The medical device industry has a good safety record, but adverse events do sometimes occur once a product has been released to the market. Though device manufacturers work hard to minimise the risk of such events, this proactive effort must be matched with the ability to respond effectively if a problem that poses a risk to patients does emerge.
Europe's medical device regulatory requirements differ in many areas from those in the US. Individual European member states' interpretations of EU medical device regulation can vary so that the Competent Authorities can sometimes impose specific requirements, such as timescales, in terms of how to respond to a post-market problem with a medical device.
It is for this reason that there has been a drive for greater clarity in Europe. Costs of non-compliance can be very high, as in extreme cases a regulatory authority can prevent a manufacturer from selling its devices on the market. It is therefore vital that device manufacturers understand their responsibilities for product vigilance and necessary corrective action.
There are three EU directives that lay out requirements for post-market monitoring of products, including the duty to report any adverse event, especially if it poses risk of death or serious injury: the Directive for Active Implantable Medical Devices (AIMD), the Directive for Medical Devices (MDD), and the In Vitro Diagnostic Medical Devices Directive (IVDD).
"Good manufacturing standards are part of all these regulations. If manufacturers become aware of a serious issue and need to take field safety corrective action (called a recall in the Medical Device regulations), then they must inform the National Competent Authorities in every EU country where the product is on the market," says Tony Sant, group manager of device technology and safety at the UK's Medicines and Healthcare products Regulatory Agency (MHRA).
Sant notes, however, that these directives only provide an outline of what must be done, hence the European Commission's recent moves to clarify medical device vigilance by issuing revised guidance.
WHERE DOES THE BUCK STOP?
So, what steps do medical device manufacturers have to take once they've identified a manufacturing issue that compromises the safety of a product? The answer has been spelt out much more clearly in MEDDEV 2.12-1 Revision 5, the guidance from the European Commission that came into effect in January 2008.
Revision 5 makes a number of changes, emphasising timescales for reporting and corrective actions, and highlights the role of authorised representatives in assisting manufacturers. The new guidance spells out that manufacturers must notify the relevant National Competent Authority about adverse incidents occurring within their territory.
Furthermore, manufacturers as part of their post-market surveillance systems must investigate these incidents and instigate corrective action, in which case they must inform each member state where a defective product has been supplied. Any authorised representatives will need to understand and ensure implementation of the requirements contained within these guidelines.
The guidance also stresses that the act of reporting an incident is not to be construed as an admission of liability.
Furthermore, Revision 5 acknowledges that the response to any adverse event is a shared effort between the manufacturer and the Competent Authorities in all relevant jurisdictions, so it clarifies the role of regulatory bodies in post-market vigilance.
The National Competent Authority must, for instance, monitor the investigation of any incident and should supplement the actions of the manufacturer. It must also play a role in disseminating information between member states once an investigation is concluded.
"One challenge with vigilance is that member state Competent Authorities do not always communicate well, but Revision 5 provides guidance on the topic and the European Commission's document soliciting public opinion about the recast of the MDD associates vigilance with some very strongly worded statements," says Dr Evangeline Loh, director of regulatory affairs at Emergo Group Inc.
"The European Commission acknowledges that there are opportunities with the vigilance system in the European community. The recast document makes it clear that there are far fewer incident reports and corrective actions in the EU compared to other regions, though it is unlikely that devices are significantly less risky than elsewhere."
COMMUNCATION, CLARITY, CONSISTENCY
As a European authorised representative for medical devices (and IVDs), Emergo acts as liaison with National Competent Authorities on behalf of companies not physically located in the EU. Its duties include registering devices with the relevant authorities before they are brought to market, and facilitating incident reporting and field safety corrective actions for device manufacturers.
This role gives Emergo a detailed view of how well Europe's regulatory environment for medical devices performs. Loh welcomes the guidance contained in Revision 5, as it goes a long way to clarifying processes and responsibilities of each stakeholder in the medical device market.
"There is recognition that member state authorities have a pivotal and challenging responsibility to keep track of what is happening in other member states," she remarks.
Furthermore, she notes that while some Competent Authorities are very proactive, others are less engaged with post-market vigilance. Some, she feels, complicate the process of incident reporting and corrective action by adding too much bureaucracy and paperwork.
