FDA representative Tremel Faison made it clear last week, during the Regulatory Panel at the Pathology Visions conference, that digital pathology systems will be classified as a class III medical device, requiring manufacturers seeking approval to follow a Pre Market Approval (PMA) process. If you have been following the regulation of digital pathology closely the news of a PMA should not be a shock. In fact this point was made by the same FDA representative in her presentation at the first FDA advisory panel meeting on digital pathology back in October 2009. In a previous blog post titled “The FDA States, WSI Systems are Not Class I Exempt” which I authored at www.tissuepathology.com I stated,
The initial presentation given by Tremel Faison, a Scientific Reviewer for the FDA, set the tone for the meeting whereby she informed the public and panel that WSI systems could not be Class I exempt, like a microscope, and are therefore subject to premarket requirements. The reason a WSI device will not be considered exempt is, as defined by21 CFR 864.9 limitations, a WSI device is considered to be different fundamental scientific technology and IVD intended for use in diagnosis.
However several manufacturers have pushed for this to be reconsidered over the past several years based on the extensive requirements and the enormous cost of the PMA process. A PMA submission to the FDA will cost a manufacturer $240K, and with extensive clinical trials needed to prepare for submission to the FDA, a manufacturer may have to invest at least $1M -$2M for a possible approval. If the approval is rejected, they will have to invest even more to redesign the trial and then resubmit. The only road map suggestion was for manufacturers to follow the path of cytology screening devices such as the ThinPrep Imaging System.
A submission to the FDA was made on January 7, 2002 for ThinPrep Imaging System and the PMA was finally awarded 17 months later on June 6, 2003. The Summary of Safety and Effectiveness Data for the ThinPrep Imaging System outlines the details of their extensive, multi-site clinical trial and it appears that the studies probably started some time in 2000, which estimates that this entire process probably took around 3 years.
The 510(k) process for clearance of quantitative IHC analysis as a class II device will remain unchanged, and will not be effected by the approval process for digital pathology systems. A 510(k) submission costs only $4K and the clinical trials are much smaller and focused. As a result a manufacturer may only have to spend between $50K-$100K to achieve a 510(k) clearance. This could be a stopgap for manufacturers. Manufacturers could focus on obtaining a portfolio of analysis algorithms that are reagent specific, and could even expand beyond the breast panel while working to obtain their PMA’s for primary diagnosis of H&E slides. Both types of clearances/approvals will be needed and they go hand in hand.
The most recent 510(k) clearance was awarded to Ventana for their Virtuoso System for HER2 using the iScan slide scanner. The clearance is for computer-assisted image analysis scoring and manual scoring of digital images of IHC stained (Ventana Pathway 4B5) HER2 slides. The FDA issued the 510(k) clearance in just over 4 months and the entire process including clinical trial work took approximately one year.
There is no doubt that manufacturers seeking FDA approval have their work cut out for them. Sadly this may be a game changer for some manufacturers. Manufacturers may have to pull back on the US market and focus their business strategies in other parts of the world or realign their market focus to research and education. This situation is not uncommon in the medical device market. A recent article in the Wall Street Journal titled “How the FDA Could Cost You Your Life” was written by Dr. Scott Gottlieb who was previously a deputy commissioner at the FDA. In the article he states,
This is an all too familiar story, the FDA impeding useful innovations in the U.S. Entrepreneurs here are forced to test promising medical devices in costly animal studies for years before they can advance their products into clinical trials. When clinical studies get started, the FDA is asking for longer and larger trials that increasingly mirror hurdles proposed for new drugs.
In response, American device makers are moving their business overseas. Between 2004 and 2010, more than half of all innovative devices were first approved in Europe. Because more devices now launch in Europe, companies increasingly study the products there. In 2004, 86.9% of all medical-device studies listed in www.clinicaltrials.gov were being carried out in the U.S. By 2009, only 45% of clinical trials were run here.
Furthermore he adds,
This is no way to run a regulatory process if the FDA is serious about promoting medical innovation and advancing the public health.
Digital pathology has the power to improve patient care, and there are a growing number of studies out which highlight how digital pathology may be better than the gold standard, a microscope. This point is articulated very well in a letter to digital pathology companies from a group of pathologists for digital pathology lead by Dr. Keith Kaplan. The pathology community is trying to help and to show the value. Now if only the FDA and its’ broken regulatory process would listen…
Stay tuned this week for blog post Part 2: Digital Pathology is not an LDT! Now what?