IVD executives discuss the importance of making diagnostic tests more available, easily accessible, and better understood.
PHOTO BY ISTOCKPHOTO.COM.
What do IVD manufacturers focused on things like blood banking, liver cirrhosis, and pharmacogenetics have in common? Besides their obvious healthcare ties, when it comes to diagnostics, companies that work toward achieving goals in vastly different areas of healthcare might have a lot more in common than meets the eye. Whether it's working to ensure the safety and availability of blood for transfusion, attempting to determine who with hepatitis C will develop cirrhosis, or performing genetic tests to establish which medications will work best for individual patients, IVD manufacturers are taking technologies to new levels for the betterment of healthcare in the United States and globally.
In catching up with three IVD industry leaders, each had a particular fondness for the company they lead and an excitement about what their companies were accomplishing. But even though each has a unique perspective, their commonalities are clear. Although they are justifiably concerned about regulatory compliance and reimbursement issues, these challenges do not begin to overshadow their contagious enthusiasm when it comes to the potential for diagnostics in medicine. They all want to get the word out about the opportunity to take advantage of diagnostic technologies so that they can serve a far greater role in healthcare. There is a hint of urgency in their voices when they speak of getting the word out. After all, the development and accessibility of diagnostic tests that alter treatment courses for patients could be a matter of life and death.
Kevin Conroy, president and CEO, Third Wave Technologies
Kevin Conroy expects to see continued growth in the IVD industry, in articular with some of the high-volume assays that are currently on the market (e.g., for HIV and hepatitis C). "We expect to see global expansion and rapid development," Conroy states. "It seems like every time an assay begins to emerge, another assay begins to grow rapidly, like we are seeing today with HPV." That particular market is growing at 35% a year, driven by the fact that the new HPV diagnostic test is an excellent test for cervical cancer. "Combined with the Pap test, it is greater than 99% predictive for cervical cancer," Conroy explains.
However, this global expansion is diverse, and as a result, the industry is seeing molecular testing and equipment in places it has not been in the past. "This technology is becoming easier to use. The equipment is taking up a smaller footprint. The challenges of processes like PCR are becoming easier to overcome," Conroy explains.
In the past, many laboratories viewed molecular testing as an area fraught with problems and were hesitant to include molecular diagnostics in their menu of tests. However, Conroy believes that as IVD companies overcome fears regarding reimbursement and concerns about intellectual property rights, more labs will be willing to foray into molecular testing. In addition, while many labs have historically believed that including molecular diagnostics would mean that their technicians would need highly specialized training, companies like Third Wave Technologies are proving that molecular diagnostic testing can be simple and that technicians can perform molecular diagnostic tests without complex training, provided they have good skills. Concerns about the length of time necessary to conduct the tests are also going away.
"We are seeing double-digit growth in this industry," asserts Conroy. "Addressing concerns about reimbursement and intellectual property rights, as well as concerns about the complexity and time commitment necessary for molecular diagnostic testing, has been important for the field."
But Conroy seems most excited when he talks about the vast changes in genetics and pharmacogenetics. "The promise of personalized medicine is being realized today and that interest level is only going to increase," Conroy comments. He explains how certain individuals carry genetic mutations that cause them to be more sensitive to the effects of certain medications. For example, irinotecan is an antineoplastic medication used to treat cancers of the colon and rectum. About 10% of the individuals who take the medication have a genetic mutation at UGT1A1. The combination of the mutation and use of irinotecan can lead to severe dehydration that can result in death. By using a test developed by Third Wave Technologies, physicians can screen patients for the UGT1A1 mutation before prescribing the medication.
"This was our first experience with the marvels of pharmacogenetic IVD testing, and it resulted in one of the first pharmacogenetic FDA-approved assays," Conroy says. "It is a major step forward for patient safety, but we still need to educate physicians to change some current practices and give them the information necessary to understand, interpret, and act upon FDA recommendations regarding this test."
To illustrate the scope of potential for pharmacogenetics, Conroy explains what is happening with warfarin, for which pharmacogenetic testing is in the pipeline. "Dosing variability in this population is significant, in which racial variations are up to tenfold. Some individuals require a lower dose of warfarin, especially since the medication can cause both intracranial and intraabdominal bleeding if a patient takes too much," he explains.
