Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Valsartan Case and its Consequences for Regulatory Affairs Activities of Marketing Authorization Holders

Elisabeth Lieschke (Abschlußjahr: 2022)

Summary
Language: English
The recall of valsartan in 2018 triggered an Article 5 (3) procedure of the European Medicines Agency and initiated a call for review by the Committee for Medicinal Products for Human Use regarding the contamination with nitrosamines. The continuous detection of impurities in active pharmaceutical ingredients is still present in regulatory affairs activities as different sartans are contaminated with nitrosamines and new kinds of impurities can be detected. The aim of this master thesis is to find out whether the current control strategy of APIs and their impurities can prevent marketing authorizations holders from recalls such as it happened with valsartan.
Different aspects with the focus on risk assessments, dossier sections, studies, and guidelines regarding impurities are investigated. Risk assessments are discussed as one powerful tool in the overall control strategy of pharmaceutical companies within their change control system. Furthermore, the affected dossier sections are covered regarding their different ways of submission to competent authorities. Additionally, the fate and purge studies from the development of active pharmaceutical ingredients with the associated responsibilities of the marketing authorization holders are discussed. Also, the guidelines and monographs are analyzed for their actuality. Especially in the life cycle management they play an important role. Although the marketing authorization holder is responsible, authorities have a control function which is only as good as the documentation is given by pharmaceutical companies. The results of the European Medicines Agency are also taken into account within their published lessons learnt document.
In conclusion, the life cycle management, with its change control system and involved risk assessments, is the most powerful tool for the control of existing medicinal products. Ideally, the basis is already formed in the development of active pharmaceutical ingredients with appropriate fate and purge studies to control impurities and their degradation pathways. If marketing authorization holders apply their life cycle management effectively and consequently use the established controls in the regulatory field of medicinal products, recalls could be prevented. Generic companies are exposed to enormous pressure with rising costs to produce cheaper, but the life cycle, with its risk assessments, must not lose importance.
Pages: 51
Annexes: 2, Pages: 25