REKS Yearbook 2019
In 2019 we launched the Estonian Medicines Verification System (EtMVS). All Member States of the EU, as well as Norway, Switzerland and Liechtenstein have joined the European Medicines Verification System, which is the first of its kind. Greece and Italy will aso join the system in the coming years.
REKS was founded by the Association of Pharmaceutical Manufacturers of Estonia (RTL), the Estonian Association of Pharmaceutical Wholesalers, and the Estonian Pharmacies Association. The work of the organisation is managed and organised by a six-member Supervisory Board chaired by Riho Tapfer as of 26 October 2016. The Estonian Society of Hospital Pharmacists is also represented in the Supervisory Board via the Estonian Hospitals Association. On a daily basis, the activities of REKS are managed by Raul Mill. As of 2018, REKS employs three people. REKS would like to thank all the founders and members of the Supervisory Board for their substantial and significant contribution to the system's development. Special thanks also goes to the members of RTL whose loans and advances made it possible to build the system.
As of the end of 2018, the Estonian Medicines Verification Organisation (REKS) was convinced that the end-user software used in Estonia would be finished on time. A large part of the software was technically ready by the beginning of 2019 and users started implementing the processes.
In addition to the technical preparedness, it was also important to raise the awarness of people working in hospitals, retail pharmacies and wholesale about the importance of verifying medicines.
In cooperation with the State Agency of Medicines and professional societies, important information was forwarded to a large number of people in order to ensure the conscious preparedness of all parties.
In January 2019, REKS signed contracts with a significant number of end-users of the system and assisted them in creating administrator accounts.
On 29 January 2019, the REKS FMD Implementation Seminar took place and was attended by all parties involved in the implementation of the system: end users, marketing authorisation holders, representatives of manufacturers of medicinal products and a representative of the State Agency of Medicines.
During the seminar, end users provided an overview of the pilot period of the system. The State Agency of Medicines pointed out the most important aspects of the guideline that lays down the rules for the handling of serialised medicinal products in Estonia. REKS reiterated the most important points related to the use of the system and interfacing. The process of verifying the authenticity of serialised medicinal products was also described in detail at the seminar.
During the peak period of joining, around 20 accounts were created per day. REKS also had to provide technical suport, as dowloading the EtMVS certificate was a new process for the users. The end user software developers who supported clients with the system interface were also very helpful.
By 9 Februrary 2019, all end-users handling seralised products had joind and many of them had also started verifying the authenticity of medicinal products. The technical interfacing process was successful. Following this, the users primarily had to deal with changing and implementing their operational processes.
At the exact scheduled time, on 9 February 2019 at 01.00 Estonian time (00.00 CET), the system went live. It is noteworthy that it took place at the same time in all the countries that had joined the system, as provided for in the project.
Prior to the launch of the system the following risks were considered: end user connection capability, marketing authorisation holders uploading the data of serialised products to the system, and the real capability of the end users to verify medicinal product packages.
In reality, these risks did not materialise as such. What proved to be a problem was a large number of false positive alerts, which triggered the need for a transition period in almost all the countries that had joined the system.
Several representatives of Member States also introduced the sanctions imposed on organisations that fail to verify the authenticity of medicinal products. Reportedly, no penalties were imposed in any of the countries during the transition period. By the end of 2019, the transition period had been concluded in seven countries.
In Estonia, the State Agency of Medicines extended the transition period twice. The Estonian transition period will end on 1 September 2020.
The Medicines Verification System was established based on the assumption that generally only prescription medicinal products will bear the unique safety features.
After the official implementation of the system it became apparent that in addition to prescription medicinal product packages, some non-prescription medicinal products, medicinal devices or medicinal products that have to bear a core but whose code is meant for another system than the European Medicines Verification System may also bear a similar code.
There were also packages that had the corresponding security code printed on them. However, because the product had been released to the market before 9 Feburary 2019, the data of the 2D code of the medicinal product package had not been uploaded to the system.
In all the above mentioned cases, the EtMVS system issues an alert when the package is being scanned. If it is not a serialised product, it will be considered a false positive alert. In 2019, there were, on average, 1500 - 2000 false positive alerts per week in Estonia.
For example, a false positive alert is generated if the product data has not been uploaded to the system. In this case, the end user will receive an alert code NMVS_NC_PC_01 or "unknown producr code". The alert indicates that the unknown product code (GTIN) does not match any medicinal product in the system. This alert code is also issued when a medicinal device or a non-prescription medicinal product is being scanned and their data are not in the system
The various EMVS alerts are categorised into levels 1-5, according to the danger of potential falsification. Level 5 category alerts indicate products with the highest potential falsification:
) (this alert was removed from level 5 category due to its frequency but was added back in 2020).
