Beyond Clinical Applications

Developing IVDs is still a priority John Conroy

In a scary world, nonclinical diagnostic testing spies a few challenges and many opportunities.

s anthrax scares go, this one had that false alerts have become a fact of 1 Environmental and biowarfare. The as benign a beginning and ending life for lawmakers and their staffs. "We report noted that new technologies A as possible in today's terror- get a few of these a day," the spokesman have emerged since the 9/11 attacks to obsessed world. A New York City mu- told the Houston Chronicle. improve the detection, prevention, and sician who returned from Africa in As these stories attest, challenges and surveillance of bioterrorist attacks. February with unprocessed animal skins opportunities abound for IVD firms in a These technologies include rapid tests tested positive for anthrax. The 44-year- world where infectious diseases and for smallpox, anthrax, and salmonella, old man bought the skins, which con- bioterrorism agents are just a plane as well as improved vaccines and in- tained anthrax spores, to make tradi- flight, mail drop, cargo dock, or car ride formation-awareness networks to ex- tional African drums, authorities said. away. Market applications include tests pedite tracking the symptoms of chem- Complaining of flu-like symptoms, the for biodefense, avian flu, West Nile ical and biological events. musician collapsed while on tour with virus, food, animals and pets, water qual- his dance troupe in Pennsylvania, where ity, and genetically modified food. Test- • Food microbiology. In 2003, the glob- he was hospitalized. ing formats include ELISA, rapid later- al market for food microbiology tests Notable for their slightly more prosa- al-flow technology, and real-time was an estimated $864 million with an ic origins, similar stories of viral, toxic, polymerase chain reaction (PCR). annual 9% growth rate. A worldwide or bacterial misadventures have made emphasis on production of safer foods news of late. In France, government au- Market Analysis has sparked a sharp increase in the thorities reported finding cases of a pos- In a report on the IVD market, Kalo- number of tests performed, according sibly deadly strain of H5N1 bird flu on rama Information (New York City) pro- to Kalorama. In 1999, users ran 440 a turkey farm. In the United States, 60% vided an in-depth look at three of these million tests. The 2003 report estimat- of Americans are worried about the nonclinical market segments. Among ed that by 2005, the numbers of tests spread of the virus, according to a new the highlights are the following: run would reach 625 million, a 7% poll. A cat in Germany died after re- portedly eating an infected bird. And in early February, at least a dozen U.S. sen- ators and 200 staff members were quar- antined in a parking garage of a Senate office building after a nerve gas alarm sounded. They were permitted to leave three hours later when tests proved negative. A routine cleaning substance may have triggered the attic sensor that set off the alarm at the Russell Senate Of- fice Building. However, the false alarm points to just one of several challenges facing nonclinical diagnostic testing: Researchers at the California Animal Health and Food Safety Laboratory and Lawrence getting the right reading in a rough, un- Livermore National Laboratory demonstrated that the Newcastle disease virus could controlled environment. By the same be detected using an environmental air sampling system, which is much less labor- token, a senator's spokesman mentioned intensive and time-consuming than conventional swab sampling. in a newspaper account of the evacuation devicelink.com/ivdt IVD Technology • April 2006 37 Applications

