510(k) or PMA?

Nanosonics innovative Trophon EPR achieves US market entry with a 510(k)

Nanosonics Trophon EPRAdvances in technology fall into two camps; Evolutionary development or Disruptive game changers. Safe, non-toxic and fast disinfection of ultrasound probes was gaining gradual improvement until the development of Nanosonics Trophon EPR. Here was the disruptive solution the market needed; the superb performance is like nothing else!

Everyone knows you can’t have your cake and eat it, too. Wouldn’t a disruptive solution need a costly PMA to be sold in the US? This was the challenge faced by our client Nanosonics.  With thoughtful approaches to meet US regulatory demands and extensive communication with the FDA, Brandwood Biomedical is delighted that a carefully created submission has resulted in a 510(k) issued on the basis that the stated use has substantial equivalence to predicates.

Brandwood Biomedical congratulates all the team at Nanosonics on achievement of access to the US market, and looks forward to news of American customer delight and commercial success for the company.

By the way, if you want to read an interesting book on how the best companies achieve great outcomes in seemingly contradictory or counterintuitive circumstances, have a look at “Doing Both: How Cisco Captures Today's Profit and Drives Tomorrow's Growth” by Inder Sidhu. 

FDA Clears (Not) The First IPhone App

FDA has been approving mobile device apps for at least 5 years, the more interesting questions are about how to make sure these devices are safe, effective and - for the developer - can be easily validated

There's been a lot of excitable and breathless reporting over the last week or two about FDA's first 510(k) clearance of an iPhone app (the Mobile MIM).  Even august journals such as Scientific American got in on the act.  But not so fast.  FDA has been quitely approving iphone and other portable/remote software apps for some time now. More about that in a moment.    The novelty in this latest approval was that it was the first app for the specific application of viewing diagnostic radiology images from CT, PET and MRI.  Essentially this particular app allows the images to be sent to the physicians iPhone for instant viewing remote from the radiology clinic.  

Records System or medical device?

FDA overseas medical devices - which are essentially any thing (including software) with a direct therapeutic or diagnostic functionality.  Software that simply acquires, stores or moves to other locations medical information - including images, is generally considered a medical records system - which is in most cases exempt from FDA oversight.  Systems to ship such medical records from the clinic to remote servers and personal computers including remote laptops have been around for quite some time now, and the extension of these applications to smaller and smaller devices, including PDAs and smartphones is an inevitable progression.

A quick search of the FDAs online database of 510(k) approvals throws up several devices cleared by FDA over the last year including the Airstrip RPM (cleared July 2010).  AirStrip is an iPhone App which delivers a whole range of physiological data, gathered by bedside diagnostic devices and relayed through a clinical data management system to the physicians iPhone wherever she is.  The data displayed range from things like ECG and blood pressure waveforms, blood gases, and specific invasive blood pressure readings. These data can be presented on the iPhone along with other patient record information such as medications, allergies and laboratory data.  The Airstrip approval was based on a comparison under the 510(k) substantial equivalence rules to two other applications - including the  GE pocket viewer (cleared January 2006) as an application running on Windows Mobile PDAs and generic cellphones to view clinical data) and the Cerner iBus (cleared November 2009)

Validation of Medical Software

Crucially the MIM Mobile software includes a contrast test to ensure that the image and local lighting conditions are good enough to allow the physicain to make a diagnostic interpretation of the image, right there from the iPhone screen.  That diagnostic functionality makes it a medical device rather than simply a medical records system.  Reading the FDA press release makes it clear that FDA paid particular attention to review of the validation of the the ability of the app to prove images of sufficient quality for diagnostic purposes.  and this is the central issue.  

However, while the applications have migrated to increasingly small and mobile hardware, the regulatory framework has  remained happily agnostic to the platform.  Software with a therapeutic or diagnostic function is considered a medical device in all jurisdictions.  The revision of the European medical Devices Directive in 2007 made it very explicit that such software is a Class IIa or above medical device in Europe, and the same applies in other GHTF jurisdictions including e.g. Canada and Australia.  The current consensus standard which underpins approval in Europe or by FDA is IEC 62304:2006: Medical device software -Software life cycle processes.  This standard sets out requirements for development and maintenance of valisated software for medical use.

