Masterarbeit

Extension of PSUSA outcomes to other active substances or respective mono / fixed-dose combination product(s) ***

Dr. Mirjam Schröder (2023)

Summary
Language: English
Among European Union safety procedures, periodic safety update report single assessments (PSUSAs) have been introduced to regularly assess potential changes in the benefit-risk ratio of authorized medicinal products. Yet, PSUSA outcomes may also receive a recommendation by the Pharmacovigilance Risk Assessment Committee (PRAC) to be extended to other relevant products, for example, to fixed-dose combinations of the active substance within the scope of the originating PSUSA. Regarding the extensions of PSUSA outcomes, affected marketing authorization holders (MAHs) highly depend on the information that will be provided by the Health Authorities with the communication of the extension. Besides, there is no overview of past extensions available on the European Medicines Agency website and of the Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh) website, respectively.
Therefore, this thesis focuses on identifying PSUSA extensions recommended by PRAC in 2015-2021 and on challenges that MAHs within the scope of the extension may face. PRAC meeting highlights and minutes as well as CMDh press releases and minutes have been examined for information on extensions originating from PSUSA procedures and related subsequent clarifications. Moreover, examples of PSUSA extensions have been discussed in more detail to better illustrate potential challenges for affected MAHs.
The outcome of this evaluation shows that the extension of PSUSA procedures has become a regular Health Authority proceeding. In 2015-2021, the absolute numbers and the percentages of extended PSUSAs with the outcome ‘variation’ requesting an update of the product information generally increased over the years. Up to 12 % of PSUSAs with respective outcome were extended per year during this time, regarding only those involving only nationally authorized products up to 25 % per year. Furthermore, overall, more guidance is now available and / or provided to affected MAHs compared to the early years assessed. The extension of PSUSA procedures holds several advantages for MAHs and Health Authorities regarding patient safety and workload reduction. However, clarifications provided by the Health Authorities and examples discussed within this thesis also highlight various challenges on the MAH side that may impair some of these benefits of PSUSA extensions. Challenges concerning the PSUSA extension implementation in the product information have been identified, but also regarding the identification of an extension and of affected products. Furthermore, challenges regarding product liability might arise, especially because the underlying data would usually not be directly available to affected MAHs. Lastly, increasing numbers of safety-related product information updates such as PSUSA extensions may result in an increasingly difficult situation on production level. An evaluation of these aspects suggests that measures to improve transparency and to further reduce ambiguities within the guidance to MAHs could improve the overall situation for MAHs. Moreover, measures on Health Authority side aimed at avoiding PSUSA extensions or subsequent product information updates, if possible, could be beneficial in order to reduce the overall number of safety-relevant product information updates.
Summarized, the extension of PSUSA procedures has become a regular Health Authority proceeding that is connected to advantages for both MAHs and Health Authorities. However, the situations discussed within the frame of this thesis indicate that the MAH`s challenges may impair some of the benefits of PSUSA extensions, importantly also those regarding patient safety. Consequently, the outcome of this evaluation suggests that measures aimed at reducing challenges on the MAH side might also prove beneficial to the advantages associated with this procedure.
Pages: 83
Annexes: 3, Pages: 38