The marketplace is demanding revolutionary technologies for veterinary testing, human identification and forensics, and food safety.
The markets for molecular applied testing provide ample opportunity for growth. While human identification and forensics are established molecular marketplaces, the food- and animal-testing markets are now seeing molecular technologies gaining ground over traditional immunological tests. Across all segments of applied testing, customers are asking for the same thing: highly reliable, complete workflow solutions that produce results of the highest quality.
To learn more about the current trends in nonclinical diagnostics and how nonclinical diagnostic technologies borrow from their clinical counterparts, IVD Technology editor Richard Park spoke with Dietrich Hauffe, PhD, vice president and head of Applied Testing Business at Qiagen in Hilden, Germany.
IVD Technology: How did Qiagen first get involved in nonclinical diagnostics and developing technologies for the animal-testing market?
Dietrich Hauffe: In 1984 Qiagen started as a sample-prep company with a focus on life-science research, primarily academic. Later, the company expanded into assay technologies with a particular focus on molecular diagnostics. Around the same time, in 2004, the company decided to expand into other nonclinical commercial market segments that have a high growth profile.
Applied testing as a market segment was identified to basically pull many of the different disciplines together that were outside of human diagnostics and outside of academia. It has become a very important market segment for us, because molecular technologies rapidly disseminate into everyday life, creating numerous new applications, somewhat similar to the evolution of IT. In terms of disciplines such as veterinary testing, human identification and forensics, and food safety, we see a very strong demand from the marketplace to come up with technologies that are revolutionary to those scenes.
Applied testing shares many synergies with other customer segments for Qiagen. On one hand, we have the new innovative technologies from life-science research that are fed into applied sciences. On the other hand, we have regulated applied-testing scenarios where we’re coming close to molecular diagnostics. All three segments are strongly linked to each other and thus provide synergies for our innovative research.
Further expansion in applied testing was facilitated by dissemination of the PCR technology as the standard in many areas, including veterinary, food testing, human identification, and molecular diagnostics. These underlying technologies are similar in all customer segments, such as sample preparation for DNA and RNA, and PCR for detection.
What might be interesting in this context is that approximately sixty percent of human pathogens are zoonotic, which means they originate from animals—production animals as well as wild animals, such as bats. We have examples, like influenza with humans, birds, swine, and horses; SARS; rabies; and so forth. And in such cases, there is a strong link between human diagnostics and veterinary diagnostics.
Are the animal-testing technologies that Qiagen is working on adopted from other previously developed clinical diagnostic technologies? If so, how did Qiagen adopt those technologies to be used for animal-testing purposes?
Yes, most of the animal-testing technologies are adopted from clinical diagnostic technologies. Most Qiagen products serve more than one customer group, which is at the core of Qiagen’s strategy to leverage our leadership in sample and assay technologies across the markets.
So what we address in molecular diagnostics may work for applied testing, and vice versa. Innovative technologies that we discover for life sciences may lead directly into applied testing, and in parallel may also lead into molecular diagnostics.
Take, for instance, PCR. Real-time PCR is state of the art for pathogen detection because of its sensitivity, and it is also employed in most of Qiagen’s molecular diagnostic products—mostly in profiling and in the personalized healthcare segment.
The same goes for Qiagen’s point-of-need testing platform that we acquired last year. It employs an isothermal amplification technology, HDA, and it can benefit from work done on Qiagen’s prevention platform. Also, our automation, instrumentation, liquid handling, all the way to complete workflow platforms are adapted to the nonclinical sector. These technologies are highly versatile and thus often utilized in different customer segments, from food testing to veterinary testing to human diagnostics, et cetera.
Depending on the sample material of interest, those platforms may vary slightly. But in general, within the disciplines, whether it’s life science, applied testing or molecular diagnostics, they are in principle very, very similar to each other, if not the same.
Please talk about the project Qiagen is involved in with the United Nations.
We have initiated this project to explore emerging markets, but also to provide our technologies to them, to address animal and veterinary testing in developing geographies.
