Once submitted, phase II and III CTAs and their amendments are subject to a 30-day default review period from the date of receipt by Health Canada. Health Canada also targets to review applications to conduct comparative bioavailability trials and phase I trials in healthy adult volunteers within 7 days (except those using somatic cell therapies, xenografts, gene therapies, prophylactic vaccines or reproductive and genetic technologies). Each submission is issued a control number and you will be requested to refer to this number in all correspondences. All CTAs and CTA-Amendments will be screened for acceptability, and deficiencies identified at screening will be addressed with sponsor. Due to tight deadlines with respect to review, requests for clarification issued usually as a fascimile must be answered in writing within 2 calendar days. After the review period, if the CTA is deemed acceptable, a No Objection Letter (NOL) will be issued within the review period. A Not Satisfactory Notice (NSN) will be issued if significant deficiencies are identified during the review of the CTA or if a timely response to the clarification request issued has not been provided. Prior to initiating or implementing a change to a clinical trial at a site, the proposed trial protocol and informed consent must be reviewed and approved by a qualified Research Ethics Board (REB). Amendments Sponsors must file a CTA-A when the proposed changes to the protocol: affect the selection, the criteria for selection, monitoring, or dismissal of a clinical trial subject affect the evaluation of the clinical efficacy of the drug alter the risk to health of a clinical trial subject affect the safety evaluation of the drug; or extend the duration of the clinical trial. Amendments are also subject to a 30-day default review.