Masterstudiengang "Drug Regulatory Affairs"

Master-Thesis

Vigilance experience for high risk in vitro diagnostics: Risk assessment by the German competent authority and possible implications for the parties involved in the European medical devices system ***

Dr. Folker Spitzenberger (Abschlußjahr: 2006)

Language: English
 
Since December 2003, any in vitro diagnostic medical devices are placed on the European market according to the new IVDD requirements. Due to safety reasons, especially high risk in vitro diagnostics covered by Annex II of the Directive are the focus of public and regulatory attention. In order to ensure a high level of public health protection, the installation of a complex postmarket information system is required that constitutes a safety network with interfaces between the parties involved in premarket conformity assessment and in postmarket surveillance activities.

By review of the incident notification data registered by the competent authority PEI during the year 2004, the present study evaluates the European and German vigilance system for high risk in vitro diagnostics and discusses possible implications for the bodies related to the European medical devices system.

The total number of 52 cases was analysed on the basis of criteria used for risk assessment of the incidents and near incidents. Vigilance reports were communicated in one third of the cases enabling the Member States to take adequate measures to protect the health and safety of patients and IVD users all over Europe. In general, the information exchange at the national level was effective and included the relevant parties, as there are manufacturers, PEI, competent market surveillance authorities of the Länder, users, the conformity assessment bodies and the designating authority ZLG.

Whereas the notification practice seemed adequately established among the IVD manufacturers, the low contribution of medical practitioners (IVD users and EQAS organisations) to incident notification suggested the need for increased informing of these professionals about the IVD vigilance system.

For the majority of (near) incident notifications, product defects could be confirmed. Because remodelling of cases was often insufficient or impossible, no root causes could be verified for nearly one third of cases. Unfavourable patient sample characteristics, user mistakes and shortcomings in the regulatory framework were of minor importance for the evaluation of incident causes.

In most cases, the extent of corrective actions initiated by the manufacturers correlated with the seriousness of the incidents demonstrating that risk assessments were usually performed adequately and in close cooperation with the competent authority. However, preventive actions that refer to processes during premarket conformity assessment, especially adequate revisions of the risk management systems and of performance evaluation concepts, constituted major challenges for the manufacturers.

As revealed by this study, enhanced activities should therefore be performed by manufacturers to continually monitor and analyse any post-production information on devices in order to maintain effective risk management systems. Since product shortcomings leading to incidents mainly concerned the lack of independent diagnostic evaluation in the premarket conformity assessment phase, more emphasis should be placed on results from clinical IVD testing that constitute an essential part of the technical documentation.

In this context, this study confirmed the essential role of medical testing laboratories as conformity assessment bodies involved in the premarket performance evaluation of in vitro diagnostics. When the testing competence of these laboratories is confirmed by accreditation, this procedure should adequately consider the specific requirements for performance evaluation testing in order to ensure the compliance with legislative and normative requirements that are beyond the basic laboratory standards used for accreditation of routine diagnosis.

The data obtained during this study support the suitability of the notified bodies role as independent third parties for premarket conformity assessment. The relevance of their assessment including the verification of the manufactured products for List A devices was confirmed. However, single cases demonstrated that non-compliance with the CTS was not always sufficiently realized by the notified bodies. It is therefore essential that notified bodies continuously maintain a high level of competence that must be controlled by the designating authority.

The present study showed that vigilance monitoring by the competent authority serves as effective tool for the re-evaluation of the regulatory framework for in vitro diagnostics. Based on the PEI vigilance experience of the year 2004, a consolidation of the CTS concerning the testing requirements for the evaluation of effects of potentially interfering substances is in process. Future vigilance data will show whether further re-evaluations concerning the requirements for performance evaluation testing of IVD might be necessary. Although the relevance of independent batch testing of List A devices was confirmed during this study, the mode and frequency of the verification of manufactured List A devices so far are not harmonized on the European level and therefore remain unclear. Clear consideration of this important aspect in the European regulatory framework could contribute to more transparency.

The vigilance system for high risk in vitro diagnostics could largely benefit from enhanced data transparency between manufacturers, notified bodies and competent authorities. Where serious risks are ahead, the effectiveness of risk assessments could be improved, when competent authorities could use facilitated mechanisms for getting access to the manufacturers data. Less restricted communication of incident notifications to the notified bodies could improve the interaction between the proactive components of premarket conformity assessment and the mainly reactive characteristics of the vigilance system. When fully functional, EUDAMED could essentially improve the European information exchange system and therefore provide effective tools for risk prevention and health protection in connection with high risk in vitro diagnostics.

Pages: 44