According to EMVO statistics, the vast majority of the false positives were related to unkown product codes that led to attempts at decommissioning a product that was already decommissioned.
Reducing false positive alerts became the main priority because it was one of the deciding factors for concluding the transition period.
During the development of the system, EMVO provided statistics about the development phases of the countries. Following the implementation of the system, the statistics now reflect the interfacing of end users and On-boarding Partners (OBPs).
Statistics are also provided on the number of scans according to the size of the market and on the number of alerts in relation to the total number of products scanned.
Monthly meetings in Brussels will continue, in order to better harmonise the processes and to make them more efficient.
Due to the large number of false positive alerts, a transition period was established in Estonia and in most of the countries that had joined the system.
The main objective of establishing the transition period was to ensure the availability of medicinal products to patients/clients. After the transition period, every alert must be considered a potential falsification. In such cases, the medicinal product package must be separated from the others until the end of the procedure which, in turn, may affect the availability of medicinal products.
The transition period means that, regardless of the alerts, in most cases the medicinal product may be dispensed. In the light of the above, REKS analysed the alerts generated as a set. Following the analysis of the alerts, we contacted the marketing authorisation holder (MAH) in order to determine the cause of the alert and to find a solution for it.
If during the transition period the following code is generated: PCK_22 “Package inactive”, the medicinal product must not be dispensed. The package must not also be dispensed if any other alert is generated and the issuer has a suspicion that the package might be falsified.
The code “Package inactive” means that the medicinal product package has already been decommissioned (the status is also inactive if the package has been marked as “Exported”, “Destroyed”, etc.). In this case the person who decommissioned the package could have been an employee of the same institution, but the package may already have been inactive when it arrived at the institution. The State Agency of Medicines will determine the cause of this alert.
At first, the transition period was established in Estonia until the end of the first half of 2019. However, since the number of alerts was considerably high at that point – more than 8,000 alerts per month – the transition period was extended until the end of the year.
At the end of 2019, although the number of alerts had decreased, the number was still high, which is why it was decided to extend the transition period again until September 2020.
In the second half of 2019, approximately 65% of alerts were related to unknown product codes (GTIN). These include, for example: products with a code intended for the Indian market, products without marketing authorisation, and medical devices that do not need to bear security features and whose security feature data are not in the system.
In addition, a great many false positive alerts are related to exceptions announced by the marketing authorisation holder and/or exceptions accepted by the State Agency of Medicines. For example, these include alerts related to medicinal product statuses that have been changed accidentally or data uploading problems, including medicinal products that have been produced before 9 February 2019.
In light of the above, in 2019 REKS analysed whether it would be possible to automate the alert procedure in Estonia so that, in the event of an alert, a response would be provided to the end-user 24/7, regardless of the day and time.
In case of system interfacing or a notification sent via an online form, an automated system would allow feedback to be provided on whether a specific alert requires the procedure to be carried out or whether it is a previously confirmed exception.
The software development will be completed by the end of the first half of 2020, which will allow the dependability of the system to be tested before the end of the transition period.
The maintenance expenses of the system are borne by the marketing authorisation holders who are obliged to upload the data of security features to the corresponding national database via the EU-HUB, which is managed by the EMVO, and also to pay the database management fee in that country.
Fees and financial models differ from country to country. Several Member States have implemented a flat fee system where all users of the database pay the same fee.
Estonia has also implemented the flat fee system, however added a turnover-based exception to take into account the characteristics of the Estonian pharmaceutical market and the needs of domestic manufacturers of medicinal products.
Like end users, marketing authorisation holders have to sign a contract with REKS to use the database. This was an extensive process that began in 2018 and continued in 2019.
After the system went live, communication between REKS and marketing authorisation holders increased because of alerts that required information from marketing authorisation holders for further investigation.
During the alert procedure, REKS contacts the marketing authorisation holder to specify the reasons and solutions of alerts that they have investigated.
The cooperation has been successful and information from marketing authorisation holders has reached REKS in sufficient time. Operational information exchange has made it possible to send the result of the alert procedure to the sender (generally pharmacies and hospital pharmacies) in good time and to end the procedure.
Some marketing authorisation holders contact REKS on a weekly basis to share the alert reports of their products.
The impact of Brexit on the implementation of the project was also considered as a risk in 2019.
There are four marketing authorisation holders who have determined their cooperation agreement with REKS due to Brexit. However, these MAH's have signed a new contract with REKS in the new country of operation of the enterprise. In conclusion, Brexit has not affected the activities of REKS and the feared mass exit of marketing authorisation holders from the Estonian market has not taken place.
