Frequently Asked Questions

FAQ - Multiple Subjects

Adverse Drug Reaction Reporting

1. What are the regulatory requirements for ADR reporting?
2. What must be reported as an Adverse Drug Reaction (ADR)?
3. To whom are ADR reports sent?

Completion of Clinical Trials

1. What are the regulatory requirements for submitting a final study report?

Clinical Trial Sites

1. When is a Clinical Trial Site Information (CTSI) Form submitted?
2. A CTA has been submitted, but not all sites are on board. For sites on board, Section D and Appendix 1 of the HC/SC 3011 Form have been completed and are part of the submission. What is needed when sites come on board while the CTA is being reviewed?
3. A CTA has been submitted, but not all sites are on board. For sites on board, Section D and Appendix 1 of the HC/SC 3011 Form have been completed and are part of the submission. What is needed when sites come on board after the No Objection Letter (NOL) has been issued?
4. Are Clinical Trial Sites Inspected?
5. When is a CTSI form required in the following scenarios?

Qualified Investigator

1. Can two Qualified Investigators conduct the same clinical trial independently at the same site?
2. The Qualified Investigator has changed at a site. What information do I send to Health Canada?
3. Is a new QIU Form needed for an amendment?
4. Where can I find the HPB 3005 Form?

Research Ethics Board Attestation

1. Is it essential that the REB chairperson sign the REB attestation, or may an authorized person sign it on his/her behalf? If so, must that authorization be documented?
2. Can a REB use their own letter, or is the REBA Form needed?
3. If a REB uses their own letter, what must it contain?

Drug Submission Application Form (HC/SC 3011)

1. Is the HC/SC 3011 Form the same as the HPB 3011 Form?
2. We do not have any operations in Canada, and plan on using one of our clinical investigators as our Senior Medical Officer in Canada to sign box 87 of Appendix 3 of the Drug Submission Application Form (HC/SC 3011 Form). By signing this form, is he certifying for all five items listed?
3. Item 5 of Appendix 3 of the HC/SC 3011 Form requires records to be maintained for 25 years and made accessible to Health Canada inspectors for onsite inspections. Do these records have to be maintained by our Senior Medical Officer in Canada, or is it acceptable for us to maintain the records at our US Headquarters and make them available to Health Canada inspectors upon request?
4. Box 8 of the HC/SC 3011 Form asks for 'Brand or Proprietary Name'. What is listed when a sponsor's product is compared to a branded product?
5. Box 10 of the HC/SC 3011 Form asks for the Company Code. What is this?
6. Box 55 of the HC/SC 3011 Form asks for the Medicinal (Active) Ingredient. I have a letter of cross-reference from the manufacturer. Can I enter "See letter of authorization"?
7. Box 56 of the HC/SC 3011 Form asks for the Non-medicinal Ingredients. I have a letter of cross-reference from the manufacturer. Can I enter "See letter of authorization"?
8. Who signs box 71 on the HC/SC 3011 Form?

Drug Master Files (DMFs) in support of CTAs Involving Pharmaceutical Drugs

1. What is a DMF?
2. Why have a DMF?
3. What is the process for submitting a DMF?
4. What is required from the DMF holder?
5. What is required from the CTA sponsor?

Adverse Drug Reaction Reporting

1. What are the regulatory requirements for ADR reporting?

This is covered by Part C, Division 5 of the Food and Drug Regulations.
See C.05.014 for Serious Unexpected Adverse Drug Reaction Reporting.

2. What must be reported as an Adverse Drug Reaction (ADR)?

Serious and unexpected ADRs, subject to expedited reporting, are those considered to be drug specific. Clarification and details are included in Section 12.3 of the Guidance for Clinical Trial Sponsors: Clinical Trial Applications.

3. To whom are ADR reports sent?

Refer to the Contact Information page for relevant fax numbers. The ADR reports are also sent to the REB and investigators as per the Health Canada/ICH Guidance Document E6: Good Clinical Practice: Consolidated Guideline. Also see the Health Canada/ICH Guidance Document E2A: Clinical Safety Data Management: Definitions and Standards for Expedited Reporting.

Completion of clinical Trials

1. What are the regulatory requirements for submitting a final study report?

For a study that has completed, the sponsor is encouraged to submit a notification to Health Canada indicating that the trial is now completed; however, no supporting information is required with the notification, i.e. a final study report is not required.

Clinical Trial Sites

1. When is a Clinical Trial Site Information (CTSI) form submitted?

The CTSI Form is submitted once fully completed, i.e. only if the dates for boxes 35 & 47 are known. A fully completed form must be provided for each site. It is submitted with the CTA or CTA-A, only if all the information is known at the time of the application. For consistency, the sponsor should also ensure that the complete name (i.e. first and last name) along with the appropriate prefix (e.g. Dr.) and the area code for fax and telephone numbers are provided in the relevant sections of the CTSI Form.

