Other Technology Solutions » 

Technology can be a powerful asset in the fight against counterfeit medication. By boosting Drug Regulatory Agency (DRA) staff productivity, inter-agency communications and even decreasing unwitting consumer demand for counterfeit products, technology’s impact can be positive. However, as technology matures, costs decrease and know-how disseminates, allowing counterfeiters to manufacture even more sophisticated products, prompting the need for a continuous cycle of innovation. Let's look at the prominent technology solutions proposed for stemming fake drug trade. They can be grouped into three main categories, ranked by complexity:¹

• Direct Authentication
• Mass Serialization, Track and Trace
• Forensic, Chemical and Physical Tests

You can also go straight to a comparison of key technologies for developing nations.

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Direct Authentication » 

Direct authentication technologies use a feature incorporated in the product to easily discern genuineness. Such methods can be overt, like product packaging, to more complicated covert insignia, like watermarks and biologically-reactive holograms. Direct authentication technologies generally require no specialized methods or equipment to identify genuine products, and are thus often designed for end-consumers.

Distinct Packaging

The need for creative and safer product and packaging design has pushed manufacturers to explore new means of delivering their products to consumers. Today’s packages vary widely in form and function and can be protected via design patents. Tablets now come in a variety of non-trivial shapes. In addition to providing a distinct look, custom product design and packaging form a rudimentary authentication device – consumers associate a characteristic container with a certain company’s product or brand. The patented transparent Coca-Cola® bottle is a classic example: a dark drink in such a bottle may very well be taken for the real product upon sight, compared to a dark drink in a square bottle.

For drugs, the high start-up cost of uniquely-shaped tabletting molds could also serve as a hurdle to counterfeiters. However, with increasing global free trade with regions that may have lower enforcement of Intellectual Property (IP) rights and the continually decreasing cost of technology, advanced product packaging is no longer an effective anti-counterfeit method. Counterfeit products used to exhibit inferior packaging with typographical errors and no manufacturing addresses or expiration dates exceeding several years but this is a decreasing trend: the figure to the right shows a convincing counterfeit vial only 1 mm taller than the original.

Unfortunately, direct authentication is no longer a reliable means of catching fake drugs today. ↑ top

Diffractive Optical Elements (Holograms)

Introduced by Glaxo in 1989 on their Zantac® product, holographic packaging has grown to be a very popular means of assuring consumers of genuineness.² Holograms have appealed to manufacturers over the ages due to their relatively low cost, flexibility in manufacturing process integration and instant primary feature identification by consumers, with obvious branding advantages.

The most basic common hologram is a rainbow hologram. It generates a rainbow-like radiance by diffracting white light into the spectrum of visible light. Stereograms are rainbow holograms composed of a number of images arranged to provide an animation upon tilting. Newer dot matrix digital holograms are comprised of microscopic pixels, each in itself a hologram, that combine to produce one coherent holographic image.³ By altering the holographic recording medium, hologram designs can be integrated in transparent foils to produce distinct packing tape. Holographic designs can also be made on tamper-evident seals, protecting consumers from mal-handled or illegally-refilled products. Though the conventional means of generating a hologram is via lasers impinging on a recording medium, high resolution holograms are typically made by more precise electron beams (e-beams).

In general, holograms have two sets of security features: primary and secondary. The primary features consist of overt patterns, easily inspected by the naked eye. Such features include the general radiance of a rainbow hologram and intricate designs. Secondary (covert) features provide well-equipped authenticators with a means to obtain additional confidence of the hologram’s genuineness. This often entails the use of specialized readers like polarizing sheets, Ultra Violet (UV) radiation or chemical reagents. For instance, a newly commercialized hologram reacts to moisture, revealing a covert image – consumers can breathe onto the hologram to confirm a product’s genuineness.⁴

The success of basic holograms as an anti-counterfeit measure has degraded over time due to low-cost reproductive equipment and unregulated mass-suppliers available over the Internet. Jeff Allen, a holography pioneer asserts that:⁵

Another hologram security expert confirms this trend:

Counterfeiters are now applying knock-off holograms on their products, making it almost impossible for the average consumer to tell the difference between real and fake drugs. In some cases, counterfeiters even put holograms on fake products when the genuine versions have no holograms!

