Assess whether to drop a secondary endpoint that will dominate the AdCom

SITUATION An FAERS cluster in a demographic the trials under-enrolled put CMC comparability package for a site change in front of regulatory-affairs lead in a safety team sitting on a new disproportionate signal. This Pharma & Life Sciences / CMC and Development Pathways close is to drop a secondary from CMC comparability package for a site change, and the live options are Proceed under protocol, Pause the pathway, Escalate safety review.

DECISION Regulatory-affairs lead in a safety team sitting on a new disproportionate signal must choose Proceed under protocol / Pause the pathway / Escalate safety review / Hold using CMC comparability package for a site change after an FAERS cluster in a demographic the trials under-enrolled.

HYPOTHESES TO TEST 1. Authorize Proceed under protocol now; CMC comparability package for a site change already has the discriminator after an FAERS cluster in a demographic the trials under-enrolled. 2. Keep Pause the pathway in force until CMC comparability package for a site change is completed after an FAERS cluster in a demographic the trials under-enrolled for regulatory-affairs lead. 3. Treat CMC comparability package for a site change as Escalate safety review because both readings appear after an FAERS cluster in a demographic the trials under-enrolled. 4. Refuse a Pharma & Life Sciences close: regulatory-affairs lead does not have the decision to drop a secondary turns on in CMC comparability package for a site change.

ANALYSIS REQUIRED 1. Separate an isolated adverse event from a systemic quality issue. 2. Test a protocol deviation versus a safety signal versus a filing gap on to drop a secondary. 3. Check whether CMC comparability package for a site change supports the labeled claim regulatory-affairs lead would keep. 4. For this Pharma & Life Sciences CMC and Development Pathways file, read CMC comparability package for a site change against an FAERS cluster in a demographic the trials under-enrolled and write the one fact that would move to drop a secondary for regulatory-affairs lead.

RECOMMENDATION Choose Proceed under protocol / Pause the pathway / Escalate safety review / Hold on this Pharma & Life Sciences / CMC and Development Pathways packet (CMC comparability package for a site change after an FAERS cluster in a demographic the trials under-enrolled). The follow-on CMC and Development Pathways action is what regulatory-affairs lead does next: implement the option, assign an owner, and log the missing fact.

COMMAND RETURNS - Bottom-line Pharma & Life Sciences option on to drop a secondary, then the evidence in CMC comparability package for a site change, then the action for regulatory-affairs lead - Hypothesis scorecard against CMC comparability package for a site change: supported / rejected / untestable - Owner and next date for regulatory-affairs lead in a safety team sitting on a new disproportionate signal - What changes to drop a secondary if an FAERS cluster in a demographic the trials under-enrolled is later withdrawn