III-1.3 : Annales de la régulation (Annals of Regulation), 2009, Volume 2, Directed by Thierry Revet and Laurent Vidal

The major part of these annals is consecrated to health regulation. They begin by a summary by Laurent Vidal, which highlights both the interdisciplinary nature of healthcare regulation, and the need to find a balance, to restore order, in a word, to regulate. In this respect, Professor Frédérique Dreifuss-Netter emphasises in her article entitled {Ethique et Régulation en santé} (Ethics and Regulation in Healthcare), regulation’s very particular role. On one hand, science, progress, research and development (which all entail investment), are compared on the other hand to ethics, patients’ rights, and regulation. More or less formalized systems coexist, either from self-regulation or consecrated in the form of heterogeneous committees on ethics, which appear to be different attempts at emulating regulation, and most of which derive from the Kouchner Act of 4 March 2002 ({Loi Kouchner}). The heterogeneity of this poorly organised system reflects the complexity of the questions raised by the healthcare sector. After the initial description of the fundamental problems in healthcare regulation, the {{ {first part} }} of the study is devoted to healthcare regulators. Professor Cécile Moiroud first introduces {la regulation et les agences sanitaires françaises} (regulation and French public health authorities), a presentation that bears witness to the diversity of regulatory systems: research committees, commissions, and biomedical agencies, committees in charge of protecting vulnerable people, all of which compete in producing ‘soft law’ rules, alongside and ethics, which is becoming a principle of regulation in healthcare. Therefore, the clinical ethics centre of the Hôpital Cochin in Paris was created to allow patients to ask for motivated opinions on situations they encounter, even though these decisions do not bind the doctor, who retains his decision-making responsibility. Alongside ethics committees, public health authorities are in charge of evaluating and managing risks, in an approach dictated by the idea that everyone has a right to healthcare security. In this framework, the notion of a ‘product’ is cardinal, because the major areas of healthcare regulation are built around categories of products (animal health, human health, dangerous products). These public health authorities are exceptional for the diversity of their organisation: (i) new communities of institutions through the creation of Public Interest Groups ({groupements d’intérêt public}), which promote the development of institutional relationships between different actors in the sector, for any relevant public or private legal person may join; (ii) new public institutions, where public health authorities replace private structures or are born from the merger of public or private organisations, or where they seem to be independent from the administration and above its supervision. The variety of structures corresponds to a broad palette of responsibilities, subtly decanted in function of each authority’s nature: (i) expertise authorities in charge of evaluating (French Food Safety Agency—AFFSA), (ii) authorities in charge of informing and monitoring (Sanitary Surveillance Institute—INVS), (iii) sanitary inspection authorities, national decision-making agencies (French Anti-Doping Agency—{agence de lutte contre le dopage}), or regional decision making agencies (Regional Hospitalisation Agencies—ARH). Separating decision-making from expertise; information from management; these are the principles that form the basis for healthcare regulation’s institutional framework. Next comes an article by Mr. Laurent Degos, President of the French National Authority for Health ({Haute autorité de santé}), introduces the authority he manages and reminds us of its concern for (i) improving the therapeutic and humane character of healthcare, (ii) reinforcing the system’s organisational coherency, (iii) providing guidance as to the optimal allocation of resources in order to promote the long-term viability of healthcare’s solidary method of financing. As concerns these goals, a quality healthcare system is defined as a system where “healthcare is as effective, safe and accessible as possible, and provided in the fairest and most efficient way.” In order to achieve these goals, the HAS, an independent public authority with legal personality, publishes recommendations and scientific opinions for the representatives of the State, sick insurance funds, healthcare professionals and patients. The HAS is therefore at the crossroads between different actors of the healthcare sector, which allows it to cover all viewpoints in any given scientific approach, and to seek to harmonize these points of view in order to take a decision acceptable to all. At the same time, the HAS is also a regulator at the service of professionals, through the recommendations on “good practices” it publishes, and whose concrete and everyday application is ensured through the procedure of hospital certification, where hospitals are evaluated by an independent third-party. The role of the HAS was enlarged by the Social Security Finance Act of 2008, which gave the HAS responsibility for recommending the most effective strategies for care, prescription and management of different illnesses. The qualitative goal means always promoting public debate on the quality of the French healthcare system, involving patients in quality improvement schemes, having clear, coherent, and understandable tools at hand to improve professional practices, strengthening the place of ‘quality’ in decision making. These are the stakes facing the HAS