Subscribe in a reader
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.
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?
Olympus CEO Mark Gumz announced some exciting news today in a blog article/interview written by Steve Tobak. Olympus is applying for FDA approval in digital pathology, and he also used digital pathology as an example to highlight “Enterprise Innovation” at Olympus. Every FDA approval gained in digital pathology is a huge step forward for our industry and it’s great to see that Olympus is applying to the FDA for approval. The blog post, titled “Enterprise Innovation: A Key to Untapped Business Growth“ summarized a recent interview with the CEO.
Enterprise innovation is defined as “Transformative business processes, practices, organizational planning and models that enable a business of any size to operate more effectively, profitably, and/or competitively,” according to this article and a Harris Interactive survey of Fortune 1000 executives. Mark Gumz states in the article,
…The status quo is the greatest inhibitor to growth. Enterprise innovation is something that’s within our control as an industry and as a nation.
The FDA quote from Mark Gumz is as follows:
We’re currently applying for FDA approval for clinical digital pathology, the ability to send a clinical slide over the Internet. During a surgical procedure, a surgeon could take a biopsy and send it to a pathologist anywhere in the world to get a second opinion – do I take out more or not? That will ultimately be a huge cost saver. Ultimately, enterprise innovation has to come down to return on investment.
So what do you get if you put Mr. Gumz’s vision of “Enterprise Innovation” together with an application for FDA approval of clinical digital pathology? My guess…not a whole lot in the near future! There are too many unanswered questions and likely a lot of work to be done. Some of these unanswered questions are:
I realize that all companies working toward FDA approval are faced with many questions and tough regulatory hurdles, especially since the FDA has not provided any clear guidance to manufacturers on this topic. However, based on the current public information out there about Olympus, their digital pathology product portfolio, and the information displayed on their website (which is 100% research and/or education focused) I have to imagine their FDA application is probably a rough draft and a long way off from being complete.
Patients do not understand the importance of a pathologist in the diagnosis of their disease. They also have no idea about digital pathology. But that could all change with a simple, powerful marketing campaign by GE’s Healthymagination. Can you imagine it? I can, and I have been for years. A Healthymagination commercial would bring attention, good attention to the practice of pathology.
Although no commercial has aired, it has been a busy week for GE in the world of pathology. On October 22nd GE announced the purchase of Clarient in a $587 million deal to accelerate GE Healthcare’s ability to predict and diagnose diseases; and yesterday GE healthcare’s joint venture with UPMC, Omnyx, announced the start of clinical trials for their digital pathology solutions. Although Omnyx was not involved in the purchase of Clarient, it makes sense that they will come together to further GE Healthcare’s $6 billion healthymagination initiative to improve cost, quality, and access in healthcare; or in our world- pathology.
In addition, GE and Omnyx executives spent the past few days promoting their innovation and advancements at two conferences in San Diego, CA- Pathology Visions and TEDMED. At TEDMED Mike Barber, GE’s VP of Healthymagination, gave an 18 minute power presentation which included digital pathology. Mr. Barber was quoted,
I don’t say this lightly – while digitization may seem like a relatively simple change in today’s tricked-out techno world, it’s a revolutionary step in pathology that may lead to the transformation of the practice, and the evolution of our understanding of cell biology.”
Digital pathology is no longer a new topic in pathology. However, it needs to become a new topic in healthcare and with patients. So while we wait for a Healthymagination commercial let’s start to spread the word of our amazing future to anyone who will listen.
Flagstaff, AZ (PRWEB) July 19, 2010 Flagship Biosciences LLC, a provider of digital pathology services, announced today an exclusive partnership with PrognosDx Health to provide pharmaceutical companies and cancer centers with access to tissue-based, global patterns of histone modification patient profiling for use in early stage drug discovery and various phases of clinical trials. PrognosDx Health is an early-stage epigenetics company with unique global patterns of histone modification patient profiling technology.
