Packaging is the sound requirement for any type of protection to the dosage form. A counterfeit medicine is one which is purposely mislabeled in accordance to identity and/or source and passing it off as the genuine product. The counterfeit drugs are the major cause of morbidity, death and failure of public interest and confidence in health care systems. The high priced medicines and well known brands make the Pharma market most vulnerable. According to the international regulatory body near about 75 percent of fake drugs are marketed in India and China. Cardiovascular, obesity, Antihyperlipidemic and sildenafil are top priority drugs for the counterfeiters. Packaging may include the Overt, Covert, Forensic and Track and Trace technologies like, holograms, barcodes, tamper evident, Taggants and RFID to preserve the integrity of the pharmaceutical product. Recent developments in the analytical techniques and even the photographic film also help in deterring the counterfeit by identifying the high color resolution. But still on today all of techniques available are synthetic and has strengths and limitations to beat it, which can be overcome by natural and nanotechnology applied techniques.
Keywords: Packaging, Counterfeit drugs, Overt, Track and Trace, Nanotechnology.
1. Introduction to packaging
Packaging is a link connecting production with marketing and goods will reach from the production center to the consumers in a safe and sound condition and with minimum overall cost [Devi et al., 2007]. Packaging can also be defined as the coordinated system which can enclose or protect the products for distribution, storage, preservation, transportation, information and sales [Soroka, 2002].
1.1 Packaging as a means for anti counterfeit
The products having the domination in the form of security, easily produced, high priced and desirable brands are targeted the most [Nitin Shukla, 2009]. This makes Pharma sector the most vulnerable. Counterfeit is a problem of product security. Product that is for example, sidetracked from its suitable distribution channel, or sold past its date, or by modification of the package is associated with the problem of counterfeiting [Carl olsmats, 2002], [Dr. Rajiv Dhar, 2009].
2. Introduction to counterfeiting
Counterfeits are reproductions of a trademarked brand, which are closely similar or identical to genuine articles [Cordell et al., 1996], [Ian Phau, 2009]. The first international meeting on counterfeit medicines was held from 1 to 3 April 1992 at World Health Organization (WHO) in Geneva and the following definition was accepted.
A counterfeit medicine is one which is purposely and falsely mislabeled in accordance to identity and/or source. Counterfeiting can pertain mutually to branded and generic products. Counterfeit products may comprise of products with the accurate ingredients or with the incorrect ingredients, lacking active ingredients, with scarce active ingredient(s) or with forged packaging [WHO, 1999]
Nigerian National Agency for Food and Drug Administration and Control (NAFDAC) has identified counterfeit drugs as those with the same quantity of active ingredient as the genuine brand , those with insufficient or no active ingredients, expired medicines, herbal preparations that are toxic or ineffective and medicines which do not bear the name and address of the manufacturer [C. Clark, 2003].
2.2 Preface to counterfeiting
Counterfeiting is a high-volume, high-profit business which poses health risks, infringes intellectual property rights, medicines legislation and other aspects of criminal law [Counterfeit medicines, 2010]. Counterfeiting and piracy are in spirit the same since they are both the reproduction of identical copies of the genuine product [Lai, Zaichkowsky, 1999], [Ian Phau, 2009]. The most common counterfeit drugs in industrialized or developed countries are so called lifestyle drugs. The individuals often buy these drugs from the internet or unlicensed pharmacies [Business Insights]. Counterfeit drugs are the major cause of morbidity, death and failure of public buoyancy in medicines and health structures [Swaminath G., 2009]. India is the country where consumers reported the wide use of counterfeit and pirated products through reused, repaired and refilling [BASCAP, 2009]. Repackaging is one of the sources of fake drugs in Europe and US [ETH Zurich, 2007]. Estimates put the total loss of life to counterfeit pharmaceuticals between 500,000 and one million people per year [Cockburn, Robert, 2005].
3. Market trends
3.1 US report
U.S. sales of anti counterfeiting packaging technologies to the drug and food industries increased to approximately dollars 34.2 billion in 2006. Sales are likely to reach dollars 43 billion in 2012, viewing a compound annual growth rate (CAGR) of 3.2 percent over the episode of five years from 2007 to 2012 [BCC Research, 2007].
