders or authorized MF agents may also convert their MFs from the non-eCTD format to the eCTD format. As a baseline requirement when converting MFs from the non-eCTD format to the eCTD format, the MF holder or authorized MF agent must include a copy of the entire MF in their first eCTD transaction. Any changes/updates filed with a conversion will be subject to update fees.

The following documents are required with a conversion transaction:

Do not include:

It is not enough to convert the MF into the eCTD format by simply submitting the next transaction in eCTD format using the CESG. For example, do not submit an LoA or update in eCTD format as a subsequent transaction for an MF currently in non-eCTD format. If such a transaction is submitted, it will be placed on process hold until the conversion is complete.

Master Files in Paper Format

Health Canada will no longer assess MFs that have not yet been converted from the paper format to the electronic format. We will also not accept updates and cross-references.

We will suspend the MF until the MF holder submits a cover letter to us along with a copy of the complete MF in the eCTD format (including any applicable updates since the date of suspension or closure). The same MF number will be retained and fees for a new MF registration will be applied.

Official Language of Correspondence

An MF may be filed in either of Canada's official languages (English or French).

Letter of Access (LoA)

MF holders or authorized MF agents file CBI directly with Health Canada. The information may be referenced to support an applicant's drug submission, DIN application or CTA with respect to quality information. Health Canada will only use this information to assess the applicant's drug submission, DIN application or CTA if the MF holder provides a signed LoA on official company letterhead. All LoAs are valid throughout the life cycle of an MF.

A list of authorized applicants is an administrative document. It does not grant an applicant access to an MF. Access is granted through an LoA that:

When providing a list of authorized applicants, please ensure to include the applicant's company name and the date of the LoA for each entry on the list. Any applicants listed on the list of authorized applicants for which a signed and dated LoA has not been received by Health Canada, or for which an LoA is not considered administratively complete, will not be granted access to the MF.

Information to include in the Letter of Access

The following information must be included in the LoA:

Do not include:

Sample Letter of Access

The applicant's name on the LoA should be the same as the company name on the application form submitted by the drug sponsor with their drug submission. LoAs naming third parties filing or managing regulatory activities on behalf of the applicant will not be considered acceptable. Only 1 applicant can be named for each LoA.

Note: "Affiliates" constitutes multiple entities and will not be accepted on an LoA.

A list of authorized applicants is not required to be submitted with MF transactions for LoAs. If such a list is provided, it will not be verified to validate that all listed applicants have access to the MF.

Filing a Letter of Access

A separate LoA is required for each applicant that cross-references the MF in their drug submission, DIN application or CTA.

Each LoA must be:

The LoA should be sent to the MF Administration Unit in the eCTD or the non-eCTD format, as appropriate, using the CESG and to the applicant before they file their drug submission, DIN application or CTA.

LoAs provided to the applicant must be identical (have the same date, same content, same signature) to those provided to the MF Administration Unit. Any discrepancies between LoAs provided to the applicant and those provided to the MF Administration Unit may delay Health Canada's assessment of the drug submission, DIN application or CTA. This is why we recommend that MF holders wait to receive an acknowledgement letter for information received from the MF Administration Unit for any LoAs before they provide applicants with a copy of the LoA.

As an MF number is assigned at the end of the registration process, any LoAs submitted at the time of the initial new MF registration should include "MF number unassigned" on the LoA. The LoA should not be revised and/or re-filed at a later date to include the MF number. Any LoAs re-filed to include the MF number or to change information will be subject to additional fees.

For Type I, IV and V MFs, an LoA grants access to an MF in its entirety. The LoA is valid for all products and submissions from the applicant that cross-references the MF. Therefore, only 1 LoA is required per applicant for the duration of an MF's lifetime.

For Type II and III MFs, an LoA can grant access to specific components within an MF or an MF in its entirety. When granting access to multiple components within the MF or the MF in its entirety, only 1 LoA is required per applicant for the duration of the MF's lifetime. When granting access to an additional component that is not included in the first LoA, a new LoA is required and fees will apply.

