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Analytical detection techniques help combat counterfeit drugs.
Pharmaceutical manufacturers can choose from a variety of anticounterfeiting technologies to deal with the ever-growing problem of counterfeit drugs in the supply chain. FDA and industry experts recommend a layered approach to protecting the integrity of the supply chain, which combines technologies for antitampering, serialization, and authentication (in the form of overt, covert, or forensic features) applied to the packaging or dosage form. Analytical detection methods can confirm the authenticity of a drug product by using technologies such as portable spectrometer-based readers that authenticate in the field, thin-layer chromatography kits that quickly verify the presence and amount of active pharmaceutical ingredient (API), or analytical laboratory screening services that offer extensive testing of packaging and finished dosage forms for counterfeits.
PHOTO COURTESY OF TRUTAG TECHNOLOGIES
TruTag Technologies in Honolulu developed an anticounterfeiting solution in the form of a covert silica microtag that is edible, economical, heat resistant, and can be mixed into a coating, dye, or ink. The microtag is encoded with a spectral pattern chosen from a library of up to a trillion unique patterns, Peter Wong, chief operating officer of TruTag Technologies, explains. "Therefore, our microtag is like a covert, 'edible barcode' and is as flexible a business tool as a traditional printed barcode," he says. The company's product was recently recognized as a promising new technology for anticounterfeiting by winning "Most Likely to Succeed" in the life sciences category at the Launch: Silicon Valley 2011 competition, an event focused on identifying emerging technology startups.
The microtags, which can be applied to a solid dosage form or to packaging components, are authenticated using a portable spectrometer-based optical reader. Wong says the company has received "quite a bit of interest" in applying the microtags to bulk API and are open to testing with an interested partner. TruTag's portable readers can confirm the authenticity of the product through a clear blister pack, so the product does not have to be destroyed. The microtags can also link to additional information stored in a manufacturer's database, such as e-Pedigree and track-and-trace systems.
Wong says that in the company's development work, the application of the microtags has been relatively straightforward. TruTag was able to combine small quantities of microtags with a tablet-coating mix, which was then sprayed onto solid oral dosage forms using standard industry pan coaters. Because silica (silicon dioxide) is a generally-recognized-as-safe (GRAS) material, says Wong, under the framework of FDA's draft guidance, Incorporation of Physical-Chemical Identifiers into Solid Oral Dosage Form Drug Products for Anticounterfeiting (1), the agency's filing process may be as simple as including the addition of TruTag microtags as an annual reportable change if the product already had silica as an ingredient, or require a CBE-30 supplement if silica is a new ingredient to the product.
Thermo Fisher Scientific in Wilmington, MA, offers several lightweight, handheld spectrometers designed to rapidly verify the identity of both raw materials and finished products. The company's TruScan and TruScan RM analyzers are based on Raman spectroscopy, and the microPHAZIR RX provides Near-Infrared (NIR) analysis. The analyzers are designed to support 21 CFR Part 11 compliance. No extensive training is required for operation, and the devices offer a simple pass/fail result by using proprietary algorithms for comparing authentic references with samples. Nondestructive testing can be done through clear packaging materials and can quickly identify substandard materials and drugs.
Pharmaceutical companies and regulatory agencies use the devices to verify raw materials and finished products, according to Duane Sword, senior director of strategic growth of Thermo Fisher Scientific's portable optical analysis business. "This method provides a more significant deterrent to counterfeiters since security measures based on packaging are often easily replicated by counterfeiters, whereas imitating the exact chemical formulation of a product is extremely difficult (and not cost-effective for counterfeiters)," he says.
Advanced analytical services
Another way that a drugmaker can identify counterfeits in the supply chain is by using the services of an analytical laboratory. Manufacturers send a sample of suspected product for testing, and the medication and the packaging can be analyzed.
