Medical Device Link.

Originally Published IVD Technology January/February 2004

IN PERSON

When developing new and improved instruments, IVD manufacturers must incorporate cutting-edge technology with a practical design and price tag.

David Okrongly, PhD, is senior vice president of research and development in the laboratory testing segment of Bayer Diagnostics (Tarrytown, NY). He can be contacted at david.okrongly.b@bayer.com.

With the arrival of a new year, laboratorians expect to see new advancements in the IVDs available to them. For IVD companies, staying ahead of the latest technological advances while releasing products that provide both state-of-the-art capabilities and staying power can be quite a challenge. These IVD manufacturers must address the varying needs of laboratories. From high-volume to low-volume laboratories that may provide specialized or a full range of testing, all strive to provide the most accurate results and up-to-date testing possible. Only a few IVD companies have managed to continually meet the demand of a wide portion of the IVD marketplace by offering a vast portfolio of products. One such company is Bayer Diagnostics (Tarrytown, NY).

In pursuit of the company's recipe for success in the development of its products, IVD Technology editor Richard Park spoke with David Okrongly, PhD, senior vice president of research and development (R&D) in the laboratory testing segment of Bayer Diagnostics. In this interview, Okrongly discusses the nuts and bolts of the R&D process, how R&D teams meet a variety of challenges, and the latest trends in instrumentation development.

IVD Technology: What have been the biggest technological advances in instrumentation development during the past few years, and what are the latest trends?

David Okrongly: Over the last five years, manufacturers have pushed to extend the capabilities of the first generation of immunodiagnostic and clinical chemistry instrumentation. Improvements in sensitivity and throughput, as well as being able to run different protocols on the same platform without interrupting throughput, led to the development and launch of new immunodiagnostic and clinical chemistry testing platforms.

The newest trend in hematology is the reporting of new cell types beyond the differential. So, all major manufacturers now report reticulocytes, which had previously been an off-line or separate-platform type of assay. New and interesting developments are emerging; the ability to do multiplex testing allows for the measurement of multiple analytes simultaneously with smaller volumes, thereby increasing throughput and overall system sensitivity. I think a big part of the future is going to be platform consolidation or integration of testing. As a result, we will see consolidation of immunodiagnostics and clinical chemistry. In the future, we will be talking about immunochemistry, and it really will not matter whether we are measuring traditional homogenous clinical chemistries or heterogenous immunoassays. They will be conducted on the same platform.

In addition, instrumentation is moving to the next level of integration, which is total lab automation. Huge factories of instruments are being brought together in a more and more completely automated way. Then, of course, the information technology will have to be developed to tie it all together.

When expanding on the capabilities of IVDs in these ways, what are the primary challenges that IVD companies encounter?

The primary challenges fall into a couple of areas. There are technical challenges. Obviously, trying to do something that no one has done before requires breakthrough research and development and very bright scientists with good, innovative ideas and technologies. The other challenge that may arise is the regulation of those new products and reporting parameters that are classified in a way that will circumvent the need to go to PMA trials and allow for 510(k)-type trials.

We have even seen a lot of companies classifying their products as analyte specific reagents (ASRs), thereby avoiding the regulatory route altogether as a strategy for bringing new instruments and new technologies to the field. Significant challenges are posed by the validation and clinical regulation of new equipment. Other obstacles are created by the need to educate the agencies, FDA in particular, about new technologies and about how those technologies can be viewed as substantially equivalent to an existing technique or technology.

Addressing Customer Needs

How do you determine what laboratorians need from their instruments? Do you use surveys, focus groups, or in-house services?

It is a combination of all of the above. Fortunately, our customer training and R&D departments are located in Tarrytown, along with our headquarters. So there are frequent opportunities for us to interact as an R&D organization with customers here, and the customers' input is very important for us in terms of thinking about future products.

Does your R&D team also go out in the field and go to laboratories to seek input from the laboratorians?

Yes. Our user meetings are organized by our branches located around the world. So, in our various locations, we hold user meetings where customers get together, usually to present their own work and to hear thought leaders in their fields who will come and give presentations.