One of the mutations occurs in about 80% of Asian-Americans, 40% of Caucasian Americans, and 20% of African-Americans. "Knowing whether an individual has this mutation enables the physician to adjust dosing schedules accordingly at the onset. To avoid bleeding currently, patients initially have daily blood tests to check their INR levels and then progress to weekly blood testing once their INR seems stable," Conroy explains. A pharmacogenetic test could help stabilize the dosing schedule at the onset. "Not only does an assay reduce adverse reactions, it also reduces the amount of waste and can reduce healthcare costs."
Currently, an FDA subcommittee is working to recommend what the specific diagnostic test should be and create recommendations about the test.
"Genetic information like we see in the case of warfarin will change the ways drugs are prescribed and the ways patients are treated, living up to the promise of personalized medicine." He adds, "However, like with any dramatic paradigm change, it takes time. For example, it takes time for physicians to change behaviors related to information based on adverse drug reactions."
When talking about the rapid development of the IVD industry, Conroy mentions that, "in a regulated industry, there is always a challenge to ensure that you are developing safe, high-quality tests." Then he adds, "but that is a good challenge to have. That challenge will not stymie industry leaders."
Kathy Ordonez, president, Celera Diagnostics
As president of Celera Diagnostics, Kathy Ordonez keeps her finger on the pulse of the diagnostics industry. Like Conroy, Ordonez says industry growth is largest in the molecular segment. "We are seeing the introduction of many new and exciting tests based on our expanding knowledge of the human genome and new proteomics-based technology that will truly impact the practice of medicine."
One area Celera has focused on is liver cirrhosis. Hepatitis C virus (HCV) affects about 4 million people in the United States, and 85% of those acutely infected ultimately become chronically infected. However, the percentage of those who develop cirrhosis, which can lead to end-stage liver disease in one out of five patients, has historically been unclear. "Clinical factors alone are not very useful for helping physicians determine the best course of treatment," Ordonez says. "Genetics work at Celera has identified a series of markers that are predictive of people likely to develop cirrhosis. With the right genetic information, physicians can intervene earlier in the disease process and target patients that are more appropriate for particular treatment options." Celera's HCV diagnostic tests can help clinicians determine whether patients will develop progressive liver disease with up to 75% accuracy, compared to about 50% accuracy when clinicians evaluate the disease without such tests.
Ordonez says that the sequencing of the human genome and large-scale experiments have advanced the understanding of diseases like cirrhosis. "This will change the current paradigms in medicine, allowing us to identify people at risk for a disease or to classify the disease so that physicians can identify optimal therapeutic options and better monitor management," she says.
Ordonez also talks about HIV testing, which was at the forefront of the paradigm shift toward making therapeutic choices based on information gained from diagnostic testing, and using diagnostic testing to monitor the efficacy of therapy. For example, viral load testing helps classify the seriousness and the status of HIV disease, and genotyping of the virus can identify which mutations are occurring so that clinicians can target therapy and monitor treatment effectiveness. As a result, combination therapies and protease inhibitors now more specifically target the virus so that those infected can live longer and better manage their disease.
"The availability of viral load testing and viral genotyping has been very important for HIV treatment and monitoring," asserts Ordonez. In fact, viral genotyping via ViralSeek, an FDA-approved test and one of Celera's key products, in combination with viral load testing through Celera's alliance with Abbott, has been very important for HIV treatment and monitoring. "Newer, parallel products for hepatitis C diagnostics underscore the tremendous opportunity to improve patient care using diagnostics," she says.
But Ordonez says such advances do not come without challenges. In addition to the importance of keeping on top of regulatory guidelines, she says that reimbursement is a major issue for the IVD industry. "The value of diagnostic procedures is currently underappreciated," she says. "These procedures represent about 4% of healthcare costs, but if used appropriately, they can result in significant savings. IVD testing can increase cost-effectiveness and efficiency in the healthcare system because testing can result in physicians identifying people before disease occurs, so that they can work toward preventive measures to delay onset or preclude disease. And the goal isn't just to save money. It's to improve quality of life. The real challenge is getting the word out about the tremendous opportunities that exist."
In addition, many new IVD procedures will work hand and hand with new imaging procedures. "New paradigms of diagnosis and treatment will progress in IVDs based on diagnostic and imaging tools," Ordonez explains. "For example, protein-based tests can identify people who have certain proteins circulating that could be indicative of the potential for cancer. Coupled with follow-up imaging, diagnosis could happen earlier." This differs from the current approach, where imaging often occurs after the patient develops signs or symptoms of disease. "If we look at lung cancer, it is often too late to treat effectively after diagnosis by imaging or biopsy alone," she says. "But if we could identify people early on, we could treat them earlier. At the same time, imaging today has too many false positives, and combining imaging with serum testing will improve diagnostics." Celera's work in proteomics to identify cancer proteins in high-profile cancers such as those of the breast and lung can also apply to coronary artery disease and stroke testing in the future, any of which could improve upon the benefits of imaging alone for diagnostics and monitoring.