“Epigenetic changes in gene regulation that are not specifically due to direct alterations in DNA have been demonstrated to drive tumor progression and response to therapy,” commented Amato Giaccia, Ph.D., Professor of Radiation Oncology and Associate Director for Education at the Comprehensive Cancer Center at Stanford University. Dr. Giaccia added: “The ability to detect changes in histone methylation and use them to assess tumor progression or predict response to therapy is a powerful new approach that has significant clinical implications, which was recently demonstrated in a study published in the Journal of Clinical Oncology that showed high levels of H3K4me2 and/or H3K18ac were predictive for increased survival. These exciting studies represent the future of molecular pathology.”
“Pharmaceutical oncology clinical programs and cancer centers are both struggling with the ability to effectively profile their patient populations during clinical trials,” said John Bloom, a well-known leader in companion diagnostics development and a board member of Flagship Biosciences. Dr. Bloom added: “Epigenetics is an emerging valuable addition of information that may help to drive better prognostic decisions from study enrollment through late-stage trials. We are excited to see PrognosDx’s technology platform be made readily available to these pharmaceutical and cancer center groups through the services and partnership with Flagship Biosciences.”
Flagship and PrognosDx have agreed to a profit sharing business arrangement, which primarily is based on providing laboratory testing services to companies with early stage drug discovery programs as well as those companies needing to test their preclinical or clinical phase tissue samples. These services will be launched in Q3, 2010 and will initially focus on testing of specimens related to therapeutic oncology programs within pharma where global patterns of histone modifications patient profiling may identify sub-population of the patients who will be the likely responders to the drugs in development. These testing services will also apply to animal studies, target identification, target validation, and efficacy studies especially for HDACi class of compounds, various pro-drugs, certain chemotherapeutics, compounds inhibiting the nucleotide synthesis process as well as those compounds impacting certain proprietary metabolic pathways.
Kamran Tahamtanzadeh, Founder and CEO of PrognosDx, stated, “Flagship Biosciences brings a unique combination of pathology expertise and image analysis talent, and the ability to run preclinical and clinical trial studies in a regulated environment. This partnership will meet the demand from our pharmaceutical clients for easily-available, high-quality clinical trials patient profiling services. We see great benefit in partnering with Flagship’s leaders, who are well-known experts in digital pathology services wherein a foundation of test accuracy and reproducibility is required. Furthermore, we believe that the highest-quality IHC and digital analysis is critical to quantitative histopathologic evaluation and we are confident that Flagship has the expertise to deliver this important test in support of cancer patients.”
About Epigenetics
Epigenetics refers to the regulation of genes with mechanisms other than changes to the underlying DNA sequence and such processes are widely believed to play a central role in the development and progression of almost all cancers. Such epigenetic processes are controlled by DNA methylation and histone modifications.
About Flagship Biosciences
Flagship Biosciences is a pathologist-owned company whose mission is to improve tissue assessment in pharmaceutical and medical device development. Flagship’s services include quantitative pathology assessment on-demand, low-cost digital pathology slide scanning, secure hosting, pathologist-supervised IHC and histology placement, and custom image analysis and companion diagnostics development. All of their services are reviewed and supervised by board-certified pathologists. For more information, please visit the website www.flagshipbio.com
About PrognosDx Health
PrognosDx Health, Inc. is an early-stage life science company formed to significantly improve the treatment of cancer and other complex diseases by developing novel, semi-quantitative and quantitative laboratory products based on global patterns of histone modification through technology it has exclusively licensed from the University of California, Los Angeles (UCLA). This platform technology has broad potential uses in the development of cancer prognostic assays, therapeutic response prediction assays, as well as research tools and reagents. A network of renowned academic researchers and clinicians supports PrognosDx Health, with expertise in the fields of cancer and epigenetics. The company has its headquarters in Palo Alto, California. PrognosDx is currently in the process of selecting strategic diagnostic partners for development of advanced IVD products for variety of cancer indications. The company also has plans to form strategic partnerships and license out its high value, histone-based biomarker tests to select and highly specialized CLIA laboratories in the US and abroad. For further information, please visit the website www.prognosdx.com.
Read the Press Release through PRWeb
Learn more about Epigenetics in the TIME article “Why DNA Isn’t Your Destiny”
Subscribe in a reader