In addition, these meetings are an opportunity for our R&D people to present their new work and then to get feedback from customers about that new work. They also engage in conversations with them about the issues and challenges the customers face in their laboratories.

Designing New Systems

When developing lab instruments, do IVD companies try to come up with completely new instruments, or do they build on current product offerings in the form of upgrades and modular additions?

That is determined by the product segment we are going after. In our software, mechanical, and reagent development, we strive for the ability to build on our existing technological base. This effort provides continuity to our customers because they will not have to retrain personnel or restandardize their practices, and also it allows us to be more efficient in manufacturing and developing a product. However we also have to be responsive to the changing needs of the marketplace.

So, on any given generation of instrument or any new release of product, we are looking at the delta between our existing product and what the market needs are. When it comes to the ADVIA Integrated Modular System (IMS), Bayer's integrated system for chemistry and immunology, we went to something that neither we, nor anyone else, had ever done before. It is a very market-dependent decision.

It seems that, particularly in total lab automation, system design depends on the customer's needs.

We tend to take a scalable approach to the integration of testing. In addition to the integration of immunodiagnostic and chemistry testing, we also offer a sample-handling system that combines our two high-throughput immunoassay and chemistry instruments. That system is called the Work Cell.

Laboratories are integrating, in terms of the types of testing that they do. That trend is happening worldwide, and increasing year by year. The challenge for us as manufacturers is to find a way to scale that to the size of the lab that has undergone this clinical chemistry and immunoassay integration. We are trying to find those instrumentation solutions that allow us to serve the largest possible portion of the market.

By "scalable solution," do you mean that you are trying to adjust simultaneously to the needs of smaller labs and of larger labs?

Correct. That is one area in which we often take existing products and reuse them. For instance, in the case of the Work Cell, the sample-management part was new, but the engines that drove it were existing platforms.

However, at the lower-volume end of immunodiagnostics and clinical chemistry integration, we did not have a preexisting platform that was integrated to the level that we wanted to provide in the long run. We could have strapped two small systems together, but for the volume of work done by that segment of the market, that option would not have made sense because we would have been using obsolete technology. For that lower- to mid-volume immunochemistry laboratory, we designed a completely new instrument.

What role does connectivity play in instrumentation development?

Connectivity plays a huge role, and it is getting bigger. Long ago, there was a need to connect information from a stand-alone platform to the laboratory information system (LIS). Now, that information needs to be utilized in more general ways for integrating laboratories together.

In the near future, we see the evolution of lab instrument connectivity going a step further. We believe that our customers would like our instruments to be able to notify our service support people when something is going wrong on the system so they can get out and fix it before the customer is even aware of it. We are going to have to continue to evolve our instruments to be adaptable to the highly networked solution that the hospitals and our customers are developing.

Do your customers expect that your company's instruments will be able to connect with an LIS or to an HIS?

Yes, that expectation has been there for a while. Now, people want to see a higher level of networkability. For instance, the blood gas analyzers used at the point-of-care level in our near-patient testing group need to be networked back to the core lab where the personnel who perform the quality control are located.

Our customers have also expressed that they want to network satellite instruments from, say, an oncology or neonatal clinic back to a centralized database. As a result, as those patients move around within a healthcare system, their information will be accessible to each healthcare provider within the network. So we have to keep pace with that in our instrument design as well.

Point-of-Care Tests

How has the emergence of point-of-care testing affected instrumentation development?

With point-of-care testing, there are a lot of challenges. People want to get the same results from point-of-care testing as they would get if they sent a sample to a core laboratory for testing. And that is difficult to achieve.

Right now, the products that can best meet the challenge of delivering the same precision and accuracies in a point-of-care setting as those of the core labs, are the coagulation products. In addition, we have been able to meet that challenge in our urine testing.

What causes point-of-care tests to be less accurate than laboratory tests?

