According to the WHO definition, a counterfeit is a medicine which is deliberately and fraudulently mislabelled with respect to identity and/or source. Counterfeiting can happen in both branded and generic products and counterfeit products may include products with correct ingredients or with wrong ingredients, without active ingredients, with insufficient active ingredients or with fake packaging.
A marginal phenomenon just a few years ago, counterfeit has now become a global problem affecting all countries in the world. Anti-diabetic traditional medicine contained six times the normal dose of glibenclamide was reported in China. Metakelfin (antimalarial) lacking sufficient active ingredient was discovered in 40 pharmacies in United Republic of Tanzania. Xenical (for fighting obesity) contained no active ingredient and sold via Internet sites operated outside the USA. Viagra & Cialis (for erectile dysfunction) were smuggled into Thailand from an unknown source. Both, Zyprexa (for treating bipolar disorder and schizophrenia) and Lipitor (for lowering cholesterol) lacked sufficient active ingredient which were detected in the legal supply chain in UK. Counterfeit versions of Serostim (growth hormones) and Nutropin (cancer drug) have been found in the US. A substandard counterfeit growth hormone also has been found in Europe, and in Asia, one report cited an estimate that 90% of Viagra sold in Shanghai, was counterfeit. Death of dozens of children reported in Haiti and Nigeria was due to counterfeit medicinal syrups that contained diethylene glycol. A multinational survey of fake anti-malarias in Southeast, found that none of the 188 tablet packs labelled 'artesunate' contained any artesunate, and 9% of the mefloquin samples analyzed contained <10% of the expected amount of the active ingredient. The WHO has estimated 25% of medicines in developing countries are counterfeit, with a figure as high as 50% in some places, and that malaria, TB, and HIV/AIDS drugs are most counterfeited.
The financial consequence of drug counterfeiting also pose a hazard to the pharma industry because it constitutes theft of an innovator’s IP and of business from other authorized manufacturers. The loss of revenue in the global pharma industry as a result of counterfeiting is estimated to be in the billions of dollars per year. Actually, medicine counterfeiting is much more of a threat to public health than to company revenues. Recognizing the magnitude of the issue, health authorities at national, regional and international levels are trying to fight against this scourge using various strategies including the setting-up of effective quality control that need to be reinforced through generic, fast and specific detection methods.
Innovations in packaging
Innovations in packaging technology have come to play an important role in helping the consumer identify the authentic products. Pharma manufacturers try to prevent or discourage counterfeiting as much as possible by making products and packaging that are difficult to copy. Various authentication systems for packaging are available; however, determined counterfeiters can steal or copy these systems as well.
At present, drug counterfeiting is becoming more and more sophisticated. The growing circulation and variety of counterfeit medicines all over the world forces analysts to design different methods to recognize fakes. As counterfeit medications are imitations of their authentic counterparts so that analysis of both physical (as crystal form, particle size or morphology, and thermal behaviour) and chemical (an impurity profile and excipient identity) properties helps to discriminate between them. One or more properties may serve as a 'fingerprint' for a given manufacturer’s product. Analytical profiles, including major and minor components, impurities, and isotopic ratios, have been used as fingerprints to determine the source of illicit drugs. Analytical methods like gas chromatography (GC), high-performance liquid chromatography (HPLC), mass spectrometry (MS), Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRPD), thermal gravimetric analysis (TGA), microscopy, and various other forms of chromatography have been used to check for fake.
XRPD is well established as a key analytical tool in the pharma industry. Now new developments, such as ultra-fast X-ray detectors, make the technique a powerful tool for quality control. XRPD analysis of tablets in intact packaging is a non-invasive technique that provides high quality information on the structure and composition of materials. Analysis can now be conducted, through even fully opaque blister packs. This allows effective, quick and reliable screening. High throughput is achievable with latest generation systems. This innovative method for monitoring drug quality can be used to differentiate between authentic drugs and counterfeit products.
Balayssac et al. outlined the capability and applicability of Nuclear Magnetic Resonance (NMR) spectroscopy in screening counterfeit herbal medicine. Diffusion ordered spectroscopy (DOSY) NMR method allows precise analysis of complex mixture without any prior separation of different components. This method does not require complicated setups and method can be easily standardized and automated, and non destructive nature of NMR is added advantage. DOSY NMR spectra clearly show similarities and differences in the compositions of pharmaceutical preparations and giving chemical fingerprint of the preparation and signature of the manufacturer. This spectral signature includes not only active pharmaceutical ingredients but also the excipients.
Raman spectroscopy offers a rapid, sensitive and non-destructive technique for screening of counterfeit pharmaceuticals. Hand-held Raman instruments offer the advantage of carrying the laboratory to the sample and giving a rapid pass or fail answer for the suspect product. It can identify pharma preparation regardless of its physical form. However, technique is limited as not all species of the medicine have a Raman scattering. Also there is a variation between Raman signal using hand-held and lab instruments. It is reported that transmission mode gives better scattering than reflectance mode in lab based instruments. Therefore, it is better to use the hand-held instrument initial screening, and then further analysis could be made on suspect using lab based instruments.
Near infrared (NIR) spectroscopy is ideally suited for screening counterfeit medicines because it is non-destructive, fast, require no sample preparation and provide a fingerprint of the physical and chemical composition of a product. The counterfeiter must not only strive to get physical characteristics of the product the same as the authentic product but also the chemical makeup: same API and excipients at the same concentration. Thus counterfeit products are comparatively easy to screen by NIR spectroscopy, which can detect both physical as well as chemical differences between products. NIR equipment is now widespread among analytical laboratories, as spectrometers have become cheaper and more reliable. On-site usage of inexpensive portable NIR spectrometers is feasible. Regulatory agencies around the world are beginning to use NIR spectroscopy to screen for counterfeit medicines entering their country or for surveillance operations. Olsen et al. has been demonstrated the potential for NIR as a rapid screening tool to detect counterfeit drug products using Prozac and generic fluoxetine hydrochloride products as examples.
Analytical methods that provide most information on excipients composition are solid state methods such as Raman spectroscopy, NIR spectroscopy, XRPD, and NMR spectroscopy where as chromatographic methods provide an accurate identification of active ingredients but do not provide information on excipients, also time consuming and labour intensive, and they cannot generally be used for screening analysis. Analysts therefore have to design special methods to be a part of their ‘analytical toolbox’, which are simple, sensitive, rapid, and can be applied directly on site and face the challenge of the modern counterfeit market.
(Dr. Rashmin B. Patel is with AR College of Pharmacy & GH Patel Institute of Pharmacy, Vallabh Vidyanagar 388 120. Prof. BG Patel is with Institute of Science & Technology for Advance Studies & Research, Vallabh Vidyanagar and Mrunali R Patel is with Indukaka Ipcowala College of Pharmacy, New Vallabh Vidyanagar 388 121).