Making Tabs Using the Tabs Template provided, make tabs for the headings, depending on whether drug under investigation is a Pharmaceutical or Biologic/Radio-pharmaceutical and arrange them in a binder. It is not necessary to make tabs for sections that are not applicable. For example, if no Investigator’s Brochure is necessary, the tab for section 1.2.3 may be left out.       Place these tabs either in a red binder or a binder having red-colored front/side labels.   Cover Letter The cover letter should be placed at the beginning of Module 1 before the first tab. The intent of the cover letter is to summarize the information included in the CTA and should be signed by the appropriate investigator who is acting as the sponsor. The submission is sent to the appropriate Directorate and as such the address appearing on the letter will depend on whether the drug is a Pharmaceutical or a Biologic/Radio-pharmaceutical Drug.   Pharmaceutical Drugs Dr. John Patrick Stewart A/Director, Office of Clinical Trials Therapeutic Products Directorate 5th Floor, Holland Cross, Tower B AL 3105A 1600 Scott Street Ottawa, Ontario K1A 0K9 Canada Biological and Radiopharmaceutical Drugs Regulatory Affairs Division Centre for Policy and Regulatory Affairs Biologics and Genetic Therapies Directorate Health Products and Food Branch 1st Floor, Building #7, A/L 0701A Tunney's Pasture Ottawa, Ontario K1A 0L2 Canada   1.1 Table of Contents The Table of Contents is a complete listing of the contents of all of the modules (Modules 1 through 3, if applicable). Using the Table of Contents templates below, create your table of contents. Revise as needed and copy the file to your personal computer. For a section which does not apply for a particular CTA, keep the section in the Table of Contents and indicate with “N/A” that they are not applicable. In the Common Technical Document (CTD) format there is no need to submit volume and page numbers. Template (Biologics)  Template (Pharmaceutical) Several forms have been provided in *PDF (Portable Document Format) with helpful notes to address issues specific for an investigator-initiated trial. The forms should be saved on our personal computer and printed for inclusion in the CTA. *If you are unable to view the PDF files you can download the FREE Acrobat Reader from Adobe . 1.2.1 HC/SC 3011 Form A completed and signed Drug Submission Application form 3011 must be included in section 1.2.1. Using the "helpful notes" provided with the HS/CS 3011 form, complete Part 1 (Boxes 5–52) and Part 2 (Boxes 57–77). For all other sections of the form, If drug used in trial is from the Canadian market, indicate 'Marketed Product' in theses sections of the form If drug used in trial is either not approved in Canada or not from Canadian market, refer to cross-referenced letter provided in section 1.2.10. Appendix 1 and 2 are only submitted if applicable. For investigator-initiated trials, Appendix 3 of the form may be signed by the appropriate Department Head in lieu of the Senior Executive Officer, and the qualified investigator may sign in lieu of the Senior Medical or Scientific Officer. 1.2.2 Information on prior related Applications A list of ongoing clinical trials (with protocol title) by the investigator with the drug under investigation will need to be provided in this section. 1.2.3 Investigator's Brochure If the drug under investigation has not been approved for market in Canada, the most current Investigator’s Brochure (IB) must be submitted. However, if the manufacturer of the product has previously submitted the most current IB as part of another CTA, a letter authorizing cross-reference may be submitted in lieu of the Investigator’s Brochure (IB)—see section 1.2.10. For a marketed product, the Product Monograph may be submitted in lieu of the IB.  If additional relevant safety information is available, it would need to be submitted annually as an "addendum" to the PM. If being submitted, an electronic version of the IB or PM also needs to be sent on a CD-ROM, included in Section 1.3. 1.2.4 PCERT Template or submission rationale For a pharmaceutical drug, a PCERT Templatemust be completed, which is simply a copy and paste of the contents of the protocol into the appropriate sections. For a biologic/radiopharmaceutical drug, a submission rationale and a brief summary of the drug product being proposed for use is described in this section. As there is no official template available through Health Canada, this can be copied directly from the protocol into a Word document. An electronic version also needs to be sent on a CD-ROM, included in section 1.3. 1.2.5 Study Protocol (s) A copy of the final proposed protocol should be submitted in this section. An electronic version also needs to be sent on a CD-ROM, included in Section 1.3. 