5. Investigator and Investigational Product
- 13 Mins to read
- DarkLight
5. Investigator and Investigational Product
- 13 Mins to read
- DarkLight
Article summary
Did you find this summary helpful?
Thank you for your feedback
5.1 Does the local regulation require PI/CI to be approved/registered by any regulatory authority (e.g., RA/EC)?
The Qualified Investigator (“QI”) must be a physician in good standing with a professional medical association and is responsible to the sponsor for conducting the CT at the CT site in accordance with the protocol approved under the CT application, including obtaining informed consent from subjects and reporting to the sponsor and the REB in the event of any adverse drug reactions.
The term “qualified investigator” is defined in the Food and Drug Regulations and must be a physician (or a dentist where the trial involves a drug for dental purposes only) who is a member of the applicable professional medical (or dental) association. The QI is generally accountable to the sponsor for the conduct of the CT at a given site. In Canada, there can only be one QI per site but there could be sub-Investigators (Sub-I) delegated to different tasks during the course of the study. More specifically, the QI is generally responsible for the supervision of medical care and medical decisions relating to the CT at each site.
The QI is required to sign an undertaking or an 81(k)-investigator agreement that he/she will conduct the CT in accordance with good clinical practices and that in the event of a discontinuance of the CT, he/she will immediately inform the trial subjects and the REB of the discontinuance, the reasons for the discontinuance, and any potential health risks. The written undertaking must be retained together with the records for the CT, and all of these records must be kept by the sponsor for a minimum period of 15 years.
The functions of a QI are also outlined in the ICH Guidance, which sets out the processes and practices for obtaining informed consent from the trial subjects, assigns responsibility for the study drugs at the trial site to the QI, and provides details on the reporting duties of the QI.
Please refer to Part C of Division 5 of the Food and Drug Regulations: https://laws-lois.justice.gc.ca/eng/regulations/C.R.C.,_c._870/page-85.html#h-577856
The sponsor should select the investigator(s) and the institution(s) for the clinical trial, taking into account the appropriateness and availability of the study site and facilities. The sponsor must also ensure that the investigator(s) are qualified by training and experience. Furthermore, the sponsor must sign an agreement or contract with the participating institution(s).
Prior to initiating a clinical trial, the sponsor must ensure that a Qualified Investigator Undertaking (QIU) form (or similar documentation that meets the requirements such as the 81(k)) has been completed and kept on file by the sponsor. The form certifies that the QI will conduct the clinical trial in accordance with good clinical practices and will immediately inform trial participants and the REB of trial discontinuance, and the reason for this discontinuance.
5.2 Does the local regulation require any specific documents if PI/CI is based outside the country?
A sponsor may be domestic or foreign. A foreign sponsor is required to have a senior medical or scientific officer residing in Canada to represent the sponsor, and to sign and date the application and the clinical trial attestation form.
5.3 Does the local authority allow electronic ICF administration including electronic signatures?
Yes. Information is provided in section 7 on Remote Monitoring.
5.4 Does local regulation require ICF to be administered as audio/visual and do these need to be recorded?
Yes. Please refer to section 7 on Remote Monitoring.
5.5 Are there any specific information/requirements on data capture/management (e.g., privacy regulations, etc.)?
When using electronic trial data handling processing systems, the sponsor must ensure and document that the electronic data processing system conforms to the sponsor’s established requirements for completeness, accuracy, reliability, and consistency of intended performance. To validate such systems, the sponsor should use a risk assessment approach that takes into consideration the system’s intended use and potential to affect human subject protection and reliability of trial results. Furthermore, the sponsor must maintain SOPs that cover system setup, installation, and use. The SOPs should describe system validation and functionality testing, data collection and handling, system maintenance, system security measures, change control, data backup, recovery, contingency planning, and decommissioning. With respect to the use of these computerized systems, the responsibilities of the sponsor, investigator, and other parties should be clear, and the users should receive relevant training.
If electronic records are generated during a clinical trial, then the electronic system must be validated to confirm that the system’s specifications meet the goals and requirements for the clinical trial. This evidence of validation should be kept for the required record retention period and available for inspection by Health Canada inspectors.
Records Management
The sponsor must record, handle, and store all trial-related information to allow complete and accurate reporting, interpretation, and verification. The sponsor must maintain all trial-related records for a period of 15 years. The sponsor must submit requested records to Health Canada within 48 hours if safety concerns arise. Additionally, to facilitate inspection of a site, the sponsor must submit information to Health Canada within seven days of a request. An attestation must be completed by the REB that reviewed and approved the clinical trial. The completed attestation must be retained by the clinical trial sponsor for a period of 15 years. The attestation should not be submitted to Health Canada unless requested.