As a final note, Ordonez says that if the value of diagnostics has been underappreciated, she and other IVD industry leaders should work harder to make people aware of IVD advancements. "We owe a tremendous amount to the diagnostic industry," she concludes. "These tests are a godsend, and we need to get the word out."
David Perez, president, Gambro BCT
It is not difficult to admire a man like David Perez of Gambro when speaking with him. His passion for saving human lives comes through in everything he says, and that positive intensity filters throughout the company. He doesn't talk about business in that typical corporate, bottom-line way. He really cares about the progress of the company and with good reason: its goal is to save lives.
Gambro's presence in the blood banking business is multifaceted. Gambro's automated blood separation technology maximizes donation opportunities every time they present. Efficiently automated separation of platelets, plasma, and red blood cells can help increase the quantity and safety of the blood supply. "Through this technology, we can partner with blood centers to help them meet their needs and save multiple lives." Gambro technology also helps with therapeutics by automating processes such as plasmapheresis that might be necessary, for example, when a child with a plasma disorder like sickle cell anemia requires plasma exchange. The company also works down the line to help specific-component labs automate.
From a blood banking perspective, this is a very exciting time. According to Perez, the next five years will witness more exciting technology and innovation than the last 25 years in total.
What is perhaps the most exciting, however, is Gambro's work to improve the safety of the blood supply through Navigant Biotechnologies Inc., Gambro's wholly owned subsidiary. Its unique Mirasol pathogen reduction technology uses riboflavin, a B vitamin that has a unique property in that it binds to either RNA or DNA. If added to platelets contaminated with viruses such as HIV, West Nile, or hepatitis, riboflavin intercalates into the virus's genetic material. Exposure to specific wavelengths of light breaks the RNA or DNA strands apart so that the virus is no longer infectious. "This is phenomenal technology, because it can significantly reduce the risk associated with receiving a lifesaving transfusion," Perez adds.
"In line with others in the industry, we are dedicating significant resources to research and development as well as to global processes," says Perez. "We are excited about innovation and moving forward, and we are working closely with FDA to meet clinical and regulatory trial requirements."
But in order to help the blood banking industry remain profitable and thereby help the greatest number of people, Perez says the company is working harder than ever with its customers to ensure proper payment and reimbursement for these technologies.
"It is so important for us to have an effective trade association in this business," says Perez, who is on the board of AdvaMed. "We work very hard to maintain a strong relationship with FDA through AdvaMed, Jack McGuire at the American Red Cross, Jim McPherson of America's Blood Centers, and Karen Shoos Lipton of the American Association of Blood Banks," he continues. "This is a small community, and we rely on strong collaborative relationships with customers. That's true not only for Gambro, but also for every company that does what we do. Our customers are truly our partners. We have the same ultimate goals."
Perez believes that good collaborative relationships among Gambro, its customers, and AdvaMed is vital for improving the delivery of blood components and developing a much stronger voice within the IVD industry at large. "Strong collaboration means a more effective process for everyone involved," he says.
While complex regulatory requirements in an increasingly global market have proven challenging for every organization focused on diagnostics, Perez feels there is an opportunity for harmonization within the IVD industry. "We are developing some large clinical trials in the area of pathogen reduction technology around Mirasol for devices to collect, process, and test products for transfusion, and the requirements for these differ around the world," adds Perez. "One thing we've learned from the pharmaceutical industry is that there is a real benefit to developing a harmonized approach to clinical trials in the United States and Europe."
Perez believes that a harmonized approach will result in the use of fewer resources, the reduction of delays, and optimal safety. "Stringent regulatory guidelines merely reflect our obligation to protect public health," says Perez, "but if we successfully harmonized one area at a time, such as clinical trials, that could be a huge benefit to our industry. It might take years to accomplish, but it is something we can bring to the table: value-added innovation that meets the requirements necessary to use this technology around the world.
"Less is not necessarily more," Perez continues. "We shouldn't stifle innovation based on the fact that it might seem more expensive to press forward or more challenging to meet regulatory requirements when in the end the results of both can lower healthcare costs overall."
When Perez recites Gambro's company motto, "Progress-It's in our blood," one can't help but believe him