But isn't it different for iPhones - after all, Apple is famous for its jealous protection of its software and hardware IP - how do you validate the iPhone and the iPhone operating system if you don't have the source code?  This too is not a new problem and medical device software developers have been validating aplications running on proprietary platforms - typically Windows for years.   Typical solutions involve black box validations in which the system is tested for robustness of output based on extreme data inputs.  interestingly in the case of Mobile MIM, the validation has relied on inclusion of a straightforward control image to verify that the lighting conditions allow for the clinician to view and discern adewquate levels of image contrast.  

So is it a brave new world - not necessarily so.  In fact FDA Guidance on validation of "off the shelf" software has been around since last century :). 

Developing a medical device software application?  Contact Us for a free  no obligation appraisal of your regulatory obligations

No Risk means can't decide? -Interesting analysis of FDA's 510(k) review

There's been a great deal of interest in the FDA review of the 510(k) processes.  One of the more thoughtful discussions of the recently published FDA report comes from Barry Sands at WMDO.   Barry pointed out the "unusual level of openness and honesty" in the report, then went on to say:

I actually believe the review hit upon the majority of issues that are of concern and some of the recommendations are sound. However, there appears to be an underlying belief that this regulatory process should produce a risk free regulatory decision with regard to the premarket clearance/approval decision. I believe that one needs to understand that the regulatory process itself has risks that cannot be mitigated to zero. Just like every single medical device available on the market today possess risk, so does the regulatory decision to allow or not allow a medical device to enter and remain on the market. 

Sands points out some specific concerns about knowledge base and inconsistency of interpretation, but then returns   to a discussion on risk that goes to the essence of the different approaches of the US FDA compared with the "GHTF model" regulators such as Europe, AUstralia and Canada. 

The core issue raised is whether FDA has a mandate to consider device "benefit" rather than "effectiveness" (Sands argues not).  The former is a measurement of clinical outcome, the latter a measure of engineering performance. 

In the non-US, GHTF world, it's quite clear that the onus on the manufacturer is to demonstrate effectiveness, the benefit is more a matter for clinician decision and choice based on the performance claims and evidence.  That's why clinical trials to support CE mark tend to be simpler, faster and cheaper than those to support US approval (particularly PMA).  THe European trials in essence focus on confirmation of real world performance of the device, which can be done more quickly than an efficacy study which may need to follow long term clinical outcomes.

It remains to be seen where the FDA review will lead, but Sands raiises a very important issue.  he put it very well:

If we attempt to drive the associated risk of the regulatory decision to zero, we may very well have a process that cannot make a decision.

First Steps towards 510k reform

In response to growing concerns about the 510(k) process raised by numerous parties include the US Congress the FDA has initiated a review of the 510(k) program. As a first step the FDA has conducted an internal review and they have recently released these internal reports for public comment. The key findings and recommendations presented in the reports are outlined below:

• The de novo process was found to be significantly overburdensome and it is recommended that steps be taken to streamline the process including limiting the regulatory oversight based on appropriate risk assessment.
• To date it has been very unclear which 510(k) submissions require clinical evidence. The FDA proposes to establish a new Class IIb classification for products that would require clinical evidence in a 510(k) submission. 
• Introduction of a “Notice to Industry” system that would provide more timely guidance to industry on changing regulatory expectation, than the current formal guidance process.
• New and explicit requirements for manufacturers to submit a summary of all known scientific information related to the safety or performance of the device in a 510(k).  This is aimed directly at preventing the selective presentation of only favourable evidence to FDA.
• The FDA proposes to include much more detailed device information in 510(k) database including photographs, up-to-date labelling, design schematics as well as the FDA review decisions.
• FDA seems to be aware of a lack of expertise and consistency with its reviewers and are planning on taking steps to increase reviewer knowledge and consistency of review practices across the CDRH.

Note that all these are simply recommendations at this stage and open to public comment. Watch this space for announcements on comments!

It is still VERY early days in this process. The FDA has commissioned the Institute of Medicines to undertake an independent review of the 510(k) and their report is not expected until July 2011. Expect further consultations and eventually updates to the regulations and potentially the Act, all of which will take time.

In some ways these reforms represent some small steps towards the GHTF  regulatory model – this is essentially introducing a four step classification and is placing a greater emphasis on clinical evaluation – which, following the recent MDD reviews is now very explicitly part of the European requirements (and also in Australia and other jurisdictions).  There’s still a long way to go on the road to global harmonisation but a journey of a thousand miles starts with a single step…

The full reports are available here: http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHReports/ucm220272.htm

Josh Griffin
Josh@brandwoodbiomedical.com.au