initial, patient number), protocol description and number, if assigned, brief adverse event description, and notation that additional or follow-up information is being submitted. (The patient 39 Protocol: 2014-0443 Version 2.1 Version Date: 11 April 2016 identifiers are important so that the new information is added to the correct initial report.) The CRO, IND sponsor or Galena Biopharma may contact the reporter for additional information, clarification, or current status of the patient for whom an AE was reported. For questions regarding SAE reporting, you may contact the Quality Assurance (QA) Officer. Study Drug Relationship: The Investigator will determine which events are associated with the use of study drug. For reporting purposes, an AE should be regarded as possibly related to the use of vaccine components if the Investigator believes: • There is a clinically plausible time sequence between onset of the AE and administration of vaccine components; and/or • There is a biologically plausible mechanism for vaccine components to cause or contribute to the AE; and • The AE cannot be attributed solely to concurrent/underlying illness, other drugs, or procedures. 5.3 Reporting requirements for IND holders For Sponsored IND Studies, there are some additional reporting requirements for the FDA in accordance with the guidance set forth in 21 CFR § 600.80. Events meeting the following criteria need to be submitted to the FDA as expedited IND Safety Reports according to the following guidance and timelines: 7 Calendar-Day Telephone or Fax Report: The Sponsor is required to notify the FDA of any fatal or life-threatening AE that is unexpected and assessed by the investigator to be possibly related to the use of the investigational product. An unexpected AE is one that is not already described in the Investigator Brochure for the vaccine. Such events are to be reported by the sponsor to the FDA and within 7 calendar days of first learning of the event. 15 Calendar-Day Written Report: The Sponsor is also required to notify the FDA and all participating investigators, in a written IND Safety Report, of any serious, unexpected AE that is considered reasonably or possibly related to the use of the study agents. An unexpected AE is one that is not already described in the Investigator Brochure for vaccine. • Written IND Safety Reports should include an Analysis of Similar Events in accordance with regulation 21 CFR § 312.32. All safety reports 40 Protocol: 2014-0443 Version 2.1 Version Date: 11 April 2016 previously filed with the IND concerning similar events should be analyzed and the significance of the new report in light of the previous, similar reports commented on. • Written IND safety reports with Analysis of Similar Events are to be submitted to the FDA and all participating investigators within 15 calendar days of first learning of the event. The FDA prefers these reports on a FDA Form 3500A (MedWatch) but alternative formats are acceptable (e.g.