3.2 OECD report
According to a statement released by the Organization for Economic Co-operation and Development (OECD), three fourth of forged drugs supplied world over have some birth in India, followed by 7 and 6 percent from Egypt and China respectively [OECD, 1998]. OECD estimates the international trade in counterfeit goods at $200 billion dollars per year as of 2005, or about 2% of global goods trade [OECD, 2008]. China ranks first for the counterfeit products, US at second and India at the fourth globally [Harvey Bale, 1992].
3.3 WHO report
The World Health Organisation estimates that up to 1% of medicines available in the developed world are likely to be counterfeit. This figure rises to 10% globally, although in some developing countries they estimate one third of medicines are counterfeit [Professor Kent Woods, 2007-2010].
4. Medicines a target for counterfeiting
Table 1: Medicines a target for counterfeiting
Reasons for attraction towards medicines
Absence of or weak National Medicines Regulatory Authorities (NMRA)
High prices of medicines
Lack of control over export medicines
Trade through several intermediaries
The risk of prosecution and penalties for counterfeiting are inadequate
[WHO, 1999], [WHO, 2009]
Lack of criminal sanctions
Lack of aid between stake holders
Consumer's lack of awareness
Weakness of the supply chain
Well known brands
High priced medicines
Fig.1: Drivers of counterfeit
[Glaxo Smith Kline, 2009], [OECD, 2008].
5. Drugs counterfeited worldwide
The largest number of reports relate to antibiotics, antiprotozoals, hormones and steroids [WHO, 2009]. The forged drug Tamiflu had no active ingredients, but vitamin C in the capsules. A counterfeit Viagra factory was discovered in North London in 2005 [Cpl. Warren MacInnis, 2006]. In 2003 the FDA investigated counterfeiting of cholesterol lowering drug Lipitor and epoetin alpha, an anemia treatment used in the people who have cancer and AIDS [Anil K. Deisingh, 2005], [FDA consumer magazine, May-June 2004]. The FDA has also dealt with several high profile cases in the past year, including the discovery of counterfeit lots of Pfizer's huge selling statin, atorvastatin [The Lancet, 2003].
Table 2: Counterfeit medicines globally
A cough mixture diluted with poisonous solvent. Over 100 children die.
At least 59 children died after taking counterfeit syrup used to treat fever.
Ineffective contraceptive pills resulted in unwanted pregnancies.
Diethylene glycol poisoning killed at least 30 children.
At least 30 deaths result from counterfeited malaria drugs.
Anti diabetic traditional medicine contained 6 times the normal dose of glibenclamide, 2 people died and 9 were hospitalized.
[American Bank Note Holographics, 2002], [Anil K. Deisingh, 2005], [E. Wondemagegnehu, 2003], [ICC, 2003]
6. Authentication techniques
Authentication is the act of establishing or confirming something as genuine [An ICC initiative BASCAP].
Overt (Visible) Features
Overt features are projected to facilitate end users to confirm the genuineness of a pack. Such features will usually be significantly visible, and complex or expensive to reproduce. [Dr. Rajiv Dhar, 2009]. It may include optical variable coatings with changing color, Thermochromic inks and coatings, and watermarks [Jotcham R., 2003].
6.1.1 Tamper evident packaging systems
The tamper-evident feature helps maintain the integrity of drugs by preventing profiting by repackaging or reselling important pharmaceutical products [Pharmaceutical technology, 2003].
Some packages are innately tamper proof, like a tin can hermetically preserved, an aseptically packed multilayer carton or a vacuum or the rejoined pack. Other than the tamper evident system declared elsewhere other systems are:
a) Film wrappers: A transparent film with a characteristic design is covered securely around a product or product container. The film must be cut or torn to open the container and remove the product. Substrates options include ultra destructible films, voidable films that provides image when removed and Solvent sensitive papers.
b) Breakable caps: Such caps break when an effort to open is made. These caps provide external tamper evidence and can also be united with the internal seals thereby assisting double security [Dr. Rajiv Dhar, 2009].
Fig. 2: External and internal tamper evident feature [Dr. Rajiv Dhar, 2009].
6.1.2 Ink jet
Ink jet is commonly used for printing variable text on packaging. The process can be untidy and does not always provide the print quality essential to create small codes that must stay clear for weeks or months.