We’re doing this together with the Food and Agriculture Organization of the United Nations, FAO, and the International Atomic Energy Agency, IAEA. This collaboration is formed around our point-of-need testing platform, around the actual hardware that we have, which is a small device. It’s of the size of an office telephone, and it can provide very rapid testing results in five to fifteen minutes.
We provide this hardware instrumentation for a pilot project that was kicked off in thirty-five countries, mainly in Africa. And initially, the focus is on tests for avian flu, peste des petits ruminants in sheep and goats, and contagious bovine pleuro-pneumonia, also known as lung plague, in cattle, which are major issues in those countries.
Whether this proves to be a success is not only a question of clinical utility but also of how you really establish a first-response system in those countries, and what you do with this actual information to prevent the diseases from further spreading. If the project is successful, it might be extended to up to 10 different pathogens and additional countries.
What is the process involved in developing animal-testing technologies?
The technological foundation is always quite similar for all customer segments. We try to identify those segments’ demands and see what we already have available to meet them. And we also look at what needs to be newly developed.
In terms of where we kick-off the actual development, either direction is possible. For zoonotic diseases, those that occur in both humans and animals, for instance, it is possible to adapt existing IVD assays. If a disease only affects animals, we would have to develop the assay from scratch, using the same proven innovation processes that we use in molecular diagnostics. We have done that in the past, and we will do that in the future, as well. This includes rare diseases, for instance, in horses all the way to very, very common diseases in production animals.
The main differences concern the sample preparation. While in human diagnostics we consider it rather easy to collect a sample, it is different in the veterinary arena. Take testing for flu, for instance. If you take a human sample from a respiratory tract versus a bird sample using a swab, those two procedures are very different. First of all, animals don’t stand still. They just move. They are also much more nervous and frightened than humans, who have adapted to doctor visits and the like. Clinical validation, as well as regulatory approval of the assays, is another of the key components that we need to address. But the underlying technology development is not different in applied testing or in molecular diagnostics, so we can benefit from our rich experience with assays for the detection of pathogens.
Regarding avian flu, we were the first to have a validated assay in the marketplace. We also launched a clinically verified product for the detection of H1N1 less than three weeks after the outbreak in 2009. So development steps are adopted for, in our case, the veterinary assays, which is the Cador product line, or for food assays, the Mericon product line.
What are the primary challenges involved in developing animal-testing technologies? And how do IVD companies overcome such challenges? As you mentioned, clinical validation and regulatory approval are two of those challenges. Are there others?
Yes, certainly those are challenges, and I can expand a little bit on them. Number one, the veterinary diagnostic scenario is quite different from our human diagnostic environment. There is no such thing as the FDA for veterinary and food testing, but rather several different agencies and offices that are dispersed worldwide. In some areas, it’s really complex, and we have to adapt to local needs and local regulatory scenarios. Take, for instance, the food environment. There’s AFNOR in France. There’s the AOAC in the United States. China, again, responds to the regulatory recommendations of the AOAC, so they use their methods for quality control of their export shipments into the United States.
On the veterinary side, things look a little different. The United States Department of Agriculture, or USDA, is as stringent as the FDA, which is clearly demanding regulation and certification of a test. For veterinary, we work with the USDA on getting a certain scenario regulated, but it may be different in the European countries, where in Germany, for instance, we have the FLI. That regulatory body requires each individual batch of an assay to be screened for validation, and that is a different scenario than what we see with USDA.
We have to respond to each of these needs. This is a pretty big challenge, actually, for applied testing, as we need to make significant investments to respond to those needs and get approvals.
The other challenge is sample collection. In veterinary diagnostics it’s not standardized. In one country, we take ear notches from cattle. In the other country, we have pigs in a pen licking at a cotton rope that’s coming from the ceiling. You wring the rope to get a batch of that saliva, and you have a very, very coarse buccal swab of, let’s say, ten animals in one. You then do a batch analysis with that on a specific diagnostic test. So the sampling and the sample collection are rather different, and certainly not standardized. This means we have to ensure that our workflow solutions for the detection of pathogens will work with a variety of sample materials of differing quality. It’s challenging to adapt our assays and certainly the sample preparation to those needs.
