Sandor Kerpel-Fronius

Pharmaceutical Medicine (PM) was defined by its founding pharmaceutical physicians as a “medical/scientific discipline concerned with the discovery, development, evaluation, registration, monitoring, and medical aspects of the commercialization of medicines, for the benefit and the health of the community.” Conceived as a medical specialty, the discipline encompassed several health-related professions and occupations, such as medicine, pharmacy, clinical pharmacology, drug safety and pharmacovigilance, pharmaceutical sciences, biology, health economics and others. Historically, non-medically qualified medicines development scientists from health-related disciplines have gradually grown into the medical roles within pharmaceutical organizations, regulatory agencies, and contract research organizations and today physicians and non-physicians lead drug development groups. Medicines Development Sciences (MDS) has been accepted as an alternative name. The practice of the disciplines involved in PM/MDS has evolved from an occupation to be accepted as a distinct profession, by meeting well established criteria. Despite thousands of health professionals participating today in medicines development, their awareness of the existence of this discipline, and its evolution from occupation to profession is low. The lack of professional identity and a clear career path have been identified as key factors limiting the advancement of this profession. This position paper aims to consolidate PM/MDS as an advanced profession in health sciences and propose a career path that is envisioned and championed by educational standards setting organizations like the International Federation of Association of Pharmaceutical Physicians and Pharmaceutical Medicine (IFAPP), PharmaTrain, and Global Medicines Development Professionals (GMDP) Academy with education and training as pillars for its achievement.

Pharmaceutical medicine professionals have to face many ethical problems during the entire life span of new medicines extending from animal studies to broad clinical practice. The primary aim of the general ethical principles governing research conducted in humans is to diminish the physical and psychological burdens of the participants in human drug studies but overlooks many additional social and ethical problems faced by medicine developers. These arise mainly at the interface connecting the profit-oriented pharmaceutical industry and the healthcare-centered medical profession cooperating in medicines development. In 2002, the International Federation of Associations of Pharmaceutical Physicians and Pharmaceutical Medicine developed the International Code of Ethical Conduct for Pharmaceutical Physicians for providing ethical advice for their members to manage the frequently competitive goals characteristic for their specialty. The ethical framework compiled by the International Federation of Associations of Pharmaceutical Physicians and Pharmaceutical Medicine serves its members by presenting morally acceptable or inacceptable behaviors in frequently encountered controversies arising from competing industrial and healthcare interests in medicines development. The authors selected this format to encourage reflection and debate for finding optimal moral conclusions in specific issues. Many recent examples of serious scientific-ethical misconduct, such as the oxycodone tragedy, the recommendations of unproven useless occasionally dangerous therapies during the coronavirus disease 2019 pandemic, and the withdrawal of many papers containing non-reproducible results, contributed to the increasing loss of trust by the public in science including pharmaceutical medicine. We are convinced that the ethical guidance developed by the International Federation of Associations of Pharmaceutical Physicians and Pharmaceutical Medicine will encourage its members to reflect intensively on optimal ethical behavior in drug development for strengthening the trust of society in innovative new medicines. Finally, considering the increasingly active participation of non-medically trained scientists in producing and applying complex biological medicines, distant monitoring methods coupled together with artificial intelligence technology in innovative clinical trials, the Ethics Working Group recommended already in 2017 measures to optimize their smooth cooperation and underlined their joint ethical responsibilities in guarding the safety and human dignity of trial participants.

The pharmaceutical medicine course at the Semmelweis University of Budapest, Hungary, was initiated as part of the Innovative Medicines Initiative (IMI is the main program, IMI-PharmaTrain is one of the IMI projects) Pharmaceutical Medicine Training Programs (16 IMI Call 2008/1/16). The aim was to extend training in the development of pharmaceutical medicine to those EU member states where no such education was present. The final program envisaged the development of a cooperative education supported by universities located in Central and Eastern Europe. It was considered to be the economically and scientifically most viable approach to combine the expertise from these countries to form a united teaching staff and provide education jointly for young professionals of the region. Semmelweis University was selected to manage this coordinated program. In this report, we describe the organization and functioning of this international university-based pharmaceutical medicine education project called the Cooperative European Medicines Development Course (CEMDC) and evaluate its successes and shortcomings. During the pandemic, the educational course was interrupted. The follow-on program is reorganized as a postgraduate MSc course named “Semmelweis Pharma MBA” and will be started in 2025. It will continue the established PharmaTrain educational tradition. However, it will deal in more detail with the transition from basic pharmacological to industrial research, as well as biopharmaceutical formulation and manufacturing and marketing aspects of medicines development.

