RISK-BASED MODELLING IN MONITORING THE QULITY OF PHARMACEUTICAL PRODUCTS Review Article AMJAD M IDRIES 1 , KAMAL E IBRAHIM 1,2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Khartoum, Sudan, Mailing address: Chemin de Blandonnet 8 | 1214 Vernier - Geneva, Switzerlan. Email: amjadwedaa@gmail.com 2 Received: 28 Apr 2014 Revised and Accepted: 05 May 2014 ABSTRACT According to WHO reports, low quality medicines represent about 10% of the global pharmaceutical market of which about 40% were substandard medicines. Most of the studies of quality of medicines recommend development of additional innovative techniques to control the existence of substandard medicines in the market. Based on recent assessment by WHO, systems applied to detect substandard and/or counterfeit medicines in developing countries were not effective enough. A strong post marketing surveillance system would be a more powerful tool for detecting sub standard medicines. In some countries, it was proven that strengthening the system by applying risk-based model for supporting the decisions is useful and possible approach. This exploration work aimed at exploring possible options to develop a risk-based quality monitoring model for pharmaceutical products. The model proposed based on this review work should help medicines regulatory authorities in resource limited settings to improve surveillance systems. The model was tested for its usefulness and effectiveness and the results obtained showed potential applications of the model in improving the system. This would include its use in the selection technique of products for inclusion in post-marketing quality monitoring. It can also be applied to increase the detection rate of low quality products. Keywords: Quality of medicines, quality assurance, post-marketing surveillance, testing, risk management, modelling. INTRODUCTION Partners in areas related to pharmaceutical services are focusing their efforts intensively on assuring the safety, efficacy and quality of pharmaceutical products. By reviewing the global policy directions of most of the initiatives introduced during the last two decades, it is possible to observe a clear focus on safety and efficacy as important dimensions, with safety always put first [1, 2]. Among the three dimensions, quality receives relatively less attention, not because it is less significant but usually due to complicated management systems. Quality management systems rely greatly on national authorities on the one hand and on manufacturers on the other hand. As part of a quality monitoring system, post-marketing surveillance (PMS) for monitoring quality is no exception and has received little consideration in relation to drug monitoring information systems. Unlike the monitoring of adverse drug reactions (ADRs) which has improved markedly during the last 10 years, PMS has not been the subject of major changes aimed at improving the process or outcomes. However, there have been some specific and exceptional initiatives in some countries that have aimed to improve PMS and develop new approaches. The justification for establishing PMS in most countries is that the authorities have only a slight influence on premarketing quality management, which relies rather on the compliance of the pharmaceutical industry with regard to quality assurance schemes. The need for strong PMS was the driving force for all of these initiatives. The main goal of this review is to encourage countries to develop risk-based quality monitoring schemes in relation to pharmaceutical products, and to examine potential options and practical models to increase the efficacy of quality monitoring systems using routinely available data [2]. The review team under took a systematic review of current projects to compare different approaches attempted in this area. The review focused primarily on measures currently implemented by the European Union member states and members of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (known as ICH). This helped, to a great extent, to inform the way in which this review was designed and recommendations were formulated to expand PMS in resource-limited settings. Review outcomes European Union (EU) member states have implemented mutual recognition procedure for the provision of marketing authorization (MA) of pharmaceutical products since 2005. This procedure is usually coordinated by the European Medicines Agency (EMA) but the authorities in each member state should issue MAs separately. Monitoring the quality of any registered product is maintained as part of the responsibilities of each individual member state [3]. EMA created a voluntary surveillance scheme at the EU level in the field of the independent official control of registered products [4]. The design of the surveillance scheme under this initiative is a risk-based model and uses risk evaluation approaches to target medicinal products for surveillance testing [5, 6]. The scheme began with a pilot phase in 2007. The most remarkable outcome of implementing this risk-based approach is its use in establishing more ‘informed testing plans’ [7]. The new system has enabled member states to focus on certain trade products with sufficient available evidence to justify testing-targeted decisions. By implementing this strategic change, member states are able to avoid unnecessary tests and reduce the load on individual laboratories. The Food and Drug Administration (FDA) in the United States currently uses the Drug Quality Reporting System (DQRS).In this system, there are both voluntary and mandatory reporting schemes that enrich the data contributing to quality risk management (QRM). This was initially used in the premarketing phase of product lifecycles and was extended later to include the post-marketing phase. Based on the FDA experience, it is clear that to build a risk assessment model many factors may need to be considered in terms of the assumptions to support the model. Decision making based on this model is similar to that in ‘problem tree analysis’ in which different decision nodes can be identified based on the anticipated risk(s) at each stage. The FDA includes QRM as part of its routine regulatory operations, especially inspection and assessment activities. This model was considered for many reasons, particularly its ability to assist in allocating resources and prioritizing testing activities. In addition, it becomes less complicated to evaluate the significance of quality defects, potential recalls and inspection findings, for example [8]. In 2010, the World Health Organisation (WHO) published an overview of the findings from 26 assessment reports of regulatory systems governing medicines in sub-Saharan African countries. One of the weaknesses identified in this review is the poor implementation of PMS (WHO, 2010).The report states: ‘Quality monitoring was not prioritized based on risk, but was generally performed in case of complaints if at all’ [9]. In addition: ‘Fourteen of International Journal of Pharmacy and Pharmaceutical Sciences ISSN- 0975-1491 Vol 6, Issue 6, 2014 Innovare Academic Sciences