"When there is a field safety corrective action (FSCA) – or recall – in the EU, a manufacturer must report it to the authorities in all member states where the device is sold. If there is a need for FSCA this involves multiple authorities and is a very complex process. Each authority will ask for different documents, so levels of responsiveness are very variable."
The UK's MHRA is certainly among the more proactive regulatory bodies, and has taken a lead on promoting vigilance and providing simple tools for reporting.
It has recently launched a comprehensive upgrade to MORE, its online reporting environment for manufacturers. MORE II allows manufacturers or their authorised representatives (or even suppliers) not only to inform MHRA about adverse incidents and field safety corrective actions but to produce, organise and consult on draft reports via online collaborative tools.
This helps manufacturers, authorised representatives and suppliers consult more easily and submit accurate and up-to-date data on reported incidents and corrective actions, and provides the tools to make incident reporting simple. There is also a developmental module for exchanging reports electronically in XML format in compliance with EU initiatives.
In publishing all field safety notices relevant to the UK on its website, the MHRA is adopting a similar strategy to the US FDA.
"We have a steadily improving system in the UK," says Sant. "Manufacturers have better awareness of their responsibilities so they are reporting more incidents. We have robust internal processes governing what we do with that data and how we can help with notifying the public and the medical community,"
In the UK, the number of reported incidents is on the rise, but this is not because there are more defective products on the market or because the quality of manufacturing processes is declining. The growing number of reports is most likely due to the fact that manufacturers are better informed about how and when to make a report to the MHRA.
Viewed this way, the higher number of reported incidents has positive implications for patient safety and means good business for device manufacturers as they can ensure they remain compliant and can respond to any adverse events quickly and effectively with the help of the regulator.
Looking at Europe as a whole, however, complexity remains an issue, particularly as different member states interpret the EU directives.
"Part of the challenge is that the industry is regulated at a national level and implementation remains a local activity, even though the directives are visualised as pan-European," says Loh.
Revision 5 is intended to cut through some of this complexity, and it is deliberately as compliant as possible with the guidance of the Global Harmonization Task Force (GHTF), a voluntary group of representatives from medical device regulatory agencies and the regulated industry. In particular, Study Group 2 (SG2) guidance which focuses on post-market surveillance and vigilance examines existing processes for adverse event reporting and post-market surveillance.
One of its key projects is the National Competent Authority Report exchange programme, which brings regulators together to identify ways in which common processes can be achieved.
COOPERATION AND COLLABORATION
While non-compliance can carry a heavy penalty, the attitude of regulators in the EU is supportive where manufacturers and their authorised representatives are taking action to report and address safety problems. In line with the tone of the revisions to guidance from the EU, their focus is to involve all of the necessary parties in vigilance procedures and ensure that robust processes are in place. "Our impression is that they want manufacturers to remain compliant by choice, not because they fear draconian measures," says Loh.
A key consideration for the future will be the question of whether there is a need for a single, centralised focus for regulatory activity in the medical device sector. In the US, the FDA is perceived as benefiting from its role as the single body for handling vigilance, reporting and corrective actions.
Whether Europe can install an organisation at the level above National Competence Authorities, with a brief to ensure consistency and standardisation of vigilance processes, remains to be seen. The level of cooperation between national regulators is improving, but there is still a long way to go before all of the complexity is ironed out of the system.
"In general I am optimistic, but we do see differences in the way EU member states are transposing the regulations into national law," says Loh. "In some cases, countries are increasing the complexity and bureaucracy, which was not the intention of the regulations. Rev. 5 of the vigilance guidance document hopes to facilitate a more harmonised vigilance system. And, Emergo encourages its manufacturers to carefully consider the document.
"We believe responsiveness will improve as all parties get better access to information on medical devices. Acknowledging the weakness in current processes is what leads to improvement."
Though both the market for medical devices and the regulatory environment in Europe will continue to evolve, for now the industry has taken a big step forward in terms of understanding how and when to report adverse incidents. Though there is still much work to be done, there is now a much clearer platform from which the industry and its regulators can embrace the issue of vigilance.