Beyond sample collection, you then have different clinical questions. You also have the identification of different strains and changes of the pathogen, similar to what we have seen with AIDS, similar to what we have seen in human diagnostics. We’re facing the same scenario that we have with a sudden outbreak: it may be one particular pathogen that we have assays for, but not for that particular strain.
So genotyping will become a very, very strong push in the future, in order to identify different virulent strains that may impact animal production or even humans.
Have animal-testing technologies been developed for all of the major pathogens? And which agents are Qiagen and other IVD companies still working on and developing animal-testing technologies for? What is the status of those tests?
Overall, we’re talking about 1600 pathogens. Of those, maybe fifty to one-hundred are economically important, maybe even important for human health. So, yes, I would say that at the moment, the industry has developed tests for all of the major pathogens.
Qiagen has focused mostly on widespread livestock diseases that cause much economic damage. Where molecular testing can make a difference in Europe, for instance, is with two main pathogens of concern, BVDV, bovine viral diarrhea virus, and BTV, bluetongue virus, in ruminants. We have those two covered at Qiagen with dedicated assays since 2008. So initially we have focused entirely on these two assays, but we’re moving forward and expanding that scenario.
Take, for instance, our assays for agents of Equine metritis in horses. We got a request from customers in the Arabian countries, as well as from the UK and the United States, where horse breeding is a very, very important issue. We also have a whole range of open reagent kits which play a vital role in veterinary testing.
Additionally, we’re focusing on technologies, as I said before, for genotyping of pathogens, as well as of the animal population. Such technologies include pyrosequencing, which we acquired in 2008, and certainly also high-resolution melt analysis on our Rotor-Gene Q instrument, which is our real-time PCR cycler setup.
In developing further assays, we look very much into partnering with external sites, like research institutions and certainly also with industry partners. We are especially interested in focusing on commercially significant diseases and pathogens. We also are in the process of launching an additional series of assays for food-safety testing, aiming to cover the entire food-processing chain.
Here, the initial focus is on pathogens such as salmonella or listeria. We’re extending our pathogen panel, but we are also moving into GMO and animal and plant identification in order to have a suite of assays available for food-adulteration analyses in the marketplace, especially in the food-processing industry.
What efforts will Qiagen continue to make in order to develop animal-testing technologies that are better and faster?
In general, the applied-testing business at Qiagen benefits strongly from our R&D investment; we’re putting about eleven percent of our sales into R&D.
That means the future holds innovative technologies, innovative products, and certainly workflows—solutions that allow customers to click a button and get a result from sample to result. So progress in areas such as workflow automation directly translates into all customer groups.
Our overall goal is to make molecular testing—not only in applied testing, but also in other segments—more reliable, even faster, more efficient, and easy to use, in order to drive the dissemination of molecular technologies. We believe that applied testing as a segment within Qiagen will be leveraged out of molecular diagnostics and certainly out of life sciences, but will become a very independent pillar, also, and a very strong pillar of the Qiagen business overall.
We see a potential for the emerging point-of-need applications. Such applications may influence our future in the segment of human identification as well as forensics, the food testing market, and the veterinary market. Consider the beginning of the food chain, which is basically processed meat or even shipped cattle. Having an export from a specific country, let’s say South America importing into the United States or to Europe, allows utilizing point-of-need technologies to very rapidly test whether the shipment is approved to be imported or not.
Those are the things that give us great potential right from the start, where the food chain actually occurs, all the way to the fork where retail will, in the end, possibly in ten years, be able to generate assays with a very simple point-of-need device that says green, red, or yellow. The device would essentially differentiate between contaminated and noncontaminated foods or even veterinary products.
Our group is growing fast, and so is the market. We’re growing nicely in double digits; our applied testing revenues, adjusted for swine flu–related products, climbed twenty-two percent in 2010. We are looking forward to a very strong market now with a portfolio that we have generated over the last eighteen months that allows us to actually go from sample purification into detection. We are investing heavily in this group, and we are happy to see that market moving forward with Qiagen as well.