MFs can also reference other MFs and be referenced by other MFs. In such cases, MF holders or authorized MF agents must file an LoA granting access to their MF to another MF holder. For example, when a Type IV MF references a Type I MF, the Type I MF holder or authorized MF agent must file an LoA granting access to the Type IV MF holder. Separate LoAs must also be filed granting the applicant access to the Type I and IV MFs.

The fee for processing an LoA is applicable each time an LoA is filed. LoAs should only be revised and re-filed when the applicant's name is changed. In these cases, MF holders will be charged the applicable fees. If the MF holder is changing their company name, the MF holder or authorized MF agent may submit a letter stating that their name has changed but that all previous LoAs (issued under previous MF holder name) are valid. No fees will be applied for a name change where no new LoAs are issued.

Please contact the MF Administration Unit before re-filing an LoA to confirm requirements.

Note: The declaration of access section in the CEP is not equivalent to an LoA. Furthermore, the CEP or a copy of the declaration of access section in a CEP should not be submitted with each LoA.

Letters of Access for Clinical Trials (Pharmaceuticals and Biologics)

The LoA should name the sponsor of the CTA and the name of the clinical trial as it appears on the application form submitted with the CTA. LoAs naming third parties to file or manage regulatory activities on behalf of the applicant are not acceptable. Additional information such as hospital information, principal investigator and protocol number can be provided.

Certificates of Suitability to the Monographs of the European Pharmacopeia (CEPs)

At the time of filing of a Type I MF, MF holders are encouraged to include the CEP (as applicable) or confirm on the cover letter for the transaction that no CEP is available. If a CEP is not available when the MF is filed, it should be provided as soon as it becomes available. In this case, no fees will be applied.

If the MF is revised or updated at the same time a CEP is submitted, applicable fees will apply. Revised CEPs will be accepted with or without simultaneous updates to the MF.

Send all CEPs to the MF Administration Unit with the relevant attestations. Provide new attestations for revised CEPs and indicate the CEP number in the attestations.

A CEP can be submitted as supporting information for an MF when the MF is not completely identical to the CEP dossier. Even if the MF is different from the dossier submitted to the European Directorate for the Quality of Medicines & HealthCare (EDQM) (for example, USP standard is declared), providing a CEP may expedite the assessment process and avoid unnecessary questions being sent to the MF holder. The attestations can be altered appropriately in this case. Any differences between the MF and the CEP dossier should be clear. We recommend using a table that compares the MF and CEP and providing this table in Module 1.0.7 Note to Reviewer.

Please note that CEPs can also be provided directly in the applicant's drug submission or DIN application instead of providing a Type I MF.

For more information on how to use this alternate procedure, consult the following guidance document:

Appointing an Authorized Master File Agent or Authorized Third Party

MF holders may appoint an agent or third party to act on their behalf. This includes signing documents and managing regulatory transactions on behalf of the MF holder. An agent or third party filing on behalf of the MF holder who is appointed by the holder (refer to MF agent or third party authorization letter sample) is responsible for all correspondence related to the MF. This may include, among other tasks, the following:

An MF agent or third party authorization letter signed by the MF holder is required with the initial MF registration transaction (including conversions) and any transaction where a new agent is appointed or the agent's role has changed.

When the MF holder is not based in North America, to speed up communications, we recommend that an agent or third party filing on behalf of the MF holder be located in North America. Once appointed, an authorized MF agent or authorized third party filing on behalf of the MF holder may perform all functions listed in this guidance document on behalf of the holder.

When to file a New Master File Registration

When 2 or more MFs are being filed for similar active substances and differ only due to additional processing steps or minor variations, include cross-references to the other related MFs in the cover letters. This will speed up the assessment of the common information. Include a table that compares the MFs in Module 1, Section 1.0.7 General Note to Reviewer.

