Falsified Medicines Directive: Are We Heading in the Right Direction?

Abstract

Falsified medicines for human use are an increasing problem in Europe. The Falsified Medicines Directive (FMD) 2011/62/EU provides measures to prevent the entry of falsified medicines into the legal supply chain by requiring the placing of safety features consisting of a unique identifier (Ul) and an anti-tampering device (ATD). Some concerns have arisen from patients regarding the effectiveness of UI and ATD in terms of safety. In contrast, the relevance of the supply source as a key point for patients and pharmacists, especially in hospitals, has not been sufficiently considered by the FMD. Endorsing more Good Procurement Practices and Good Distribution Practices may be more effective. The implementation of the FMD in hospitals is wasting human resources and increasing costs, which will likely result in a poor positive outcome. At both European and national levels, it is now urgent to mitigate the consequences of the FMD by updating the legislation.

Introduction

It is important to distinguish between “falsified medicines” defined as “fake medicines that are designed to mimic real medicines” and counterfeit medicines, which are “medicines that do not comply with intellectual property rights” (1). This article refers only to falsified medicines and their consequences for patients both in the community and in hospitals.

Falsified medicines for human use are an increasing problem in Europe (1). Falsified medicines entered the market some years ago mostly for lifestyle medications, but recently they have included other drugs, such as oncology medications. As a consequence, Directive 2001/83/EC was amended in 2011 by the Directive 2011/62/EU on falsified medicines (Falsified Medicines Directive [FMD]) (2) and by the recently published Delegated Act 2016/161 (3). Basically, the FMD provides measures to prevent entry of falsified medicinal products into the legal supply chain by requiring the placing of safety features consisting of a unique identifier (UI) and an anti-tampering device (ATD) on the packaging of certain medicinal products for human use, for the purposes of allowing their identification and authentication. In addition, the FMD provides a tool to aid security when buying medicines on the internet.

The FMD states that any falsified medicine “poses a particular threat to human health and may lead to a lack of trust of the patient also in the legal supply chain” (2). Therefore, it is important to underline that the scope of the directive is to protect patients from the health consequences of falsified medicines.

The economic impact of falsified medicines in the supply chain is very high and estimated to be €10.2 billion every year (4). However, these data include all medicines–not just the prescription ones as covered by the FMD. Nevertheless, this fact explains why the pharmaceutical industry is interested in implementing the UI and the ATD despite the costs shared by industry (mainly), and wholesalers and pharmacies. The implications for pharmacies in terms of hardware and staffing are relevant, especially in hospitals handling huge amounts of single packages, and should be viewed in relation to the effect on patient safety.

How effective are UI and ATD?

Some concerns have arisen regarding the effectiveness of UI and ATD in terms of safety from the perspective of patients.

First, the FMD covers only prescription medicines and not over-the-counter (OTC) products, with the only current exception of omeprazole; however, paracetamol was also falsified. Falsified medicines can contain no active pharmaceutical ingredient, but can contain toxic substances, which put patients at risk. Thus, from the perspective of patients, by definition the FMD is covering the interests of the pharmaceutical industry that produces prescriptions drugs rather than the needs of consumers.

Second, some doubts arise from research regarding the reliability of scanning 2D codes in practice. In a study performed in the UK (5) with 4,192 packages containing 180 falsified, expired, or recalled boxes, despite 100% technical detection only 31.8% of falsified medicines, 58% of recalled drugs (product and batch), and 64% of expired medicines were excluded from dispensing. Due to human factors, intensive training seems to be necessary to achieve the goal to exclude, in practice, the use of medicines identified by technology as falsified.

In a trial at the St. James Hospital in Dublin (Ireland) (6), which simulated the model proposed by the delegated Act (3), 18 of the 50 falsified medicines were incorrectly verified and dispensed to patients (in simulation only). Despite the commercial purpose of these results in promoting a different system, the trial revealed the biggest weakness of the FMD: if hackers acquire the list of random codes, they could put the UI on falsified packages and enter the drugs into the market. The code (right one or falsified) which will be decommissioned as first will be recognized as authentic even if it was on the falsified package. Thus, criminals can enter falsified medicines onto the market with the right codes before the authentic medicines can reach the pharmacies, due to the complex supply chain; therefore, such falsified drugs will be dispensed as authentic. The authentic medications will be identified as falsified also, and consequently, this will force the manufacture to recall at least the whole batch, even if only just one code was misused. This may cause an unintended shortage of medicines. In this context, it is also uncertain what would happen if authentic medicines delivered to pharmacies will not be decommissioned either by error, technical problems or even by criminal intention let-ting therefore some UI reusable for falsified medicines.

Supply chain and risk

According to data from Austria, using internet pharmacies poses a major risk for patients to purchase falsified medicines. The Austrian Health Authority found that 95% of prescription drugs purchased via the internet were falsified (7). In contrast, over a 10-year timespan, only 11 cases of falsified medicines were found in the legal supply chain in the UK- 9 of which were due to parallel importing (8).

