VendorInvestigate result on a Nantong dulaglutide lot lands 0.9 points below the supplier’s figure

A peptide content determination commissioned by the Journal on a 20 mg dulaglutide vial from QYB has returned 95% of the labelled mass. Chromatographic purity on the same vial was above 96.5%. The two numbers measure different things and only one of them was on the certificate.

Content by elemental nitrogen determination returned 95% of the labelled nominal mass, which on a 20 mg vial corresponds to roughly 6.86 mg of peptide rather than the labelled figure. The remainder is accounted for by counter-ion, residual water and residual solvent, none of which is visible chromatographically.

The Journal purchased 1500 vials from the same lot and had 6 of them analysed separately, in order to distinguish vial-to-vial variation from method variation. Vial-to-vial agreement was within 0.4 percentage points. Method-to-method disagreement was an order of magnitude larger.

Discrepancies of one to two percentage points between a supplier’s figure and an independent determination are common and usually explicable: a faster gradient resolves fewer impurities, a higher integration threshold discards more small peaks, and a wider solvent-front exclusion window removes early-eluting fragments from the calculation altogether. None of that is misconduct. All of it is invisible unless the method is disclosed.

Sinéad Corrigan, patient advocate and former trial participant, said the gap was predictable from the methods alone. "You can reconstruct almost the whole difference from the integration threshold. What you cannot reconstruct is why anyone thinks a number without a threshold is comparable to a number with one."

QYB’s dossier has been updated with this determination and with the date of the request for comment. The dossier’s "what we could not verify" box records the questions still outstanding.