41 6.3 Toxicity Criteria ............................................................................................................. 43 7 SAFETY REPORTING REQUIREMENTS/DATA AND SAFETY MONITORING PLAN 43 7.1 Definitions ...................................................................................................................... 43 7.1.1 Adverse Event ......................................................................................................... 43 7.1.2 Suspected adverse reaction ..................................................................................... 43 7.1.3 Unexpected adverse reaction .................................................................................. 44 7.1.4 Serious..................................................................................................................... 44 7.1.5 Serious Adverse Event ............................................................................................ 44 7.1.6 Disability ................................................................................................................. 44 7.1.7 Life-Threatening Adverse Drug Experience ........................................................... 44 7.1.8 Protocol Deviation (NIH Definition) ...................................................................... 45 7.1.9 Non-compliance (NIH Definition) .......................................................................... 45 7.1.10 Unanticipated Problem............................................................................................ 45 7.2 NCI-IRB Reporting ........................................................................................................ 45 7.2.1 NCI-IRB Expedited Reporting of Unanticipated Problems and Deaths ................. 45 7.2.2 NCI-IRB Requirements for PI Reporting at Continuing Review ........................... 45 7.2.3 NCI-IRB Reporting of IND Safety Reports ............................................................ 46 7.3 IND Sponsor Reporting Criteria .................................................................................... 46 7.3.1 Reporting Pregnancy ............................................................................................... 46 7.3.2 Paternal exposure .................................................................................................... 47 7.4 FDA Reporting Criteria .................................................................................................. 47 7.4.1 IND Safety Reports to the FDA (Refer to 21 CFR 312.32).................................... 47 7.4.2 FDA Annual Reports (Refer to 21 CFR 312.33) .................................................... 48 7.4.3 Expedited Adverse Event Reporting Criteria to the IND Manufacturer ................. 48 7.5 NIH Office of Science Policy (OSP)/Institutional Biosafety Committee (IBC) Reporting Criteria ...................................................................................................................................... 48 7.5.1 Serious Adverse Event Reports to OSP/IBC .......................................................... 48 7.5.2 Annual Reports to OSP/IBC ................................................................................... 49 7.6 Data and Safety Monitoring Plan ...................................................................................