Outline of the Process

1. What types of clinical trials must be filed?
2. How long does it take to receive authorization?
3. In what situation do I have to file an application?
4. What are the roles and responsibilities of a sponsor and a Qualified Investigator when conducting a clinical trial?
5. Do I need to apply for a pre-CTA meeting?
6. What data must be submitted to Health Canada?

1. What types of clinical trials must be filed?

Clinical Trial Applications (CTAs) must be filed with Health Canada for review and authorization for drugs not marketed in Canada for Phase I, II and III clinical trials, as well as for comparative bioavailability trials. If the drug has received a Notice of Compliance (NOC) or a Drug Identification Number (DIN), clinical trial applications must be filed where the use of the product in the clinical trial is outside the parameters of the NOC and/or DIN, i.e. one or more of the following is different:

• indication(s) and clinical use;
• target patient population(s);
• route(s) of administration; or
• dosage regimen(s)

If a new indication for a marketed drug is to be investigated, the clinical trial is considered to be a Phase II or Phase III trial.

For drugs that have received a Notice of Compliance with Conditions (NOC/c), clinical trials conducted within the parameters of the NOC/c must be filed with Health Canada for review and authorization. Please note that sponsors are not required to file a CTA for clinical trials involving marketed drugs where the investigation is to be conducted within the parameters of the authorized NOC or DIN application. These trials are referred to as Phase IV clinical trials.

2. How long does it take to receive authorization?

Health Canada commits to a 30-day default, review period for authorization. That is, if Health Canada does not issue a Non Satisfactory Notice, during the review period, the trial may proceed on the basis of default authorization. Health Canada has an administrative 7-day review target for comparative bioavailability trials, and some Phase I trials in healthy humans volunteers.

3. In what situation do I have to file an application?

A CTA has to be submitted:

• for a new drug
• for an already marketed drug, if one or more of the following is different than "label-use":
  • indications and clinical use
  • patient population
  • route of administration
  • dosage

A CTA is not required for Phase IV trials.

4. What are the roles and responsibilities of a sponsor and a Qualified Investigator when conducting a clinical trial?

Sponsor

The sponsor is defined as an individual, corporate body, institution or organization that applies for authorization to conduct a clinical trial in Canada and is responsible for meeting the regulatory requirements and conducting the trial according to the generally accepted principles of good clinical practices.

Qualified Investigator

The Qualified Investigator is a person who is:

• a physician and a member in good standing of a professional medical association
• in the case of a clinical trial of a dental drug, a physician or dentist and member in good standing of a professional medical or dental association
• responsible to the sponsor for the conduct of the clinical trial at the clinical trial site
• responsible for medical care and medical decisions at the clinical trial site
• entitled to provide health care under the laws of the province where that clinical trial site is located
• there may be only one Qualified Investigator per clinical trial site

5. Do I need to apply for a pre-CTA meeting?

Health Canada invites sponsors to request a pre-CTA consultation meeting, but such meetings are not mandatory. Such consultations may be particularly useful for new active substances or applications that will include complex issues that may be new to Health Canada. For more information please consult the section related to pre-CTA meetings. Details

6. What data must be submitted to Health Canada?

A Clinical Trial Application contains information and documentation to support the objectives and goals of the proposed clinical trial including scientific evidence supporting the use of the drug product within the context of a trial . It also includes data to support the quality of the drug product to be used in the trial. For more information please consult the section on Clinical Trial Applications. Details

Filing of Clinical Trials

1. My company currently has an ongoing IND in the USA, and would like to expand to include Canadian investigators. How is this done?
2. My trial was filed as an Investigational New Drug Submission (INDS) prior to September 1, 2001. Do amendments have to be filed?
3. I was not required to file my trial prior to September 1, 2001. Do amendments have to be filed?
4. The PSEAT-CTA is not requested in the Regulations. What is it, and why does the Guidance for Clinical Trial Sponsors request it for Pharmaceuticals (Section 5.2, 1.2.4)?
5. What are the fees for CTA and CTA-A submissions?
6. Are there any color requirements for the binders of various Modules?
7. Are there any requirements for the types of binders used?
8. My clinical trial involves a pharmaceutical and a biological / radiopharmaceutical drug. What do I have to submit?
9. My clinical trial involves a pharmaceutical drug and an investigational medical device. What do I have to submit?
10. My clinical trial involves a biological / radiopharmaceutical drug and an investigational medical device. What do I have to submit?
11. My clinical trial involves a pharmaceutical drug and a natural health product. What do I have to submit?
12. What documentation is required in order to ship an investigational drug into Canada?
13. How do the Therapeutic Products Directorate (TPD) and the Biologic and Genetic Therapies Directorate (BGTD) track Clinical Trial Applications (CTAs) and Clinical Trial Applications-Amendments (CTA-As)?
14. Are Annual Clinical Trial reports required?

1. My company currently has an ongoing IND in the USA, and would like to expand to include Canadian investigators. How is this done?