for the future. Mr. Jean Marimbert, director of the French Agency for Sanitary Safety of Healthcare Products (AFSSAPS), then presents his article called {La régulation et sécurité sanitaire des produits de santé} (Regulation and sanitary safety of healthcare products), which is marked by the paradox of healthcare regulation: healthcare regulation’s lack of economic concern. The AFSSAPS, a public administrative establishment under the responsibility of the Ministry of Health, is emblematic of this paradox, which one must look beyond in order to understand the AFSSAPS’ economic impact in terms of healthcare costs and the way its activity interferes in the path to market access. Furthermore, the independence inherent to regulation seems to be absent from the AFSSAPS, but we can see that this independence is truly present through its production of reference documents, evaluation criteria, and delegation of sanitary inspection powers. The AFSSAPS’ activities are therefore similar to regulatory activities, and certain core parallels can be drawn: a concern for modifying behaviours, diverse methods of intervention (opinions, recommendations, orders…), an obligation to be legitimate and therefore to produce intelligible procedures in order to be credible. The AFSSAPS is therefore a form of regulation, without needing to become independent from the Ministry of Health, and thereby participates in the revival of public intervention. The presentation of the AFSSAPS is followed by the presentation of the {Agence Française de Sécurité Sanitaire des Aliments} (AFSSA – French Food Safety Agency), by Madame Pascale Briand, the general director of the AFSSA, which was created in response to the food safety crises of the 1980s and 1990s, and to contribute to the protection and improvement of food sanitation. Some of the missions of the AFSSA that seek to strike a balance between product risk and benefits include the management of nutritional and health safety risks, evaluation, surveillance, representation, and the granting of veterinary authorisations. The difficulty of finding such a balance is twofold: it resides in the polymorph nature of risk, in human, economic, media, and legal aspects, but also in the specificities of each branch or each product, which means that they each need a specific approach. Moreover, health regulation is certainly a national issue, but it is also European. In this respect, the first part of the study includes a presentation of the European Food Safety Authority (EFSA), by Madame Catherine Geslain-Lanéelle, its executive director. This Authority, in charge of managing food crises and improving public confidence, operates according to a principle of separation between evaluation and risk management. The goal is therefore to evaluate food safety risks on a European level, and to publish appropriate, opportune and detailed communication in order to provide the public with coherent and detailed information. The EFSA includes an executive board, a consultative forum at the heart of the strategy of cooperation, open to Norway, Iceland and Switzerland, and a Scientific Committee in charge of producing opinions and convening meetings of experts. In five years’ time, the Authority’s workload has considerably increased. Now, it is necessary to best respond to risk managers’ expectations. Therefore, an accelerated quality examination programme has been put into place. It is also necessary to organise a worldwide risk analysis: therefore, scientific programmes on the European level are being developed, but also internationally, with the signature of agreements on information exchange with the United States, New Zealand, and Australia. Globalisation creates new risks, so it is necessary to improve cooperation, externalise work, and deepen the projects decided upon by the consultative forum. After this presentation of regulatory authorities, Mr. Michel Lièvre, a member of the pharmacology department at the University of Lyon 1, wrote an article entitled {Rôle de l’expertise à l’AFSSAPS} (The role of expertise at the AFSSAPS), which introduces the question of the role of the expert within regulation. The work of commissions, committees, and groups of experts, as well as outside experts, constitutes the foundation of the AFSSAPS’ decisions. Three major functions are therefore assigned to experts: health product surveillance, preliminary supervision of biomedical research, and supervision by the healthcare products commission. Each commission has a decision making process based on expert opinions, working with agency evaluators and sometimes outside experts. Despite the existence of two categories of experts, a common regime of obligations is applicable: impartiality, independence, public declaration of interests, scientific competence, availability and assiduity, but also an obligation of discretion and professional confidentiality. This general presentation of the role of expertise in the AFSSAPS is completed by Professor Joël Moret-Bailly’s article, {un point de vue externe sur le rôle des experts au sein des agences de securité sanitaire} (An outsider’s point of view on the role of experts within public health authorities), which presents the activity of experts from a legal point of view. Expertise is therefore a means by which the administration makes decisions, whose legitimacy is linked to the legitimacy of the expertise. Therefore, illegal conflicts of interests by experts to the Court of Cassation are a criminal offence. Experts are, however, special actors in administrative decision-making, and they are subject to a particular normative framework. The prevention of conflicts of interest is managed by a declarative system, and experts are subject to