Masterstudiengang "Drug Regulatory Affairs"


Risk-based management of GMP audits within the context of supplier relationships – an approach for a medium-sized pharmaceutical company ***

Viola Hieble-Gerhard (Abschlußjahr: 2009)

Language: English

The aim of this master thesis is to develop a risk-based audit programme taking into account all risk factors resulting from the GMP audit system and from the supplier base of a pharmaceutical company. Due to the particular meaning and the special challenges of medium-sized pharmaceutical companies the focus is thereby on this company type. Moreover, emphasis is placed on the necessary measures to be taken by the management and on the use of the risk ranking technique in order to obtain a programme for prioritizing manufacturing sites for GMP audits. Furthermore, an operational audit plan will be outlined for an exemplary case study of an API manufacturer.

Within the EU the manufacturing of medicinal products has undoubtedly reached a very high quality level in the meantime. But a relevant part of the quality of finished products depends on the quality of the purchased starting materials, especially of the active pharmaceutical ingredients (APIs) which enter the production chain at an early stage. And the manufacturer of the finished pharmaceutical product is responsible for the overall operations affecting the product quality, i.e. including the choice of the API suppliers and manufacturers. At the same time it becomes more and more obvious that the inflow of Counterfeit APIs and Rogue APIs from third countries into the EU is larger than originally feared. In the framework of globalisation and due to the ever-increasing cost pressure within the health care systems, APIs and also critical excipients are sourced in a worldwide market. In this way the risk of sourcing substandard, contaminated or adulterated products is existent. Over the past few years, diverse incidents with serious or even fatal consequences - as illustrated by the recent heparin affair for example - revealed severe defects of medicinal products regarding the source and quality of the contained APIs and excipients.

Indeed, full assessment of GMP compliance of API suppliers represents a cost-intensive and resource-requiring process. But APIs with insufficient quality may threaten patients' health, environment as well as the reputation and continued existence of the pharmaceutical companies. In order to protect public health a thoroughly established risk management takes on greater significance for the supplier qualification. This is all the more necessary because each supplier naturally holds inherent risks which have to be controlled. Today risk management should principally be applied to improve the risk awareness of the management in order to take corporate decisions - also within the context of the supplier selection and qualification process in the pharmaceutical industry where diverse interfaces and overlaps with other risk management processes exist. Of vital importance for an effective and efficient risk management is the implementation of an integrated company-wide system.

One of the raised concerns regarding the supplier qualification is that GMP compliance levels established at the diverse API manufacturing sites of the world could vary considerably and often are not comparable with EU standards. Reasons may be another GMP interpretation, a lack of understanding, of training, of organisation, of time, of resources, of discipline or simply the wrong attitude towards quality and its priority. Furthermore, if manufacturing sites abroad operate under GMP conditions and in parallel under non-GMP conditions for customers from other sectors of industry, they are often far away from the necessary GMP awareness.

Of course, it has to be taken into account that most of the long-term relationships with suppliers are reliable, that many of them invest in modern buildings, equipment and new technologies and show the readiness to continuous improvement. It has to be also considered that the API industry currently must operate in a very complex regulatory framework which is changing profoundly. Many new initiatives have been started by the authorities and the pharmaceutical industry during the last months in order to avoid the use of Counterfeit-APIs or Rogue APIs and unclear supply chains. Some legislative procedures are pending for an indefinite time. The key issues for the years to come comprise the building up of a regulative system for a better supervision and the enforcement of API-GMP compliance, but also the increased exchange of information between competent authorities and between pharmaceutical companies, e.g. in terms of shared audit reports, and consequently the avoidance of duplicate inspections resp. multiple audits. On the one hand GMP audits are necessary to assess the suitability of suppliers and to find out which fields offer the potential for improvements. The agreed corrective actions ensure the quality of the concerned medicinal products and protect the health of both individuals and public at large - which is given top priority of course. On the other hand an unnecessary overload of the auditing company as well as of the auditee should be avoided to guarantee that the supply capacity of both parties is sustained. Therefore, the quality management systems of the pharmaceutical manufacturers need to become adjusted to the challenge of globalisation. Self-responsibility and self-regulation by means of a comprehensive risk management are demanded of the pharmaceutical industry for the fulfilment of legal obligations. Setting reasonable priorities within the framework of the GMP audit system and the audit programme of a pharmaceutical company becomes possible through a risk-based management.

Within this master thesis, at first an approach out of the macro perspective of the top and senior management of a medium-sized pharmaceutical company is applied. In a second step a more detailed operational approach is used putting oneself in the position of the audit team who has to prepare and manage a discrete GMP audit based on quality risk management principles.

Pages: 108