With the World Health Organisation reporting that over half of all drugs purchased from online pharmacies are suspected counterfeit, and the number of illegal online pharmacies increasing dramatically since the start of the COVID-19 pandemic, there is a growing recognition that serialisation alone will not solve the problem of falsified medicines.
The Royal Pharmaceutical Society is also warning that the UK could see “an influx of counterfeit medicines” after the Falsified Medicines Directive ceases to apply at the end of the Brexit transition period on January 1, 2021.
In addition to the use of security tags on packaging, there is now a move towards ‘on dose authentication’, which is achieved by incorporating microtags into the core ingredients or coatings of pharmaceutical and nutraceutical products. These covert microtags can be detected using either field or lab-based equipment to mitigate counterfeiting and product diversion, assist quality control, returns monitoring and product recall. A further innovation is leading to the introduction of associated phone apps, enabling simplified field-based authentication by patients and caregivers.
Recent trends and the threat of illegal online pharmacies
Globalisation and outsourcing have resulted in complex supply chains for many pharmaceutical products. This makes them vulnerable to counterfeiting and diversion and can result in health risks and loss of trust for the consumer, as well as loss of revenue and reputational damage to the brand owner. Despite the widespread introduction of serialisation, the supply of counterfeit drugs is continuing to rise, and brand owners must develop robust strategies to safeguard consumers and protect their supply chain from external threats.
Many falsified drugs are produced in developing countries, where an estimated 10% to 30% of medicines are counterfeit. These drugs may contain little or no active ingredient or, in the worst cases, dangerous ingredients. They are often found in high-quality packaging or in real packaging that has been stolen and reused.
The International Federation of Pharmaceutical Manufacturers and Associations reports that every medicine is potentially affected by counterfeiting, including life-saving ones. Whether a medicine is brand-name, generic, prescription or over-the-counter (OTC) it is at risk for falsification. And while counterfeiters often target lifestyle drugs, life-saving medicines are the fastest-growing category of falsified medicines.
The Pharmaceutical Security Institute has collected data on the incidence of counterfeiting, illegal diversion and theft incidents in the US for eighteen consecutive years. Figure 1 gives totals for the last five calendar years and shows that incidents increased by 69% over the period. Figure 2 provides details of the therapeutic categories that were targeted in 2019. Almost two thousand different medicines were involved in these incidents, and as many as 122 different medicines were discovered in a single raid.
There is widespread agreement that the internet is the primary market for counterfeit pharmaceutical products. The COVID-19 pandemic has led to a dramatic rise in online sales, and it is estimated that one in four US consumers now buy their medicines online. According to the Alliance for Safe Online Pharmacies, 100% of online searches to buy medicine return links for illegal pharmacies. These online pharmacies frequently operate without certification, prescribe drugs without adhering to legal guidelines and may knowingly distribute counterfeit medicines.
Increasingly well-organised counterfeiters backed by sophisticated technologies are continuing to profit from drug counterfeiting at the expense of patients and legitimate companies. They see both Brexit and the COVID-19 pandemic as an opportunity to expand their operations. The widespread use of pill presses means that we are now dealing with counterfeiters who can change production and ingredients rapidly to satisfy market demand. In addition to counterfeit tablets and capsules, these organisations have expanded into the more expensive parenteral drugs such as the injectable cancer medication Avastin.
An analysis by Krebs on Security shows the number of domain names being registered from the middle of January 2020 to the beginning of April. The blue and red lines represent how many websites were being registered each day with either 'Coronavirus' or 'COVID' in their names. The blue line represents websites with a low-risk score of being scams while the red line, showing large increases, is for websites that are likely to be scams. Legitimate organisations tend to be a few weeks and thousands of daily registered domains behind the scammers.
Figure3: Total number of domain names registered per day that contain a COVID-19 related term
On-dose authentication for smarter medicines
Many countries have introduced legislation to enforce serialisation, requiring product identifiers to be affixed to each package to provide traceability throughout the distribution supply chain. Although this allows the packaging to be traced, it may be impossible to determine if the medicine inside is real or fake and whether it has been diverted.
The use of on-dose taggants is a practical solution and is easy to implement since the FDA issued guidelines that allow drug manufacturers to incorporate physical-chemical identifiers (PCIDs) into their products without having to repeat clinical trials. The guidelines state that when PCIDs are pharmaceutically inactive and incorporated into new or existing drugs, they can be treated as excipients. This allows for their inclusion into drugs already on the market.
Through on-dose authentication, microtags that are customised with unique information for product verification and traceability are embedded into each pill. For example, theTruTag platform uses microscopic silica particles, each of which bears a unique spectral signature, while Applied DNA Sciences uses unique molecular tags that can be detected at parts per billion or trillion. These covert taggants can be incorporated directly into the tablet coatings or inks used on tablets, capsules, vials and even the excipients used in the dosage form. Crucially this requires no additional manufacturing equipment or processes. The materials have ‘generally recognised as safe’ (GRAS) status and are resilient for the entire product lifetime, providing an individual ‘barcode’ that cannot be broken.
Recent work has focused on developing convenient and reliable mobile and smartphone readers, which allow drug products with taggants to be verified directly in the field. Specialty excipient and film coating manufacturer Colorcon is now able to incorporate these covert taggants into film coatings and inks, which can be authenticated at the patient level using a smartphone app. This not only offers instant verification, but it also provides the opportunity to connect the brand directly with the patient.
Brand owners, product security teams and senior management must determine the most appropriate solution for their product. Those products with high gains for counterfeiters, whether in terms of volume or value, will benefit most from this technology and mitigate the risk to patient safety while protecting brands.
Through a secure link between the physical and digital world, medicines are made smart with on-dose taggants that can be authenticated throughout the supply chain.
Gary Pond is global program leader, Authentication, at Colorcon