The challenge really lies in the precision of the point-of-care tests rather than the accuracy. Obtaining a level of precision similar to that of laboratory tests requires a lot more control of the sample and reagents than we are able to deliver in something that can sit on a benchtop in a physician's lab office and be operated by a nurse or other nonlaboratory operator. There are very few products out there delivering quantitative results at the point of care with the same precision as results generated by a core laboratory.

Do your point-of-care tests have technology in common with that of your larger laboratory instruments?

Our urine testing is really the only area where there is an overlap. The same base technology is used in both the core lab and the point-of-care urine tests. Both development and sales for these systems have not been a huge challenge for us.

Staying Abreast of Research

How have recent developments in molecular diagnostics affected instrumentation development?

Right now, we are in a discovery mode with the new proteomic platforms and array platforms for single nucleotide polymorphism analysis. The results of this discovery will tie in to patient management and care. Whether those formats will evolve into something more transferable to a laboratory environment has yet to be determined. These developments will eventually impact instrumentation.

More ground needs to be covered in the research before it can actually impact the instrumentation. The people who pay the bills—the managed care providers and the government payers—are going to want to see that patient outcomes are really impacted by this testing. Then, because this testing is expensive, they are going to have to see where they can get the money to justify that added cost.

I would presume Bayer is watching the progress closely.

Yes, and Bayer is an active participant in the discovery process as well. We are conducting research in key areas, one of which is oncology. We are looking at the relationship between genetic predisposition and people's response to different therapies as reflected in their array profiling or the expression arrays that are generated out of their treatment.

Since 9/11, another big trend that has emerged has been biodefense. How has the focus on biodefense concerns affected instrumentation development?

Bayer is not involved in biodefense products. However, I think the impact of this shift in focus will be that more-robust technology will be developed for testing. The development of biodefense testing platforms is going to include a focus on highly sensitive, very robust assays that can work under some pretty extreme conditions and can be run by people who are not necessarily trained as laboratory technicians.

So, it is likely that this work will lead to better technology in general for doing IVD testing. The ability to make these improvements is really going to be driven by how willing the government is going to be to invest in this research. Since 9/11, the federal government has expressed a strong interest in different research initiatives in that area.

Future Developments

What challenges do you expect to emerge in instrumentation development during the next few years or so?

In addition to making IVDs smaller, faster, and cheaper, there is a constant demand to demonstrate medical value and better patient outcomes with the new tests we introduce.

At the same time, we face the challenge of pushing costs lower and lower while being competitive with technology that is available from others.

What new trends can we expect to see in the area of instrumentation development in the next few years?

To answer this question, we should consider instruments, software, and methods separately. On the instrument side, there will be a continued focus on productivity. People still want to get faster results out of their instrumentation.

As far as software goes, people want it to be simple. The user interfaces that the software presents to the customer need to be relatively straightforward and easy to understand. For larger companies that turn out several product lines, people will want the same user interface on their chemistry, hematology, and immunoassay systems.

For methods, the need for accuracy and precision are a given. What customers will now want to see is how they can better utilize the tests to improve the quality of patient outcomes. For instance, they will want to have fewer biopsies for their prostate specific antigen patient testing or a better B-type natriuretic peptide test that will allow them to have fewer echocardiograms. They are pushing us to deliver validated clinical results that show the value of new markers, and I think that is going to continue to be a priority.

What technological developments does Bayer have planned for 2004?

We have a new chemistry platform that represents a departure from what we have traditionally offered in the lower-volume chemistry area. In order to address the needs of our customers, we are really trying to stay with one reagent line, but provide a smaller platform that will fit into the lower-volume-testing part of their business. We are also going to be introducing a mid-volume immunodiagnostic system. We will release the ADVIA 2120, which adds a hematology system with a slidemaker stain to our ADVIA line.

In the methods area, we are pushing to have a comprehensive menu for infectious-disease diagnostics. We have our IVD Directive CE marked panels complete. We are now in the process of starting the filings with FDA for launch in the United States. So, in 2004, we hope to have completed all of our HIV, and hepatitis C, B, and A applications.

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