Laser imagers can produce high-quality small images and two dimensional bar codes, although symbologies support may be limited. Users must make sure that there is sufficient print contrast between light and dark bars to produce a legible representation [White paper, 2004].
6.1.4 Biometric Fingerprints
Launched by Bayer Group, The one-mega-watt diode lasers analyze the innate surface makeup of each article. Microscopic irregularities caused, for example, by the setting of paper fibers or plastic, result in spreading of the laser beam by laser speckle event. By measuring the dispersal of the light at various angles, surface uniqueness is recorded. The scanner can sense irregularities of less than a few hundred nanometers in size. Laser surface authentication combined with RFID tags at pallet level could provide an all surrounding anti counterfeit solution [Rupal Mehta, 2007].
6.2 Covert (Hidden) Features
The rationale of a covert feature is to facilitate the brand owner to recognize counterfeited product. The general public will not be conscious of its presence nor have the resources to confirm it. A covert feature should be difficult to sense or copy without specialist knowledge [Dr. Rajiv Dhar, 2009]. Covert features include microscopic particles of specific colors, Labels printed with color combinations, or Holograms containing microtext [Jotcham R., 2003].
6.3 Forensic Markers
There are an extensive variety of high technology solutions which necessitate laboratory testing or devoted field testing kits to logically attest genuineness [Dr. Rajiv Dhar, 2009]. It may include taggants like spectroscopic, physical, biological, chemical and DNA itself [Anil K. Deisingh, 2005], [Paul Osborne, 2007].
6.4 Track and Trace Technologies
These are high density linear or two dimensional bar codes incorporating product individuality down to unit pack level, which are scanned and sent to the central database. The codes are printable by online methods counting inkjet or digital printing [Dr. Rajiv Dhar, 2009].
An RFID tag comprises of an antenna with a microchip at its centre. This includes batch information which can be interrogated at a distance, and without necessitating line of sight (unlike bar codes). RFID allows recognition of objects through a wireless communications in a set frequency band. Three vital components in any RFID system are: the tag, the reader and the software. The tag is an Integrated circuit containing an exclusive tracking verifier, called an Electronic Product Code (EPC), which is transmitted via electromagnetic waves in the radio spectrum. The reader captures the transmitted signal and provides the network connectivity between tag data and the system. For their track and trace usage the diverse RFID tags that are used are active, passive and semi active tag [Dr. Rajiv Dhar, 2009], [Ustanso A., 2005]. The high cost of RFID tags (20 to 50 cents as opposed to a 2 cent barcode), however, might forbid companies from implementing it [George Koroneos, 2004], [S.H. Choi and C. H. Poon, 2008], [White paper, 2004].
6.5 Pack sealing systems
6.5.1 HoloSeal TM
HoloSeal TM is a patented pressure sensitive, tamper-apparent holographic security label that features a customized tamper-apparent fracture pattern, black light verification system and machine readable entrenched code. For tracking purposes, HoloSeal can be numbered or personalized to give accountability by region, plant or product.
6.5.2 HoloCap TM
HoloCap is comprised of several different heat-sealable films that are attached directly to containers utilizing highly developed induction sealing technology. They unite to form a single holographic inner seal that is model for adding a higher level of defense to containers or bottles.
6.5.3 HoloSleeve TM
HoloSleeve™ is a heat-shrink seal stamped with a holographic strip that can be applied to the lid of bottles. It has a customized tamper-apparent fracture pattern and an embedded black light verification system [American Bank Note Holographics, 2002], [Hallie Forcinio, 2002].
6.5.4 Secure Packaging Tapes
The secure packaging tape is prepared with a highly forceful adhesive and features an exclusive design. The continuously changeable notched edge, rhombic pattern and semi-transparent finish denotes clearly that tape has been cut through and pasted over again [Dr. Rajiv Dhar, 2009].
