Forensic formulation fingerprinting of falsified medicine by Raman hyperspectral imaging

With the Medicrime convention (in 2010) and the European Parliament directive 2011/62/UE (in 2011), the notion of pharmaceutical crime appeared allowing effective, proportionate, and deterring sanctions against the falsifiers. However, to be able to apply these sanctions, the authorities must collect information allowing them to go up to the manufacturing sites. This is however extremely complex at a global scale. The opportunity to link several falsification cases is one more brick laid in building the investigation. Hyperspectral imaging is not a new analytical tool and has been used in many research papers some of them about falsified medicines. However, the time has come to re-evaluate its place in the suspect formulation workflow. From our point of view, after a formulation is confirmed falsified (or substandard) by a first line investigation (e.g. visual inspection, handheld Raman or colorimetric testing), hyperspectral imaging should always be performed when possible (solid pharmaceutical forms). Indeed, in a single imaging analysis, one may access qualitative, semi-quantitative and distributional homogeneity of organic and inorganic constituents of the formulation. These inform on the risk of taking the medicine but most of all it provides a unique fingerprint of the production allowing the linking of falsification cases. To illustrate this, six artémether/luméfantrine formulations (two batches of Combiart 20/120 and four batches of Coartem 20/120) have been analyzed for falsification suspicion. Handheld Raman spectroscopic analysis rapidly confirmed the falsification and possibly the absence of active compound. Once confirmed falsified, one tablet of each formulation underwent Raman hyperspectral imaging on the whole sample surface. A chemometric analysis of the spectral data revealed the presence of traces of two active compounds (sildenafil and ciprofloxacine chlorhydrate monohydrate) and the same excipients (organic and inorganic) in five formulations (2 Combiart and 3 Coartem) allowing us to link these cases.FakePhare; Vibra4Fak