EDQM’S SUSANNE KEITEL ON PH. EUR. HOT TOPICS In the last of four presentations at the opening plenary session of the international conference on the European Pharmacopoeia held in Tallinn, Estonia, EDQM Director Susanne Keitel reviewed EDQM’s role in the European regulatory framework, the ninth edition of Ph. Eur., and four “hot topics” now on the forefront of Ph. Eur. attention. The four topics, each of was discussed at a breakout workshop, are: ● setting pharmacopeial standards for biotherapeutic products ● the control of elemental impurities ● new technologies, and ● excipients, other components and international harmonization. I have the feeling that I could do away with about half of my presentation, because the previous speakers have already touched upon the topics that I was planning to cover. But as one of my colleagues just said to me, repetition is always good for the learning effect. I was planning to talk a little bit about the EDQM and the European regulatory framework, and you have already heard a lot about that. But I am definitely going to speak about the Ninth Edition of the European Pharmacopoeia — what is special and specific about it. And then I am going to finish by touching on current hot topics. The idea is to provide you with sort of an introduction or a teaser to the workshops in order to avoid your running away this afternoon and enjoying the sunshine outside and visiting the beautiful town of Tallinn. So I am trying to do my best to keep you here with us at the conference. I have to start with a few words about the parent organization of the EDQM, the Council of Europe. It is the oldest pan-European organization, founded in 1949, which has as a goal the development of European common and democratic principles. It should not be confused with the European Union. It has 47 member countries, and it is headquartered in Strasbourg. The core values of the Council of Europe are the protection of human rights, pluralist democracy and the rule of law. You can see on the right-hand side, first of all, a map which shows all the member states of the Council of Europe, and you can see that it extends far more to the east compared to the European Union. For example, the Russian Federation is one of the member states, Turkey, Ukraine, Azerbaijan…. And then you see on the top, the flag that was created in the ‘50s for the Council or Europe, which now-a-days is also used by the European Union, and also by the EMA. So every time you see this flag in the future you will ask yourself, is this indeed the European Union or is it not the Council of Europe? Now the EDQM, our European Directorate for the Quality of Medicines & HealthCare, is a Directorate of the Council of Europe…based on the ‘Convention on the Elaboration of a European Pharmacopoeia,’ which was signed by eight ‘visionary’ countries, as [Moderator Jean-Louis Robert] has referred to them, in 1964. Our mission is to contribute to a basic human right, which is access to good quality medicines and healthcare… Now we have heard already that a lot of things have moved forward in the last fifty years or so. The European Pharmacopoeia started in 1964 with eight visionary founding member states of the Council of Europe. Today, the European Pharmacopoeia and the EDQM have 38 signatory parties – that is 37 countries plus the European Union. And you see them depicted in green. You can also see 26 of the currently 28 observers in yellow, and you can see that they really come from all over the world and cover all continents. And marked in the pink, you can see two parties with whom we have a very special relationship. These are our sister pharmacopeias in Japan and the United States. And [Swissmedic’s Petra Dorr], I think, has already referred to the Pharmacopeial Discussion Group [PDG] – slow but steady – and we will come back to that. With the signature of the Convention on the Elaboration of a European Pharmacopoeia, a country commits to making the standards of the European Pharmacopoeia legally binding on their territory. The last country that decided to accede was Ukraine in 2012. But I thought it would be worthwhile – and I think [Paul-Ehrlich-Institute President Klaus Cichutek] has already referred to it – to make a note about the special status of the European Pharmacopoeia in the European Union pharmaceutical legislation. It is referred to in the pharmaceutical legislation and Directive 2001/83/EC, for example, in the annex. There it is clearly stated that with respect to the quality part – they are talking about marketing authorization applications – all monographs and general chapters of the European Pharmacopoeia are applicable. So the European Union pharmaceutical legislation makes the European Pharmacopoeia binding. Only in the case when there is no text in the European Pharmacopoeia, reference can be made to a national pharmacopeia of a member state. So each member state may require observance of its own national pharmacopeia. And only if there is no monograph either in the European Pharmacopoeia or in any one of the member states pharmacopeias, reference can be made to a third country pharmacopeia. What has to be submitted in a marketing authorization application is a bit more extensive – for example, as regards validation of the analytical procedures contained in the monograph. And this is stated in the legislation. This is a topic that we have heard a lot about before the coffee break, and I am quite happy because basically I can restrict myself to showing this slide. I don’t have to explain to you again that there is a close collaboration between the European Union – the Commission, the lawmakers, and the European Medicines Agency – and the national authorities of all our member states, be they EU or not. If I talk about national authorities, I am really talking about licensing authorities and inspectorates – OMCLs, the control laboratories, but also national pharmacopeia authorities and us, the EDQM of the Council of Europe in Strasbourg. And it has been said before, clearly the mission is to make best use of scarce resources to ensure complementarity and to avoid duplication. And clearly, as I said, [like] the European Medicines Agency in London, the EDQM could not do anything without the unwavering support of the member states and the national authorities. Ninth Edition of European Pharmacopoeia Enough about the position of the EDQM and the European regulatory framework. We are now going to talk about the Ninth Edition of the European Pharmacopoeia. I would like to start by talking a bit about the pharmacopeia. As you all know, the governing body is the European Pharmacopoeia Commission, which holds three sessions per year, so it meets three times, in Strasburg. It is composed of 38 delegations, the 37 member states plus the EU. And all delegations are entitled to submit up to three representatives. What is unique about the European Pharmacopoeia Commission is that all technical decisions are taken by consensus. And you can imagine that this is not always the most easy task to achieve. So there is no voting. If there is one member state that does not agree, forget about it. But I think over the last 52 years or so, everybody on board has learned that it is compromising. It is give and take. So normally it works. And the European Pharmacopoeia Commission is also very happy that quite a number of the current 28 observers regularly come to the sessions of the European Pharmacopoeia Commission to participate in its work. This is the portfolio that the European Pharmacopoeia currently covers. As you can see, more than 50% of the texts are still dedicated to…chemically defined substances. You can see that the next group of importance are herbals. Herbals are gaining more and more attention. Then you can see that basically the pharmacopeia covers a lot of different issues from dosage forms, radiopharmaceuticals, vaccines – be they human or veterinary – plastic materials, blood derivatives, antibiotics, medicinal gases, homeopathy and also biologicals – again, a topic which is getting more and more important. I am quite proud to say that the European Pharmacopoeia really is a success story. It is a unique example of an efficient collaboration between member states – 37 member states who have decided to contribute their resources to a collaborative process, instead of trying to develop their own national standards. And this is also imbedded in the rules of the European Pharmacopoeia: that as soon as there are two members states interested in one topic, it is brought to the attention of the European Pharmacopoeia Commission and normally added to its work program…. The member states can only develop an individual monograph if there is nobody else interested. And secondly, they have to notify the European Pharmacopoeia Commission. The opportunities I believe are evident in saving our resources, and also that the outcome is always a harmonized text, which does not need any further harmonization. The concrete outcome that we talked about with the European Pharmacopoeia 9th Edition are 2,329 monographs and 358 general texts which have been published in the 9th Edition. I have mentioned the European Pharmacopoeia Commission – the governing body – is very important. But at least equally important are the numerous experts who participate in the elaboration or revision of the text of the European Pharmacopoeia. Currently we count 58 active groups of experts in working parties. This is something that changes over time because new working parties are created as new topics arise or others are disbanded.