DIAGNOSTIC EXECUTIVE PROFILE
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As the IVD industry continues to grow rapidly, it faces a number of challenges. IVD Technology asked the top executives at two successful IVD companies, Gen-Probe Inc. (San Diego) and Pathwork Diagnostics (Sunnyvale, CA), as well as the director of FDA’s Office of In Vitro Diagnostic Device Evaluation and Safety (OVID) about those challenges. They predict that the industry will continue to rise to meet them head-on and, in doing so, will continue to play an increasingly important role not only in the diagnosis but also the management of many difficult diseases.
They expect that start-up and existing companies will continue to build and deliver new tests based on genomics that will provide physicians and their staffs with high-value information that, in turn, will enable them to deliver higher quality, cost-effective care faster to more patients. They see the regulatory requirements helping to assure the quality and the safety of the tests that are already on the market and those that soon will become available, and as a result will increase their acceptance among practitioners.
They see IVD companies, large and small, start-up and existing, finding ways of meeting their many challenges and as a result saving the healthcare system money by reducing the use of nontargeted, broad-based therapies and their associated toxicities. Hank Nordhoff, chairman and CEO of Gen-Probe, sums up their outlook when he says, “We’re doing great things now, and it will only get greater.”
Deborah J. Neff, president and CEO, Pathwork Diagnostics
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Deborah Neff |
Deborah J. Neff expects that in the near future, more companies will, like Pathwork Diagnostics, develop tests based on information from the human genome project that will make it easier for physicians to deliver personalized medicine to their patients that can improve patient outcomes. In April, the company launched the Pathwork Tissue of Origin Test through its CLIA-certified Pathwork Diagnostics laboratory. The new test uses gene expression profiling to aid in the diagnosis of tumors of uncertain origin. An estimated 200,000 patients each year in the United States have uncertain primary tumors. Pathwork is working with FDA so that the test, among the first microarray-based diagnostic tests for cancer available in the United States, can be offered as a diagnostic kit directly to clinical laboratories in medical centers. “The test is under what we hope are the final stages of FDA review,” Neff says.
Neff is excited about the future of not only her company but also the industry because diagnostics such as the Tissue of Origin Test can provide the first pieces of information that oncologists need to be able to choose the therapy that will work best on a patient’s cancer. “Knowing the primary tumor site with greater certainty enables more-appropriate cancer treatment. The growing trend in cancer care is the use of therapies that target specific tissues and their genomic components, rather than relying on a one-size-fits-all treatment approach. We believe the Pathwork Tissue of Origin Test will help provide more certainty in tumor diagnosis, which will enable more patients to realize the benefits of this new era in genomics-based diagnostics.”
Pathwork is a small company that was created through a merger in 2006 and has 30 employees. Neff believes start-up companies with quality products will be able to grow and “build a real market presence,” either independently or as an acquisition of a larger company. Neff believes that the recent spate of mergers and acquisitions in the industry will continue because it gives the partners the leverage they need to develop and market their new products in this tough economic environment.
The key, she says, is for the company to have robust science to back its claims. “You have to develop evidence in the market that your test adds value, and if you can demonstrate repeatedly and over time that you make a difference in the choice of care, that you can help the pathologist or physician make more-informed decisions sooner, you will have great success in getting your product adopted” by the clinicians, Neff says.
Neff believes that FDA is working hard to understand all the new, complex genomic tests that companies are rather rapidly developing and is taking a responsible approach to regulating them. Right now, she says, companies have the option of developing their tests through a CLIA-lab as Pathwork has done with its Tissue of Origin Test. “I think that’s an acceptable way to bring tests to the market, provided they are backed by strong validation data like our test is,” she says.
Neff expects that more IVD companies will, again like Pathwork has, also be interested in developing their tests as a kit available through diagnostic laboratories and thus seek FDA approval. “In our case, we decided it was worth it because of our desire to have our test challenged for clinical performance and to be able to sell it directly to labs.” FDA clearance, she says, will lend credibility to the test and will advance its adoption.
One of the many challenges the IVD industry faces, Neff says, is to prove to physicians and to payers that their new, complex genomic tests provide important information that they did not have before, or at least could not obtain as easily. Those companies that are able to demonstrate to the practitioners and the payers that the information they are providing adds clinical value over and over again, will see their tests adopted, she says. Neff believes that momentum is moving in this direction, and she cautions IVD companies to be vigilant so as “not to do anything that will damage the credibility that many of us are now building with payers and heathcare providers.”