Submit a Clinical Trial Application to Health Canada for review and authorization. DETAILS

2. My trial was filed as an Investigational New Drug (IND) submission prior to September 1, 2001. Do amendments have to be filed?

Yes, amendments have to be filed.

Investigational New Drug (IND) submissions filed prior to September 1, 2001 are not subject to Part C, Division 5 of the Food and Drug Regulations. However, amendments to Investigational New Drug Submission(s) submitted prior to September 1, 2001 should be filed in accordance with the requirements of Part C, Division 5 of the Food and Drug Regulations.

3. I was not required to file my trial prior to September 1, 2001. Do amendments have to be filed?

It is recommended that amendments be filed for trials exempted from IND filing with a marketed drug for a new indication and initiated by a medical practitioner. State clearly on the cover letter that the original trial began on xx/xx/xx, prior to the requirements of Part C, Division 5 of the Food and Drug Regulations.

Amendments do not have to be filed for trials using a marketed drug as per NOC / DIN.

4. The PSEAT-CTA is not requested in the Regulations . What is it, and why does the Guidance for Clinical Trial Sponsors request it for Pharmaceuticals (Section 5.2, 1.2.4)?

PSEAT-CTA stands for: Protocol Safety and Efficacy Assessment Template - Clinical Trial Application. The "Protocol Synopsis & Evaluation" module of the PSEAT-CTA is tailored to provide a detailed summary of the protocol information required for the evaluation of the clinical trial(s) proposed in Canada. Information should be summarized under the various headings provided, where applicable. The PSEAT-CTA is an operational request, and is used to ensure that the target review times are met.

5. What are the fees for CTA and CTA-A submissions?

There are no fees.

6. Are there any color requirements for the binders of various Modules?

There are no color requirements.

7. Are there any requirements for the types of binders used?

While there are no requirements for the types of binders used, 3-ring binders are preferred.

8. My clinical trial involves a pharmaceutical and a biological / radiopharmaceutical drug. What do I have to submit?

• If the focus of the clinical trial pertains to the pharmaceutical drug, the Therapeutic Products Directorate (TPD) takes the lead, and the application is submitted to TPD in duplicate.
• If the focus of the clinical trial pertains to the biological / radiopharmaceutical drug, the Biologics and Genetic Therapies Directorate (BGTD) takes the lead, and the application is submitted to BGTD in duplicate.
• Authorization for use of the pharmaceutical, as well as authorization for use of the biological / radiopharmaceutical, must be obtained prior to the initiation of the clinical trial or implementation of a protocol amendment.
• The lead Directorate will be responsible for communicating the regulatory decision to the sponsor.

9. My clinical trial involves a pharmaceutical drug and an investigational medical device. What do I have to submit?

• If the focus of the clinical trial pertains to the pharmaceutical drug, the Office of Clinical Trials of TPD takes the lead, and the application is submitted to the Office of Clinical Trials in duplicate.
• If the focus of the clinical trial pertains to the medical device, the Medical Devices Bureau of TPD takes the lead, and the application is submitted to the Medical Devices Bureau in duplicate.
• Authorization for use of the pharmaceutical, as well as authorization for use of the investigational medical device, must be obtained prior to the initiation of the clinical trial or implementation of a protocol amendment.
• The lead Office/Bureau will be responsible for communicating the regulatory decision to the sponsor.
• It is advised that for Clinical Trial Applications and Clinical Trial Application Amendments that involve unauthorized medical devices, the sponsor first contact the Medical Devices Bureau to determine if there are additional filing requirements, for the device, which must be met prior to its use in the proposed clinical trial. A record of these communications should be included in the submission.

10. My clinical trial involves a biological / radiopharmaceutical drug and an investigational medical device. What do I have to submit?

• If the focus of the clinical trial pertains to the biological / radiopharmaceutical drug, the Biologics and Genetic Therapies Directorate (BGTD) takes the lead, and the application is submitted to the BGTD in duplicate.
• If the focus of the clinical trial pertains to the medical device, the Medical Devices Bureau of TPD takes the lead, and the application is submitted to the Medical Devices Bureau in duplicate.
• Authorization for use of the biological / radiopharmaceutical drug, as well as authorization for use of the investigational medical device, must be obtained prior to the initiation of the clinical trial or implementation of a protocol amendment.
• The lead Bureau/Directorate will be responsible for communicating the regulatory decision to the sponsor.
• It is advised that for Clinical Trial Applications and Clinical Trial Application Amendments that involve unauthorized medical devices, the sponsor first contact the Medical Devices Bureau to determine if there are additional filing requirements, for the device, which must be met prior to its use in the proposed clinical trial. A record of these communications should be included in the submission.

