INTRODUCTION

Falsified medicinal products represent one of the most significant challenges for global patient safety, and remain a key issue of public health at the beginning of the twenty-first century.¹,²,³ The struggle with the increasing number of falsified medicinal products affects the activities of all parties involved in drug distribution – manufacturers, wholesalers, community and hospital pharmacies; and on the other hand, presents challenges for policy makers responsible for the drug safety of the European Union (EU).⁴,⁵ The fight against illegal places of pharmaceutical distribution is not only European domain, but it is also part of the global action initiated by the Food and Drug Administration (FDA).⁶ While the phenomenon of the illegal trade of drugs outside the pharmaceutical distribution chain described in the law is a well-recognized matter, the scale of this phenomenon in the legal distribution remains poorly defined.⁷,⁸ Current activities in the EU are focused directly on improving the safety of the pharmacotherapy of patients at the international level. This is done by monitoring drug distribution in countries belonging to the EU and introducing common mechanisms to verify the authenticity of pharmaceuticals in Member States.⁹ This action is supported by the Council and the European Parliament’s Falsified Medicines Directive and by implementing rules adjusted to this regulation – the so called Delegated Act, constitutes a joint effort of the EU to challenge illegal pharmaceuticals.¹⁰,¹¹,¹² It is worth noting that according to EU rules, a falsified medication is any medicinal product which has been falsely presented in: i) identity of the product, including its packaging, labeling, name, or its’ ingredients list, including excipients, and the strength of those ingredients, or ii) in regards to the country of origin, including the manufacturer, country of manufacture, and the holder of the marketing authorization, as well as the history of medicine’s trading, including the records and documents related to the used channels of distribution. This definition does not include unintentional quality defects and is without prejudice to infringements of intellectual property rights.¹³

In the context of pharmacy practice, these new obligations will be introduced into routine settings, and can often be time-consuming for the staff of community and hospital pharmacies. However, it should be noted that due to the solutions proposed by the EU Parliament, the role of the pharmacist will increase. In particular, at the time of drug dispensing, the pharmacist will be required to scan the package’s unique serial identifier in the form of a technologically advanced matrix, allowing them to check the authenticity of the drugs. This safety feature will be obligatory for all prescription drugs, as long as separate documents do not state otherwise. Moreover, some over-the-counter (OTC) drugs will have similar security regulations if they are listed in the delegated act. Apart from a unique identifier, the directive recommends implementing a mandatory security measure located on the external package (tamper evident feature) to protect the drug against undesired opening. The verification process – authentication - will therefore be nothing other than a basic element of pharmaceutical care, optimizing pharmacotherapy and increasing the level of patient safety.¹⁴,¹⁵,¹⁶

The actions described above are a great challenge for individuals responsible for drug policy who will be in charge of organizing the institutions that supervise these new regulations. It should be noted that at the European level this will be EMVO (European Medicines Verification Organization), and at the national level - NMVO (National Medicines Verification Organization). Their main task will be to create data repositories necessary to authenticate individual drug packaging.¹⁷ The new amendments will be constituted in 2019 and new security measures should be introduced no later than the 9th of February 2019.¹⁸,¹⁹

Effective introduction of the described solutions depends to a large extent, on the awareness and knowledge of the managers of pharmaceutical companies, as no legal regulation can be effectively implemented without properly organized human resources. Pharmaceutical companies should take an active part in the implementation of the drug authentication system in the EU. The aim of our project was to investigate the awareness of pharmaceutical companies managers of the legal regulations related to the implementation of FMD. This work constitutes a unique voice in the discussion on the falsified medications trade within the legal distribution chain and the place of community pharmacies in the implementation of EU regulations.

