July 23, 2006
Our file number: 06-116801-306
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Contact: OCT BEC Enquiries
This notice provides information on the Therapeutic Products Directorate's (TPD) and Biologics and Genetic Therapies Directorate's (BGTD) requirements related to the screening for tuberculosis (TB) of healthy volunteers involved in Phase I clinical trials involving immunosuppressant drugs or drugs with immunosuppressant properties.
Proposed clinical trial participants must have a normal physical exam and laboratory results within the normal laboratory limits. Protocols should contain criteria to exclude patients with latent or active TB, history or possible exposure to endemic areas, current or recent infections. To ensure such persons are excluded from participation in the trial, the sponsor must undertake the following prior to the commencement of the clinical trial:
Administer a standard TB Medical History screening questionnaire to each proposed clinical trial participant (see Appendix 1 for additional information).
When the half-life (t1/2) is known and the clinical trial involves the administration of a single or multiple doses of an immunosuppressant drugs or drugs with immunosuppressant properties, administer a TST to each clinical trial participant with a negative TB Medical History if the t1/2 is greater than 24 hours. If t1/2is not known, TST is required for all participants, unless justified by a rationale that is supported by the appropriate scientific evidence.
Repeat TST testing prior to each dosing period is not required for clinical trials involving more than one period of exposure (e.g., QTc study).
The TST positive threshold limit for the purposes of these screening requirements is 5mm induration. If the first TST is negative (defined as 0-4mm induration), further testing is not required. If the first TST test is positive (defined as 5+mm induration), exclude person from participation in the trial and refer to a specialist with expertise in TB for further investigation. Prior BCG vaccination should not be taken into account when interpreting the TST result.
(Source: Public Health Agency of Canada)
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If a participant has lived in or visited a country with high TB incidence, defined as one with a WHO estimated sputum smear positive pulmonary TB rate (3 year average) of 15 per 100,000 or higher, then there is a possibility that they were infected while there and it is too early for the TST to turn positive. Such participants should be excluded until at least eight (8) weeks have passed since they have left such a country and then a TB skin test is to be administered. If the TST is 5+mm induration, the participant is to excluded from the trial)