Pharmaceutical Packaging How to Fight Pharmaceutical Counterfeiting
Counterfeiters are increasingly targeting the pharmaceutical supply chain – a dangerous trend that can have fatal consequences. All supply chain players can contribute to increased safety, from producers of Active Pharmaceutical Ingredients (APIs) to packagers and equipment manufacturers, supported by numerous initiatives and legislative efforts.
Counterfeit pharmaceuticals are those that have arrived on the market as licensed drugs without having passed through the official channels. In such cases, the counterfeit drugs may contain wrong or any active ingredient or the correct active ingredient in an incorrect quantity.
The bestcase scenario may find a drug becoming ineffective and in the worst case, fatalities may occur if the illegitimately made drugs do not have the desired effect. Counterfeiters not only manufacture imitations of prescription-only drugs, but also over-thecounter (OTC) products, generics, originator products and traditional drugs.
New Distribution Channels
The World Health Organization (WHO) estimates that every second pharmaceutical product purchased via the Internet is counterfeit. Anabolic drugs and potency pills range among the most frequently ordered products. Apart from these so-called lifestyle medicines, more and more prescription drugs like antibiotics and medicines for cancer treatment are sold by online pharmacies. A study conducted by the European Alliance for Safe Medicines (EAASM) found that in 90.3 per cent of all cases, no prescription was required for the online purchase of prescription-only drugs.
More than 50 per cent of medicines purchased from illegal websites concealing their physical address have been found to be counterfeit. But the Internet is not the only channel by which counterfeits enter the market. The pharmaceutical wholesalers too are targeted by counterfeiters. By introducing large quantities of falsified medicines into the legal supply chain, lucrative transactions are made in a very short time. This depends strongly on the geographical area. For example, in most of Europe, the amount of falsified medicine is estimated at approximately one per cent, while the developing world sees figures up to 50 per cent of counterfeit pharmaceuticals.
How can patients be protected from this growing threat? Drug manufacturers assume an important role in the fight against counterfeiting by applying one or more of the technologies described below.
Overt, Semi–Overt and On–Product Marking
Holograms can display a wide range of images and are printed onto folded boxes, blisters or labels in the pharmaceutical industry. Other Optically Variable Devices (OVD) are similar to holograms but without the three-dimensional effect. Packaging can also be marked with color-shifting security inks or films, which change color depending on the viewing angle. With different security graphics, an additional text or image appears only when viewed with a magnifier.
Product numbering – sequential or randomized –, which is printed on the packaging, is the most common semi-overt anti-counterfeiting technology. Some anti-counterfeiting measures can be applied directly onto the product instead of traditionally onto packaging materials. For example, color-shifting inks are admixed to film-coated tablets, changing color depending on the viewing angle. Microtaggants and mechanical micro imprints can be administered to the film coating and identified using special equipment.
Individualizing pharmaceutical products in terms of color, form and graphic or mechanical features also helps to protect patients by making drug copying a more laborious business.
Covert Technologies and Forensic Markers
A number of anti-counterfeiting features on the market are invisible to the naked eye. For example, special ink that is printed onto primary or secondary packaging can only be seen under ultraviolet (UV) or infrared (IR) light. Digital watermarks are only decodable using special software programs. The finely structured pattern of the so-called ‘anti-copy’ or ‘anti-scan’ design only becomes visible when copied or scanned.
Microscopically small color-codes, in turn, consist of multiple color layers. They can be applied onto the packaging either manually or by means of dispenser technology. Techniques used for producing banknote papers are also applicable to packaging.
More recent technologies rely on chemical and biological parameters, and belong to the category of forensic markers. Chemical taggants are added to inks and result either in a characteristic peak in the IR spectrum or in particular chemical reactions. Biological markers can be incorporated into product formulations or coatings, or onto the packaging. The latter also applies to DNA taggants. In addition, packages can be examined for their isotopic ratio, which is stored as a natural fingerprint. Microtaggants are unique numeric code sequences in a multi-color layered format that can be applied either on or in the packaging.
Tamper–Evidence and Serialization
Closure seals are a classic tamper-evident method applied to packaging. An intact seal proves that the package is being opened for the first time by the patient. While they do not actually prevent counterfeiting, tamperevident features nonetheless protect patients by clearly indicating whether a package has been opened before it reaches them. This also applies to the so-called VOID foils, which immediately tear when tampered with.
As soon as someone tries to open the package or remove the foil, the lettering ‘void‘ appears under the damaged surface. Perforation is a further means of making packaging tamper-proof: the packaging is irreversibly damaged once the perforation is torn. Serialization with adaption of a machine readable code is one of the most important strategies laid down in recent guidelines and legislation. A serialization number is a unique number attributed to pharmaceuticals on package or bulk level.
This number can be applied to the package by various technological means. One of them is the data matrix code which contains a distinct serial number attributed to the package, as well as variable data like batch number and expiry date. A radio frequency identification (RFID) label checks and records each product movement. In the long term, data matrix codes are intended to serve as traceability devices for all supply chain players.
Due to globalization and production outsourcing, the supply chain of pharmaceutical products includes many different steps between the producer and the end-consumer. In most cases, pharmaceutical companies opt for a combined strategy, depending on the individual counterfeiting risk, budget and technical abilities. Several layers of security can be created by combining tamperevident, serialization and authentication technologies to form a multi-layer approach for the best possible patient protection.
Recently, international organizations such as the World Health Organization (WHO) have worked alongside governments and producers, largely through their International Medical Products Anti-Counterfeiting Taskforce (IMPACT), to help curb this damaging practice. Future initiatives to combat counterfeiters will also rely heavily on manufacturers. International guidelines and regulations have been developed, but regional and local regulations still vary considerably and in parts they are contradictive.
EU serialization is due to be introduced in 2014, followed by the longawaited Food and Drug Administration (FDA)/California serialization standard, expected to be launched in 2015. The main goal of these regulations is to harmonize the coding of pharmaceutical products on an international level.
International Guidance and Legislation
The FDA’s final guidance for the standardized numerical identification of prescription drug packages recommends the introduction of a serialized National Drug Code (sNDC) at package level. This code is composed of two distinct codes: the National Drug Code (NDC) contains labeler, product and packaging code. The unique serial number is composed of a maximum of twenty characters. The implementation of California’s ePedigree for full traceability is now due to take place on a staggered basis from January 2015 to July 2017. Most of the guidance and regulations concentrate mainly on serialization to make pharmaceuticals traceable throughout the supply chain.
In June 2011, the European Union published its Directive 2011/62/EU. In addition to the introduction of serialization standards for prescription medicines, the directive initializes the search for appropriate safety features. It also provides for stricter regulations regarding the import of active substances and the improved control of the supply chain, including wholesale. Regulations for Internet trading of medicines, the harmonization of Good Manufacturing Practice (GMP) inspections and the introduction of a pan-European early warning system are also an integral part of this Directive.
Moving in the Right Direction
Uniquely coded, serialized packs for almost all prescription drugs are the Directive’s most important component. But the EU also recognizes the need for a combined strategy and requires a second layer of security, that is tamper-proof closures. These security components will be obligatory for nearly all prescription drugs, but not for OTC drugs. The required safety feature – the so-called ‘unique identifier‘ – will be determined in delegated acts, whose aim is to define the characteristics and technical specifications of the unique identifier, as well as the modalities of verification and the establishment, management and accessibility of the repositories system (database).
It will be some time until all required steps are implemented and harmonized on an international level but as of now the industry is clearly moving in the right direction in its fight against pharmaceutical counterfeiters.