Regulatory Open Forum

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  • 1.  Updated Investigator Brochure

    Posted 07-Apr-2022 13:16

    RAPS email.

    Hello RAPS collective wisdom!

    I have questions about communicating to Health Canada with respect to an Investigator's Brochure (or Canadian Product Monograph, or US Package Insert, used as the "IB").

    The project has an active CTA with Health Canada (HC). The need to communicate with HC has been low – no amendments or other notifications (yet). Per HC CTA guidance about IB updates:

    In accordance with ICH GCP, the IB, including all safety information and global status, should be reviewed at least annually and revised as necessary.  More frequent revision may be appropriate depending on the stage of development and the generation of relevant new information.  If the sponsor is planning to submit a CTA, or planning or required to submit a CTA-A or CTA-N, the updated IB should be submitted with the application.  Otherwise, the updated IB should be submitted separately as a CTA-N, and include a statement confirming that the protocol and/or ICF of all ongoing trials do not require changes as a result of the updated IB.  In all cases, the updated IB should be accompanied by a list of changes that clearly describes the sections that have changed, including a rationale for each change.

    All this is fine, but I note that within this text there is no guidance on what to do if there are "no changes" to the IB and we have no other communications planned. Does one send a "stand alone" Notification (email) to HC stating "no change"? Why?

    Further, what if we were using an approved, Canadian marketed drug? In this case we would usually use the Canadian Product Monograph as the "IB". And since we are not the drug's manufacturer, we don't control the PM. Do we review HC's drug product database for an updated PM? Yes, we do this.

    But again as above, what if there is no change/update? Does one send a "stand alone" Notification (email) to HC stating "no change" in the PM? Why, especially given that HC already knows (has access to) the PM and would know that there is no change?

    Finally, same scenario and question as the Canadian Product Monograph, but with a US marketed drug. We import the US drug into Canada for our study (there is no comparable drug version approved in Canada; e.g. pediatric doses approved in USA but not Canada). We are using the US Package Insert as our reference/safety information. We are not the drug's manufacturer, so we don't control the package insert. Yes, we review yearly for an updated package insert.

    Thanks for all your help.


    David Jensen PhD, RAC
    Regulatory Affairs Scientist
    Durham NC
    United States

  • 2.  RE: Updated Investigator Brochure

    Posted 08-Apr-2022 08:07
    Hi David,

    If there is no change in the product information, regardless of the various scenarios you present, there is no need to notify HC that no changes have occurred.

    Glen Park PharmD
    Vice President, Regulatory Affairs and Quality Assurance
    New York NY
    United States

  • 3.  RE: Updated Investigator Brochure

    Posted 08-Apr-2022 10:29
    Agree w/Glen, if no changes just state no changes to the IB. Do you submit DSUR report annually? If so you need to address IB update question in this report annually!


  • 4.  RE: Updated Investigator Brochure

    Posted 08-Apr-2022 17:54
    I agree with the above and add that your SOP on IB generation (hopefully you have one) clearly includes the requirement for IB annual review. Make certain  that you have objective evidence (documentation) that an annual review of the IB was conducted and no IB revision was required. An IB revision should be determined by your lead clinical representative (CMO, VP clinical development or lead medic for the project) or however your organization is organized after discussions with your toxicologist, CMC, etc to ensure all aspects of the IB are considered in the annual review process. 



    Darlene Rosario MBA, RAC
    Principle Consultant
    Ventura CA
    United States