11. My clinical trial involves a pharmaceutical drug and a natural health product. What do I have to submit?

• If the focus of the clinical trial pertains to the pharmaceutical drug, the Therapeutic Products Directorate (TPD) takes the lead, and the application is submitted to the Office of Clinical Trials in duplicate.
• If the focus of the clinical trial pertains to the natural health product, the Natural Health Products Directorate (NHPD) takes the lead, and the application is submitted to the NHPD in duplicate.
• Authorization for use of the pharmaceutical, as well as authorization for use of the natural health product, must be obtained prior to the initiation of the clinical trial or implementation of a protocol amendment.
• The lead Directorate will be responsible for communicating the regulatory decision to the sponsor.

12. What documentation is required in order to ship an investigational drug into Canada?

When a drug is imported into Canada to be used within the context of a clinical trial, please include / attach a copy of the No Objection Letter (NOL) for the applicable trial with the drug shipment.

13. How do the Therapeutic Products Directorate (TPD) and the Biologic and Genetic Therapies Directorate (BGTD) track Clinical Trial Applications (CTAs) and Clinical Trial Applications-Amendments (CTA-As)?

New control numbers (i.e. a six digit number) are assigned to all CTAs, and any subsequent CTA-As, to enable tracking of protocols and their amendments within a given file. Cover letters accompanying CTA-As should clearly state the control number of the original (parent) CTA. A telephone enquiry / voice message about a protocol or its amendment should clearly state the assigned control number.

A CR file number (i.e. 9427-#####-##C) is the number assigned by HPFB's Central Registry to a file for a particular product from a particular sponsor. Data received for a product is added to the appropriate file and to the electronic database. The CR file number is used by HPFB to locate information pertaining to a particular product from a particular sponsor.

The control number, assigned by HPFB, is used to identify a particular trial for a particular product from a particular sponsor. Clinical trial data is added to the appropriate file and to the electronic database. The control number is used by both sponsor and HPFB to locate information pertaining to a particular trial.

All clinical trials involving drug products are also required to have a protocol number which is assigned by the sponsor. The protocol number, control number and CR file number all appear on the correspondence (e.g. the No Objection Letter) sent by the Directorate to the sponsor.

14 . Are Annual Clinical Trial reports required?

Annual Clinical Trial (Investigational New Drug (IND)) reports, under the old regulatory framework, have been replaced by the annual updated Investigator's Brochure.

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.

• Drug Importation
  
  1. What documentation is required in order to ship an investigational drug into Canada?
  2. For a CTA, if the clinical trial sponsor is located outside Canada, and the drug is being sent directly to each clinical trial site, what are the documents required?
  3. For a CTA-A, where the clinical trial sponsor is located outside Canada, and the drug is being imported for the purposes of the trial, do section D and Appendix 1 have to be completed for each importer?
  4. If the Authorization for a Third Party to Import the New Drug (Appendix 1) is submitted after the initial CTA was submitted, is there a waiting period before the drug can be shipped to the site?

• Record Keeping
  1. My clinical trial began prior to September 1, 2001, before the requirement to maintain all records for a period of 25 years. How long are my records to be kept?

Drug Importation

1. What documentation is required in order to ship an investigational drug into Canada?

When a drug is imported into Canada to be used within the context of a clinical trial, please include / attach a copy of the No Objection Letter (NOL) for the applicable trial with the drug shipment.

2. For a CTA, if the clinical trial sponsor is located outside Canada, and the drug is being sent directly to each clinical trial site, what are the documents required?

If the drug is sent directly to each site, then each site is listed as an importer.

• Enter the name and address of one importing site in Section D of the Drug Submission Application Form (HC/SC 3011), and use an additional sheet of paper to list all other sites.
• The name can be that of the Qualified Investigator or the pharmacy receiving the drug at the clinical site.
• Appendix 1 is completed for each site listed as an importer in Section D of the Drug Submission Application Form (HC/SC 3011).

3. For a CTA-A, where the clinical trial sponsor is located outside Canada , and the drug is being imported for the purposes of the trial, do section D and Appendix 1 have to be completed for each importer?

Enter the name and address of one importing site in Section D, and use an additional sheet of paper to list all other sites.

If the importers have not changed when a CTA-A is filed, Appendix 1 does not need to be resubmitted.

4. If the Authorization for a Third Party to Import the New Drug (Appendix 1) is submitted after the initial CTA was submitted, is there a waiting period before the drug can be shipped to the site?

Once a No Objection Letter (NOL) for the trial in question has been obtained from Health Canada , include / attach a copy with the drug shipment to Canada.

Record Keeping

1. My clinical trial began prior to September 1, 2001, before the requirement to maintain all records for a period of 25 years. How long are my records to be kept?

Prior to September 1, 2001, the ICH Good Clinical Practice Guidelines (Section 4.9.5) were followed:

"4.9.5: Essential documents should be retained until at least 2 years after the last approval of a marketing application in an ICH region and until there are no pending or contemplated marketing applications in an ICH region or at least 2 years have elapsed since the formal discontinuation of clinical development of the investigational product. These documents should be retained for a longer period however if required by the applicable regulatory requirements or by an agreement with the sponsor. It is the responsibility of the sponsor to inform the investigator/institution as to when these documents no longer need to be retained (see 5.5.12)."