The sponsor and investigator/institution should maintain a record of the location(s) of their respective essential documents including source documents. The storage system used during the trial and for archiving (irrespective of the type of media used) should allow for document identification, version history, search, and retrieval. The sponsor should ensure that the investigator has control of and continuous access to the data reported to the sponsor. The investigator/institution should have control of all essential documents and records generated by the investigator/institution before, during, and after the trial.
5.6 Does the local regulation allow Home Healthcare Professional Visits (HHCP) in decentralized and/or hybrid studies? If yes, explain if there are any specific requirements to fulfill these obligations.
Yes. Please refer to section 7.5 on Home Nursing.
5.7 Does local regulation allow Direct-to-Patient (DTP) study product delivery (such as home delivery) in clinical trials? Are there specific requirements to fulfill (e.g., acknowledgment of/signature for a product by the patient, etc.)?
Yes, subject to certain conditions.
Direct-to-participant approaches may increase the burden on patients and sites and may not be appropriate for all study populations or study types. Participants may be identifiable to the 3rd party vendor and processes must be put into place to ensure vendors do not pass the participant information to the sponsor. It is also necessary to ensure compliance with provincial privacy regulations, as well as professional and regulatory requirements for health care providers.
https://ethics.gc.ca/eng/policy-politique_tcps2-eptc2_2022.html
The reference below refers to the REB for Ontario as an example but ethics application follows the provincial laws where it is subject.
5.8 If a clinical study involves a study product such as OTC and this is provided via pharmacy/amazon, etc., are there any specific regulations for IP management that need to be followed?
From the research conducted, there are no specific regulations that address this issue.
5.9 For a marketed study product/OTC, can a participant be compensated after confirmation of the purchased study product, or upfront prior to product acquisition? Does compensation in any way impact how the study is viewed (i.e., RWE vs Interventional Study)?
Who covers the cost of providing a study drug is not specifically regulated in Canada. The general practice is that the sponsor provides the study drug (or investigational device testing) free of charge to the Clinical Trial subjects. Many CTs offer some form of additional financial remuneration. In the event that the sponsor itself cannot provide the study drug for use in a CT, the sponsor will generally reimburse the QI or the institution conducting the CT for the cost of the study drug.
The cost of medical procedures and tests that are part of the CT protocol is typically negotiated by the sponsor and the QI and/or institution involved in conducting the CT and is covered under the CT application. If the CT involves a normal standard of care for patients, the cost is typically covered by the medical or research institution. Where the required care, however, is outside the normal standard, the sponsor is more likely to cover the cost of the tests and procedures.
5.10 Is it permitted to pay participant stipends (i.e. is it permitted to pay the patients for their participation in the clinical trial)? If so, what is the average range?
Canadian regulations do not require compensation for trial participation. However, the informed consent form (ICF) should contain a statement with a description of the anticipated prorated payment to the participant(s) that is reasonably expected for participation in the trial. Any compensation or incentive to participants must not be so excessive that it may unfairly influence participants or cause them to overlook important facts and risks. The REB states that the ICF should describe any compensation, incentives, or reimbursements to be paid or given to participants and how participant withdrawal will affect the offered compensation (e.g., prorated remuneration). https://www.canada.ca/en/health-canada/services/science-research/science-advice-decision-making/research-ethics-board.html
If no compensation will be provided, this should be stated.
https://laws-lois.justice.gc.ca/eng/regulations/c.r.c.,_c._870/page-85.html#h-577812
5.11 Specific labeling requirements for the clinical study product
Investigational product (IP) labeling in Canada must comply with the requirements set forth in the Food and Drug Regulations, Guidance Document for Clinical Trial Sponsors: Clinical Trial Applications, and GCP. For an IP to be used in a clinical trial, it must be properly labeled in both official languages: English and French. Sometimes other languages could be added. IPs are required to be packaged and labeled under the supervision of personnel who have had satisfactory technical, academic, and other training. The packager and/or labeler must have written procedures and ensure that the IP is packaged, labeled, and tested in compliance with those procedures.
The following information must be included on the IP label:
- A statement indicating that the drug is an investigational drug (or the medical device (MD) is for research use only) to be used only by a qualified investigator
- Name, number, or identifying mark
- Expiration date (not applicable for MD)
- Recommended storage conditions
- Lot number
- Sponsor’s name and address
- Protocol code or identification
- Radiopharmaceutical information, if applicable
The information must be visible to enable the intended user to make an informed choice with respect to the drug/device, and to permit the post-market identification of a drug/device during a product recall.
