Document Type

Theses, Ph.D


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Publication Details

Successfully submitted for the award of Doctor of Philosophy (Ph.D) to the Technological University Dublin, 2007.


This research work was concerned with investigating the risk-based regulatory requirements that are currently in place in the European Union governing the manufacture of medicinal products. The main goal of this research was to develop a practical Quality Risk Management methodology that served as a solution for facilitating compliance with the EU GMP requirements in the area of risk-based Qualification, Validation and Change Control, and which was fully in line with the principles and guidance of ICH Q9, on Quality Risk Management. Following extensive testing and evaluation activities with a range of key stakeholders including the pharmaceutical manufacturing sector in Ireland, the UK and the US, and GMP Inspectors from a wide range of countries, this work resulted in a formal, readily usable, rigorous and complete Quality Risk Management Methodology. It is designed to facilitate compliance with the risk based qualification, validation and change control GMP requirements of the EU, and is fully in line with ICH Quality Risk Management principles and guidelines. A practical and detailed training programme on the use of this methodology is also presented. This provides comprehensive training materials for facilitating training activities, as well as a documented strategy for the provision of such training in a timely and resource-efficient manner. In a comprehensive benchmarking exercise, this approach to Quality Risk Management was compared with the application of Risk Management in two industries that are considered mature and advanced in their application of Risk Management principles and methodologies. These were the US aeronautics industry, as represented by the work of the National Aeronautics Space Administration (NASA) and the US nuclear power generation industry, as represented by the work of the US Nuclear Regulatory Commission (NRC). The methodology performed very favourably in this benchmarking exercise, and many examples of common best practices were identified. The Quality Risk Management methodology developed in this work has attracted wide interest, not only from within the pharmaceutical manufacturing industry, but also from the GMP Inspectorates of several countries, from academic bodies involved in the teaching of pharmacy and pharmaceutical-related sciences in Ireland, from the publishers of research journals involved in pharmaceutical science, among others. The methodology has already found application in several multinational pharmaceutical manufacturing and other companies, and has served as a valuable educational and training resource in the practical application of Quality Risk Management in the GMP environment. The application of formal Quality Risk Management methodologies in the EU pharmaceutical manufacturing environment is still at its early stages, relative to that in other industries, and several opportunities to further develop and build upon this research work has been identified. The intention behind these recommendations for further work is to promote the continued development of Quality Risk Management methodologies and approaches within the GMP environment, so that the risks posed by medicine to patients and animals may continually be reduced and managed.


Kevin O Donnell Vol 2.pdf (6218 kB)
Kevin O Donnell Vol 2.pdf

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