Key Issues in Clinical Development for Interventional CV Devices | Page 9

In comparison, device trials often have long list of potential AEs that

single Notified Body, regardless of country of origin, is sufficient for

may include all events ever observed with that type of device from

all countries in the EU, the European Free Trade Association, and

any manufacturer. As a result, AEs that do occur may be subject to less

Turkey.15,16,18 Standards do vary by Notified Body, but, in general,

scrutiny, and the opportunity to prevent future AEs may be lost. While

relatively little data are needed to obtain a CE marking. For devices

these concerns are driving the FDA toward more rigorous expectations

that are substantially equivalent to an existing product, a comparative

of safety reporting, including more thorough analyses of AEs (eg, more

literature review may be sufficient. Highest-risk devices almost

in-depth AE narratives), budget cuts and uncertainties surrounding

always require human data, but the trials need not be randomized

regulatory change are increasing review times. For example, from 2005

and often evaluate safety but not efficacy.19

to 2012, the average total time for FDA review of a 510(k) application
rose from 90 to 140 days (an increase of 55%).5

Figure 8. Marketing Approval Process: EU

However, those timeframes are short compared to a PMA review, which
regulations allot 180 days but the FDA freely admits will probably take
longer.10 Of larger concern to most sponsors is the length of the entire
PMA process, including the collection of adequate preclinical safety
data before initiation of human trials. The differing requirements in
the EU and other parts of the world prompt many sponsors to seek
ex-US approval first and then use accumulated safety and efficacy data
to support the initiation of a clinical development program in the US.3
European Union
In the EU, the processes for drugs and devices are completely separate.
Devices receive a CE (Conformité Européenne) marking, which is an
indication that the product has been assessed and meets EU safety,
health, and environmental protection requirements.14 Requirements for

Proponents of the current EU system point to 2 main strengths: (a)

CE marking are based on risk, and high-risk interventional CV devices

the relatively streamlined processes mean that devices are available

must be evaluated by an independent standards organization, called

in Europe an average of 43 months before they are marketed in

a Notified Body, which is certified by a country’s national competent

the US (based on data from 2000 to 2011);20 and (b) comparisons

authority to assess and grant CE markings.15,16 In 2011, there were 74

of serious recalls of medical devices have found little difference

separate Notified Bodies across 25 countries with the authorization

between the EU and US despite significant differences in the approval/

to issue CE markings for medical devices. Certification from any

certification process.17,21

17

clinipace.com

8