99% of what? The case for comparability standards in oligonucleotide raw materials

Two suppliers quote the same LNA phosphoramidite. Both certificates of analysis show ≥99.0% purity with HPLC. Your CDMO switches to the new cheaper supplier, and three months later, the news arrives in the first in-process control samples after cleavage and deprotection, in the campaign that is meant to supply the clinical trial your peers are trusting you to supply and that your investors are funding. The ≥99.0% purity was never comparable. Each supplier runs its own synthesis route and its own release method, and your CDMO’s incoming goods method was built around the first route, not the second. Nobody reported a wrong number, but the two purity specifications were never measuring the same thing.