Many of the new IVD tests that have been made available or are close to market are related to cancer. Pharmaceutical companies are working in conjunction with the IVD companies to develop drug therapies that can help cancer patients. “There are approximately 20 cancer-specific drug therapies that have been developed, which are relevant to our test,” Neff says. “That’s where we believe our Tissue of Origin Test will help physicians. Knowing the origin of a patient’s cancer with greater certainty will enable them to make better treatment choices.” Neff says Pathwork’s example is but one of the many she sees with great potential for collaboration between the pharmaceutical and IVD realms.
While much of the recent emphasis is on cancer, Neff adds, the technology developed from genomic science is promising for the early detection and treatment of Parkinson’s and other immune system diseases as well. This is yet another reason why Neff remains optimistic about the IVD industry and the growing role that it will play in advancing medical care in the 21st century.
Hank Nordhoff, chairman and CEO, Gen-Probe Inc.
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Hank Nordhoff. |
Gen-Probe has been at the forefront of molecular diagnostics since its founding in 1983. Like Neff, Hank Nordhoff is excited about the future of the IVD industry, particularly its molecular side.
The molecular side of the IVD industry has been growing at a much faster pace than the rest of the industry, Nordhoff says. “Fortunately for us it’s often more profitable, so it’s a nice part of the industry to be in.”
Nordhoff believes industry’s growth comes from its ability to translate discoveries about pathogenic mutations in DNA and RNA samples into tests that can aid in detection, diagnosis, subclassification, and prognosis of disease and in monitoring response to therapy. “The molecular side of the IVD industry has been the greatest beneficiary of the genomic revolution,” he says. “A lot more so than pharmaceuticals,” adds Nordhoff, noting much of his career was spent in senior positions with Pfizer Inc.
Nordhoff says there seems to be growing acceptance of the fact that molecular diagnostics are able to deliver accurate results, faster than traditional methods such as antibody and culture testing. During the last 25 years, it has become clear that “molecular diagnostics perform better than other types of diagnostics,” he says. “The immunoassays just don’t have the same sensitivity and specificity that we can provide.”
Unfortunately, Nordhoff says, reimbursements for molecular diagnostics have remained the same for the last five years. “In order to innovate, you have to have a profit incentive,” he says. However, he says, he is hopeful that people in appropriate places are beginning to recognize the value of molecular diagnostics. They can promote early detection, which can lead to more-appropriate treatment, which in turn can generate not only better medical but better economic outcomes as well. “The market truly values such outcomes, and should be willing to pay higher prices for it,” he says.
While Nordhoff believes that molecular diagnostics have taken advantage of the information gleaned from the human genome, he sees the IVD industry aligning itself more closely with the pharmaceutical industry to bring new tests and therapies to market and sooner. In the past, he says, promising drugs have been killed because they have been shown to have detrimental side effects in some, but not all patients. Working together, he says, molecular diagnostic tests can help clinicians to identify those patients who are likely to have adverse side effects and those who will not. Nordhoff can envision a scenario in which clinical trials are smaller and the approval process for new drugs faster because working in conjunction, “the diagnostic and the pharmaceutical companies will be able to quickly differentiate responders from nonresponders to their new therapies.”
One of the reasons that Gen-Probe has been able to successfully launch new products is that it also developed its own testing instruments. Its Tigris system automates all phases of molecular diagnostics testing from sample preparation, amplification, and detection to reporting results. Gen-Probe is developing two other instruments, Nordhoff says, one of which is automated like the Tigris but has a lower throughput and cost. The Tigris system is Gen-Probe’s solution to helping reduce the cost of molecular testing, Nordhoff says. He says it is a good example of the innovation in the molecular diagnostics industry and how it uses new developments to meet its challenges head-on. Such innovation, he says, is why he believes the molecular diagnostics industry will continue to be more attractive and garner much more attention in healthcare now and in the future.
While all of Gen-Probe’s growth has been internally generated, Nordhoff envisions the IVD industry continuing to grow through mergers and acquisition. “A lot of the recent growth we have seen among life sciences companies is through mergers and acquisitions, and I believe that we will continue to see that trend,” Nordhoff says. Nordhoff does not “see another Siemens, which is into laboratory diagnostics, imaging, and IT solutions for healthcare, and which has had an enormous appetite for diagnostic companies.” But he does see other companies not already in molecular diagnostics wanting in on the industry in some way “because of its unprecedented growth and the opportunities that abound.”