The FMD includes a regulation concerning the authentication logo for internet pharmacies. This is an important step in protecting patients from falsified medicines. Nevertheless, the regulation can be effective only if patients are educated in how to distinguish fake pharmacies from real ones. How the authentication logo can be promoted to patients and how effective this will be remain unanswered questions and challenges.

The relevance of the supply source is a key point for patients and pharmacists, especially in hospitals. The efficacy of the FMD can be evaluated only when all aspects of the process and workload are considered.

Some questions

Who will benefit from the FMD, and how smooth and safe will be its implementation? The patients are obviously not the main focus of the FMD. In contrast to the eTACT drug traceability system proposed by the European Directorate for the Quality of Medicines & Healthcare (9), the FMD does not give the patients any opportunity to check the authenticity of the drugs they purchased. This is surprising as the internet is a major source of falsified medicines (7).

Creating patient awareness of the opportunity to use the authentication logo for internet drug purchasing requires intensive education and the results need to be evaluated. The effectiveness of the logo has yet to be demonstrated.

The UI depositories will produce substantial data, which will be kept for years on the servers of the European Medication Verification Organisation. This will allow competent authorities to follow the detected incidents. The FMD does not sufficiently restrict access to the data as other parties also may be granted data access rights for pharmacovigilance reasons. The pharmaceutical industry may be very interested in such data – but not only for pharmacovigilance reasons.

The system implemented by the FMD is highly dependent on a good internet connection. This should not arise as an issue in most cases, but hospitals in rural regions may experience major problems requiring extra financial investment that is not currently budgeted.

The technical prerequisites in hospitals are according to the data of the survey of the European Association of Hospital Pharmacists (10) are insufficient and require further relevant financial investments.

Hospital pharmacies purchase drugs in huge amounts either directly from the manufacturer or from qualified wholesalers. Scanning single packages from a bulk order will require additional time and hospital workforce to remove and repack single packages. An optimistic time of 2-3 seconds per scan using the appropriate technology can be easily calculated for a big pharmacy delivering 2.5 million of packages per year, which equates to at least one full-time equivalent staff member. The FMD requires that decommission of drugs should be cost neutral for pharmacies. The question of who is going to cover the costs of any additional workforce and technology remains unanswered.

The whole system implemented by the FMD is not sufficiently evaluated in terms of effectiveness and efficiency and has not been compared with other initiatives, such as the MEDICRIME Convention (11) in terms that justify the costs shared by all stakeholders. By excluding all OTC medicines, the FMD may be ineffective from the perspective of patients.

Heading in the wrong direction

The FMD (2) and the Delegated Act (3) have placed a heavy burden on the shoulders of pharmacies in terms of time and workforce resources. Especially in hospitals, where huge numbers of packages are supplied usually to the wards rather than directly to patients, the time for scanning every single package is challenging. Thus, it is of paramount importance to clarify whether the system implemented by the FMD really enhances the safety of patients. This is highly questionable for hospitals because hospital pharmacies usually purchase the medicines directly from the manufactures or other reliable sources. The FMD is not sufficiently weighing the risk of the source of the drugs purchase or the complexity of the supply chain, and puts the supply via the internet or parallel imports at the same level as a purchase from the original manufacturer. It is surprising that the FMD has put little apparent effort into distinguishing the sources of purchase and into differentiating the risks. In addition, no technical solution is without failures. Even if packages had very low level false positive or false negative scanning output, the total amount of wrong scans would be considerable. The time spent in clarifying the incidents will hamper the efficiency of the distribution process in pharmacies, both in the community and in the hospitals. In contrast, the safety of patients will not significantly increase, because a reliable source of purchasing is the key point in protecting patients from falsified medicines. Pharmacists are already obliged to check the quality of the medicines they provide to patients. To prevent falsified medicines entering the market, it is necessary to have stronger controls regarding the implementation of Good Procurement Practice (GPP) (12) and Good Distribution Practices (13) in every pharmacy, in the community and in the hospitals. The FMD only implements a bureaucratic system, which consumes huge staff resources at every step of the supply chain. Especially in hospitals where the risk of falsified medicines is minimal, the value of the FMD is more than questionable. On the other hand, purchasing from the internet, where the risk is very high, is not sufficiently protected by the FMD as patients were excluded from the verification process despite the technical possibilities to allow their involvement. It is particularly noticeable that hospital needs were not adequately assessed, which shows the Commission's lack of understanding of the supply chain process for which they were legislating, and that other interests, such as those of the pharmaceutical industry, were allowed to dominate and overly influence the outcome. Hospitals now have to deal with a regulation based only on the processes of retail pharmacies. This solution is not feasible in practice because hospital pharmacies do not supply single packages like the community pharmacy. The implementation of the FMD in hospitals is wasting human resources and increasing costs, quite likely with a poor positive outcome. Other pharmacy services, which target the needs of patients more in the clinical context, may be reduced if no additional staff is possible due to financial reasons. At both the European and national levels, it is now urgent that the consequences of the FMD be mitigated for hospitals that have already developed a secure and efficient supply chain by implementing GPP. Aggregate codes for the decommission or even the exemption of scanning drugs purchased directly from the manufacturer are examples of how the directive could be changed in a practical sense in hospital pharmacies.