Is Qiagen involved in developing technologies for other areas of nonclinical testing; for example, biodefense, environmental testing, or others? How does Qiagen plan to parlay its animal-testing technologies and experiences into the development of other nonclinical diagnostic technologies?
Our applied testing group is primarily focusing on human identification and forensics, food, and veterinary testing at this point in time. While human identification and forensics is an established molecular marketplace, in food and veterinary testing we see molecular technologies increasingly gaining ground over traditional immunological testing methods.
There are also other areas that are starting to convert from traditional methods, be they microbiology culture cultivation or immunoassays. We see that in the plant-agro arena. We see that in biodefense, certainly. We see that definitely in environmental and water testing.
So we are looking at several different areas for future growth. We explore on one side, but at the same time definitely develop into several focused areas. What really unites all of our customers in applied testing is the demand for highly reliable, complete workflow solutions guaranteeing the highest quality of results.
We believe that we will become the most trusted provider, or even the most trusted partner for our customers. We are looking into other areas that refer to applied testing, such as data processing, data management within the scenario, especially when we come to regulated environments where data sourcing—as well as sample sourcing, all the way down to results and data management—is a very, very important factor.
We also leverage our experience made in individual customer segments, and we evaluate whether these technologies can be adapted for applied-testing settings. As mentioned, the life-science segment has always been a source of innovation for our applications. Same applies to acquisitions that Qiagen has made in the past and that have leveraged from the molecular diagnostic field into our field. So we’re on the way to exploring the opportunities ahead of us.
What future challenges do you foresee in developing animal-testing technologies?
It’s really the complexity of sample material. It’s not only for molecular testing, it’s also for immuno testing. You have a big variety of samples that cannot be standardized, and you need to cover the entire food-processing chain. You need to understand the food-processing chain from the production animal and the diseases that may occur, which maybe relate to or even flow into the food chain. Take ground beef. It is certainly different testing salmonella in this environment than salmonella in drinking water, for instance. The complexity of sample material is a critical scenario.
In addition, there are increasing requirements for cost efficiency, speed, and sensitivity. An immuno assay or even a cultural assay may not make sense for a specific customer anymore, but it is a challenge to match the cost efficiency of these technologies. This is true not only for Qiagen, but for the whole world of companies that are investing into molecular testing technologies.
We also see, as I said before, an increased demand for regulated products, coupled with diverse regulatory requirements across different geographic markets. Another challenge that we have seen lately is the emergence of new pathogens and mutations of existing ones, in addition to regional pathogens and animal variety.
For instance, BTV types and susceptibility in sheep breeds can be a problem, as well as the globalization of food processing, so diseases occur in Europe that were not identified fifty years ago. Those are definitely future challenges that we’re facing.
What are your overall views and impressions of the nonclinical diagnostics market?
I think if you apply that to Qiagen specifically, applied testing is a very important area of growth for us. Currently, we account for roughly six percent of our global revenues, and as you know we are north of one billion, so we currently are in good shape.
The applied testing business jumped by twenty-two percent in 2010. We’re looking into similar growth rates in the future. We expect molecular technologies to further disseminate and a number of new applications in this growth dynamic to last or even improve going forward. And similar to molecular diagnostics, the markets for molecular applied testing still provide a tremendous opportunity for growth. For example, the share of PCR-based methods in food-safety testing is currently about fifteen to twenty percent of the overall two-billion-dollar market. Likewise, many customers in veterinary testing still rely upon traditional technologies that will be forced out by molecular tests in the future.
Dietrich Hauffe, PhD, is vice president and head of Applied Testing Business at Qiagen (Hilden, Germany). In 1997, Dietrich joined Qiagen to lead Product Management Automation, and he later joined Dionex Corp. as the country manager for Dionex Germany. He was appointed vice president, corporate marketing and business development in 2005 at Dionex Corp. In October 2010, Dietrich returned to Qiagen at its headquarters in Hilden, Germany.
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