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  • 1.  Labeling non-investigational drug for clinical trial

    Posted 17-Aug-2015 13:47

    For our US clinical trial, our investigational drug may cause nausea or vomiting, therefore we also plan to administer to all patients an antiemetic.  We are considering either repackaging the antiemetic or simply providing in the commercially approved packaging.  My questions follow.

                                                                                                                                                                                  

    1.         If we repackage, would any quality documentation need to be submitted for the antiemetic? And would we in this case also have to submit labels for the antiemetic?

     

    2.         If no repackaging is done, would we need to submit any labels for the antiemetic? e.g. if only a small label is used that does not cover any of the original information on the commercial packaging?

     

    Thank you in advance for any feedback from those who have been involved in a similar scenario.

     

    Tom Stothoff

    Regulatory Affairs

    Lundbeck LLC

     



  • 2.  RE: Labeling non-investigational drug for clinical trial

    Posted 18-Aug-2015 08:42

    Hi Tom.

    Without completely running this through all of the requirements here are my "knee-jerk" reactions to both these questions:

    First, if you do anything to the original packaging of the commercially available product I would think you would then become responsible for the product that ultimately leaves your warehouse.  So yes, you would be responsible for quality issues such as microbiological purity and potentially even stability since you will be changing the environment in which the product was originally packaged and for which the owner has stability information. 

    Second with respect to the labeling, you are going to need to provide sufficient information for the product to be used safely.  If this is an Rx antiemetic then you really need to provide the subject with sufficient information to make an informed choice of whether or not to participate in the study as well as ensuring that your co-op medical personnel provide sufficient information on dosing for the trial.  If the antiemetic is OTC, you really need to provide whatever the labeling states.  As I understand the rules, that is the entire point behind OTC - a product is for a condition that is self-limiting and able to be self-diagnosed and the product labeling can be written such that a layperson can be able to safely and effectively use the product to treat said condition.

    Some other things to consider in this study design since you are adding additional products:

    1. You really need to understand the profile of the antiemetic for AE's.  You also should ensure that your protocol calls for either requiring all subjects to take the antiemetic regardless of which treatment arm they are assigned to or to really understand what the antiemetic safety profile is so as to understand what AEs might be linked to the antiemetic and which are likely linked to your product.

    2. Obviously your informed consent for the project will require that the subject be made aware of the fact that the product may cause GI issues and that they are being given an antiemetic along with the study drug to counteract that possibility.  You also need to account for the antiemetic product in your screening process for the study.  This is especially true for allergenic reactions....

    3. You at least theoretically can provide the labeling in truncated or non-identifiable form especially for an OTC antiemetic simply by typing the Drug Facts Box information up and providing it to the subjects.

    4. If you decide to provide a "placebo" antiemetic for the placebo testing arm you need to consider how that might impact your data because you will have the confounding situation of essentially 2 different products in the test arm with 2 placebos in the placebo arm.

    5. You need to understand the potential issues of using an antiemetic essentially without need in your placebo arm.  For your test arm where you have data that shows a potential for nausea the antiemetic will help rather than hinder the majority of your subjects.  However in the placebo arm the antiemetic could potentially harm a subject depending on the mechanism of action.

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    Victor Mencarelli
    Sr. Manager - Regulatory Affairs
    United States
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    Original Message


  • 3.  RE: Labeling non-investigational drug for clinical trial

    Posted 19-Aug-2015 15:15

    Thank you Victor for your thoughtful feedback.  The antiemetic is prescription and there is no placebo-arm in the study (I should have mentioned this).

    Thanks again

    Tom

     




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  • 4.  RE: Labeling non-investigational drug for clinical trial

    Posted 20-Aug-2015 09:40

    Please make sure your IND reflects the fact that you are co-administering or recommending the co-administration of another drug. Your IND - and the protocol and consent that are included there - should also include how you are providing it. If not, an IND Amendment should be considered.

    Here is a link to FDA investigational guidances:  http://www.fda.gov/RegulatoryInformation/Guidances/ucm122046.htm
    Here is a link to CDER's Small Business Office; they get questions like this all the time: http://www.fda.gov/Drugs/DevelopmentApprovalProcess/SmallBusinessAssistance/   301-796-6707, CDERSmallBusiness@fda.hhs.gov.

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    Andrea Chamblee RAC, FRAPS
    This information is provided in my capacity as an FDA and compliance professor at Johns Hopkins and George Washington universities, and does not represent official FDA current thinking.
    Silver Spring MD
    United States
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    Original Message