Article 25 of the Act on the Rights and Obligations of Civil Servants ({loi portant droits et obligations des fonctionnaires}). These rules are unfortunately incomplete. They do not manage negative conflicts of interest, and contracts reported under the “anti-gifts scheme” are not accessible…It would therefore be necessary to give a bigger role to employers, increase disciplinary sanctions, and involve patients in order to avoid “intellectual corruption”. Faced with the non-respect of rules on conflicts of interest, deontological procedures are a possible, didactic, symbolic and precise response, but criminal sanctions should remain fundamental. It would be judicious to enlarge the application of such sanctions to pharmaceutical laboratories, in order to punish those who benefit from experts’ silence. The {{ {second part} }} of the study is consecrated to medicine regulation, with an article by Jean-Marc Husson, Professor and co-director of Eudipharm, and Jean Pierre Osselaere, Professor of Pharmacy and Managing Director of EPMC Pharma, on {l’ICH, conférence internationale sur l’harmonisation des demandes techniques pour l’enregistrement de nouveaux médicaments à usage humain} (The ICH, international conference on the harmonisation of technical requirements for registration of pharmaceuticals for human use). The ICH was born from the realisation that a harmonisation of the rules and standards regulating the technical contents and obligatory format of pharmaceutical registration requests was necessary in order to facilitate the development of innovative medicines. The Steering Committee, at the heart of the ICH, has included, since its creation, the World Health Organisation, Canada, Switzerland, the European Union, Japan, and the United States. Rounds of conferences are organised in order to reflect on common themes and to prepare a consensus around the adoption of a tripartite harmonised text. This harmonisation activity is based on scientific consensus and fulfils a need for global security. It is nevertheless essential to limit the duration of proceedings and to lower the cost of developing innovative medicines. The {{ {third part} }} concerns the regulation of healthcare costs, presented first from the point of view of the articulation between obligatory health insurance programmes and complementary health insurance plans. Professor Anne-Sophie Ginon’s article {les instruments de régulation : les enseignements du nouveau partage entre assurance maladie obligatoire et assurance maladie complémentaire} (Regulatory Instruments: The lessons from the new repartition between obligatory and complementary health insurance plans) presents the evolution of this articulation, and especially the reversal of the traditional opposition between these two approaches to the risk of illness. Thus, we see that legislation¬—beginning with the Evin Act ({Loi Evin}) in 1989, continuing with the Universal Medical Coverage Act ({CMU}) in 1999, and finally the 2004 Health Insurance Reform Act ({réforme de l’Assurance Maladie})—has implemented a specific right to complementary health insurance coverage, which tends to nuance the original opposition between complementary and obligatory schemes. Common rules now apply to all organisations providing complementary health insurance, and public policy rules shape the procedures for subscription and pricing, which makes the complementary sector resemble the obligatory one. At the same time, the State, through tax incentives, also encourages the rapprochement between the two regimes by setting a common goal for both of them. “Solidarity Plans” fight the classic application of principles of selection and proportionality, while “Responsible Plans” attempt to make patients aware of their responsibilities and implicate them in public healthcare cost management schemes, especially through the “coordinated care procedure” ({parcours de soins coordonnées}), by which patients must choose a general pratitioner, and must obtain a referral from him before visiting a specialist, in order to be fully reimbursed by their obligatory and complementary health insurance plans. These policies are supported by tax incentive measures, which, however, raise a question relating to the interdiction of State Aid in European Community Law, derived from Article 87 of the Treaty establishing the European Community. The European Court of Justice has already stated that organisations managing complementary health insurance schemes are businesses, subject to national and European competition law. Similarly, the exoneration from paying the tax on insurance contracts for “Solidarity Plans” was already deemed to be a State Aid by the European Commission. It remains to be seen if tax exonerations on “solidarity” and “responsible” health plans can be justified. To this effect, a recommendation by the European Commission says that State Aids that are social in nature are justified as long as they are attributed to individual consumers without product discrimination. The principle of solidarity is at the heart of the justification for tax breaks, which raises difficulties as to the reasons for signing “responsible plans”. It would therefore be better if Parliament paid closer attention to Competition Law when implementing rules for complementary health care insurance. This European approach to French health insurance regulation is completed by the comparative approach of Mr. Bruno Palier, a researcher at the National Centre for Scientific Research (CNRS). In his article {Quelle régulation pour la santé ? Un regard comparatif} (Which regulation for healthcare? A comparative approach), Mr. Palier begins by noting that the differing global evolutions in health spending come