annual increase. Listeria monocyto- test kits from Bio-Rad Laboratories for highly sensitive, field-type tech- genes, , and Vibrio (Hercules, CA), Idexx Laboratories niques for pathogens that are likely to parahaemolyticus are among the (Westbrook, ME), and other IVD spill over into clinical testing in micro- microorganisms that can cause food- manufacturers. biology and virology." related illnesses. In addition, no rapid assays to test in- Given the state of the world these dividuals for infection by biowarfare • Veterinary medicine. Global concern days, the environmental and biowarfare agents or other similar pathogens are on about the spread of bovine spongiform sphere presents a world of business op- the market, Kalorama said in the 2004 encephalopathy (BSE), or mad cow portunities. In its report, Kalorama cited report. Many IVD companies have been disease, has increased the market for the U.S. Project BioShield program, a working with various U.S. federal agen- BSE test kits, the research firm says. In $5.6 billion program featuring expedit- cies to develop rapid-response diagnos- 2003, the market in Europe and Japan ed approvals and government procure- tics and environmental sensors in order for postmortem kits stood at approxi- ment. The goal of the 10-year program to detect biological or chemical agents at mately $140 million. Kalorama fore- is to create "a medical arsenal to combat very low concentrations. However, the casts the market will double between bioterrorism." The United States spent research firm said that such tests or de- 2007 and 2009. More than 1500 cases $890 million in 2004 and authorized an vices have not reached the market, and were detected in Europe in 2002. Cana- outlay of $2.5 billion in 2005 for prod- no such products are expected to be da, which exports more than 70% of ucts such as vaccines, therapeutics, and commercially available before 2009. its beef to the United States, performed testing devices. IVD companies working with U.S. BSE tests on approximately 900 of Since the 9/11 attacks, demand has government agencies to develop rapid 11 million cows in 2003. The United increased for tests that can detect an- tests for biowarfare agents include States tested 19,900 of 96 million cows thrax, botulism, malaria, ebola virus, Invitrogen (Carlsbad, CA) and Micro- in the same year. In March 2004, the ricin, and other bioterrorist agents, Kalo- Fluidic Systems (Pleasanton, CA). The U.S. Department of Agriculture rama noted. However, few tests are avail- former company launched Biologi- (USDA) said it plans to expand its able for these pathogens. The critical cal Defense Systems (BDS) in July 2004 BSE surveillance program with rapid- need for new tests has spurred "research to further explore biosecurity applica- tions based on the company's pathogen research, according to Kalorama. MicroFluidic Systems received a $4.5 million contract from the Ad- vanced Research Projects Agency at the U.S. Department of Homeland Security (DHS) to develop an automated system for identifying airborne bacteria, virus- es, and toxins. Kalorama said the market for bio- warfare-based molecular tests, which reached approximately $31 million in 2003, will grow 2% annually and reach $34 million in 2008. The tests are being used by the U.S. government at post offices and federal buildings to detect anthrax.

Preparing for Bioterrorism Although no rapid assays exist for biowarfare agents, other such tests to de- tect anthrax, ricin, and other bacteria have been developed by a number of IVD companies. Cepheid (Sunnyvale, CA) is the main supplier of tests for the U.S. post offices. Genelex (Seattle), Ocean Optics (Dunedin, FL), and Re- A lab technician using the GeneXpert system by Cepheid (Sunnyvale, CA). sponse Biomedical (Vancouver, BC, Canada) also offer rapid tests. 38 IVD Technology'April 2006 devicelink.com/ivdt Increased demand for its point-of-care business development at Response, says lumped in with their laboratory- and Ramp system, test cartridges for West it is difficult to track the growth of non- hospital-based counterparts. Nile virus, and on-site detection of an- clinical diagnostic tests because "it's Although market numbers may be thrax, smallpox, ricin, and botulism such a segmented industry," and point- hard to differentiate, the market for non- toxin has bumped Response Biomedi- of-care and rapid field tests tend to get clinical testing products is definitely cal's revenues to $1.4 million in 2003, according to Kalorama's 2004 market report. Response sold more than 125 Ramp systems in 2003. More than 70 of the biological field detection kits have been sold to the U.S. Marine Corps, South Korea, the University of Califor- nia at Los Angeles, the New Jersey state government, and the city of Philadel- phia, as well as other public health and first-responder agencies throughout the United States. Response Biomedical says the hand- held system is 100% reliable at detecting anthrax at the 4000-spore level with no false positives. Results are available in 15 minutes instead of the two days it takes to receive results from culture- based tests, according to the company. The Ramp biodetection field testing system by Response Biomedical Corp. (Vancouver, Joanne Stephenson, vice president of BC, Canada).