METHODS

RESULTS

The study included 99 women (39.3%) and 153 men (60.7%). The percentage of respondents aged 21-29 years was 3.2%, aged 30-39 years was 13.5%, aged 40-49 years was 33.7%, aged 50-59 years was 35.3% and above 60 years of age was 14.3%. In the study group, the level of education among the respondents was as follows: completed primary education 1.6%, the level of single structure 0.8%, general secondary education 2.8%, secondary vocational education 3.2%, post-secondary non-tertiary education 7.5% and completed tertiary education 84.1%. The study involved physicians (3.6%), pharmacists (46.8%), people employed in the industry (27.8%) and people from other specialties (27.0%). Respondents could choose more than one answer. In the study group, there were significantly more male physicians (p=0.0140) and those working in the industry (p=0.0308), while there were significantly more female pharmacists than male (p=0.0482). It is noteworthy that in the study group almost half of the respondents (49.8%) are involved in the creation of NMVO. Demographic data is summarized in Table 1. From the perspective of the country of origin, respondents were mostly representatives of Belgium (10.7%), Poland (7.9%), UK (7.9%), Czech Republic (7.1%) and Romania (7.5%) as shown in Table 2.

In the study group, 95.7% of people have heard about FMD, while only 4.3% of the respondents have not heard about FMD thus far. In the study group, there were significantly more respondents who have heard about the provisions of the FMD (p=0.0001). Younger respondents and those with lower levels of education rarely have heard about this EU regulation (respectively, p=0.0014, p=0.0001). Physicians have less frequently heard about the FMD as compared to pharmacists (p=0.0063), people working in the industry (p=0.0014), and respondents with a different professional profile (p=0.0114). In the study group, 89.6% of people were aware of the NMVO role in the process of implementing the provisions of FMD into the national system of medicinal product distribution, while 10.4% of the respondents responded negatively. There were significantly more respondents aware of the role of NMVO (p=0.0001). Again, younger respondents (p=0.0027) and those characterized by a lower level of education (p=0.0186) were less likely to be aware of the role of NMVO in the process of implementing changes on the national level. Pharmacists and professionals related to the pharmaceutical industry are significantly more likely to understand the role of NMVO in the implementation of FMD (p=0.0001). There were significantly more respondents in the study population who knew the deadline for implementation of FMD i.e. 91.9% (p=0.0001), but both younger respondents and those with lower levels of education were less aware of the timing requirements that national regulators have to satisfy (p=0.0003, p=0.0023). In addition, respondents were aware of the need to choose a provider of medicinal product authentication, which is one of the basic requirements faced by those responsible for implementing new EU regulations at the national level. Only 10.4% of respondents were not aware of this obligation. There are significantly more people who were aware of this problem (89.6%, p=0.0001). It should also be noted that in the study group, 79.1% of the respondents realized that the verification of medicinal products must comply with the standards and guidelines (Blueprint) for the country as defined by EMVO (p=0.0001). However, respondents with a medical education understood the need to implement the FMD significantly less when compared to pharmacists (p=0.0064) and people working in the industry (p=0.0001). No statistically significant differences were seen in the distribution of responses between men and women. Objective data is summarized in Table 3.

DISCUSSION

Our study aimed to explore the European Economic Area (EEA) pharmaceutical companies professionals’ awareness of the implementation of the FMD. Those surveyed will be directly responsible for the changes in the marketing supply chain of medicinal products, the production of drugs (the area of industrial activity), as well as wholesale and retail (public and hospital pharmacies). Our study has clearly shown that the awareness of the legal regulations related to FMD among pharmaceutical company professionals, is high but not sufficient enough. In this context, it is worth emphasizing the fact that over 10% of the respondents are not aware of what the FMD is. In addition, those who are less aware are people with a lower level of education, those who are younger and those in the medical profession (physicians). It seems important to note that pharmacists are more aware of the consequences of FMD implementation.

