There’s nothing quite like a set of new rules to shake up an industry. In the case of the medical device sector, the European Commission-imposed MEDDEV 2.7/1, Rev4, which came into effect last year, has forced players to think about how they can conduct their clinical trials more cost-efficiently.

Under the newly revised directive, medical device companies are required to collect more detailed data, while also incorporating delivery tools, and supporting equipment and software to demonstrate the safety of products.

The days of companies using similar product data to achieve the green light over equivalence are gone. Today, all new devices need to be tested, with all study data reported independently.

Successful clinical trials, however, have always been built on the bedrock of strong partnerships, collaboration and trust. More than ever, medical device companies, as they look to outsource trials, must have complete faith in the vendors and contract research organisations (CROs) they choose to work with.

While it is commonly accepted that some vendors might not be medical device specialists, CROs must have a thorough grasp of the products in question. With new rules in play, however, the margins for error are narrower than ever, especially with regards to class III and implantable Ibis medical devices. CROs need to be competent enough to adhere to requirements laid out by the ethical committee. In other words, partnering with a CRO that doesn’t grasp the needs and goals of a trial is unlikely to end well.

“The golden rule for companies when it comes to working with CROs is cooperation,” says Torsten Kayser, senior clinical research fellow, Boston Scientific.

“You’re not just working with a vendor; you’re working with people. People are involved in your project.

“If you understand how your vendor people are operating – that’s a kind of incentive in itself.”

The golden rule for companies when it comes to working with CROs is cooperation. You’re not just working with a vendor; you’re working with people.

Time is money

Another long-standing concern for companies outsourcing to CROs is ensuring that the latter stick to timetables issued by the former.

“When it comes to management of vendors, they are always struggling with appropriate resource planning, so you need to have something like 80% chargeable time,” says Kayser.

“You need to understand how they plan, then you can give them your order of priorities, especially when you have two or three projects on the go. This means they can reach their chargeable time more easily, making planning less chaotic.”

For the reasons listed above, outsourcing and risk management strategies should go hand in hand for medical device companies – especially as they attempt to stay on budget. As Kayser explains, risks can come from all directions: not just from the vendor, “but the project itself”.

“Companies aren’t just exposed to one level of risk,” he says. “So, when looking at risk management, it’s good to focus on preparation, because every project needs to have risk planning. Then you have to ask yourself, ‘What are the timelines?’ Otherwise, the product may come too late.”

Elsewhere, strategies must be put in place around marketing and regulatory requirements. “With regulations, the strategy needs to be ironed out pretty well, because when your clinical project is late – as a result of not really understanding what you have to do – it has nothing to do with the vendor or outsourcing, but you get a ripple effect immediately.”

Kayser also believes vendors and CROs are inclined to perform better when given enough time to accrue bestquality data. To encourage them further, it’s always preferential that third parties are involved in a clinical trial early on – ideally from the design stages.

“What I always tell my peers is you have to understand how your vendor is working,” he explains.

“This entails spending some time up front, increasing your knowledge of how you organise oversight. This is all pretty beneficial, because you learn the time frames in which the vendor is working.”

For Kayser, the ideal clinical trial scenario for manufacturers is to achieve equilibrium between outsourcing and in-house resources. It is inevitable, he believes, that internal teams will have greater and more in-depth product knowledge. The key, then, is transferring that knowledge to vendors.

“Vendors need to be given time to be trained,” he says. “This can take up to three years.”

Risk assessment

In February, Kayser used his time on the podium as keynote speaker at the Fifth Annual Outsourcing in Clinical Trials Medical Devices Europe Conference, held in Munich, to highlight the importance of strategies that help companies to get notified bodies to validate post-market surveillance data.

When you go simply by the regulations, you have to study the risks – some risks are small and harder to study. Sometimes they are impossible to study.

In light of the inflection point of new regulations, it’s no small undertaking, he says.

“The regulations are not only changing for manufacturers, they are also changing for notified bodies,” he explains. “When you have a project, you also have to contact your notifying body and you have to do a kind of risk assessment of the product – basically, your goal for the residual risks.