In some cases, a new Type I MF registration is required. The following examples indicate the criteria for new MF registrations:

The following examples do not necessarily represent a new Type I MF and could be incorporated in a single MF with the same MF number:

Consult the relevant program area before submitting the MF if you are not sure if you should submit a separate MF.

Master File Fees

The MF process is voluntary and a private benefit. Thus, non-regulatory charges are fully cost-recovered under the ministerial authority to "enter into contract".

Health Canada collects fees to register and process each new MF, LoA and updates to a registered MF. Note that there is a fee each time an LoA is re-filed.

Any transactions received after 5 pm eastern standard time, during a weekend or on a statutory holiday are considered to be received the next business day. Fees are increased annually by 2% on April 1 each year. If an MF holder responds to a processing hold after 5 pm on March 31, it will be considered to have been received on or after April 1 and the new fees will apply.

All payments made to Health Canada must be made in Canadian funds. Cheques must be made payable to the Receiver General for Canada.

For instructions on the payment of fees:

Do not send payment when you file a transaction. Once Health Canada considers the transaction to be administratively complete, we will send an invoice to the designated contact that has been provided (MF holder, authorized MF agent or authorized third party).

Payment is due within 30 days from the date of the invoice. Failure to pay an invoice may delay our review of the applicant's submission and access to an MF may be denied. If fees are not paid, Health Canada reserves the right to deny service to MF holders and suspend access to an MF.

If you have questions about the fees for MFs, please email us at cost.recovery@hc-sc.gc.ca.

Processing Master Files

When Health Canada receives an MF transaction, we:

Note: For MFs submitted in eCTD format, the dossier ID is assigned before the new MF registration transaction is received using the Dossier ID request form.

Once the MF transaction is administratively complete, we:

If the required information or forms are missing, incomplete or in the incorrect format, Health Canada will place the MF transaction on administrative processing hold. Our MF Administration Unit will send an administrative process hold letter to the MF contact person asking for the missing information.

Note: A file is administratively complete when:

Process Holds

During the administrative process, it may be necessary to place the MF transaction on process hold when:

When the reason for the process hold is addressed, the MF transaction is considered administratively complete and a filing date will be issued.

We will reject the transaction without prejudice if the MF holder fails to respond to a request for additional or corrected information in the prescribed time outlined in the process hold letters. If your transaction is rejected, you must re-file the entire MF transaction, in the applicable format, using the CESG. This means all documents originally filed in the rejected transaction must be resubmitted, including a new cover letter.

Health Canada will not accept a response to a process hold after the prescribed time, which is outlined in the process hold letter.

As well, if you are re-filing a transaction in eCTD format, you must resubmit all documents in subsequent sequence under the same dossier ID (unless otherwise instructed in the rejection letter). Use operation attribute "replace" or method file reuse "replace" (if the content of the re-filed documents is not changing).

For help or if you have questions about re-filing rejected MF transactions in eCTD format, email us at eReview@hc-sc.gc.ca.

Application and File Maintenance Requirements

All correspondence (such as cover letters or LoAs) should come from the MF holder, authorized MF agent or authorized third party filing on behalf of the MF holder, where applicable. We will place on process hold any information filed by a third party for which no MF agent or third party authorization letter has been received. The file may be rejected if no authorization letter is provided.

All information included in the applicant part of the MF must be provided to the applicant of the drug submission, DIN application or CTA referencing the MF. This information must also be included in submissions or applications to Health Canada.

The contact information of the MF holder should be up-to-date throughout the life cycle of the MF. The holder must inform us of any changes to the contact information (for example, changes to the MF holder's name, address or contact person). This ensures that correspondence from Health Canada will be received by the appropriate person.

Failure to receive Health Canada-issued correspondence (such as process hold letters, notices, invoices, acknowledgement letters or emails) due to outdated contact information is not a valid reason for failing to submit a response if one is required.

For more information on filing updates to contact information, refer to the section on administrative changes.