Clearly, we cannot rely solely on holograms to help keep the public safe from fakes. ↑ top

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Mass Serialization, Track and Trace » 

Mass serialization entails marking a large collection of individual items with unique codes as tags. These tags are then used to retrieve information on the product, typically from a centralized database. Under track and trace schemes, the location of a package can be determined via a record indicating the chain of delivery as the package makes its way from one point to another. The unique identifier facilitating this chain is the mass serialization mark. Track and trace is commonly used in commercial shipping.

Barcoding

One dimensional barcodes were not developed to fight counterfeiting. In fact, barcodes are of little use without electronic point of sale systems as is the case in smaller towns and villages in the developing world. Nevertheless, the presence of a barcode on a genuine product provides the consumer with additional assurance, as it is reasoned that only genuine products with wide circulation warrant the burden of Global Trade Identification Number (GTIN) and barcode acquisition. Such assurance can be misplaced as a simple 1D barcode can be photocopied, and checkout barcode systems will identify genuine and copied barcodes identically.

There are over 50 various 1D, 2D and 3D symbologies for barcode representation. In order to achieve global interoperacy, barcode reader manufacturers typically support just the leading symbologies. Out of this set, QR Codes and DataMatrix are the leading and most promising due to their widespread adoption, well-understood implementation costs and good error resilience

The increase in data storage and encryption capabilities developed for multi-dimensional barcodes have allowed for the intersection of mass serialization and barcoding. Thus, it is possible to represent GTIN codes as encrypted 2D barcodes for Auto-ID. It would still be necessary to incorporate anti-duplication technology in the barcodes as the encryption only masks the true GTIN number. Encrypted 2D barcodes with open standards linked to a centralized database could be a potent solution against counterfeiting in the developed world. It has been considered as an alternative to Radio Frequency Identification (RFID) for America’s national drug track-and-trace system (ePedigree), since the legislature only specifies the use of an “electronically readable” technology.

Radio Frequency Identification (RFID)

RFID technology uses tiny electronic tags to identify products using specialized readers that can operate at a distance. With the advancement of technology, including the development of RFID, the U.S. Food and Drug Administration (FDA) launched ePedigree as a renewed effort in requiring that drugs sold in the U.S. contain complete pedigree information. Although ePedigree doesn’t require RFID, it has been promoted to the fore of technologies available to solve the problem, primarily by the FDA.

RFID is designed to operate with Electronic Product Codes (EPC), which support item-unique coding. Thus, with a global mass-serialized RFID scheme, such as the Worldwide Track and Trace Bank (WTTB), products can be automatically tracked from raw materials to post-consumer waste. Such a system could also be used to fight product diversion and illegal parallel trade.⁶

RFID has hit some snags in its road to replacing barcodes. Chief concerns revolve around privacy, tag costs, complicated logistics and poor read rates. Innovative tag printing techniques using metallo-organic materials may address the tag cost issue by directly printing tag antennas on product packaging.⁷

As tag prices and read error rates decline, RFID could theoretically be implemented in developing nations. RFID readers could operate in areas with poor electrical supply by integrating them with cell phones which can be charged with automobile batteries connected to solar panels. Upon reading the EPC, the cell phone could interrogate a central database to retrieve the drug’s pedigree. The industry’s response is however not encouraging – though the first RFID phone kit was released in 2004, RFID-equipped mobile phones are still rare, despite predictions that up to 50% of mobile phones will be enabled with similar remote-sensing technology by 2009.^{8, 9, 10}

Since several developing nations are cash-based societies fraught with unreliable national power grids, deploying a nation-wide anti-counterfeit barcoding or RFID system is impractical, as it requires an efficient electronic trade backbone system. ↑ top

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Forensic, Chemical and Physical Tests » 

Forensic tests are designed to provide conclusive evidence via very sophisticated methods that can constitute evidence admissible in court. These tests can be expensive to administer, require well-trained staff and costly equipment not available or sustainable in a typical developing nation. However, chemical tests are the surest way of testing for sub-standard and counterfeit formulations. Such tests have to be carried out by manufacturers and Drug Regulatory Authorities (DRAs) regularly. Physical tests provide a cheaper yet effective alternative by utilizing the oft non-conforming manufacturing environment for fake drugs as a means of discerning authenticity.