If all information is not known at the time of the application, the CTSI Form is submitted prior to commencement of the trial or implementation of the amendment and all the sections must be completed including:

• the dates for boxes 35 & 47
• the control number assigned by Health Canada in box 3
• the CR file number assigned by Health Canada in box 4

2. A CTA has been submitted, but not all sites are on board. For sites on board, Section D and Appendix 1 of the HC/SC 3011 Form have been completed and are part of the submission. What is needed when sites come on board while the CTA is being reviewed?

For sites coming on board while a CTA is being reviewed, submit a cover letter and Appendix 1. A Clinical Trial Site Information Form (CTSI Form) may also be sent, if the dates for boxes 35 & 47 are known.

3. A CTA has been submitted, but not all sites are on board. For sites on board, Section D and Appendix 1 of the HC/SC 3011 Form have been completed and are part of the submission. What is needed when sites come on board after the No Objection Letter (NOL) has been issued?

For sites coming on board after the NOL has been issued, submit Appendix 1 and a fully completed CTSI Form [showing both the control number (box 3) and the file number (box 4) assigned by Health Canada, and the dates for boxes 35 & 47].

4. Are Clinical Trial Sites Inspected?

Clinical trial sites, including those authorized under the previous regulatory framework, are subject to inspection. The "Inspection Strategy for Clinical Trials" document provides further information.

5. When is a CTSI Form required in the following scenarios?

1. 1 hospital with 2 addresses

   address 1 - where patients receive dosing,
   and address 2 - where patients receive follow-up

   A CTSI Form is needed for the primary, i.e. dosing, address.
   A CTSI Form is not required for the "follow-up" site.

2. 2 hospitals and a research centre

   2 hospitals where patients receive dosing, and
   research centre where patients receive follow-up.

   A CTSI Form is needed for each hospital i.e. dosing sites.
   A CTSI Form is not required for the "follow-up" research centre.

3. Separate hospitals within a hospital system, or other multiple site locations, with the same Qualified Investigator (Principal Investigator) and the same Research Ethics Board.

   The format for CTSI, QIU and REBA forms in capturing multiple site locations is as follows:

   CTSI Form

   Multiple sites may be identified by duplicating Part 3 as many times as necessary to capture all site addresses. These pages listing multiple clinical trial sites are attached to Parts 1 and 2, and the complete document should be paginated, e.g. 1 of 5, 2 of 5 etc.

   QIU Form

   Multiple sites may be identified by duplicating Part 3 as many times as necessary to capture all site addresses under the responsibility of the same QI. Only the final page of the QIU would contain the QI's signature. These pages listing multiple clinical trial sites are attached to Parts 1 and 2, and the complete document should be paginated, e.g. 1 of 5, 2 of 5 etc.

   REBA Form

   Multiple sites may be identified by duplicating Part 3 as many times as necessary to capture all site addresses approved by the same Research Ethics Board. Note that there is a place on Part 3B to state number of pages attached. Only the final page of the REBA would contain the REB representative signature. These pages listing multiple clinical trial sites are attached to Parts 1 and 2, and the complete document should be paginated, e.g. 1 of 5, 2 of 5 etc.

Qualified Investigator

1. Can two Qualified Investigators conduct the same clinical trial independently at the same site?

No, there must be no more than one Qualified Investigator at each site for that clinical trial.

2. The Qualified Investigator has changed at a site. What information do I send to Health Canada?

• A new Clinical Trial Site Information Form should be submitted.
• The new Qualified Investigator Undertaking Form is kept on site as part of the records.

3. Is a new QIU Form needed for an amendment?

During the course of a clinical trial plus its amendments, a new QIU Form is required only when there is a change in the form.

4. Where can I find the HPB 3005 Form?

The HPB 3005 Form has been replaced by the Qualified Investigator Undertaking Form (QIU).

Research Ethics Board Attestation

1. Is it essential that the REB chairperson sign the REB attestation, or may an authorized person sign it on his/her behalf? If so, must that authorization be documented?

The REB attestation must be signed by the REB chairperson

2. Can a REB use their own letter, or is the REBA Form needed?

• To facilitate regulatory requirement, the REBA Form was developed and revised, based on stakeholder comments.
• Comments suggested that a satisfactory REB approval letter could replace this form.
• The Guidance for Clinical Trial Sponsors states that either the REB attestation , or similar documentation , meeting the requirements of Part C, Division 5 of the Food and Drugs Regulations, is acceptable.

