Busted! : Emerging Drug Anti-Counterfeiting Technologies

By: Jess Ebert, CIS Compliance Associate
jessicaebert@cis-partners.com

Over the years, pharmaceutical companies have sunk millions of dollars into anti-counterfeiting efforts, and yet counterfeit drugs still remain a prevalent (and growing) public health concern. Not only are consumers receiving medication that they believe is safe and effective, but harm can befall the manufacturers as well. Irreparable damage can be done to a company’s reputation due to a loss of brand integrity, leading to a significant loss of profits. An influx of costly returns and recalls can also be expected, further damaging company image and possibly resulting in consumer litigation. The World Health Organization (WHO) estimates that the black market for fraudulent drugs will be worth $75 billion by 2010. It is also estimated that 10% of drugs that enter the global supply chain are counterfeit (this figure rises to more than 25% in developing countries) [1]. Considering the effects that fraudulent medication can have on consumers and manufacturers alike, the question is, what anti-counterfeiting efforts does your company have in place, and how effective are they?

The statistics above are evidence enough to show that counterfeiters are able to get around many of the roadblocks the industry is throwing at them. With every new control, we see an increase in the sophistication and technical capabilities of counterfeiters. To give you a background on the types of problems counterfeits can cause, here are six categories into which fraudulent drugs can be placed:

• Products without active pharmaceutical ingredients (APIs)
• Products with incorrect quantities of APIs
• Products with the wrong ingredients
• Products with the correct quantities of APIs but with fake packaging
• Products with high levels of impurities and contaminants
• Copies of the original product made using unlicensed manufacturing processes

The products that contain the wrong chemical composition, impurities and/or contaminants can be easily identified using a variety of techniques including nuclear magnetic resonance (NMR) and infrared spectroscopy, thin layer chromatography, and X-ray diffraction. It can become more difficult to identify counterfeit drugs that have the correct chemical composition, and those that have packaging identical to that of the manufacturer [1]. The following techniques have been developed specifically to combat these issues.

Serialization
Packaging serialization is gaining a lot of momentum lately due to its effectiveness in preventing counterfeiting, as well as allowing traceability of products from the point of manufacturing to the pharmacy. Serialization refers to a unique code that is printed on the primary package or on the unit-dose tablet or capsule. The codes are “written” onto a radio-frequency identification (RFID) tag for tracking. The codes are then uploaded into a repository database that can be accessed by pharmacists, regulatory agencies, and even the consumer. It also serves as a resource for ensuring that returned product is legitimate, and for conducting recalls more efficiently [2].

It’s always wise to stay ahead of regulatory requirements and many agencies are requiring use of serialized bar codes for products, beginning in Turkey in 2010 and in France in 2011. California has instituted a similar requirement called the ePedigree law, which takes effect in January 2015, and requires that a unique mark be placed on each product’s package [2].

Surface Analysis Techniques
Surface analysis techniques have been become invaluable to the pharmaceutical industry, because not only can they identify counterfeit product, but they can also identify whether the product was manufactured using a licensed or unlicensed process. The following are two of the techniques that have been developed:

1. X-ray Photoelectron Spectroscopy (XPS) is a technique that provides detailed information through analysis of surface material. The information includes composition and empirical formula of a drug, and detects contaminants that are present on the surface.
2. Secondary Ion Mass Spectroscopy (SIMS) is a depth profiling technique that analyzes the surface, as well as sub-surface, of a material. Information about the chemical composition is revealed by analyzing ions produced from the material [1].

Not only is it important to identify the elements of a suspected counterfeit drug, but also whether a licensed process was used to manufacture it. Even if the drug contains the correct elements in the correct quantities, any deviation from the licensed process can prove fatal to patients. The techniques described above can detect the distribution of magnesium stearate, a lubricant commonly used in the manufacturing process. The difference in distribution provides information on how the tablet was manufactured; if it differs from that of the expected manufacturing process, a counterfeit can be detected [1].

Physical Chemical Identifiers (PCIDs)
In July 2009, the Food and Drug Administration (FDA) issued a draft guidance titled “Draft Guidance for Industry: Incorporation of Physical Chemical Identifiers into Solid Oral Dosage Form Products for Anticounterfeiting.” The document provides guidance to manufacturers on the addition of inks, pigments, flavors, and other identifiers to medications in order to make them more difficult to duplicate by counterfeiters.

According to the guidance, a PCID “is a substance or combination of substances possessing a unique physical or chemical property that unequivocally identifies and authenticates a drug product or dosage form.”

In addition to inks, pigments and flavors, which are easily detectable by wholesalers, pharmacists and patients, manufacturers can also add molecular taggants. Taggants can be physical or chemical markers added to materials to allow for specific testing and identification of the marked product. In these cases, specialized instruments and techniques are needed to detect the PCIDs (e.g., photolithography, laser scanning devices) [3].

The FDA anticipates that most of the chemical identifiers will be food additives that are currently in use and have established safety profiles. Safe as they may be, the FDA is still recommending that the lowest detectable level of PCIDs be used to minimize side effects in drug products [3].

Space Age Technology (literally)
In early September, a team of scientists from Perpetuity Research and Consultancy International (PRCI) and the University of Leicester’s Space Research Centre, revealed that they discovered a way to quickly identify counterfeit drugs [5]. The technology, which can detect the differences in the characteristics of light reflecting from printed packaging of drug products, was developed from a spectrograph originally designed for the Space Research Centre.[4].

“The unique light source incorporated within the systems and the selection of the critical points in the packaging at which the tests are conducted provides a degree of randomness that is not known to the counterfeiter and restricts the ability to be replicated.” Trials so far have produced a 100% success rate of detecting differences in printed packaging that the naked eye could not detect [4].

Counterfeiters have proven that they have the knowledge and resources to keep up with the obstacles that the industry throws at them. In order to protect consumers and company reputation, manufacturers must always strive to be one step ahead, and must constantly assess their anti-counterfeiting programs and their effectiveness. The above mentioned techniques are a good place to start!

[1]- http://www.pharmaquality.com/ME2/Audiences/dirmod.asp?sid=325598564E8C4B3EB736C7159241312D&nm=&type=Publishing&mod=Publications%3A%3AArticle&mid=D3E3C719D8D44216836DCA4F4144BEC4&tier=4&id=42EFE4778B8B431A96B18708EA8262ED&AudID=
[2]- http://www.verifybrand.com/brand-protection-news/pdfs/How-serialization-can-reduce-pharma-counterfeiting.pdf
[3]-http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM171575.pdf
[4]- http://www.medicalnewstoday.com/printerfriendlynews.php?newsid=163257