We are celebrating two important jubilees this year – it’s been 20 years since HALMED was established as a regulatory body for medicinal products and medical devices, and 10 years since HALMED started taking part – as a full-time member – in the work of European regulatory network and in the implementation of European procedures. What we could highlight as a challenge is the complexity of the regulatory system for medicines at the European level, but this is exactly what makes that system so solid. I believe that we have a very good system, which certainly has room for further improvements, says Prof. Siniša Tomić, PhD, director of the Croatian Agency for Medicinal Products and Medical Devices, for Diplomacy&Commerce. HALMED actively participates in the registration procedures of innovative medicines, i.e. granting approval for placing medicines on the market. Since innovative therapies are approved through a common procedure for the entire European Union, our experts are increasingly involved in these procedures, Mr. Tomić adds.
1. HALMED celebrates 20 years of existence this year. What would you single out as the greatest challenges over the past two decades, and what would you point out as the greatest achievement of the Agency?
Today, two decades after its establishment, HALMED is recognized based on its work as a quality agency committed to its public health role, and HALMED‘s activities in many segments are recognized as good practice not only on a European, but also on a global scale, and we should certainly be very satisfied with this. We can rightfully say that we have an extremely effective regulatory system for medicines in Croatia today. We have a series of accreditations that allow us to conduct procedures for supervision and inspection of the quality of medicines, not only in Croatia but also in Europe and the rest of the world. In an increasing number of drug approval procedures in the EU, manufacturers choose Croatia as the leading member state in decentralized approval procedures, and we are increasingly more active in procedures where the drug is approved centrally for the entire EU and in procedures where the EU evaluates the safety profiles of drugs. Also, next year we will mark the 50th anniversary of the establishment of the drug safety monitoring system in Croatia, while, just to compare, the World Health Organization‘s umbrella Program for International Drug Monitoring has only existed for six years more. HALMED inherited the existing pharmacovigilance tradition in Croatia, and continued to develop it, achieving notable success. Recently, the activities of monitoring the supply of medicines to our market have become more intense. This is an extremely dynamic process where an occasional standstill can happen, for a whole number of reasons. With our commitment, we strive to ensure the most efficient management of possible shortages and, with the implementation of appropriate mechanisms, ensure continuous supply of the market. It is important to emphasize that in everything we do, the well-being of patients is at the center all the time. Protecting the health of all users of medicines and medical devices is our basic mission, and we will continue to act in this direction. I am glad to say that HALMED successfully copes with all challenges and continuously improves its expertise. Over the course of these years, we have maintained the quality of our work despite the increasing number of procedures we undertake both nationally and at the European level, which is certainly an indication that we are on the right track!
2. What are the most common problems you face and how far does Croatia keep up with the world when it comes to medicines, treatment and the health system in general?
Given our public health role, we are constantly engaged in finding solutions to achieve the sustainability of our reguatory system. All the time, we apply new ways of optimizing and rationalizing administrative procedures, because the time we save to the users of our services also means saving resources. In this way, we are trying to facilitate the position of manufacturers of healthcare products, i.e. the holders of approval, in this economic situation, bearing in mind the patients as the end users who need to ensure the availability of effective and safe therapy. I would highlight informing and conducting public campaigns on issues of interest to public health as a field where new strides can always be made, especially in the light of increasing patient awareness of the importance of health information, as well as the potential of new technologies and platforms. Our patients are increasingly proactive and informed, primarily thanks to new technologies. They regularly turn to us in search of information in the field of medicines, and we successfully answer their questions. We recognize the importance of providing information and educating patients on issues important to their health. I believe that with the provision of new information based on the latest scientific achievements and evidence, as well as with further monitoring of medicines, citizens’ confidence in medicines and the health system in general will increase.
3.We know that innovative therapies are important for people’s health, but to what extent do those for whom they are intended actually know that they exist? What is the role of the doctor, you as an institution, the public…?
HALMED conducts intensive cooperation with other stakeholders of the European regulatory system for medicines, such as the European Medicines Agency, the European Commission and the Council of Europe, as well as with stakeholders from the Croatian health system – the Ministry of Health, the Croatian Institute for Health Insurance, the Croatian Institute for Public Health and others. To the users of our services, i.e. the pharmaceutical industry and the applicants, we provide education and conferences intended at bringing the procedures we conduct even closer to them, encouraging them to better understand them and providing them with a perspective from our point of view, which can be useful to them in submitting new applications. In this way, the procedures related to the approval of medicines are optimized and their arrival on the market is accelerated. Educations from our scope of action that we hold for doctors and pharmacists strive to get as close as possible to the healthcare worker who is closest to the patient. Likewise, we have intense and direct cooperation with patients and their associations, and this is an extremely important relationship with civil society that we will continue to nurture and develop. In addition, we ensure availability and open access to information for all healthcare workers and the general public. HALMED promptly informs healthcare workers, as well as other participants in the healthcare system and the general public in Croatia, of all news related to the use of innovative, as well as all other approved drugs, through a series of direct communications.