3. If a REB uses their own letter, what must it contain?

A REB letter must attest to the following 3 points:

In respect of the identified clinical trial, I certify, as chair of this Research Ethics Board that:

1. The membership of this Research Ethics Board complies with the membership requirements for Research Ethics Boards defined in Division 5 of the Food and Drug Regulations;
2. This Research Ethics Board caries out its functions in a manner consistent with Good Clinical Practices; and
3. This Research Ethics Board has reviewed and approved the clinical trial protocol and informed consent form for the trial which is to be conducted by the qualified investigator named above at the specified clinical trial site. This approval and the views of this Research Ethics Board have been documented in writing.

The REB letter does not need to include all the elements contained in PART 1, PART 2 and PART 3 of the REBA Form.

Drug Submission Application Form (HC/SC 3011)

1. Is the HC/SC 3011 Form the same as the HPB 3011 Form?

The HC/SC 3011 Form has replaced the HPB 3011 Form.

2. We do not have any operations in Canada, and plan on using one of our clinical investigators as our Senior Medical Officer in Canada to sign box 87 of Appendix 3 of the Drug Submission Application Form (HC/SC 3011). By signing this form, is he certifying for all five items listed?

Yes, the person signing box 87 of Appendix 3, certifies for the 5 items listed on Appendix 3.

3. Item 5 of Appendix 3 of the HC/SC 3011 Form requires records to be maintained for 25 years and made accessible to Health Canada inspectors for onsite inspections. Do these records have to be maintained by our Senior Medical Officer in Canada , or is it acceptable for us to maintain the records at our US Headquarters and make them available to Health Canada inspectors upon request?

Records can be maintained either by the Senior Medical Officer in Canada , or in the US and made available to Health Canada inspectors upon request.

4. Box 8 of the HC/SC 3011 Form asks for 'Brand or Proprietary Name'. What is listed when a sponsor's product is compared to a branded product?

Box 8 lists the name under which the sponsor's product is to be sold / advertised.

5. Box 10 of the HC/SC 3011 Form asks for the Company Code. What is this?

The company code is a 4-5 digit code assigned to the manufacturer / sponsor by Health Canada.

• If not known, leave blank.
• It is not 9427 - i.e. the first 4 digits of the file number.

6. Box 55 of the HC/SC 3011 Form asks for the Medicinal (Active) Ingredient. I have a letter of cross-reference from the manufacturer. Can I enter "See letter of authorization"?

No, box 55 must be completed, stating:

• the ingredient name
• strength: amount (e.g. mg) per unit (e.g. tablet)

A useful weblink is that of Health Canada's Drug Product Database.

7. Box 56 of the HC/SC 3011 Form asks for the Non-medicinal Ingredients. I have a letter of cross-reference from the manufacturer. Can I enter "See letter of authorization"?

Yes, "See letter of authorization" is acceptable. Please note that Box 56 does not need to be completed if the drug to be used in the clinical trial is marketed in Canada .

8. Who signs box 71 on the HC/SC 3011 Form?

The person authorized by the sponsor identified in section 11 to sign this form, i.e. the person signing this form is certifying that the information provided in the form is consistent with the wishes of the sponsor.

Drug Master Files (DMFs) in Support of CTAs Involving Pharmaceutical Drugs

1. What is a DMF?

A DMF is a reference source that provides information about specific processes and components used in the manufacturing, processing, and packaging of a new drug meant for human use. A DMF is submitted by a company (e.g. manufacturer of the new drug) or its authorized agent/appointed representative, hereinafter called the DMF holder.

2. Why have a DMF?

The DMF is a useful vehicle for providing information to Health Canada , where that information is of a proprietary nature and is not available to a CTA sponsor. The information in the DMF will be used to support a CTA only if the DMF holder provides Health Canada with a letter of access^*. The DMF is kept confidential; only officials of Health Canada have permission to access the file. Health Canada does not reveal the status or content of the DMF to the CTA sponsor.

* Letter of access: a letter written by the DMF holder permitting Health Canada to reference information in the DMF in support of the sponsor's application.

3. What is the process for submitting a DMF?

Please contact the Drug Master Files Administrator for details.

4. What is required from the DMF holder?

The DMF holder is responsible for:

• filing the DMF to Health Canada^*
• providing Health Canada^* with a letter of access for the specific CTA sponsor
• forwarding a copy of the letter of access to the CTA sponsor to include in the CTA
• paying fees for the DMF and the letter(s) of access

*DMF Administrator

5. What is required from the CTA sponsor?

The CTA sponsor must:

• include the letter of access in the CTA
• ensure that the supporting Drug Master File (including submission of the letter of access and payment of related fees) has been submitted to and accepted by Health Canada (DMF Administrator) prior to filing a CTA.