from divergences in defining priorities. Therefore, national health systems offer basically free and equal access to healthcare; health insurance systems organise a repartition of the supply of healthcare between the public and private sectors, leaving the patient to freely choose between the two; and liberal systems repose upon the liberty of choice and technological performance, often to the detriment of equal access. Yet, faced with these three systems, a general observation can be made: the augmentation in healthcare spending is due to longer life expectancy and an ageing population, freedom of access to healthcare and competition between healthcare providers, and doctors’ fees. Therefore, we must ask ourselves how to define healthcare regulation, and what system should be chosen? If State regulation, such as practiced in Great Britain, allows for a very precise control of the healthcare budget, it also means long waiting times for access to basic health services. Similarly, health spending can be regulated by the market, like in the United States, where the whole population, except for the very destitute and the aged (Medicaid and Medicare), has to voluntarily contract private health insurance. Germany has a third example of regulation, enabled by staunch doctors’ unions that participate in permanent negotiations. Faced with these three systems, France has not chosen a model, and is trying to find a balance, through a long string of reforms, between financial viability, equal access to care, the quality of care, and patient freedom. The regulation of experimental practices in the medical field is the subject of the {{ {fourth part} }} of the study. As professor Jean-Pierre Boissel points out in his article on {L’efficacité des thérapeutiques: régulation par la méthodologie} (The efficacity of therapeutics: regulation by methodology), it is fundamental to strike a balance between medical initiatives and their efficacy. Therefore, the instrument of measurement—here, the clinical study—is essential, and the evolution towards a supervision of such studies began in the 19th century, following two essential steps: the construction of a conceptual, methodological, and statistical corpus to define the way such studies should be carried out, followed by government regulation taken to the European level. The goal of such supervision is to offer guarantees to therapeutic research, (i) against risk, first and foremost, by profiting from empiric advances and research into probability, (ii) secondarily, against bias, and especially the placebo effect, regression toward the mean, and the natural evolution of illness, by implementing a comparison process between treatment, placebos, and natural evolution, and conducting a double-blind study. It is also necessary to guarantee against poor quality, by controlling the respect of rules, by publishing guidebooks (of which certain are official documents), and by fighting against fraud. Therefore, in this field, professional supervision used to be the role of the State and of regulators who supported the application of such methods, introducing a rigidity that was incapable of following the necessary evolution in clinical practice, especially as concerns rare illnesses. Regulation of experimental practices includes the Committee for the Protection of People ({comité de protection des personnes}), in order to protect the subjects of experiments, researchers, and government authorities. To this effect, Mr. Jean-Paul Demarez, a consulting practitian, wrote an article entitled {Le comité de protection des personnes} (The Committee for the Protection of People), which reminds us that the idea began in the 1970s, when the importance of regulation via ethics was realised. The first step towards normative supervision was the Helsinki Declaration of 1964, which adopted the first Ethical Code on human experimentation: the research-doctor’s equivalent of the medical practitioners’ Hippocratic Oath. This first movement also included the beginning of legal regulation, pioneered by the {Institutional Review Bords} (IRB) in the United States, which authorise and supervise research projects in instutions carrying out human experimentation, and can order the suspension or abandonment of such research in case of failure to respect the rules. The IRB therefore fulfil the role of a special administrative police. Furthermore, the {Food and Drugs Administration} gave the Helsinki Declaration a quasi-obligatory status in 1975. This impulsion reached the other side of the Atlantic, and brought about the spontaneous creation of ethics committees in France, which were completed by the creation in 1983 of the {Comité consultative national d’éthique pour les sciences de la vie et de la santé} (National consultative committee on ethics in life- and health-sciences). The parallel existence of both structures led to a restructuration that created {Comités Consultatifs de protection des personnes dans les recherches biomedicales} (CCPPRB – Consultative committees for protection of people in biomedical research), which provide opinions to the competent authorities of a special administrative police force, created by law. Furthermore, the CCPPRB give their opinion on the respect of laws protecting people participating in biomedical research. In parallel to French evolutions in this domain, the European Union began to reflect upon the question, with a guide on “Good Clinical Practices for Medicine Experiments in the European Union”, published in July 1990, followed by contacts between Europe, Japan and the United States, through the ICH process, which show a desire for rationalisation, in order to guarantee the quality, security and effectiveness of