A gyorsított gyógyszer engedélyezési eljárások a súlyos, életet veszélyeztető betegségek kezelésére kifejlesztett gyógyszerek piacra jutását átlagosan 3-4 évvel rövidítik meg. A gyorsított eljárással forgalomba hozott szerek többsége egyben árva gyógyszernek is minősül, melyek fejlesztése és forgalmazása jelentős anyagi, tudományos és adminisztratív támogatást élvez. Ilyen módon a két gyógyszerfejlesztést támogató program társadalmi következményei szorosan összefonódnak. Az utóbbi években a gyorsított engedélyezési eljárást és az árva gyógyszer minősítést az esetek többségében a genetikailag azonosított ritka onkológiai betegségek esetén veszik igénybe a gyártók. A gyorsított eljárások elbírálása általában köztes végpontokon alapszik, melyek gyakran nem korrelálnak a végső kimenetellel. További gond, hogy a gyártók gyakran lassan vagy egyáltalán nem végzik el a végleges forgalomba hozatalhoz szükséges vizsgálatokat. Ilyen módon sokszor kiemelkedően drága, de nem kellően kivizsgált gyógyszerek is bekerülnek, illetve gyakran hosszabb ideig is az egészségügyi ellátásban maradnak. Komoly etikai és gazdasági gondot jelent, hogy a gyorsított eljárással forgalmazott gyógyszerek egy része nem eredményez klinikai hasznot, viszont jelentős anyagi megterhelést jelent a társadalom számára.

Editorial: Reviews in: regulatory science

This paper discusses the effects of armed conflict, economic sanctions, and natural catastrophes on ongoing clinical trials. We suggest that• stopping the accrual of new patients in clinical trials under such extreme conditions is acceptable.• research participants already receiving trial medication in such disruptive situations are to be considered highly vulnerable due to their medical dependency for ongoing treatment according to the approved clinical study protocol.• based on the present experience in Ukraine and Russia, we conclude that finishing ongoing trial treatments according to approved or amended protocols should be considered to be an ethical obligation of trial sponsors irrespective whether trial disruption is due to war, economic sanctions, or natural catastrophes.• it is important to devote more attention to the ethical challenges raised by such fundamentally disruptive situations to clinical trials generally in any region of the world.

Gene therapy orphan medicinal products constitute a unique group of new drugs which in case of hereditary diseases are usually administered only once at an early age, in the hope to provide sufficient gene product to last for the entire life of the patients. The combination of an exceptionally large single payment and the life-long clinical follow-up needed for understanding the long-term benefits and safety of gene therapy, represent new types of scientific, financial, social and ethical challenges for the pharmaceutical industry, regulators and society. With special consideration of the uniqueness and importance of gene therapy, the authors propose a three points plan for a close cooperation between the pharmaceutical industry and society to develop orphan gene therapy. (1) In fully transparent health technology negotiations a close and long-lasting, contractually fixed cooperation should be established between the manufacturers and local health-care stakeholders for sharing the medical and scientific benefits, the financial risks as well as the burdens of the post-authorization clinical and regulatory development. (2) The parties should agree on a fair, locally affordable drug price without the usually very high premium price calculated to compensate for the low number of patients. In case of high manufacturing costs, the companies should offer prolonged, 15–20 years long payment by installment with risk-sharing, especially considering that the late outcome of the treatment is unknown. Society should assist scientifically and financially organizing a specific patient registry, treatment in specialized hospitals and adequate long-term follow-up of patients, the coordinated management of financial transactions related to the risk sharing program. (3) The post-authorization treatment and prolonged observation of additional new cases coordinated by society should provide real world data needed for the modern complex regulatory evaluation of gene therapy products by the competent authorities. We assume that fair sharing of the benefits and risks as well as a well-organized cooperation of society with the industry in collecting real world evidence might result in better drug evaluation and improved accessibility due to lower prices. The outlined concept might support gene therapy more efficiently than the presently requested outstandingly high prices.

The complexity of developing and applying increasingly sophisticated new medicinal products has led to the participation of many non-medically qualified scientists in multi-disciplinary non-clinical and clinical drug development teams world-wide. In this introductory paper to the “IFAPP International Ethics Framework for Pharmaceutical Physicians and Medicines Development Scientists” it is argued that all members of such multidisciplinary teams must share the scientific and ethical responsibilities since they all influence directly or indirectly both the outcome of the various phases of the medicines development projects and the safety of the research subjects involved. The participating medical practitioner retains the overriding responsibility and the final decision to stop a trial if the well-being of the research subjects is seriously endangered. All the team members should follow the main ethical principles governing human research, the respect for autonomy, justice, beneficence and non-maleficence. Nevertheless, the weighing of these principles might be different under various conditions according to the specialty of the members.