REKS performs continuous technical monitoring of the functioning of the database as well as spot checks on data processing.
With regard to data processing, REKS must ensure that only marketing authorisation holders who have signed a contract can upload data to the database. If it is detected that a marketing authorisation holder without rights has uploaded data, they will be contacted and the process of siging a contract will being.
REKS must ensure that only end users who have signed a contract and have a valid activity licence can verify the authenticity of medicinal products via the database.
The State Agency of Medicines supervises the database and the process of verifying the authenticity of medicinal products in Estonia. In June 2019, REKS and the State Agency of Medicines entered into a contract that ensures that the State Agency of Medicines has access to the reports and data necessary for their work.
Due to the delegated regulation, NVMOs responsible for the administration of the system have to carry out regular security audits. In the fourth quarter of 2019, REKS conducted a security audit. The audit methodology complied with the requirements of ISO 27001.
The audit identified that the operational processes of REKS and the technical operation of the system fulfils the requirements.
The audit assessed the security aspects of both the processes of the organisation and the physical and IT elements. Moreover, it assessed the ability of the system to ensure continuity and the results of the security audits conducted by Arvato, the technical administrator of the system.
Although the system went live on time and its key functions have been permanently ensured, the development activities and planned upgrades of the system continued in 2019 as well as at present.
As an essential component, reports have been produced for National Competent Authorities or NCAs (generally Medicine Agencies), some of which were completed in 2019 but the development will also continue in 2020.
The development activities carried out by the technical administrator of the system, Arvato, are coordinated and evaluated by a quality assurance and technical working party appointed by 16 countries. All 16 countries have chosen Arvato as their development partner. In 2019, regular Skype meetings and monthly transnational meetings continued; a representative of Arvato was also present at those meetings and participated in the decision-making of the most important development activities.
In 2019, EMVO started to create a working group whose task was to develop solutions that would make procedure data readily available to parties through EMVS. Also, it was intended to reduce the number of alerts through more efficient communication and data sharing.
Looking back, the implementation of FMD was successful in Estonia in 2019.
The system goes live on time - 9 February 2019 at 00.00 CET.
All parties involved in verifying the authenticity of medicinal products have joined, signed contracts and REKS has created administrator accounts for them
Data for 10 102 batches have been uploaded to the system.
Data for 3552 product names has been uploaded to the system.
We live in a world that requires us to adapt to changes quickly. 2019 was a remarkable year in a number of respects. Brexit is an event that definitely deserves the status of an important historical milestone. However, the global spread of COVID-19 that started in 2019 in China – a place quite distant to us Estonians in our everyday life – has had an even greater, extraordinary impact on our lives. In most cases it seems that until we are directly affected by the materialisation of risks, we think we are immune. But we are not! These few examples illustrate the fact that we live in the moment and often cannot even predict the near future.
COVID-19 has significantly changed the world and, in addition to different aspects of economy and technology, has made us think about the development of medicinal products and their availability. As well as their authenticity. China has decided to start producing generic medicines themselves. This is probably partly related to the spread of COVID-19. As we all know, a large number of things are produced in China today. Some are excellent and some not so excellent. There was a time when things produced in Japan were, in many areas, synonymous with bad quality. Japan learned from this and incorporated technologies that took their production to world-class level. However, there are two sides to every coin. At times, the quality was so good that the technology became morally obsolete even though it still worked flawlessly. For example, the sound equipment produced at the end of the last century. There is nothing really wrong with that, but the quality is, of course, reflected in the price and that in turn affects the market for new products, i.e. the circulation speed of products. China is also striving for better quality, which is definitely positive. It is too early to say today how it will affect the global market and the availability of medicinal products if China starts to develop its own pharmaceutical industry. Will it create new risks regarding the authenticity of medicinal products that we should already take into account today or will it reduce them?
2019 was the year the Medicines Verification System was launched, and it was also a challenge for the technical operation of the system. In addition to technical preparedness, the preparedness of all people to implement the new system and to reorganise their operational processes accordingly must be highlighted. It is true that every system needs some time to establish itself. The need to reduce the amount of false positive alerts has proven to be the most important issue in regard to the implementation of the verification of authenticity of medicines. On the other hand, shared pain brings people together and we are pleased to say that the cooperation in the implementation and live use of the system has been successful with all parties. This year, we are faced with new challenges, one of which is definitely ending the transition period in Estonia, but I believe that we have created a solid foundation and can successfully work together to improve the system.
– Raul Mill, Chariman of the board of REKS