6.6 Security labels
Holography is well known for its capacity to produce striking three dimensional images difficult to get through conventional photography. A major benefit of this process is that they can be reconstructed under white light [Ari Y Benbasat, 1999]. Holograms are generated from the interference patterns obtained through the contact of laser beams. The complexity of initiation varies from the traditional three dimensional images to computer generated two dimensional diffraction patterns. Holograms are now widely available in a variety of formats such as: (i) Holographic shrink sleeves (ii) Blister packaging aluminum foil (iii) Pharmaceutical PVC (iv) Holographic induction cap seals (v) polyester-based tamper evident labels and (vi) Holographic hot stamping foil. But still it is reported that more than half the sales of artesunate drug in SE Asia are false, despite the blister pack incorporating a hologram. [Anil K. Deisingh, 2005], [Dr. Rajiv Dhar, 2009], [Ian Lancaster, 2009], [Newton PN, et al., 2006], [The Lancet, 2006]
6.7 Online brand protection
The Counterfeit Pharmaceuticals Initiative (CPI) was launched by the ICC to create counterfeit pharmaceuticals database with online search facility [Lowe P. 2003].
The model online brand protection program should be a synchronized, cross departmental and automated approach that go past the legal department and involve brand management, marketing, loss prevention, risk and supply chain management. The idyllic online brand protection approach includes both technical and managerial programs that take account of the following four steps:
Identification of all domain names in the portfolio
Managing the portfolio proactively
Monitoring for potential abuse
Respond to abuse [White paper, 2008].
World Health Organization (WHO) has set up a Rapid Alert System (RAS); the world's first web based system for spotting the tricks of drug fraud [Sukhlecha A., 2007].
6.8 Analytical techniques
Commonly used techniques for counterfeit detection are near infrared, Raman, Mass spectrometry, Chromatography, Isotopic characterization and hyphenated techniques for the spotting of active ingredients or residual solvents or impurity profiling [Anil K. Deisingh, 2005].
6.8.1 Raman Spectroscopy
Raman helps in the rapid identification of active drug along with the excipient and the degree of hydration to spot the counterfeit drugs while they are inside the pack [A.C. Dennis, 2000]. Raman allows recording the spectra noninvasively from solid samples without any sample preparation, thus greatly increasing the sample throughput [Scafi SH, Pasquini C., 2001].
In Tensiography the forming pendant drop is illuminated from within by an optic fiber generator and receiver. The technique provides fingerprint traces whose profiles depend on the surface tension, refractive index and color amongst other parameters [Anil K. Deisingh, 2005].
6.8.3 Isotopic characterization
It has been suggested that natural stable isotopic fingerprints of Pharmaceuticals can be used as a specific method for detecting the counterfeits [Anil K. Deisingh, 2005]. For this sample is burnt by oxidation or pyrolysis into a gas proceeding to its injection into the mass spectrometer source. The isotopic content is therefore the average contribution of each atom of a given element, hiding the internal isotopic distribution [Virginie Silvestre et al., 2009].
6.9 Fore coming packaging technologies
6.9.1 Holo Spot®
Holospot® is a discrete forgery proof information carrier that attaches to any product. It uses laser encryption of computer generated lithograms into small polymeric data carriers and offers multiple overt and covert security levels
6.9.2 Ident Seal®
Ident Seal® is inscribed by laser with visible text or high contrast barcodes. It offers overt protection and identification plus successful tamper evidence. Brand owners can opt between specific surface structures, non removable imprints or fluorescent UV features to add enhanced security.
The packaging features numerous hidden and forensic security features from the Merck securalic product line. The security features are built into the ivy leaf design element printed on the folded box. Securalic products are also used for both two color blisters in UV flexo printing [World Pharma, 2010].
Counterfeiting is indisputably an intricate problem in the international healthcare system that poses many cultural, political and legal challenges. However, through a carefully planned and well executed enforcement strategy, trademark owners can achieve meaningful progress in protecting their consumers and most precious brands. Tracking and tracing of pharmaceutical products is a main element in an effective solution to the problem of counterfeit medicines. Thus the principles of nature and emerging science can be combined to serve the problem at a greater extent.
Pharmaceutical counterfeiting is becoming a very serious problem globally affecting the health and economic market. This paper considers the effects of counterfeiting over the world, factors driving the counterfeit and the examples of frequently counterfeited drugs. Several detection techniques has been described which accounts of RFID, holograms, analytical techniques and packaging approaches. Still the thirst remains for complete package for deterring the counterfeit, and hope seems to be live with novel packaging techniques.