medicine. Therefore, the ICH finalised its Good Clinical Practices, and recommended that they be given force of law. The European adoption of these recommendations took the form of two European Directives (2001/20/CE and 2005/28/CE), whose transposition in France gave birth to the {Comités de Protection des Personnes} (CPP – Committees for the Protection of People), the successors to the CCPPRB. The CPP is an independent organisation with legal personality, including 14 members from different fields, divided into two colleges—one medico-scientific, one social—that give opinions, either obligatory, or requiring adoption through a consultation or assent procedure, on the conditions of validity of research. In conclusion, regulation of experimental practices has gone from ethics to law, basically framing research ethics in order to prevent human biology engineers from surpassing medical practitioners. Finally, Messrs. Gunter Hennings, consultant, and Jean Huges Trouvin, professor, analyse the tendencies in European Union biotechnology regulation, showing that public health protection measures must be taken. Only products having a positive benefit-risk analysis should be approved. However, methodological questions are also addressed, and regulation should attempt to make better use scientific results in their regulatory activities. The {{ {fifth part} }} of the study concentrates on the regulation of medical accidents, and begins with an article by Mr. Dominique Martin, director of the ONIAM, on {l’aléa thérapeutique et l’office national d’indemnisation des accidents médicaux} (Therapeutic Hazards and the National Office for the Compensation of Medical Accidents), who describes the principles applying to victim compensation, as provided by the law of 4 March 2002, which implements the right to be compensated by national solidarity funds when the healthcare professional did not commit a professional error. The procedure implemented is both administrative and amiable, essentially free, fast, and simple. Recourse to a Court of Law is nevertheless possible: the amiable procedure is an alternative, freely chosen by the parties involved. Its organisation is based on the principle of democratic healthcare, by promoting active participation by healthcare actors, patients, and professionals. Three structures are at the heart of this system, the {Commission nationale des accidents médicaux} (CNAM—National Commission on Medical Accidents), dependent upon the Ministries of Health and Justice, and in charge of establishing a list of experts and supervising the harmonisation of the compensation scheme; a {Commission Regionale d’Indemnisation des Accidents Médicaux} (CRCI—Regional commission for indemnifying medical accidents), the one-stop access points for victims, spread out across the country; and lastly the ONIAM, a public administrative establishment that provides CRCI with the necessary means of operation, indemnifying victims and intervening as a substitution to defaulting insurers. The scheme is organised according to a rather complex procedure. However, as concerns the results of this scheme: the number of requests has increased, as has the number of compensations, which attests to its utility. This success should not, however, mask the risk of dispersion amongst the various means available for the compensation of corporeal damages, which might become a source of inequality between victims; nor the necessity of this scheme to be able to operate under the conditions stipulated by law, such as the respect of certain delays and the legitimacy of its decisions. This presentation of victim compensation is followed by Professor André Lienhart’s article on {La réduction du risque anesthésique: passé, présent et futur} (Reduction of Anaesthetic Risk: past, present, and future), which highlights the link between surgical risk reduction and the progress made in the domain of anaesthetics and resuscitation: identification of target risk reduction areas, elaboration of guidelines by scientific associations, availability of safer machinery, and a reaction (in the form of a December 1994 Decree) to chronic underfunding of anaesthetic departments by hospital managers. The new means employed have been evaluated in order to shed light on their appropriateness, their possibility of creating unintended side effects, and also to identify remaining risks. Looking at these evaluations, residual mortality is still the essential preoccupation, and this sort of reflection is not limited to anaesthetics and resuscitation departments. The general tendency is towards risk reduction and the limitation of adverse effects. Therefore, the approach to anaesthesia must be harmonised, recommendations must be made on the more human aspects of anaesthesia (like what to do before and after a complication occurs), and to familiarise professionals with the demands of medical experts: the key to understanding their professional responsibility. Great progress is yet to be made in this domain: a change in strategy and culture, the development of a more systemic approach, rather than the current defensive approach taken to legal risk. The second portion, and fifth part, of the study concerns vulnerable patients, such as the aged, to whom Professor Jean-March Husson, Jean Marie Vetel, head of the geriatrics ward at the Hospital of Le Mans, as well as Laurence Hugonot-Diener, geriatrist, and Patricia Mallière, director of international regulatory affairs at Servier Group, have devoted an article, highlighting the underrepresentation of the aged in clinical studies, even though they are large daily consumers of medicines. Clinical studies must be carried out in order to understand the specificities of vulnerable