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

SITUATION CMC comparability package for a site change arrived with a pediatric ethicist objecting to the proposed design. 505(b)(2) development lead in a mid-size sponsor after a complete response letter still has an evidence gap on whether to drop a secondary endpoint that will dominate the AdCom.

DECISION 505(b)(2) development lead in a mid-size sponsor after a complete response letter must choose Proceed under protocol, Pause the pathway, Escalate safety review, Hold using CMC comparability package for a site change after a pediatric ethicist objecting to the proposed design. The question on that file is whether to drop a secondary endpoint that will dominate the AdCom.

HYPOTHESES TO TEST 1. 505(b)(2) development lead can defend Proceed under protocol from CMC comparability package for a site change after a pediatric ethicist objecting to the proposed design in a Pharma & Life Sciences challenge. 2. 505(b)(2) development lead cannot defend Proceed under protocol from CMC comparability package for a site change; Pause the pathway is what the extract actually supports after a pediatric ethicist objecting to the proposed design. 3. A pediatric ethicist objecting to the proposed design never reached the population in CMC comparability package for a site change — reopen intake, do not close to drop a secondary. 4. Two facts in CMC comparability package for a site change after a pediatric ethicist objecting to the proposed design conflict for 505(b)(2) development lead; hold this Clinical and Evidence Strategy file.

ANALYSIS REQUIRED 1. Trace CMC, labeling, or pharmacovigilance facts in CMC comparability package for a site change after a pediatric ethicist objecting to the proposed design. 2. Separate an isolated adverse event from a systemic quality issue. 3. Test a protocol deviation versus a safety signal versus a filing gap on to drop a secondary. 4. For this Pharma & Life Sciences Clinical and Evidence Strategy file, read CMC comparability package for a site change against a pediatric ethicist objecting to the proposed design and write the one fact that would move to drop a secondary for 505(b)(2) development lead.

RECOMMENDATION Treat this reading of CMC comparability package for a site change as the gate for to drop a secondary: Trace CMC, labeling, or pharmacovigilance facts in CMC comparability package for a site change after a pediatr. If CMC comparability package for a site change after a pediatric ethicist objecting to the proposed design confirms that reading, 505(b)(2) development lead takes Proceed under protocol in a mid-size sponsor after a complete response letter. If CMC comparability package for a site change contradicts it, take Pause the pathway.