Vigilance is a requirement of many regulatory systems, including that in the member states of the EU. In the EU, the directive dealing with in-vitro diagnostic (IVD) medical devices makes reference to vigilance in the context of the responsibilities of member states, the commission and manufacturers.
Vigilance provides information about how medical devices are performing. It therefore gives the device manufacturer the ability to take corrective action to reduce the possibility of ‘incidents’ and ultimately to ensure the safety of users and third parties using their devices. Vigilance is the reporting of adverse events and the process by which this information is evaluated and action taken.
THE IMPORTANCE OF VIGILANCE
The IVD medical device market represented €9,217m in 2006. IVDs have a significant role to play in ensuring the health of the EU citizen. According to the definition in the directive, they are tests performed on a specimen taken from the human body; the results of which provides information on a physiological or pathological state, congenital abnormality, to determine safety and compatibility with potential recipients or to monitor therapeutic measures.
European IVD manufacturers place their products on the market not only in the 27 EU countries, but also on a worldwide basis. Systems for vigilance handling are increasingly harmonised at a company level. Any harmonisation activity that takes place to ensure the same framework for reporting, including timeframes, definitions of what is an ‘incident’ or not and reporting information and formats, is welcomed by manufacturers.
In this context industry has been an active partner in the Global Harmonisation Task Force (GHTF) activities, since its conception in the late 1990s. GHTF is a partnership between industry and authorities, originally from the five trading blocks of Australia, Canada, EU, Japan and the US, and was created with the aim for a ‘convergence in regulatory practices’.
In GHTF the work is performed in study groups; study group 2 (Sg2) deals with vigilance and post market issues. The output of SG2 has included documents on vigilance; reporting timelines, content of reports and the exchanging of information between national authorities and will continue to influence vigilance systems worldwide.
In Europe a source of useful information and guidance on medical device legislation issues is the MEDical DEVice (MEDDEV) series of guidelines. These are published by the European Commission under their logo and on their website and represent a non-binding consensus of the parties involved in their development, including industry, national authorities, notified bodies and standards organisations.
For such non-binding documents, an extraordinary amount of effort has been expended over the years in their creation. For industry they are the closest that they can get to legal certainty without being part of a legal action. For national authorities, the guidelines enable them guidance to be created without making legislation. The MEDDEV guidelines therefore have strengths and weaknesses: non-adherence to them by stakeholders carries no legal sanctions, but they do describe the consensus view on best practises at the time the guidelines were produced.
DEVICE GUIDELINES REWORKED
The MEDDEV 2.12-1 Guidelines on a medical device’s vigilance system has recently been revised. The mandate for the revision of the MEDDEV 2.12-1 made reference to the work of the GHTF study group 2, as well as the need to update the guidelines in line with experience. The revision process started in 2004 and the revised MEDDEV was published on the Commission website in June 2007, as revision 5, dated April 2007.
The process of revision included national authorities from nine countries with the major medical device trade associations, including the European Diagnostic Manufacturers Association (EDMA) representing IVD manufacturers. Significantly for IVD manufacturers, for the first time IVDs are included within the main text of the guidelines rather than as a separate appendix. A key concept for IVD manufacturer, the issue of indirect harm, has also been defined.
IVD ISSUES TACKLED
A detailed analysis of the changes in the guideline and their impact would be rather complex and lengthy; further details of revisions can be found on the Commission’s website. However, some particularly significant issues for IVD manufacturers were discussed in the revision:
Field safety corrective action (FSCA). Not every FSCA is the result of an ‘incident’ and not every incident results in a FSCA. The definition now includes what used to be called recalls. It is argued by manufacturers that FSCAs exclude those actions taken by a manufacturer within their manufacturing facility to correct errors found as a result of the correct implementation of their quality system.
Reporting. The timelines for reporting incidents must be seen in the context of the directive on IVDs 98/79/EC7, which in Annex III (5) asks for ‘immediately on learning of them’. An attempt has been made to define the use of ‘immediately’ in the GHTF document GHTFSG2N54R8:20068: ‘As soon as possible as but not later than ten elapsed calendar days following date of awareness of the event’. In GHTF SG2/N33R11:20029, events that result in unanticipated death or unanticipated serious injury, or represent a public health threat, must be reported immediately (ten days), but all other event should be reported no later than 30 days after awareness of the event.
