Esther Abels, MSc, Chair of the DPA Regulatory and Standards Taskforce; Dir Regulatory, Clinical and Medical Affairs Philips Digital Pathology Solutions
We are charting a revolutionary pathway with regard to digital pathology and its contribution to medicine. As the lead on the DPA’s Regulatory and Standards Taskforce, it is my goal to steer us all towards a positive outcome, for the benefit of patients, vendors and the profession.
The evidence Philips has put forward demonstrating the safety, accuracy and effectiveness of digital whole slide imaging is a potent example of the paradigm of science. As new circumstances emerge, new insights will arise. That is the world we are now entering.
And how far we have come since 2009 (confirmed again in 2011) when the FDA publicly stated that whole slide imaging systems warranted a high-risk classification as Class III medical devices. This would have made it far harder to obtain initial approval, and inhibited product improvements and enhancements. But by 2014, DPA pathologists were making their voice heard in the discussion of how to appropriately assess the risk and benefits of WSI – and the formation of the DPA’s Regulatory Taskforce led to a significant shift in the FDA’s stance.
We recognized, of course, that FDA’s initial stance was based on concerns over a lack of science and data needed to assure patient safety and effectiveness, and on concerns about potential risks. Our collective challenge was to demonstrate the safety and effectiveness of the technical performance and robustness of the device itself. We also had to compare the diagnostic performance of pathologists working with WSI with their performance with a microscope.
2015 was a pivotal year, with evidence being presented in the US and Europe that challenged the initial thinking on the risks associated with this new technology, and filled in some of the data gaps. There was a better understanding amongst regulators about appropriate ways of characterizing WSI. The breakthrough came at the end of 2015, when the FDA decided WSI was a good candidate for de novo status. By allowing the more flexible de novo pathway, FDA opened the door to innovation and removed regulatory barriers to whole slide imaging.
We saw the result last month. US regulators gave the green light for Philips to market its IntelliSite Pathology Solution for use in primary diagnosis in USA − the first WSI system to achieve this milestone. In making their decision, the FDA has provided the ‘special controls’ for vendors in line with the proposal from the DPA’s Regulatory Taskforce. This move confirms that WSI systems are moderate risk Class II devices. As a result, new WSI devices will be able to use the 510(k) route.
FDA’s action also opens the door to other innovations, such as the use of deep learning techniques in the development of computational pathology, which could transform the specialist discipline of histopathology and the study of diseased tissue.
Rather than requiring a PMA for each new device, regulators were convinced by the alternative case put forward by the Taskforce that special controls were enough to ensure safety and effectiveness. A major milestone was when FDA issued a Technical Performance Assessment (TPA), which gives guidance to vendors on what technical performance assessment data must be provided for regulatory evaluation of any digital WSI system. Based on, amongst other input, communication with the Taskforce, the TPA focuses on how best to characterize the technical aspects that are relevant to WSI performance for their intended use and determine any possible limitations that might affect their safety and effectiveness.
It is all too easy when discussing regulatory affairs to talk in rather dry terms about rules, policies, and risk assessments. But it is important to recognize what has been just achieved. What we identify as “de novo thinking” can only be possible if decision-makers and innovators are willing to put to one side some of the protocols of the past and, instead, create new approaches specific to these new circumstances. Without that open-mindedness, innovation may be crushed – and we may land on the rocks.
In fact, this regulatory change simply would not have been possible without the courage of the FDA in being open-minded, willing to both review the emerging evidence presented by the DPA and other sources, and then consider its implications for pathologists and their patients. Critically, the FDA considered not just potential risks, but also the benefits of WSI.
Nor would it have been possible without the collaboration of vendors and pathology professionals under the umbrella of the DPA, determined to educate FDA and the community about the actual risks and benefits of whole slide imaging, and create clarity on the regulatory pathway. In many ways, the DPA and the call for whole slide imaging has given a voice to the pathologist, a professional all too rarely heard (and credited) in the diagnostic pathway.
The stereotypical scientist, of course, is a meant to be a serious, unemotional person more comfortable with cell analysis than human contact. I’ve always thought that was a tremendously unfair picture. Every one of us working in this field – vendors, regulators and scientists – never forgets that at the heart of everything we do is the welfare of our patients. The success we have achieved of this milestone is evidence of how we have all worked together, determined to find a way to enable WSI to enter commercial use, with the aim of facilitating collaboration, providing easier access to sub-specialists, and improving and speeding up the diagnostic process.
With the FDA’s forward-thinking, flexible approach, I am positive that they will keep their door open and continue to listen to us as we move ahead on this journey. However, I believe that it was our collective passion, conviction, collaboration, and robust science in mounting such a compelling case that persuaded them to rethink their approach to the regulatory review process.