Unannounced audits signal a new, much tougher era for EU medtech sector

There has been a largely negative response from the medtech industry to unannounced audits by notified bodies in the EU. But what is perspective from the other side? What is it like for notified bodies, who are under increased scrutiny from their designating authorities and under pressure to deliver far more stringent auditing of medtech manufacturers. Reporting from regulatory meetings in Brussels, Berlin and London, Amanda Maxwell provides a snapshot of the mood,

I was chairing a medtech regulatory meeting in London recently when a delegate came up to me during the coffee break to apologize for spending so much time on her mobile phone during the previous session. The reason, she said, was that her company’s notified body had just turned up unannounced to conduct its surprise audit.

This is the new reality for the medtech industry. A new era of deeper, more thorough scrutiny by notified bodies has well and truly arrived.

But what is it like on the other side of the fence? What is it like for the notified bodies themselves? It seems that they constantly risk finding themselves caught in the crossfire.

Notified bodies have to risk upsetting their clients by paying them unannounced audits and unleashing the necessary consequent action, but they themselves have been subject to joint audits by designating bodies. Many are just not coping; indeed, some are opting out of the devices field altogether.

Following the introduction of the joint audits by designating authorities of notified bodies (a pilot began in February 2013 and was succeeded by the official joint audits in May 2014), Erik Hanson of the European Commission reported at the TOPRA (The Organisation for Professionals in Regulatory Affairs) meeting in Brussels in October that as of that month, some 10 notified bodies had withdrawn from operating in the medical devices sector.

Several notified body representatives have observed how national medical device experts from different designating authorities have frequently been at odds during joint audits – different backgrounds and different practices have apparently led to a clash in opinions, as witnessed often by anxious company personnel. BSI, for example, witnessed different approaches being used by the German and UK designating authorities and learnt that notified bodies need to look at their services from two different angles. The German authorities focused on checking processes, while the UK were more focused on assessing output.

It is not just the audits that are stressful; what happens afterwards is also imprtant. Many notified bodies have had to deal with major non-conformities found during the joint audits, and find significant resources to put these right or drop out of the sector altogether. They have also had to hire a significant number of personnel around the world to adequately handle the unannounced audits they need to conduct globally.

In Brussels, Berlin and London, notified body personnel have also been speaking about how the monthly teleconference between competent authorities within the context of the competent authority compliance and enforcement group (COEN) are resulting in notified bodies getting more requests from regulators for information, many of which involve the need for detailed follow-up.

One notified body said that while it used to receive some 2-3 questions a year on manufacturers – in cases where the notified body was responsible for conformity assessment - through the COEN route, now it is receiving 2-3 questions a day.

Martin Penver, head of Notified Body- Medical Directives at LRQA, spoke at the Association of British Healthcare Industries meeting in London in November about the practical issues that need to be addressed so that notified bodies do not turn up at manufacturing companies only to find that they cannot carry out the audit.

Mr Penver explained that there can be a series of challenges arising from, for example, key staff at the manufacturing company being away on holiday, or cases where it is difficult to ascertain exactly where the manufacturing site is (such as the case of a virtual manufacturing company). In other cases, manufacturers do not understand basic requirements such as having a technical file at the disposal of the auditor.

Mr Penver advised industry delegates at the meeting that they need to keep their notified bodies informed about when the facilities are closed, when they are not manufacturing the devices, and also ensure that the notified body has a point of contact with someone at the organization who understands about the unannounced audits when the notified body visits.

One message that is coming across clearly is that if a notified body turns up at a manufacturing site to do an unannounced audit and the manufacturer is not in a position to host that audit, then the manufacturer will still need to meet the notified body’s costs.

The same message was repeated at the Informa drug/device combination product meeting in Berlin in November. One notified body representative told the meeting; “If I go to China to carry out an unannounced audit on your company and I cannot do that audit – for example if the company is closed for a holiday or you are not producing certain products I wish to see, then you – the company - have to pay.”

It is therefore vital that manufacturers keep their notified bodies well informed of all their movements and operations.

Practical issues

There can also be problems with work overload when more than one auditing team turns up at a manufacturing site and the manufacturer struggles to find the resources to support the auditors and address their queries. But it seems that this is a necessary fact of life that has to be managed.

Taking into to account the unpredictable nature of these surprise inspections and their potential to disrupt daily production plans, unannounced audits can still run remarkably smoothly, not least due to the preparation of the audit team, Bianca Lutters, scheme manager and technical expert at BSI, told delegates at the Informa meeting.

Factors that can help include: a good briefing in advance, a team of two auditors, and logistical elements such as notified body personnel arriving by car, thus allowing for a smooth return when occasionally at the end of the audit some tension might have been built up, Ms Lutters added.

According to Ms Lutters, a total of 17 joint audits had been scheduled in 2014, mostly in the third quarter.

These joint audits are carried out by the notified body’s designating authority, two designating authorities from other member states, as well as assessors from the European Commission.