The final text in the MEDDEV reflects the concerns of national authorities; a timeline of ten days for the reporting of incidents where ‘unanticipated death or unanticipated serious injury’ had occurred could be, for a national authority, unjustifiably long in the context of protection of public health and the political environment in which they work.
While to a manufacturer immediately means as soon as possible, the ‘not later than ten days’ meaning represents the time needed by the manufacturer to collect and interpret the data on the incident. The final text in section 5.1.7 of the revised MEDDEV represents a hard-won compromise between these different stakeholders and it makes an interesting and potentially confusing differentiation between awareness of threats and awareness of events.
Indirect harm. In the context of vigilance reporting, indirect harm is an important concept for diagnostic devices, including IVDs. In these devices action is taken or not taken on the basis of information/results provided by the device. Indirect harm may be caused by a number of issues, including misdiagnosis, delays in diagnosis, delays in treatment or inappropriate transfusion. With regards to self-testing devices, the user – in other words, the patient – may make the medical decision.
THE USE AND BENEFITS OF IVDS
The use of IVDs or in-vitro diagnostics devices has been going on for years, enabling medical professionals to accurately, and in many cases quickly, test human samples such as blood, urine and tissues. These tests are critical to ensuring that patients receive the right care after assessment. While these tests were initially used to diagnose, they are now becoming increasingly important throughout the treatment process, with carers referring to them regularly to ensure that the treatment being delivered is having the desired impact.
In recent years there has been a dramatic shift in the way IVDs are used as the technology, formula and methods have evolved. Previously, it was required that the sample taken be sent to a laboratory for evaluation. However, manufacturers are developing devices that allow for such testing to take place at the point of care.
The EDMA says that in-vitro tests are used in many ways and provide numerous benefits:
Screening large groups for diseases
- This kind of screening can often cost a great deal for public health providers. The EDMA says that this is only cost effective when the prevalence of the disease is high in the target population where a sub-population can be selected for testing, or when the disease is especially disabling or costly.
- The testing of babies before birth or just after can help identify infants who may need early treatment.
- IVDs can often provide an early and accurate diagnosis, meaning that individuals receive the care needed early, increasing the chances of a speedier recovery. This can also help keep costs down for the care provider.
Monitoring of treatment prescribed
- Measuring therapeutic levels of antibiotics and anti-depressant drugs.
- The use of biochemical parameters can help guarantee the treatment given will have the required effect and is therefore appropriate and effective.
Assessment of medical interventions
- Because resources available to public health care systems are limited, medical interventions are increasingly subject to health technology assessment (HTA). In-vitro testing is often an essential part of this assessment.
FUTURE PROSPECTS FOR VIGILANCE
The MEDDEV was published in early June 2007, with a transitional period until 31 December 2007. Industry knows that even in the European system there are different practices across member states in the legal requirements for timelines of reporting, requirement for user reporting, specific forms and practices such as recording the receipt of field safety notices.
Some of these differences are national competence and will not be changed by the introduction of a revised MEDDEV. IVD manufacturers are looking forward to the continued active implementation of the revised MEDDEV by national authorities, including changes to national law as required.
2008 will see a continuation of the dialogue between the stakeholders on the implementation of the revised MEDDEV on vigilance.
National authorities have already started the active promotion of the MEDDEV within their jurisdiction and industry has been invited to collate and present problems and solutions to a meeting of stakeholders in May 2008. Industry trade associations will provide a key link between industry and other stakeholders.
Following the implementation of the MEDDEV on vigilance, there are some key areas in which manufacturers are looking forward to further harmonisation, timelines for reporting, use of common forms for the exchange of information and use of a ‘lead’ competent authority. For device manufacturers, the MEDDEV is an opportunity for the harmonisation of vigilance practices across the EU and it is hoped that all national authorities will rise to the challenge.