1.2.6 Informed Consent(s) A copy of the Informed Consent document(s) to be used in conjunction with the clinical trials, including a statement regarding the risks and anticipated benefits to the clinical trial subjects as a result of their participation in the clinical trial(s) should be included in this section. Please include the Informed Consent Form you intend to submit, or have submitted, for Ethics approval. If no changes have been made to the informed Consent Form, this section is not applicable. 1.2.7 Clinical Trial Site Information (CTSI) Form It is necessary to completely fill out the CTSI Formand include the control # and date of Research Ethics Board (REB) approval before submission to Health Canada. These forms are typically submitted separately from the CTA by faxing to the appropriate Directorate when they are completed. Although Health Canada will approve a clinical trial application without this site information form, it must be submitted to Health Canada before commencing the clinical trial. Receipt of this form will not be subject to an acknowledgement letter. A completed CTSI Form for each proposed site should be submitted by mail or fax.   Pharmaceutical Drugs Therapeutics Products Directorate Office of Clinical Trials 5th Floor, Holland Cross, Tower B 1600 Scott Street, AL 3105A Ottawa, Ontario K1A 0K9 Canada Fax: 613-952-9656 Biological and Radiopharmaceutical Drugs Regulatory Affairs Division Centre for Policy and Regulatory Affairs Biologics and Genetic Therapies Directorate Health Products and Food Branch 1st Floor, Building #7, A/L 0701A Tunney's Pasture Ottawa, Ontario K1A 0L2 Canada Fax: 613-941-1708 If any changes are made to the CTSI form (e.g., change in investigator) a revised form should be submitted. 1.2.8 Canadian Research Ethics Board(s) Refusals The name, address and telephone number of any Research Ethics Board in Canada that has previously refused to approve the clinical trial protocol or amendment, its reasons and comments, and the date the refusal was given. If this section is not applicable, section 1.2.8 should be labeled as “Not Applicable” in Table of Contents. Once the REB has approved the CTA, an REB attestation formand Qualified Investigator Undertakingshould be completed for the investigator, at each site, participating in the trial but should not be submitted. It should be kept on file by the site. 1.2.9 Foreign Refusals Information regarding refusals by regulatory authorities outside Canada, if applicable. 1.2.10 Letters of Access If the product used in the trial is purchased from Canadian market, this section is not applicable. In certain instances, information is held by the manufacturer of an investigational drug that is not accessible to the investigator. An example of this is typically confidential information related to the chemistry and manufacturing (CMC) of the drug. However, since CMC information is relevant to the review of a CTA, investigators can request a “letter of access” from the drug manufacturer. This letter authorizes Health Canada to access the confidential information, on behalf of the investigator, in relation to a CTA. The final letter of cross-reference sent by the manufacturer will be copied to the investigator once it is submitted to Health Canada and this copy should be inserted in this section. Note: This letter of access only applies if product is not approved in Canada or if product is being supplied from an outside market. 1.2.11 Other Application-Related Information Including, for example: a copy of the record of the discussions and conclusions of the pre-CTA consultation meeting, if applicable. 1.3 Electronic Review Documents In the final section of this module, 1.3, the electronic review documents appear either on CD-ROM and/or diskette. The CD-ROM, properly labeled, contains electronic versions of the submission rationale/PCERT, protocol, and Investigator Brochure. Packaging and Shipping The Shipping address appearing on the shipping box should read: Office of Clinical Trials Therapeutic Products Directorate c/o Connie Diotte, Room 5028 5th Floor, Holland Cross, Tower B AL 3105A 1600 Scott Street Ottawa, Ontario K1A 0K9 Canada or Regulatory Affairs Division Centre for Policy and Regulatory Affairs Biologics and Genetic Therapies Directorate Health Products and Food Branch 1st Floor, Building #7, A/L 0701A Tunney's Pasture Ottawa, Ontario K1A 0L2 Canada The outer label with the mailing information should be clearly identified with “CLINICAL TRIAL APPLICATION”. Note:  CTAs that involve the use of pharmaceuticals and biologics must be submitted to the appropriate Lead Directorate in duplicate. Files A copy of the complete submission and any submission-related correspondence with Health Canada should be retained on file at the site.