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

SITUATION CMC comparability package for a site change arrived with a CRL citing manufacturing, not efficacy for labeling negotiator. That is a Pharma & Life Sciences CMC and Development Pathways decision on to drop a secondary in a 505(b)(2) program relying on literature plus a bridging study.

DECISION Labeling negotiator in a 505(b)(2) program relying on literature plus a bridging study must choose Proceed under protocol / Pause the pathway / Escalate safety review / Hold using CMC comparability package for a site change after a CRL citing manufacturing, not efficacy.

HYPOTHESES TO TEST 1. Authorize Proceed under protocol now; CMC comparability package for a site change already has the discriminator after a CRL citing manufacturing, not efficacy. 2. Keep Pause the pathway in force until CMC comparability package for a site change is completed after a CRL citing manufacturing, not efficacy for labeling negotiator. 3. Treat CMC comparability package for a site change as Escalate safety review because both readings appear after a CRL citing manufacturing, not efficacy. 4. Refuse a Pharma & Life Sciences close: labeling negotiator does not have the decision to drop a secondary turns on in CMC comparability package for a site change.

ANALYSIS REQUIRED 1. Map FDA-response timing and owner in a 505(b)(2) program relying on literature plus a bridging study. 2. Trace CMC, labeling, or pharmacovigilance facts in CMC comparability package for a site change after a CRL citing manufacturing, not efficacy. 3. Separate an isolated adverse event from a systemic quality issue. 4. For this Pharma & Life Sciences CMC and Development Pathways file, read CMC comparability package for a site change against a CRL citing manufacturing, not efficacy and write the one fact that would move to drop a secondary for labeling negotiator.

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 a CRL citing manufacturing, not efficacy). Lead with the Pharma & Life Sciences option CMC comparability package for a site change can support after a CRL citing manufacturing, not efficacy, then the two facts that force it, then the Monday action for labeling negotiator in a 505(b)(2) program relying on literature plus a bridging study.

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 labeling negotiator - Hypothesis scorecard against CMC comparability package for a site change: supported / rejected / untestable - CMC and Development Pathways finding in CMC comparability package for a site change that a second reviewer can re-perform - Missing page in CMC comparability package for a site change after a CRL citing manufacturing, not efficacy, if any