4. What are the standards for approving innovative therapies/ medicines?
Before reaching the market and becoming available to patients, all medicines go through extensive tests and approval procedures that check whether they meet the strict requirements of quality, effectiveness and safety of use.
As a rule, innovative medicines are approved by the so-called centralized marketing authorization procedure, valid for all EU member states, which is under the jurisdiction of the European Commission and the European Medicines Agency. In this procedure, the European Medicines Agency carries out a scientific expert evaluation, and based on this evaluation, the European Commission grants them a marketing authorization that is valid for all EU member states. This authorization procedure in the EU is mandatory for cancer treatment drugs, as well as for drugs for the treatment of HIV/ AIDS, diabetes, neurodegenerative diseases, autoimmune diseases and other immune dysfunctions and viral diseases; medicines obtained through biotechnological procedures (e.g. genetic engineering), medicines for advanced therapy (gene therapy, somatic cell therapy or tissue engineering) and medicines for the treatment of rare and serious diseases (so-called “orphan medicinal products”). HALMED evaluators participate in the mentioned procedure as members of EMA commissions and working groups.
5. What are the procedures when the Agency determines which drug will be approved for marketing? And what is the role of large pharmaceutical companies here?
Before the drug becomes available to patients, it goes through a complex path of development and numerous researches. Only a small fraction of the tens of thousands of substances that are investigated each year prove promising enough to continue their development and conduct non-clinical and clinical trials. An even smaller part proves to be really successful in treatment and is ultimately approved for marketing. During non-clinical trial phase, the manufacturer examines the effect of the drug in the laboratory by conducting pharmacological, pharmacokinetic and toxicological tests of the drug on animals, cells, tissues and other models. If the data in these trials prove to be satisfactory, clinical trials on humans are then carried out. Only after all these steps have been successfully completed, the company that develops and tests the drug submits a request for approval to place the drug on the market. In Croatia, medicines are placed on the market based on the approval of HALMED or the approval of the European Commission. HALMED approves medicines for Croatia through a national procedure, where the medicine is placed exclusively on the Croatian market, and through joint European medicine approval procedures, where the medicine is approved for several member states at once. On the other hand, the Commission grants approvals for medicines in the so-called centralized procedure, by which the medicine is simultaneously approved for all member states of the European Union, including Croatia. The Commission grants approval based on an assessment conducted by the European Medicines Agency, in which experts from HALMED are very actively involved. This assessment is made according to pre-defined criteria and established norms and standards in Croatian and European regulations and guidelines connected to medicines, and according to the latest scientific findings. This ensures that only the medicines that have passed all the necessary tests and approval procedures by the regulatory authorities and that are thus proven to be effective, safe and of appropriate quality, are available to patients.
6. In what direction are modern therapies developing, primarily in terms of prices? They are quite expensive. Can we expect these prices to be more affordable and thus more available the near future?
Innovative drugs bring new hope and represent important advances in therapeutic options for patients, especially those suffering from rare and serious diseases for which until recently there was no cure. However, at the same time, they represent a challenge for national health systems that need to ensure timely health care and the availability of these, as a rule, very expensive drugs. An important role here is played by the Croatian Institute for Health Insurance, which implements several financing models for particularly expensive medicines. In the regulatory sense, there are different ways to indirectly and directly reduce costs for producers, i.e. holders of approval, for example, the optimization of administrative procedures that we implemented at HALMED. Also, the European Medicines Agency has launched the PRIME initiative, which is based on improved interaction and early dialogue between regulatory authorities and drug manufacturers to optimize development plans and speed up evaluation, so that these drugs can reach patients earlier. This initiative shortens the time it takes for certain medicines to reach the market, which consequently leads to a reduction in costs for manufacturers and could ultimately affect the lowering of medicine prices. This helps patients to benefit from therapies that can significantly improve their quality of life as early as possible.
7. What would you single out as the most important segments of your business in the sense of innovative therapies?
HALMED actively participates in the registration procedures of innovative medicines, i.e. granting approval for placing medicines on the market. Since innovative therapies are approved through a common procedure for the entire European Union, our experts are increasingly involved in these procedures. I am satisfied with what has been achieved and that I can say that our experts are recognized as extremely high-quality evaluators, completely equal to colleagues from other European countries. I can exclusively confirm to you that HALMED has been nominated as the chief rapporteur in the process of innovative drug approval, which is a great recognition for Croatia and a confirmation of our quality among much larger member states. It is important to emphasize that, especially with new drugs, it is necessary to ensure their faster access to the market and to patients. Through various European initiatives of which we are a member, mechanisms are being developed to ensure the availability of various therapies. In fact, a large part of our activities is aimed at harmonizing, aligning and finding the most effective ways to facilitate and speed up the process of getting medicines to patients. The well-being of patients is definitely at the center of our activity. Our permanent goal remains the improvement of the health of each individual patient and public health in the Republic of Croatia, and we will continue to deal with these and other issues of public health importance through our activities and campaigns.