If it becomes necessary to change the expiration date, an additional label should be affixed to the IP. This additional label should state the new expiration date and repeat the batch number. It may be superimposed on the previous expiration date, but for quality control reasons, not on the original batch number. This operation should be performed at an appropriately authorized manufacturing site. However, when justified, it may be performed at the investigational site by or under the supervision of the clinical trial site pharmacist, or other health care professional in accordance with national regulations and with the sponsor’s requirements. Where this is not possible, it may be performed by the clinical trial monitor(s) who should be appropriately trained. The operation should be performed in accordance with good manufacturing practice (GMP) principles, specific and standard operating procedures, and under contract, if applicable, and should be checked by a second person. This additional labeling should be properly documented in both the trial documentation and the packaging records.
For IP packaging, the following guidance is provided:
- The risk of product mix-up must be minimized by using appropriate procedures, specialized equipment, and relevant staff training.
- To prevent errors, particularly when IPs are blinded, use heightened precautions, such as label reconciliation, line clearance, and in-process control checks by appropriately trained staff.
- The packaging must ensure that the IP remains in good condition during transport and storage at intermediate destinations; any opening or tampering of the outer packaging during transport should be readily discernible.
This document provides principles and interpretations on the environmental control of clinical trial drugs during storage and transportation, including packaging.
The IP must be coded and labeled in a manner that protects the blinding, if applicable. The IPs must also be suitably packaged in a manner that will prevent contamination and unacceptable deterioration during transport and storage.
5.12 What documents need to be submitted (including relevant fee if any), and to whom, if a permit is needed for an investigational/study product being shipped from outside the country? Are there any specific requirements for biologics?
An application by a sponsor for authorization to sell or import a drug or a medical device for the purposes of a clinical trial must be submitted to Health Canada, signed and dated by the sponsor’s senior medical or scientific officer in Canada and senior executive officer. The sponsor’s clinical trial attestation must be submitted with the application.
Health Canada can authorize the sponsor to import an Investigational Product. A sponsor who is not based in Canada must have a Canadian representative who is responsible for the import of the IP and demonstrates compliance with the applicable regulatory requirements. This representative should be the sponsor’s senior medical or scientific officer residing in Canada and is responsible for providing an attestation with respect to the CT application at the time of filing. If clinical trial drugs are to be imported into Canada, the applicable section of Health Canada 3011: Drug Submission Application Form for Human, Veterinary, or Disinfectant Drugs and Clinical Trial Application/Attestation should be completed and submitted for each importer in Canada. Canadian importer(s) must be located within Canada. As additional importers are identified, additional copies of Appendix 1 should be provided to Health Canada.
If a sponsor wants to import a drug into Canada for a clinical trial, he/she must include a copy of Health Canada’s authorization (i.e., the No Objection Letter) issued by either the Pharmaceutical Drugs Directorate (PDD) or the Biologic and Radiopharmaceutical Drugs Directorate (BRDD) for the applicable trial with the shipment. A copy of this authorization must be provided at the port of entry. Drugs without a Drug Identification Number may be imported where authorized for a Canadian clinical trial and a NOL was issued.
As for Medical Devices, anyone who imports a medical device into Canada must also meet all applicable requirements of the Canadian Food and Drugs Act and associated Regulations. Some requirements include the following:
- Class I device: The importer must have a valid Medical Device Establishment Licence (MDEL) with the activity of import unless exempted.
- Class II, III, or IV device: The device must be licensed by having a Medical Device Licence (MDL) and the importer must have a valid MDEL with the activity of import unless exempted.
- All medical device classes: The importer must ensure that the company from whom they import (foreign distributor) has an MDEL that includes the appropriate licensable activities unless exempted.
For exemption, the following website may be consulted: https://www.canada.ca/en/health-canada/services/drugs-health-products/compliance-enforcement/importation-exportation/regulatory-importing-medical-devices.html
5.13 What is the turnaround time to get an import permit?
The Government of Canada's Global Affairs Canada website describes the import permit application process.
- Import permits are issued within 10 business days of submission of a completed application.
- Requests for import permits will be accepted within 30 days prior to the expected date of arrival of the shipment in Canada for strategic goods.
5.14 Does local authority allow the destruction of clinical supplies at an off-site location (e.g. third-party vendor in or outside the country) after study completion? Are certificates of destruction required?
As per HC requirements, Part C, Division 5, of the Food and Drug Regulations “Drugs for Clinical Trials Involving Human Subjects”, the sponsor shall maintain complete and accurate records with respect to the use of an IP in a clinical trial and these records include records respecting the shipment, receipt, disposition, return, and destruction of the drug (or Device Accountability for a medical device). The regulations, therefore, imply the requirement of the destruction of drug supply and also that the destruction of drug supply is required to be documented (also applicable for medical devices). No specific guidance is provided regarding where the destruction may occur or whether a specific certificate of destruction is required. However, subsection C.05.012(4) requires a sponsor to maintain all records documenting the destruction of drug supply for a period of 15 years.
Was this article helpful?