Uncovering fake drugs with NIR
useful new tools for the detection of counterfeit medicines, to
complement their existing role in active ingredient detection and
process control.
Near infrared (NIR) spectroscopy and microscopy are emerging as useful new tools for the detection of counterfeit medicines and can even identify batches manufactured at different sites in the same company.
This is the preliminary conclusion of an ongoing collaboration between Pfizer, the UK Medicines and Healthcare products Regulatory Agency and the London School of Pharmacy, which was presented this week at the annual British Pharmaceutical Conference in Harrogate.
Pfizer's involvement in the project came about in part because it manufactures the erectile dysfunction drug Viagra (sildenafil), one of a number of so-called 'lifestyle' drugs for which a thriving counterfeit trade has sprung up.
When suspected counterfeit medicines are seized by regulatory bodies, they are either submitted to the manufacturer for confirmation of authenticity or, in the UK, to the Medicines Testing Laboratory for analysis, according to the London School of Pharmacy's Nicola Wilson.
Current approaches to this testing are cumbersome and time-consuming, based on separation techniques such as gas chromatography and high performance liquid chromatography (HPLC), analysis of residual solvents, or testing for the presence of the active ingredient and determining its quantity, she said.
Using NIR reflectance spectroscopy, tablets originating from different sites of manufacture can be distinguished from each other, and initial studies have demonstrated that the approach can reveal counterfeit Viagra from the authentic product.
"NIR spectra representative of the authentic product are stored in a library database to which unknown samples could be compared using chemometric methods of analysis," according to Wilson.
One of the primary benefits of NIR is its rapid scan time and the fact that it does not require either skilled personnel or sample preparation to acquire the data. The partners in the collaboration now hope to make the technology even more useful to regulatory enforcers, by developing a portable NIR spectroscopy instrument that would allow rapid detection of counterfeit tablets in situ.
NIR microscopy
Turning to the relatively new technique of NIR microscopy, Wilson noted that this has already been applied to tablets and blends for the purposes of process control.
Indeed, NIR has become an established method of testing for actives in pharmaceutical products, particularly now that the European Medicines Evaluation Agency has drafted a guideline on the technique. However, its use has tended to be limited to those products containing high levels of active ingredient (i.e. more than 50 per cent w/w).
Using this approach, a small area of the tablet (typically 30 microns across) is scanned to produce a single NIR spectrum from which an image map is created. Once again, this can be compared to a reference database.
"Often counterfeit products are sophisticated, containing the active ingredient in similar amounts to the authentic medicines," said Wilson. Clearly, this means that simply testing for the presence or absence of the active alone is insufficient, she added.
The use of NIR microscopy would allow for not only the identification of individual components in a product, but also determination of their relative distribution and percentage composition, all of which can be compared to the properties of the genuine product.
Wilson concluded: "It is likely that NIR techniques of analysis will play a useful role in supplementing existing techniques used to identify and verify counterfeit products."
Assay use
Meanwhile, in another presentation at the BPC, two researchers at GlaxoSmithKline Consumer Healthcare - W L Yoon and R Almond - describe a statistical technique by which NIR's sensitivity can be enhanced to such an extent that it can be used to assay an active ingredient at just 0.3 per cent w/w. The data-pretreatment method, called orthogonal signal correction, provided a leap in accuracy, validated using HPLC.
One of the major concerns held by regulators of the validity of NIR technique is that there is still too little understood about the statistical parameters used for calibration purposes, with the overall procedure considered more of an art than a science.