The voice of . in vitro diagnostics for over a decade. "IVD Technology is the premier publication for the IVD industry. Its focus on a wide breadth of subjects of high interest to those who work in this industry, and the use of subject matter experts to write articles makes reading IVD Technology the best way to keep current with important issues in the diagnostics field." Emily Winn-Dean, PhD (vice president of strategic planning and business development, Cepheid) For more information please visit: www.ivdtechnology.com jyww -Ine.com into®abionllne,com )784(us&CN) devicelink.com/ivdt IVD Technology • April 2006 39 Clinical Applications

sample in 30 minutes or less in the field, according to the company. The GeneXpert uses 13-chamber car- tridges for sample preparation, com- bined with amplification and detection in an automated instrument with a rapid nucleic acid analysis capability, the com- pany says. Skilled technicians using cur- rent manual techniques over the same set of analytical procedures require from six hours to three days to accomplish the same task. The system forms the detection en- gine of the biohazard detection system which was developed in collaboration with Northrup Grumman and . This system is used in post offices across the United States for an- The Veratox test kit by Neogen Corp. (Lansing, Ml), which is used for determining thrax testing in mail-sorting facilities. aflatoxin levels in grain. "According to U.S. Postal Service re- ports, the system has used over 2.1 mil- growing because of recent governmen- erally no regulatory requirements, or lion GeneXpert cartridges in screening tal regulations, Stephenson says. "I very low regulatory requirements, she more than 25 billion pieces of mail being know from a biosensing point of view, notes. sorted at about 275 different centers," there are now specific mandates in dif- Regarding the Canadian supplier's Persing says. ferent areas that different organizations success with public first responders, He believes the GeneXpert system is and facilities need to be prepared to re- Stephenson notes that once a rapid on- a good example of a test module design spond. . .to a biological attack and to di- site testing system becomes accepted in for nonclinical diagnostics. "It's a model agnose it and have some sort of plan in the world of hazmat teams and fire de- for how to implement the various so- place for decontamination. That's where partments, it becomes an entrenched phisticated technologies in an environ- we're seeing a lot of the growth." part of the equipment base. ment that's challenging," Persing says. These mandated plans apply to enti- "You're looking at a 20-year life span "In the industrial setting, you don't have ties such as universities and hospitals in for anything they institute when they access to highly trained and skilled per- the United States, she says, adding that start taking on new pieces of equipment sonnel on a 24/7 basis. You have to use the new rules have come into effect only or new actions," she says. "They're re- the skill set that's already there. The within the last two years. sponsible for preparing for the long challenge is designing the test to meet Response's customers are looking at term. They're continuing to train. In that the skill set of the people you're trying to its testing kits "from a productivity point world, there's no fly-by-night. Nothing market to. The most remarkable statistic of view," Stephenson points out. Large comes and goes in two or three years. is that despite these challenges, we've organizations with big mailrooms, for Once it's been accepted, it's in their psy- never had a false positive. Given the rep- example, "have a lot of potential for che from a business standpoint." white-powder incidents." If they rely on the local hazardous materials team, they Meeting User Skill Sets can lose at least half a day of productiv- David Persing, MD, PhD, executive ity following an incident. By setting up vice president and chief medical and an in-house response team, a business technology officer at Cepheid, knows can maintain productivity following a firsthand the benefits of business ac- negative reading, she asserts. ceptance on a grand scale. Cepheid is One of the key differences between the main supplier of molecular surveil- clinical and nonclinical diagnostics is lance test cartridges to the U.S. Postal the uncontrolled nature of the environ- Service. Its GeneXpert system uses real- ment for nonclinical tests, Stephenson time PCR to analyze crude samples in Dosing test strips for evaluation in the | says. In fact, both the environment and minutes. The tool integrates sample Guardian reader system by Alexeter ; training are uncontrolled. There is no preparation, DNA amplification, and de- Technologies LLC (Wheeling, IL). o consistent competency training and gen- tection, and can draw results from a raw 40 IVD Technology • April 2006 devicelink.com/ivdt