Yet another challenge that Nordhoff sees the industry facing head-on is regulatory hurdles. “It’s kind of an unusual situation,” he says, “in that labs can self-certify their tests without going through FDA. That’s what is referred to in the industry vernacular as a homebrew test, where diagnostics companies have to get their tests approved by FDA.” Nordhoff says the issue has generated a lot of good discussion in the industry with “both sides being very rational and respectful.” And he fully expects a solution that will allow ideas and products that are safe and add value to be able to move forward. It’s just another reason, he says, he has such unbridled enthusiasm for the future of molecular diagnostics.
Steven I. Gutman, MD, director, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)
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Steve Gutman |
As director of OIVD, Steven I. Gutman is as enthusiastic about the future of the IVD industry as Neff and Nordhoff. “I am continually impressed by the dazzling menu of new diagnostics that appear to be entering or are poised to enter the marketplace,” he says, “and I continue to be very impressed by the ability of this industry to build off of past experience and improve the quality of their products.”
Like many in the field, Gutman sees molecular diagnostics growing because it will enable clinicians to deliver personalized healthcare, which promises not only earlier diagnosis and more-effective treatments but also can be very cost-effective, especially in the long run.
Gutman believes that FDA plays a very important role in all that is happening in the field as it moves forward with new diagnostic tests and new applications. “It is my view,” he says, “that the FDA regulatory process is an important step in the translation of new products from the research bench to the clinical bedside. We contribute substantially to assuring the quality of analytical and clinical performance of the new tests with our independent review of the data, and we provide transparency in the credentialing process in terms of new development of new technology.”
From his perspective, Gutman says, he sees OIVD as neither the monster nor an obstacle in the room. “FDA clearance or approval is simply one part of the journey to the moon,” he says, “and I truly believe in the importance of grounding new tests in evidence-based information, utility information, medical need information, and economic information.” Obtaining all that information is necessary, he says, “to convince third-party payers to reimburse for the new tests and to convince often- overwhelmed clinicians to use new technologies well and, frankly, to use old tests properly.”
There is no question, Gutman says, that personalized medicine and genomics are the future of IVDs, and FDA is trying to be flexible and help companies that are hoping to bring new products and tests in this arena to market while protecting the public safety.
“Our group has been particularly aggressive in using the de novo regulatory process to allow products to come in,” he says. “We have also been very effective in using the protocol review process to allow for early interactions with companies to discuss new products, and we have used, when appropriate, expedited reviews. We also have used real-time reviews to bring products to market in a timely manner. So I think we have shown remarkable flexibility and facility in bringing in cutting-edge new products.”
Gutman says FDA’s role in approving in vitro diagnostic multivariate index assays (IVDMIA), tests that use mathematical formulas to interpret gene and protein data to guide medical decision making, is still under review. FDA has taken the position that such tests, ordinarily overseen by CLIA regulations, must instead be cleared or approved by the agency due to their complexity. While a draft rule is still pending, FDA has enforcement discretion, Gutman says. “Enforcement discretion suggests we believe that laboratory-developed tests are medical tests, and that the labs creating them are manufacturers and meet the definition. However, as a matter of history and deployment of resources, we’re currently not choosing to actually apply FDA regulatory processes to those particular types of tests.” Gutman refused to predict how this issue will be resolved. “I just don’t make predictions,” he says.
What new innovations does Gutman expect to see from IVD companies? “I am not prescient,” he says, “but everywhere I look, I see new detection systems, new and more- complicated software systems with interpretative algorithms. I see imaging systems and biosensors. I see the ability to make technology more compact, expansion in applications of multiplex technology, expression assays, new applications of genomics, proteomics, and metabalomics, and new applications where people will see immune response to pathological changes.”
While all of it is very exciting, Gutman says, he can’t say which areas and devices will gain the most attention and have the biggest impact as technology moves forward. All he knows, Gutman says, is that it is a “very challenging time” for FDA to “keep track of this rapidly evolving field.” As the technology becomes much more complicated, he says, “the agency has been much more involved not only in premarket review but also in development of tools for risk assessment and policy development, and it will continue to do so to protect the public health.”
Gutman recognizes that as a regulatory agency, “FDA is not everyone’s favorite.” But he believes that IVD companies and FDA recognize that they have mutual interests in improved yet safe patient care, and can and will continue to work together to promote them.
