This includes AEs for which the specificity or severity is not consistent with the description in the Investigator Brochure. For example, under this definition, hepatic necrosis would be unexpected if the Investigator Brochure only referred to elevated hepatic enzymes or hepatitis. 5.2 Reporting of serious adverse events associated with this study Each site PI will within 24 hours of notification of the event report all related or unrelated serious AEs occurring in patients enrolled at their respective study site to the Internal Review Board (IRB) of their site (see AE Reporting Algorithm, Appendix H). This will be accomplished by submitting an AE report memorandum to the IRB per the IRB’s site-specific standard operating procedures. The site PI will also, within 24 hours of notification of the event, forward a copy of the serious 38 Protocol: 2014-0443 Version 2.1 Version Date: 11 April 2016 adverse event report (CRF Form 3.1(g)) to the CRO Quality Assurance (QA) Officer or her designee, and to the CRO Regulatory Affairs Officer. In addition, the site PI will also follow the same reporting for all hypersensitivity events of grade 2 or greater in the primary series. The QA Officer or her designee will then forward the report to the Sponsor/Investigator. The Sponsor/Investigator or sponsor’s representative will review the serious AE to determine the need for expedited reporting to the FDA. If expedited reporting is required, the site nurse coordinator will be notified by the QA Officer or her designee to complete a FDA Form 3500 (MedWatch) (Appendix I). The Regulatory Affairs Officer will then submit the final report to the Sponsor/Investigator or Sponsor/Investigator’s representative who will report them to the FDA. 5.2.1 FDA Form 3500A (MedWatch) reporting guidelines In addition to completing appropriate patient demographic and suspect medication information, the report should include the following information within the Event Description (Section 5) of the FDA Form 3500A form (MedWatch): • Protocol description (and number, if assigned) • Description of event, severity, treatment, and outcome if known • Supportive laboratory results and diagnostics • Investigator’s assessment of the relationship of the AE to each investigational product and suspect medication Follow-up information: Additional information may be added to a previously submitted report by any of the following methods: • Adding to the original FDA Form 3500A (MedWatch) report and submitting as follow-up • Adding supplemental summary information and submitting it as follow-up with the original FDA Form 3500A (MedWatch) • Summarizing new information and faxing it with a cover letter including patient identifiers (i.e. D.O.B.