patients. Nevertheless, no specific regulatory framework exists in France or in Europe, even though the European Commission is taking new initiatives in this domain. The ICH has only one document specifically devoted to the aged. This should not cause us to forget the necessity of adapting research to the augmentation in life expectancy. These are precise criteria that should guide clinical studies on aged people: a correct and stratified representation, criteria of eligibility in conformity with the protocol, and free and informed consent. Moreover, studies to be conducted in geriatrics should be very precise, and highly supervised: the protocol, methodology and modelling should all be designed to optimise the results of research. The second category of vulnerable patients is pregnant women, who are the subject of an article by Timothée Fraisse. He underlines the information and research deficit, as well as the simplistic classification of the dangerousness of medicine established by the Food and Drugs Administration, despite the fact that this classification serves as a worldwide reference. Although the European Union has tried to develop its own classification, it has not become widely recognised. And yet, the situation of pregnant women is particular, especially because of the legal situation of the embryo and the risk of exposition to medicine it has while in the womb, which does not always have immediate consequences, but which can be revealed years later. The regulation of research on pregnant women reflects official reticence to allow trials to be conducted on pregnant women: there is an agreement between major medicine-producing countries and pharmaceutical laboratories not to conduct clinical trials on pregnant women unless all toxicity tests conclude that the treatment is innocuous. In France, only the direct, individual benefit that the mother and child might obtain authorises such tests. Faced with this strict limitation, it is not surprising that the market of pregnancy remains narrow, given the risks associated with research. Children are the last category of vulnerable patients studied by Messrs. Eric Sergheraert, Doctor of Pharmacology and Doctor of Law, and Jean-Pierre Osselaere, Doctor in Pharmaceutical Sciences, in an article called {Les étapes de la mise en œuvre du règlement pédiatrique} (The Steps in Implementing the European Regulation on Paediatrics). This European initiative began in 2000 and was achieved in 2006 with the adoption of European Regulation 1901/2006, prescribing the obligation to conduct clinical studies according to a Paediatric Investigation Plan (PIP) for all new medicines, to create a paediatric committee within the European Medicines Agency, a six-month extension of the Complementary Protection Certificate (CPC) in exchange for conducting paediatric studies according to an approved PIP, and included in the European Union budget financing for research on medicines intended for paediatric patients. Following the adoption of this Regulation, the Paediatric Committee was inaugurated on 26 July 2007, which evaluates PIPs that were submitted for pre-approval, according to three procedures meant to ensure a therapeutic interest for children and not to delay authorisation for medicines intended for adults: early requests for PIP approval, requests for a derogation of the obligation to conduct studies according to a PIP for medicines without interest for paediatrics, and requests for a delay in the obligation to conduct paediatric studies according to an approved PIP. Also, the Regulation planned for the implementation of a European network by 26 January 2008, in order to coordinate studies, bring scientific and administrative talents together, and avoid useless repetition of studies and trials. Since 26 July 2008, requests for marketing authorisations for a new market are valid only if the results of their studies were conducted according to a PIP. Finally, since 26 January 2009, the Regulation proposes, besides the six-month prorogation of the CPC, a new type of Marketing Approval for paediatric use when a pharmaceutical laboratory conducts paediatric trials according to an approved PIP for a medicine protected by a CPC. Trials on orphan medicines are also planned for, and the Regulation grants them extra years of marketing exclusivity when trials are conducted according to an approved PIP. The study ends with an article by Messrs. Eric Sergeheraert, Doctor of Pharmacy and Doctor of Law, and Jean-Pierre Osselaere, Doctor in Pharmaceutical Sciences, the {{ {sixth part} }} of the analysis, entitled La réglementation des médicaments à usage humain en France et en Europe (Human Medicine Regulation in France and in Europe). This article presents applicable legal dispositions for human medicine organised according to three steps. Before the Marketing Authorisation, the {{first step}} encountered by a pharmaceutical laboratory that has discovered a new medicine is intellectual property protection. Three regimes apply to pharmaceuticals: pharmaceutical inventions, biotechnological inventions, and the European Community patent. For the first regime, three separate statuses exist: exclusion from patent for methods of treatment, surgery or diagnosing; the patentability of medicines, and the patentability of a new use for an already-patented medicine. There is a developing protection of biotechnological inventions, spearheaded by Directive 98/44/CE, whose transposition into French Law limits the protection to the parts of genetic sequences that are directly linked to the function used. This is based on incomplete scientific analysis and is contrary to common law for patents. Also, it is possible for a third party to obtain a patent on