Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Coping with Drug Shortages through regulatory governance: Approaches and perspectives to a complex global challenge ***

Dr. Sarah Büchner (Abschlußjahr: 2016)

Summary
In developed countries, considerable surplus of pharmaceuticals generally exists. As new products are regularly added in pharmacies, the actual amounts of medicinal products appear high and Drug Shortage (DS) unlikely. However, upon closer inspection of certain classes of medicinal products, such as antibiotics, injectables or cancer products, the portfolio of products is in fact limited and decreases evenly.
In the majority of markets, shortages are rare due to maintenance of equilibrium between the quantity of the products supplied and the quantity of demand. By contrast, the healthcare market is inflexible and constrained in its abilities to react effectively to demand and supply changes. Low price responsiveness influences manufacturer’s inventory decisions. This makes the healthcare market particularly susceptible to DS.
DS are a complex and global phenomenon currently on the rise, affecting more than 20 countries world-wide. The causes of DS appear to be multi-factorial with the growing cost pressure in the health sector, and increasing problems with the manufacturing of medicinal products due to high regulatory requirements the major influencing factors. Various stakeholders in the health care system such as patients, pharmacists, and physicians are affected as soon as a medicinal product cannot be delivered to a patient in need. Therefore, strategies to manage and end DS are needed.
This work examined the landscape of DS in the European Union, the United States of America, Canada, and Australia; and provides insights into regulatory strategies used to govern DS situations.
Legal provisions regarding DS were analyzed and it was shown that the legislation in the EU contains provisions for responsibilities of NCAs and MAHs, but no further details regulating DS. In the USA and Canada detailed legal guidance on DS is available, whereas Australia applies a voluntary procedure under control of the TGA.
DS information on the websites of EMA, FDA, Health Canada and TGA appear to be globally aligned, whereas websites of European National Competent Authorities are more diverse. The majority of analyzed reporting websites showed low to medium granularity of information regarding DS, while only a few showed high granularity. The leading regulatory agencies EMA, FDA, Health Canada, and TGA were found to be as heterogeneous as the National Competent Authorities in the EU. Investigations revealed 4 different types of DS reporting systems on the websites: 1) searchable databases, 2) shortage lists 3) tables in PDF or Excel format, and 4) DS information within other reports. It was shown that a well-structured and organized DS reporting system is important for the users to easily and rapidly find that information they need. However, a direct practical benefit of transparent reporting websites was not addressed in this work.
In the EU and USA, the regulatory authorities are responsible for leading DS management strategies, while in Canada and Australia a multi-stakeholder approach is applied. In the USA and Canada new legislations have been introduced that changed the landscape of DS management by handing over more legal power to the regulatory authorities. This is not the case in the EU and Australia. EU-wide, the Incident Management Plan was implemented to cope with DS that affect more than one MS. In the US, FDA was required by law to establish the DS Staff to secure appropriate DS management including rapid notification, reporting, and communication. In Canada, the multi-stakeholder approach to tightly regulate DS management will become mandatory in 2017. In Australia, no provisions are foreseen to force the regulation of the multi-stakeholder approach to manage DS. Although there is no common approach of all countries, it was examined that the three pillars notification as early as possible, structured assessment, and coordinated responses seem to be the most crucial factors. Whether these processes need to be initiated by a higher regulatory body or provisions are required to regulate these processes need to be investigated further.
Regulatory prevention and mitigation strategies were examined and it was found that administrative, legislative, and industry approaches to address DS have focused on the symptoms rather than the causes. Regulatory authorities are constrained in their actions due to limited of legal power. No novel regulatory measurements were implemented except a reporting system. Instead, already existing measures, e.g. expediting reviews, were focused and extended. Potential regulatory actions can be implemented on a short- to long-term perspective and were found to be interdependent to each other. Potential strategies comprise a global pricing system and financial and economic incentives for the pharmaceutical industry, and the development of an essential pharmaceuticals list and a standardized risk assessment including guidance on available treatment alternatives, respectively.
Overall, it could be shown that DS are still an ongoing problem and the termination of DS situations is a challenging and global multi-stakeholder task. Early and rapid notification is the basis to efficiently prevent and mitigate DS and they require distinct and sophisticated management. Various national approaches exist but these need to be aligned more to become globally effective.
Pages: 76, Annexes: pages: 12