The most contentious hurdle that steals competitiveness and commercial opportunities for medical devices is the regulatory review process. It has already been very challenging for regulators to strike a balance between assuring device safety and ensuring access to the best treatment.

1. The Less Burdensome Pathways to US FDA
Approval
The most contentious hurdle that steals competitiveness and commercial opportunities
for medical devices is the regulatory review process. It has already been very
challenging for regulators to strike a balance between assuring device safety and
ensuring access to the best treatment. However, where regulations threaten to stifle
innovation and deprive the medical device industry of its value, this becomes the
critical turning point for a change to take place. Leading the way in finding the least
burdensome approach (FDA Modernization Act of 1997) to regulatory scrutiny is the
US FDA. In 2011, it introduced the Innovation Pathway to facilitate device
innovation and expedite the review of breakthrough technologies. Through this
programme, the FDA aims to engage with innovators much earlier and more
interactively during device development to identify just the right investment of time,
efforts and resources to achieve regulatory compliance. The three programmes
already proposed to reduce time and cost of the regulatory process are detailed below.
1. Downclassification of PMA devices
The US FDA classifies medical devices into three categories - Class I, Class II and
Class III - based on the products perceived risks. The higher the risk (Class II and III)
the greater is the degree of regulatory control. The level of risk in a product depends
on its intended use. However, under the US FDA, assigning classification to a
medical device based solely on intended purpose is not enough. For example, to
secure the lighter 510(k) approval route for Class I and Class II devices, a
manufacturer must further demonstrate substantial equivalence (SE) to a predicate
legally marketed device of the same classification; failing which, the device will be
regarded as a new technology classified under Class III and subject to the more
stringent Pre-Market Approval (PMA) review. In a recent review of PMAs approved
before 2010, the US FDA has proposed the loosening of controls on 44 device types.
This regulatory relief is given in the following forms:
i. Reclassification to the Class II category
ii. A shift from pre-market data collection to postmarket controls or postmarket
data collection
iii. A reduction or shift in data collection and/or reclassification in 2014, during the
review
The Center for Devices and Radiological Health (CDRH) has made it their strategic
priority for 2014/2015 to explore ways to expedite the evaluation of new device
technology, especially where it is of particular importance to public health. The 21
devices candidated for downclassification to Class II includes short-term and semi-
permanent invasive devices, but does not include permanent implants. This brings the

2. US FDA slightly closer to the way these devices are classified under the EC rules,
within which they already fall under either Class IIa or Class IIb devices. However,
the reason for downclassification is less for harmonisation purposes and more because
the device technology has become the standard, effective, safe and highly demanded
mode of treatment. It would not be wrong to presume that these devices would also
need to meet some essential criteria such as:
i. have sufficient clinical data and post-market experience
ii. demonstrate exemplary safety records
iii. Have been in the market for 5 years or more
iv. Are widely available and used on/by patients
On the other hand, the shift from pre-market data collection to post-market controls
for breast implants may be counter-intuitive for a device that has been subjected to
recalls and scandals. However, this is clear proof that lengthy pre-market review
would not necessarily increase the safety and effectiveness of a medical device. In
this case, the US FDA is wise to employ a "bootstrap" strategy that applies just the
right amount of review with more specific end-points continuously throughout the
commercial lifetime of the device. The right balance of assumption (pre-market) and
fact (post-market) will help create a more complete safety and effectiveness picture
for a medical device.
2. Expedited review process
For PMA devices not targeted for downclassification, the US FDA has introduced two
programmes: the De Novo device classification and the Expedited Access Pathway
(EAP). Both pathways are voluntary, meaning manufacturers need to make a
submission to the US FDA requesting for the devices to be considered under these
programmes. The De Novo classification allows what would normally be a Class III
device to be reviewed via the Class I or Class II routes despite having no substantial
equivalence to a legally marketed device. These devices approved under general
controls or 510(k) will then be classified as Class I or Class II. They can be marketed
immediately and serve as the predicate device. To qualify for the De Novo process, a
device must meet the following criteria:
i. The device should demonstrate a risk level equivalent to a Class I or Class II
medical device, meaning low to moderate risk.
ii. A comprehensive risk-benefit analysis must be performed. The manufacturer
must be able to understand, explain and mitigate all known risks as well as
provide assurance of effectiveness using general or special control principles.
An EAP designation, on the other hand, allows a shift from the pre-market data
collection approach to a post-market data collection approach. It is an interactive
review process, in which the US FDA and manufacturer work hand-in-hand to

3. establish the appropriate data development plan under either a PMA or De
Novo route. The data development plan should adequately describe the pre-market
and post-market data (clinical and non-clinical) to be collected and analysed within
agreed timelines. Devices that qualify for consideration under the EAP should meet
the following criteria:
1. The device is intended to treat or diagnose a life-threatening or irreversibly
debilitating disease or condition.
AND
2. The device meets at least one of the following criteria:
 No appropriate alternative treatment or means of diagnosis exists.
 The device represents a breakthrough technology that provides a clinically
meaningful advantage over existing legally marketed technology.
 The device offers significant, clinically meaningful advantages over existing
legally marketed alternatives.
 The availability of the device is in the best interest of patients.
AND
3. The sponsor submits an acceptable draft Data Development Plan.
3. Foreign clinical data
More recently, the US FDA has released a draft guidance for the acceptance of
clinical data obtained from studies conducted outside the United States (OUS) to
support pre-market submissions. In making this move, the FDA acknowledges the
increasing globalisation of clinical trials and seek to find ways to prevent unnecessary
duplication of clinical studies. For the FDA to accept OUS clinical data, certain
criteria needs to be met:
i. The clinical studies are conducted under an investigational device exemption
(IDE)
ii. Sites in the United States are included as part of the clinical study
iii. Clinical studies conform with the Declaration of Helsinki or a similar
declaration under the laws or regulations of a country
iv. Valid scientific evidence is produced from a well-controlled studies presided by
qualified experts
v. Compliance with Good Clinical Practice
vi. Considerations have been given to:
 Differences in clinical conditions
 Differences in study populations
 Differences in regulatory requirements
Nealda Yusof is a medical technology writer and founder of Semoegy.com. Click
here to contact the author.

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Original article: http://medtechupdates.semoegy.com/2015/05/the-less-burdensome-
pathways-to-us-fda-approval/