the same sequence if they can prove that there is another application for that sequence. The transposition of the directive is therefore source of many divergences, which means it is necessary to harmonise the European patents system, especially since the Community Patent is not an adequate response. Even though it provides a single regime, and potentially a single jurisdiction for the first hearing following the Commission’s proposition of 1st August 2000, it would be better to follow the Commission’s plan to create a single interpretation and a single regime, in order to improve proximity with users. The {{second step}} is that of clinical trials, modelled after the principles of protection of human rights, and respect of human dignity, and regulated by Directive 2001/20/CE. This text defines the role of (i) ethics committees, whose favourable verdict must be obtained in order to start trials, and which protect participants; (ii) authorities in Member States, who authorise trials, verify the conformity of the trials with good clinical practices, and good manufacturing practices, and thereby have the power to suspend or forbid the trial, as well as (iii) promoters and investigators who must obtain the aforementioned authorisations and verdicts, with the possibility of modifying the protocol, and are required to notify any serious undesirable effects and events to the authorities and committees, as well as of the end of the study. This scheme could be improved by a European Regulation that would improve harmonisation: application of ICH standards by ethics committees, clarity of the scheme, balanced composition of ethics committees, revision and precision of definitions used by competent authorities, obligatory reports on suspicions of undesirable effects, optimisation of the use of collective data, these are food for thought for the upcoming reform. The {{third step}} is that of the Marketing Authorisation, which can take two forms: a centralised procedure detailed in EC Regulation n° 726/2004, where the authorised product has, for an unlimited period of time, the same rights in every member state as though it had been authorised in that state; and a national authorisation procedure with mutual recognition procedures between states, according to the dispositions of Directive 2001/83/CE. There are other particular cases for Market Authorisations, however. First of all, the Temporary Use Authorisation (TUA) can be used for compassionate use of unauthorised medicines, and is derogatory to the classical procedure. Thereby, unauthorised medicines can be provided to patients suffering from serious or invalidating illnesses that cannot be treated by authorised medicines. Created by Directive 2001/83/CE, this procedure was transposed into French Law with some notable particularities: the conditions for authorisation, duration and suspension are identical to those of Directive 2001/83/CE, but French law distinguishes group TUAs from individual TUAs. Also, three categories of medicine benefit from a special regime. First of all, generic drugs have a special regime, and can benefit from an exemption of pharmacological, toxicological and clinical trials, or an exoneration from bioavailability trials, they have an abridge procedure and are subject to special industrial property rights. Next, bio-similar drugs (me-too drugs) can be submitted to extra examination if they have significant differences with the reference medicine, or submitted to the regime for generics if they correspond to the definition of a generic. Industrial property rules and market authorisations are very specific to this category, and poorly unified at the European level. Finally, orphan drugs enjoy commercial exclusivity because of the narrow market to which they are addressed. The orphan character of the drug is controlled by the EMA, which adds and removes such drugs from the register of medicines. Once the Market Authorisation has been obtained, the {{fourth step}} concerns the lifespan of the authorised medicine. First and foremost, obtaining a French or European CPC allows for compensation of the period between the request for a patent and the market authorisation, which offers a reduced level of protection. Next, and once the Marketing Authorisation has been obtained, any modification of the Marketing Authorisation must be approved. Procedures differ depending on the type of modification requested, which has led the Commission to announce its intention to implement a clearer and more understandable framework, as well as a better-harmonised regime. Furthermore, the lifespan of a medicine includes its commercialisation, and especially advertising taken in a broad sense, which is limited according to the medicine itself: it is forbidden to advertise any prescription medicine or any medicine containing narcotics; it is forbidden to provide advantages to healthcare professionals. Also, distribution and wholesale of medicine is subject to authorisation, and has strict conditions, such as how medicine is warehoused, and how qualified the employees are. Although importation and parallel distribution is tolerated within the European Union, they are largely limited by particular procedures and specific conditions. The last aspect of the lifespan of a medicine concerns pharmacovigilance, or the obligation to nominate a person responsible for monitoring and notifying any undesirable effects to competent member state authorities, who themselves have a responsibility for monitoring authorised medicines. This allows us to take account of the density and the number of evolutions in medicine regulation, which still has a number of challenges to overcome in terms of clarity, harmonisation and surveillance.