Master File Performance Standards

Health Canada's MF Administration Unit will process all information and material filed with an MF transaction within 30 calendar days of receiving a complete package (the date the MF is considered administratively complete). MF holders are strongly encouraged to register MFs or new LoAs at least 2 months ahead of an applicant's drug submission, DIN application or CTA.

Assessing Master Files

MFs are always assessed along with a drug submission, DIN application or CTA. Decisions about quality-related data in an MF will pertain to the drug seeking market authorization or to the clinical trial authorization.

Note: The requirements of Division 2, Good Manufacturing Practices (GMP) of the Food and Drug Regulations apply to all buildings that fabricate, package, label or test APIs and dosage forms.

For more information, consult Division 1A and 2 of the Regulations.

For technical requirements of an MF, consult the following guidance documents that apply.

For pharmaceuticals:

For biologics:

For veterinary drugs:

For specific information on the content of MFs not covered in the above-noted guidance documents, contact the relevant program area.

Solicited Information

For Type I MFs, include all non-CBI on the drug substance in the drug submission, DIN application or CTA.

Communications concerning the restricted part of the MF during the assessment of an applicant's drug submission or CTA will be kept exclusively between the MF holder and Health Canada officials. Relevant comments about the restricted part of the MF will be forwarded 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 (related to, for example, analytical methods, stability data) may also be forwarded to the MF holder.

If there are deficiencies within the MF's restricted part, we will notify the applicant that outstanding issues must be addressed before the MF is acceptable to support the drug submission, DIN application or CTA. Other applicants cross-referencing the deficient MF (for which a response to the MF letter of deficiency or clarification request has yet to be received) will receive the same notice.

We will not issue a new letter of deficiency to the MF holder unless new comments need to be forwarded (for example, different requirements for APIs used in a different dosage form).

Clarification Requests and Letters of Deficiency during MF Assessment in support of a submission

During the assessment of an MF, if we need any information to be clarified, we will issue a clarification request for this information by email or fax. The MF holder will have 15 calendar days to reply. If the holder does not respond within the given timeframe, or if the MF has a significant number of deficiencies, we will issue a letter of deficiency.

The MF holder must respond to the letter of deficiency within the timeframe specified in the letter. If the holder needs more time, they should contact the relevant applicant for the drug submission. The applicant will then contact the director of the relevant assessment bureau to request an extension.

At the time we are deciding on the applicant's drug submission, we will issue a notice of non-compliance (NON) to the applicant if:

No additional correspondence will be sent to the MF holder. The holder is, however, expected to respond within the timeframe given to the applicant to respond to the NON.

MF transactions for responses to quality clarification requests and letters of deficiency should only include solicited information. Unsolicited information (for example, new LoAs) filed with a response to such requests or letters may result in an administrative process hold. This may also delay our review of the applicant's drug submission, DIN application or CTA.

Clarification Requests during MF Assessment in support of a CTA

If we require further information during our assessment of an MF in support of a CTA, we will issue a request for clarification within 2 calendar days to the MF holder. The applicant will be notified in writing.

The applicant should ensure that the MF holder responds within the time period. Failure to provide a satisfactory response within the specified period could result in the CTA being withdrawn or a not satisfactory notice (NSN) being issued.

Consult the following guidance document:

Responses to Clarification Requests and Letters of Deficiency

For MFs filed in non-eCTD format, responses to clarification requests and letters of deficiencies must be sent to the MF Administration Unit in non-eCTD format through the CESG.

Consult the following guidance document:

Responses to clarification requests or to letters of deficiency that are in the incorrect format will be put on administrative process hold until we receive the response in the correct non-eCTD format through the CESG.

For MFs filed in eCTD format, submit responses as a new sequence in eCTD format through the CESG.

Updating a Registered Master File

Updates are to be filed by the MF holder and submitted through the CESG. Updates to the MF are not required on a timed basis, but are required when changes are in accordance with the relevant reporting categories. Consult:

All updates are subject to fees.