The organization of both the European and national data repositories will require close cooperation of the participating parties.²⁰ Hamilton et al. indicates that these actions should focus on multi-faceted interventions; initially, based on the certification of medicinal products and secondarily, on the effective prosecution of pharmaceutical crimes and a strong, partnership of all the parties.⁴ In this regard, the awareness of the respondents seems insufficient. As suggested by Naughton et al., it is necessary to implement Good Authentication Practice (GAP), a collection of standards and procedures aimed at improving the process of verification of medicinal products, particularly in the stage of the flow of medicines between the pharmaceutical wholesalers and the community pharmacies.²¹ The introduction of such procedures could significantly improve awareness of the provisions related to the new EU regulations. While such actions are only theoretical at this point, they must be considered the next step in the process of shaping legislation in the area of authentication procedures. In this context, once again it is worth emphasizing the topicality and innovation of our study, as it is the awareness of the decision-makers that will determine the efficiency of the process. Until now, awareness of the dangers of falsified medicines has been studied primarily in the context of the distribution of medications in illegal places, i.e. bazaars, gyms or purchased over the Internet, especially in relation to sexual potency drugs and anabolic steroids. One study showed that 90% of physicians, 80% of nursing staff, but only 40% of people not connected to the health sector were aware of the risks associated with the pandemic of falsified medications produced in Ukraine or China.²² Despite this, awareness of the procedures necessary for verification of a medication’s authenticity among health care workers should be considered highly insufficient.²³ While the risk of falsification is disproportionately smaller in the case of legally purchased or hospital dispensed medicines, it is the healthcare professionals who should have an increased awareness and vigilance of the potential risk of falsification.²⁴ In this context, the results of our survey should be considered important, as they show that knowledge of the procedures related to the implementation of anti-falsifying regulations is small among doctors professionally linked to regulatory affairs and pharmacovigilance.

This study is an important voice in the discussion about implementing the Falsified Medicines Directive to the European system of medicine distribution. It seems necessary to introduce the solutions of the authorities of the Community to popularize this knowledge among Member States pharmaceutical company representatives. Important communication tools could be conferences on an international scale, as well as European associations of representatives of innovative or generics pharmaceutical companies, organizations of pharmaceutical wholesalers or pharmaceutical lines of work. A huge responsibility rests also on the people responsible for shaping drug policy, both at a central and national level. Our study should be regarded as useful for European decision-makers. As there is little time remaining before countries of the European Union must implement these new legislations, remaining months should be spent in intensified efforts. The pharmaceutical company representatives’ awareness of the financial consequences of the regulations remains an open question. Although awareness of financial responsibility was not part of the aim of this study, it could be a preliminary start for future research projects. It should be highlighted that implementation of FMD should be considered as a starting point for deeper collaboration among stakeholders. For instance, thanks to these new regulations, the system of monitoring of adverse events should improve the collection of safety alerts. However, these amendments will necessitate excellent cooperation among stakeholders involved in drug distribution and require detailed procedures.²⁵ Moreover, as suggested by Naughton et al., current technology needs further improvement before there can be harmonization with the current workflow in community and hospital pharmacies.²⁶

Our study can lead to some practical implications. First of all, the intensification of efforts to popularize knowledge about the fight against falsified medicines in the legal supply chain among people responsible for the implementation of FMD guidelines in the Member States of the European Community should be undertaken. A special beneficiary of such actions will be individuals with a medical education, younger and those with lower levels of education. From a scientific point of view, further representative studies are needed to achieve a higher generality. Secondly, we could consider collecting data from one selected stakeholder, for instance from a wholesaler, which could provide a more insightful perspective. Moreover, to investigate more subtle barriers and to find an explanation as to why some parts of FMD legislation are less known, qualitative studies could be considered useful. Above all, highly effective communication between stakeholders involved in the implementation of FMD is necessary to improve knowledge and the understanding of the barriers which hinder the harmonization.

CONCLUSIONS

Bearing in mind the limitations of our study, particularly the limited number of respondents, we can still declare that awareness of the regulations related to the implementation of FMD among pharmaceutical companies’ professionals in the EU, although relatively high, is still insufficient. Further educational initiatives and research are warranted.