Using Intertek's nuclear magnetic resonance spectroscopy (NMR) services, for example, can determine whether the API is present, and if present, at what levels. These results can show whether the sample is "a genuine attempt to make a copy or simply a mock product with no intent to contain an active ingredient," says Phil Norman, vice-president of Intertek Chemicals and Pharmaceuticals Division, based in Manchester, UK. This information, says Norman, can indicate the sophistication of the counterfeit and also helps the drug manufacturer make important decisions relating to public safety. "The investigation can also reveal if the packaging is not consistent with the reference product and potentially provide a rapid option for screening out counterfeits from the marketplace," he says.
Sample investigation uses a range of analytical detection technologies, such as spectroscopy (NMR, Fourier transform infrared, NIR, and Raman); liquid chromatography–mass spectrometry; gas chromatography–mass spectrometry; and microscopy, depending on what is the best approach for the manufacturer's specific problem. This type of advanced screening is typically used in specialized cases where a high level of detailed analysis is required, Norman says. "These laboratory investigative techniques are not an alternative to portable analytical detection devices, rather they offer options for clients who require that further, more detailed step, in obtaining data to confirm that a sample is counterfeit," he says.
Examples of these situations, he says, include cases where authorities have seized product as it is imported into a country, as well as where non-governmental organizations have sourced medicines from online pharmacies as part of their own investigations, which show a high proportion of counterfeits. "It is concerning to observe that a proportion of samples arriving at Intertek laboratories for investigation have come from legitimate supply chains," he says.
Counterfeiters are hard at work finding ways to replicate, trick, mimic, and dodge each new technology that stands in their way. Drug companies must continue to fight back with constant vigilance and new security methods to protect the pharmaceutical supply.
"The rising number of counterfeit drugs reaching even legitimate distribution channels coupled with the increasing sophistication of these copies, means that reliable and advanced analytical detection is a key part of a drug manufacturer's overall strategy to combat this problem," Norman says.
Combining anticounterfeiting measures designed to prevent counterfeits from reaching consumers such as anti-tamper packaging and overt authentication features, a robust serialization system, and technologies that detect the presence of adulterated and substandard medicines, drug manufacturers can work to protect their supply chains, brands, and customers.
Alexis Pellek is the custom digital content manager for the pharmaceutical group of Advanstar Communications and is a regular contributor to Pharmaceutical Technology.
1. FDA, Incorporation of Physical-Chemical Identifiers into Solid Oral Dosage Form Drug Products for Anticounterfeiting (Rockville, MD, July 2009).
Detection of counterfeits in developing countries
One solution for detecting counterfeit pharmaceuticals in developing countries is the use of thin-layer chromatography (TLC) methods. The World Health Organization estimates that potentially more than 30% of pharmaceuticals in developing nations could be counterfeit. Portable TLC kits are economical, do not require extensive training for use, and allow for rapid screening of product in the field (1). An example of such a portable laboratory is the GPHF-Minilab, which was developed by the Global Pharma Health Fund (GPHF), a charitable organization funded by Merck KGaA.
Thomas P. Layloff, PhD, senior quality assurance advisor for the Supply Chain Management System, part of the President's Emergency Plan for AIDS Relief, explains the advantages of TLC in protecting consumers from counterfeit pharmaceuticals. "The use of TLC to determine whether the right drug is present in approximately the right amount is very widespread because of ease of application, sustainability, low cost and very minimal support infrastructure required. For example, more than 300 GPHF TLC-based Minilabs have been sold and put in use all over the world. The Minilab technology requires no laboratory facilities or electricity; detection is based on visual comparisons. Since the TLC plates are single use, there is no maintenance of the chromatographic media."
Other technologies, he says, are more expensive and require more training but are also more accurate. A limitation of TLC, for example, is that "cogeners of the parent drug cannot be discerned by the technology, but fortunately these types of counterfeit products are expensive to manufacture and they occur in the high-cost markets such as the United States," he says. "The TLC stands out for speed and cost but there is a tradeoff in the ability to detect sophisticated counterfeit products."
To read the full Q&A with Layloff, see the expanded version of this sidebar.
1. J. Sherma, Acta Chromatographica, 19, 5–20 (2007).