A single electronic copy of the update should be filed with a signed and dated cover letter. The cover letter should clearly indicate:

Additional required administrative documents include:

Include all affected data in Module 3.

MF holders no longer need to submit a list of authorized applicants with their updates to a registered MF.

When filing an update to Type II and III MFs for an additional formulation or component, a limit of 50 components or formulations for each MF will be enforced. Additional components or formulations should be filed in a new MF. Include a current numbered index listing all components or formulations in Module 1, Section 1.0.7 General Note to Reviewer. Highlight in the numbered index which components or formulations are being added to the existing components or formulations.

Only affected sections of an MF should be filed with an update. An entire MF should not be filed with an update unless the transaction is also a conversion to the eCTD format.

For drug submissions and DIN applications:

File updates to MFs when the applicant for an associated submission is required to submit a Level I, supplement (such as a major quality change) or a Level II, notifiable change. Include any changes made in the interim period that are considered Level III, annual notifications.

Consult:

This does not exempt applicants from reporting Level III changes in their annual report to Health Canada. MF holders or authorized MF agents should communicate these changes directly and in a timely manner to each applicant referencing the MF.

All changes to an MF should be accompanied by a table that compares the changes to the previous MF. Indicate each change and note whether the change falls under Levels I, II, III or IV.

Consult:

All Level III changes to an MF should be filed when the next Level I or II changes are submitted. While it's not necessary to report Level IV, MF holders should note if Level IV changes are made in the documentation submitted in an MF, for historical purposes.

It's not necessary to provide an update to an MF solely for Level III or IV changes. MF holders may file an update at any time.

Note: Fees for all updates filed with Health Canada will apply.

With respect to DIN products, updates to MFs should be filed when the applicant for the associated application is expected to submit a notification that necessitates an assessment (PDC).

Consult the following guidance document:

The MF holder should also notify each applicant that has been granted access to the MF before implementing the change(s). This is so that applicants can update their records and file the appropriate submission or PDC to Health Canada.

Consult the following guidance documents:

The MF update should be filed and an MF acknowledgement letter should be received by the MF holder before Health Canada receives the applicant's:

For clinical trial applications:

The MF holder should update MFs if the previously filed information is not current. The holder should also notify each clinical trial applicant who has been granted access to the MF of the changes. This is so that sponsors can update their records and file either a CTA-A or a CTA-N to Health Canada.

Consult:

The MF update should be filed and an MF acknowledgement letter should be received by the MF holder before Health Canada receives the CTA-A or CTA-N by the clinical trial applicant.

Administrative Changes

Administrative changes to an MF may be filed at any time throughout the life cycle of the MF. There are no fees for filing administrative changes to an MF.

Transfer of Ownership and Substantive MF Holder Name Changes

MF holders should advise Health Canada in writing if the:

Substantive administrative change transactions should be filed to the MF Administration Unit in non-eCTD or eCTD format, as applicable, through the CESG.

File all administrative change transactions with a signed and dated cover letter. The following items are required in the cover letter:

Health Canada also requires the following documents, as applicable:

Health Canada will place administrative change transactions on administrative process hold if any of the applicable required documents have not been provided.

When multiple MFs are affected by an administrative change, a transaction is required for each MF. For example, if a company name change affects 10 MFs, we require 10 administrative change transactions to be filed (1 for each MF).

Health Canada will issue an acknowledgement letter to the MF holder once the administrative change transaction is considered to be administratively complete.

Non-substantive Changes to MF Holder Contact Information

MF holders should advise us in writing of any non-substantive changes to their address or MF contact person.

Note: We may consider minor, non-substantive name changes to the MF holder company name if the name is largely the same (for example, "Limited", "Ltd", "Incorporated" or "Inc." has been added or removed). Contact the MF Administration Unit if you are not sure whether an MF holder name change is considered non-substantive.

Non-substantive changes to an MF holder's contact information should be sent to the MF Administration Unit by email at dmf.enquiries-fmm@hc-sc.gc.ca. There is no need to inform us of such changes through the CESG.

