Italy's AIFA: Agenda for Regulatory Leadership

Interview Exclusive: AIFA’s Agenda for Regulatory Leadership

Pharm Exec shares an interview conducted last month by Chiara Moroni, a public relations executive, pharmacist and former member of the Italian Parliament, with Dr. Sergio Pecorelli, Chairman of the Italian Medicines Agency [AIFA]. AIFA carries a high profile in global regulatory circles due to its precedent-setting work on advanced cost-effectiveness metrics as well as novel risk-bearing schemes like conditional reimbursement. It is also unique in Europe in combining roles as both a medicines licensor and negotiator of reimbursement prices under the Italian universal health care system. In the interview, Pecorelli outlines the progress of recent AIFA initiatives to raise the timeliness and efficiency of decision-making, although real challenges remain – especially in reconciling its mandate at the level of individual regions, where the industry sees significant discrepancies in price negotiations and access times due to a fragmentation of authority and process overlaps – William Looney, Editor in Chief.

The Italian Medicines Agency (AIFA) was created relatively recently. What has changed about the access of drugs to the Italian market since the agency was established?

AIFA has just turned 10 years old, but it has grown quickly over a short period of time. With its powers and dynamics, it plays a crucial role in defining drug policies in our country, becoming a point of credible and authoritative reference to European and international level. The primary objective of a regulatory agency is to ensure timely access to innovative medicines, and to make them safe and effective for all those who have a real need. In a universal healthcare model like Italy’s, this guarantee must recognize the sustainability of the health care system. Marketing authorization must be accompanied by the decisions on reimbursement of drugs. And in this AIFA is truly unique in the panorama of European regulatory agencies, as it combines licensing and negotiating activities. This has allowed us to test Health Technology Assessment [HTA] tools, strategies for negotiating pricing, and conditional reimbursement with drug manufacturers. Managed Entry Agreements – agreements between the welfare system and manufacturers for reimbursement under certain conditions – are used by AIFA to ensure the sustainability of costs and establish a direct relationship between the clinical outcome and the real–life use of the medicine. We believe the choice of pharmaceutical policy adopted by Italy, and promoted by AIFA, has been successful in granting access to new medicines.

AIFA also promotes independent research, supporting those projects that do not meet the interest of pharmaceutical companies as in the case of rare diseases. Over the course of five different open bidding competitions, AIFA has supported more than 200 projects with a financial commitment of almost € 100 million. We provide high technical and scientific advice and policy for the Government, the Parliament, the State-Regions Conference and recently became the only central competent authority in the field of clinical trials in our country. But that's not all. In recognition of the importance of knowledge transfer, to promote the prescription suitability and proper use of the drug, in recent years we have intensified the dissemination of public and independent information through communication initiatives aimed at the general public and health professionals. Some examples are a communication campaign that is currently airing regarding the use of medication during pregnancy and the use of medicines in children. Both of these have received a great response from both the scientific community and general public.

What should the international pharmaceutical industry know about AIFA that it might not realize today?

AIFA is an agency on the cutting edge, looking to the future and to new global challenges. We’ve become a worldwide reference point for the activities of Health Technology Assessment. In recent years, AIFA has focused on a "key" activity, which is the Scientific Advice, providing scientific advice to companies on a national and European level even in the early stages of drug development. In doing so, we help to ensure that important scientific questions regarding the efficacy and safety of medicines are answered during the process leading to the creation of a new molecule. I believe that AIFA’s recent capabilities, its long-term vision and our policy of transparency and efficiency constitute attractive elements for the international pharmaceutical industry and investments in research and development in our country.

What is the relationship and division of tasks between the European regulatory authority EMA and national regulatory authorities as AIFA?

In general, issues that concern the placement of the product on the pharmaceutical market in Europe, the specific rules related to certain types of drugs and the promotion of research in areas such as orphan drugs, fall within the competence of the EU. The definition of pharmaceutical policies and the relative allocation of resources are national competencies and include, in addition to the marketing authorization (MA), decisions on pricing and reimbursement of drugs. In Italy, AIFA makes those decisions. The European medicines regulatory system is based on a network composed of the regulatory authorities of the 31 Member States of the European Economic Area, the European Commission and the European Medicines Agency (EMA). This network - through which systems for the exchange and sharing of experiences, information, skills are implemented - is what is unique about the EU regulatory system.

The EMA is responsible for scientific evaluation, mainly with regard to innovative and high-technology drugs, developed by pharmaceutical companies for use in the European Union. For these drugs, in fact, it is mandatory to have a centralized procedure for marketing authorization, which allows the holder to market the drug in the entire European Union.

Most drugs are not covered, however, within the scope of this centralized procedure and are authorized by the competent national authorities, such as AIFA. The company that intends to market a new drug may require authorization in more than one Member State, provided they do not fall within the scope of the mandatory centralized procedure. Or, a second procedure--the mutual recognition procedure—may be required, through which the company that obtains the authorization in one EU member state, may also obtain recognition in other EU countries. This process allows European countries to share scientific evaluations. The rules and requirements are the same everywhere, regardless of the authorization procedures adopted at national level.