The type of non-conformities that are being picked up include the following four areas, Ms Lutters said, giving examples regarding some clinical aspects:

• organizational and general requirements – concerning in-house clinicians, for example;
• quality management system requirements – review of clinical data;
• resource requirements – pool of external clinicians; and
• process requirements – review of clinical data.

So far, Ms Lutters said, these audits are more related to what accreditation bodies should have picked up and, she suggested, there is less focus on design dossier review and clinical details.

Separate TEAM-NB compliance audits identify staffing issues

Ms Lutters also noted how staffing issues are requiring a great deal of attention.

The notified body association, TEAM-NB, is working on a new version of its Notified Body Code of Conduct – which TEAM-NB members have to sign – to raise qualification levels of notified body staff, she indicated.

The latest 3.2 version covers: frequency of unannounced visits; focus of unannounced visits; and details of code of conduct compliance audits by TEAM-NB auditors – another layer of auditing that notified bodies must contend with.

So far, during these code of compliance supervisory audits, the area with the most shortfalls is in the qualification and assignment of notified body assessment personnel – which has accounted for 63% of the non-compliance findings, said Ms Lutters:

Neil Adams of BSI told the ABHI conference that the new requirement for notified bodies to make unannounced visits to manufacturers, critical subcontractors or crucial suppliers, in addition to planned audits, means that there is a significant increase in notified body workload and that extra product and quality management system assessors are needed.

Also speaking at the TOPRA meeting, Dr Adams noted that while BSI had some 25 technical specialists eight years ago, it now has 80-90 and is still recruiting.

Drug/device combination products companies: a minefield?

Turning to the areas of drug/device combination products in particular, Ms Lutters highlighted in Berlin the fact that not only will the number of notified bodies per se reduce as a result of the stricter requirements and joint audits, the number of notified bodies whose scope includes combination drug/device products may also drop as a result of the fall-out of the joint audits.

This is particularly due to the complexity of such drug/device combination files and the challenges in having adequately qualified staff in these areas. Indeed, some notified bodies are hiring people with pharma backgrounds to keep up with the demands of changing technology.

Where notified bodies cannot keep up and decide to exit this space, or are de-designated, there will be particular problems for manufacturers in this area. Indeed, one delegate told the meeting that while it may appear easy, on paper, to switch notified bodies, in reality, it can be very complicated.

A discussion ensued at the Informa meeting with the following concerns being highlighted:

• if a notified body exits the medtech area, can companies simply transfer to other notified bodies, or does the de-designation of their notified body also undermine the regulatory status of their products and would a manufacturer have to recall their products as a result of a notified body losing its certificates?
• how can companies even find out which notified bodies are alternatives to whom they can transfer if they are operating in an environment where there are many notified bodies to choose from? (The European Commission’s NANDO database of notified bodies is notoriously behind when it comes to being updated)
• should the new notified body help the manufacturer in this situation, as is suggested in guidance from the EU Notified Bodies Operations Group?
• does the competent authority that designated the notified body in the first place have public health responsibility over the implications of the continuation, or of the removal, of these products from the market?

The debate on these subjects revealed that there is much uncertainty even among experts in this area.

Mika Reinikainen, managing director at Abnovo UK medtech consultancy, suggested at the Informa meeting that if the notified body’s designation was valid at the time that the conformity assessment certificate had been granted to the manufacturer, then “the legal position has to be that you can go on until the certificate expires”. Mr Reinikainen said later that this is true provided that the CE marking is not challenged on some other basis, for example lack of safety of the product. This might be the case if it was thought that the original notified body had failed to verify adequately evidence of safety.

But others at the Informa meeting had received anecdotal evidence to suggest that companies were being told by authorities that their certificates were no longer valid because the notified body was no longer active.

Reasonable or going too far?

This increased scrutiny is resulting in much higher costs all round – authorities having to find resources for increased review of notified bodies; notified bodies having to increase resources to cope with managing unannounced audits, as well as higher demands in general regarding their auditing capacity; and manufacturers having to bear the brunt of the additional costs and staffing capacity related to unannounced audits.

There will be a big impact on the European system as tighter requirements surrounding unannounced visits and additional clinical requirements, for example, will also cost more for the manufacturer.

So how will these costs be recovered? Bassil Akra, director clinical affairs at the T?V S?D notified body, told delegates at the Informa meeting that many small manufacturers will simply be unable to manage these increased resource needs and will therefore disappear.

The big question that remains, Mr Akra said, is whether this much more expensive system will actually be better for patients. Will products, in fact, actually be safer as well as more expensive and potentially taking longer to reach the market?

Lee Leichter, chair of the drug/device combination product meeting and president of US consultancy P/L Medical reflected that Europe could be at the top of a reactive cycle: it begins with an outcry concerning product safety, the reaction leads to more stringent regulations, this results in costs going up and products not being approved. The next stage is a reaction against delays in product availability and increased costs, which leads to the regulations becoming less onerous, until – again – there is another outcry and they are tightened again. “I have been through some four cycles of that [in the US],” Mr Lechter said.