An Evidence-Graded Framework for Pharmaceutical Route Selection and Process-Risk Prioritization: A PN6047 Case Study

Version v3. Language edit (Rubriq) merged selectively into the manuscript: American spelling, number formatting and comma edits only; no change to results, numbers or claims. A copy without line numbers is included for ChemRxiv. A literature- and document-based screening study. No synthesis was performed; no yield, impurity level, cost or timeline is predicted. Prepared for submission to the Journal of Pharmaceutical Innovation (Springer). The operations of the only publicly exemplified route to the drug substance of PN6047 (patent documents WO 2016/099393 and WO 2022/013153) are inventoried, each transformation and its conditions are graded A-D by the strength of public evidence, documented regulatory and hazard attributes are flagged, two process-oriented variants are screened, and a risk register is tested for the sensitivity of its prioritisation to the author-assigned ratings. The contribution is the reusable framework; PN6047 is the case study. Not claimed: that any proposed route works; any freedom-to-operate conclusion; any economic prediction. The author has no affiliation with the patent applicant. Code, data and analysis: https://github.com/sandlerleon/pn6047-route-design, archived at 10.5281/zenodo.23200725.