How does AIFA balance the need for patients to access the most innovative therapies with the objective to reduce spending on pharmaceuticals in Italy?

The AIFA is committed to implementing prescribing and reimbursement strategies suitable to ensuring timely access to care and economic sustainability. I mentioned earlier the innovative approaches that make Italy the leading country in conditional reimbursement of medicines.

The ability of the Agency to conduct negotiations with companies has already made Italian drug prices among the lowest in Europe for certain key anticancer drugs.

Of course, drug policies represent a crucial challenge for policy makers, since upon those policies depends not only the availability of safer and more effective therapies (and therefore the possibility of improving the health and quality of life of citizens), but also the sustainability of financial systems, given the impact of pharmaceutical expenditure on total health expenditure and, in turn, health expenditure on public budgets.

The market entry of the first new drug for chronic hepatitis C is, for the high costs and the huge expectations of patients, a clear example of the ethical and economic challenges that public health authorities will face in the near future. All medications, in fact, have to overcome a long and rigorous pathway before landing on the market, whether they are intended for audiences more restricted, such as new products, or whether they are used in millions of patients like the old “blockbuster.” Scientific knowledge is providing us with molecules that will soon be able to improve, for example, the treatment of pancreatic cancer and lung cancer. There are also many new drugs coming to market at a total cost of billions of euro that rely on advanced platforms like nanotechnology, which until recently seemed relegated to the distant future. All this requires regulatory agencies to reshape their future strategies, as the regulatory world as we have known is about to change forever.

AIFA is ready to face these challenges. However, we are aware that drug regulation policies must be framed within the context of complex health policies that require global, integrated approaches. Sustainability of the system in a changing world cannot be separated from the transfer of knowledge. There is also a need for a culture change in health care workers and citizens, covering education to health and disease prevention through the promotion of healthy lifestyles. It is recognized by the scientific community that healthy lifestyle habits, such as a balanced diet and regular exercise, make it possible to prevent most of the chronic diseases, which account for 80% of the diseases that we encounter today. On the other hand, thanks to advances in science, the average age of the population has risen and it is becoming more and more imperative that, in addition to adding years to life, we must ensure life to years.

In other words, we engage so that the quality of life and quantity of life in good health in an aging population will continue to increase. Europe has set itself this goal by using clinical, diagnostic, therapeutic and innovative information. To this end it has launched the European Innovation Partnership on Activeand Healthy Ageing, which I have the honor to represent on behalf of Italy. Within this partnership, our country, along with Scotland and Spain, leads the Action Group on prescribing and adherence to therapies. I believe that investing in prevention, especially in view of the emerging problem of microbial resistance, and the confluence of new and old infectious diseases, can no longer be ignored as, unfortunately, it has been in Italy in recent years.

How does AIFA perceive the “value” of a drug? How is this similar or different than in other European countries?

Many actors contribute to the proper functioning of the healthcare system. In AIFA’s opinion, at the center must be the patient, not only as a recipient and user of drugs, but also as an informed and aware stakeholder, able to represent their needs and expectations and return valuable feedback for those who, like AIFA, have to make difficult fiscal choices. I think the old economic-centered vision must be overcome. That vision that saw the drug only as a cost factor; we must now consider, instead, the value of a drug in relation to the amount of health produced, and also its ability to reduce the total costs related to the disease.

AIFA is also aware of the strategic role of the pharmaceutical industry for research and testing of new drugs. Given the increasing complexity of production processes and the development and the number of high-cost biotechnology products that will soon be on the market, the pharmaceutical industry can play an important role in the knowledge economy, as long as they know how to combine the legitimate pursuit of profits with the ethical aspects of social responsibility.

Physicians, pharmacists, and family care-givers also play key roles. All actors are crucial in ensuring the appropriateness of prescribing and adherence to treatment, as well as to monitor the effects of drugs (in terms of efficacy and safety) in real life.

We have heard of a possible imminent reform of AIFA; what can you tell us about this?

I very much welcome the commitment made by Minister of Health Lorenzin for a reform of AIFA. To face the challenges that I have tried to outline, it is necessary, as the Minister explained, to have an agency "enhanced" in skills, with regulatory instruments that will allow it to take technical and scientific decisions in a timely fashion, and to make these decisions actionable and uniform across our entire national territory. We must operate in a more flexible and efficient way as well. With its current structure and staffing, the Agency has achieved truly amazing goals, but now we need a further leap in quality, which will allow AIFA to become the first pharmaceutical hub in Europe. I’d like to add that AIFA is the European agency with the lowest number of staff per million inhabitants, compared to the other countries. It has, in fact, only 400 employees, the same as in Denmark, which has only a tenth of the population of Italy. Meanwhile the French regulatory agency, which has just been reformed, has over a thousand employees and is not concerned with, for example, price and reimbursement and the assessment of pharmaceutical dossier submissions.

Chiara Moroni is Director of Public Affairs for GLOBALHealthPR partner Noesis Communicazione. She can be reached at chiara.moroni@noesis.net.