“When you go simply by the regulations, you have to study the risks – some risks are small and harder to study. Sometimes they are impossible to study. Then you have a kind of synopsis of a protocol and you go to your notifying body, and you present this entire strategy.”

The strategy presented to a notified body at this stage of the product’s development doesn’t have to be finalised, but a draft is necessary. “You have to have a first round of discussion of your entire strategy. Then, of course, you can go later on and submit the entire protocol.”

There are other challenges just around the corner for the industry, too. If all goes according to plan, Eudamed – the new database system for European medical device companies – will be available in 2020. Open to the public, product data will be under unprecedented scrutiny.

It will also allow companies a clearer peek into what their competitors are up to, while medical devices under preparation for clinical trials will require even stronger documentation.

Eudamed falls under the wider bracket of the new, revised Medical Device Regulation (MDR), published by the European Parliament. Aimed at creating a more rigorous, transparent regulatory environment in which medical device players can operate, it will have an impact on everything from reclassification – including legacy products – and clinical evaluation, to labelling and unique device identification (UDI).

The new rules under MDR mean players have to think more deeply about the sort of data they have to collect. For instance, class III devices usually contain complex systems; they may include, say, an electrode, pulse generators or equipment guide wires. Software, too. The new regulations mean companies need to be able to have data on every feature of a device.

“You really need to have some sort of information from all of it,” says Kayser. “It’s not just a case of simply saying, ‘Then we put some software on it…’. You need to study the software and understand how to collect the data.”

Sooner is better

Times are changing. If a company is unable to provide data on a guide wire, for instance, it will be unable to release the product, as the guide wire might be essential to implant that device. “I think [that] notifying bodies are good partners to have when it comes to doublechecking that the right things [are in place],” says Kayser.

Like in any industry affected by changing regulations, those who set about complying with MDR sooner rather than later will prosper most.

A medical device company will, for the most part, have the upper hand when it comes to specialist knowledge over the product it wishes to trial. In an ideal world, many management teams would choose to conduct trials independent of a CRO or vendor.

Indeed, Frank van Leeuwen, senior director of clinical affairs at Elixir Medical Corporation, and fellow speaker at this year’s Munich conference, used his time on the dais to explain how his company managed to conduct an in-house trial. Van Leeuwen highlighted the potential of making use of automation to save on time and costs.

However, the fillip of cheaper costs alone will mean outsourcing is set to remain a growing concern. According to recent research conducted by business consulting firm Grand Review Research, the rate of medical device clinical trials has grown by 63% since 2012, with the attendant CRO market expected to continue expanding by 11.5% a year.

According to the research, such a growth rate means the CRO market can expect to attain a value of $13 billion by 2023.

With a chronic lack of funding still a concern within the medical device industry, some may see this projection as overly optimistic, but the importance of building solid partnerships with CROs in clinical trials should not be underestimated.

MDR explained

The main changes made by the European Parliament to MDR are:

  • Eudamed: a new EU database that will collate and process data concerning devices on the market, conformity assessment, notified bodies, certificates, clinical investigations, vigilance and market surveillance. The European Commission is aiming to have the database up and running by 2020.
  • A new UDI system: this is designed to improve post-market vigilance and traceability of devices.
  • Greater supervision of notified bodies: notified bodies will be required to step up to meet higher requirements with regards to their organisational structure, competency, skilled personnel and level of liability insurance. The supervisory position of national competent authorities will also be increased.
  • More power to notified bodies: under the new rules, notified bodies will be free to carry out unannounced on-site audits and lab tests to ensure manufacturers remain compliant after initial certification.
  • Financial coverage for defective devices: manufacturers need to provide sufficient financial coverage regarding their potential liability for defective devices. Coverage must be proportionate to the risk class, type of device and size of the enterprise.
  • Premarket assessment procedure: a so-called ‘scrutiny procedure’ will be compulsory for high-risk products. Notified bodies are required to inform the competent authorities and the commission when a process begins.