Nano and Micro Structures, Taggants and DNA Coding

Taggants are uniquely-formulated microscopic objects covertly incorporated in products or their packaging. The assurance of security lies in the difficulty or cost-ineffectiveness in reverse-engineering taggant particles and the distinct decoding signatures they produce. Popular taggant products are often a proprietary combination of micron-sized, inert or rare elements, or fluorescent fibers. These items are either added to the packaging manufacturing process or sprayed onto the finished product prior to leaving the factory.^{11, 12} Taggant technology has its roots in plastics and explosives, thus taggants tend to withstand high temperatures used in making primary packaging products.

DNA techniques require a pair of complementary single strands of synthetic DNA to interlock as a double-helix structure, proving authenticity. The plurality of nucleotide combinations provides a wide array of possibilities for the lock and key DNA strands.

Verification occurs via readers – as simple as UV lamps and stereo microscopes to complicated synthetic DNA ink pens or “energy meters” that respond to proprietary florescence signatures or magnetic responses sent by taggants reacting to electric fields. The strong non-duplicable characteristics of these products offer a high level of protection if accompanied by effective regulator inspections.

Characteristic Surface Mapping

Improvements in laser scanning techniques now allow brand managers to uniquely identify products by imaging microscopic deformations on the surface of packages. The distinctive microscopic patterns are a result of minute manufacturing differences on a per-item basis. One can interpret such “natural randomness” as a product’s fingerprint. Surface fingerprints can be captured by measuring the speckle backscatter from an impingent laser beam scanned over the surface of interest. Upon rescanning the same section, a distinct spike (or the lack of it) in the cross correlation can indicate positive authentication (or otherwise). Whereas this method is generally resilient to reasonable surface fatigue, if the scanned section is not delimited or severely damaged, no authentication can take place. Developing nations typically offer a more challenging handling environment.

Laser surface mapping is very rapid, with some vendors claiming up to 300 scans per second. It also doesn’t require any modifications to products packaged with a flat surface. Being new, the technology’s efficacy is yet to be studied extensively.¹³

Chemical-induced Color-based Detection

Analytic chemical methods are the ultimate drug pedigree tests, in that they can determine with a high degree of certainty if a sample is truly as specified by a manufacturer. The tradeoff is typically high complexity, lack of equipment or trained professionals in deprived areas, cost and availability of supplies, and the need to tamper with medication. Chromatography and Spectrophotometry have become the de-facto tests under this category. The objective results from these methods can be compared to standards in national pharmacopoeia and other pharmaceutical compendia.¹⁴

Colorimetry is a much simpler method than chromatography. It involves observing distinct color changes with specific reagents based on the presence of a specific active pharmaceutical ingredient. Though this test is semi-quantitative, it can provide a basic “yes/no” response that can screen samples for further testing, saving resources.¹⁴ The “Fast Red TR” colorimetric test, a quick, simple and inexpensive test for assessing the authenticity of Artesunate anti-malarials, only requires Fast Red TR salt, sodium hydroxide, acetic acid and distilled water in small volumes. It can be carried out with equipment from a high school chemistry lab.¹⁵ Unfortunately, counterfeiters are catching on to such tests by adding fractions of the recommended amounts of active ingredients to fake drugs.

Hardness and Dissolution Tests

Hardness and dissolution tests can be surprisingly effective and cheap. Manufacturing processes need to be fine-tuned to obtain tablets of appropriate bioavailability. This can involve a significant research and development effort – something not of much interest to counterfeiters. Thus, though two pills may look alike, their dissolution profiles in solvents simulating the human gastric system could show a marked difference. By recording the percentage of dissolved medication over time, researchers have been able to show high selectivity in determining drug genuineness of common anti-malarials in seven African nations.¹⁶ Dissolution and hardness tests are essential since drugs that don’t dissolve in time could simply be passed out of the human system with little therapeutic benefit, irrespective of the percentage of active ingredient present.

Chemical tests, while very important, are typically not scalable in resource-constrained regions of the world. The equipment is typically expensive, and reagent supplies can be erratic. There is a need to have another tier of technology that's designed specifically for developing nations that can allow crowd-sourced anti-counterfeit intelligence to refine the scope of chemical test samples, thus saving money. ↑ top

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Comparison » 

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