Include a cover letter that contains the following required information:

Health Canada will send an email to the MF holder after the holder requests non-substantive changes to the MF holder's information confirming that the requested changes have been made.

All subsequent MF transactions must accurately reflect the changes to the MF holder's information in the MF application form. If the MF application form for subsequent transactions does not reflect the approved changes, we will issue an administrative process hold letter.

Change of Authorized Master File Agent or Authorized Third Party

If the MF holder wishes to change the current authorized MF agent or authorized third party, the MF holder should send a letter to the MF Administration Unit in the proper non-eCTD or eCTD format, as applicable, through the CESG. This letter is also required if the MF agent or third party company name is changing.

The MF holder must make sure that the new appointee has all the information required (such as historical records). Health Canada is not responsible for providing duplicate information to a new appointee.

If the authorized MF agent or authorized third party address or contact information has changed, the authorized MF agent or authorized third party should advise the MF Administration Unit by email at dmf.enquiries-fmm@hc-sc.gc.ca. There is no need to inform us of such changes through the CESG.

Finally, if the MF holder wishes to withdraw the authorization for an MF agent or third party, the MF holder should file a transaction in the proper format through the CESG for each affected MF with a cover letter indicating the intention to withdraw authorization.

Withdrawing Letters of Access

MF holders who wish to withdraw an LoA for a particular applicant should advise the MF Administration Unit of the reasons for doing so. Submit a cover letter in proper non-eCTD or eCTD format, as applicable, through the CESG. You may list multiple applicants whose access is being withdrawn in a single cover letter.

Do not include withdrawal of access letters in Module 1.2.6. Authorization for Sharing Information.

For MFs in the eCTD format, the attribute "Delete" must be applied to all LoAs for applicants whose access is being withdrawn. This should be done in Module 1.2.6 Authorization for Sharing Information.

The MF holder should inform the applicant whose LoA is being withdrawn from the MF of the withdrawal. The letter should clearly state the date after which the material will no longer be supplied to the applicant. Substances supplied before the date the LoA was withdrawn due to the termination of a supply agreement may still be used in authorized products, according to the conditions of authorization. However, the MF may no longer be referenced in subsequent applications.

Do not provide Health Canada with copies of correspondence given to applicants regarding withdrawal of access.

Health Canada will keep the withdrawn LoA according to appropriate procedures established for record retention and disposal, in accordance with the Library and Archives of Canada Act. When an LoA is withdrawn, the previously manufactured drug substance or material will no longer be supplied to the applicant.

Master File Closures

MF holders who wish to close an MF should notify the MF Administration Unit in writing. The cover letter should:

On closure, MF holders should provide a list of all applicants using the MF to Health Canada.

When an MF is closed, the product referred to in the MF can no longer be manufactured for use in Canadian marketed drug products. As well, the MF may no longer be referenced in subsequent Canadian drug submissions, DIN applications or CTAs unless the CBI is submitted directly to the applicant who will include the information in their drug submission, DIN application or CTA.

APIs manufactured and tested in accordance with the registered procedures and manufactured and shipped to the drug product manufacturer before an MF is closed can be used in Canadian marketed drug products until the stockpile is depleted or the API has expired, whichever comes first. Complete records for the shipment should be maintained in accordance with Canadian GMPs.

Health Canada will assess the reasons for the closure and start post-market activities, if necessary. If the reasons for closing the MF are related to safety, the MF holder should:

Health Canada will retain the MF following appropriate procedures established for record retention and disposal in accordance with the Library and Archives of Canada Act. We may access the MF after the file is closed in accordance with the law.

Health Canada will close and archive an MF that we have:

MF holders who wish to reactivate a closed MF with Health Canada must:

The same MF number will be retained and fees for a new MF registration will be applied.

For more information on filing requirements for MF reactivations, refer to the section on format and structure of the master file.

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