People make mistakes all the time. To err is one of the well-recognized characteristics of being human. Alexander Pope is credited with having written, “To err is human, to forgive divine.” In our highly complex society, we might rightly expand on Pope to say, “To err is human; to really mess up takes a system with a convoluted user interface.” Unfortunately, in medical technology, as well as in other safety-critical systems, mistakes can lead to serious, often catastrophic consequences requiring much more than divine forgiveness.

As the interaction between humans and their machines became more complex, the science of human factors evolved to study the ways humans relate to the world around them. Human factors engineering (HFE) is a branch of engineering devoted to applying the science of human factors to the design, development, and deployment of systems and services. HFE is sometimes referred to as usability engineering and internationally as ergonomics. One objective of HFE is to improve both operational performance and safety.

An aspect of the HFE process is the development of a taxonomy, or system for classifying interactions between humans and machines. Understanding the taxonomy is important to appreciating how mistakes in using a medical device can contribute to medical error.

Medical errors of all kinds are often cited as a significant cause of death in the United States.¹ Accurate numbers are hard to come by because they depend on a reporting process that is frequently criticized for underreporting of adverse events. Also complicating the situation is uncertainty in ascertaining the root cause of error. However, there is general agreement that medical error is a serious problem in the United States. In the publication To Err Is Human: Building a Safer Health System, the Institutes of Medicine issued a call for reform in the healthcare system to address what it considered the nation’s “epidemic of medical errors.”

Taking up the call, FDA has increased its emphasis on usability in the design of medical devices, including those intended to be used for in vitro diagnosis. Having analyzed the event reports in the Medical Device Reporting system, FDA concluded that device use error is a significant but addressable cause of serious consequences for patients (illness, injury, or death). FDA sees that many use errors are not just random human error, but are often induced by the design of the device and its labeling. Through its Human Factors Program, FDA has strongly encouraged manufacturers to embrace the principles of HFE. FDA defines HFE as “the science and the methods used to make devices easier and safer to use.”² HFE takes into account how users interact with a device. It sets out a process for identifying the issues that may prevent the device from being used as intended.

For some reason, the formal application of HFE in the medical device sector has tended to lag behind some other sectors. From a standards point of view, some of the first formal work in this area was done by the Association for Medical Instrumentation (AAMI’s) Human Factors Engineering Committee. AAMI/HE48, Human factors engineering guidelines and preferred practices for the design of medical devices, was published in 1993. The focus of this document is on the ergonomic aspects of medical device design. The AAMI committee followed this up with the publication in 2001 of AAMI/HE74, Human factors design process for medical devices. The AAMI committee is close to publishing its opus on HFE for medical devices, AAMI/HE 75, Human factors engineering—Design of medical devices.

Using the AAMI work as a springboard, the International Electrotechnical Commission (IEC) and the International Standards Organization (ISO) jointly published IEC 62366, Medical devices—Application of usability engineering to medical devices, in 2007. IEC 62366 describes a usability engineering process and provides guidance on how to implement and execute that process to enhance the safety of medical devices.

At the center of the HFE process described in IEC 62366 is understanding how humans behave when faced with a task that requires the user and the medical device to interact. This is particularly important when the interaction occurs in an emergency or other stressful situation, or when the user is fatigued or uses the device infrequently.

This understanding enables the Human Factors (HF) Engineer to classify the causes of various types of errors that might be made using the device. Several standards offer systems, or taxonomies, for classifying error types. Figure 1 shows a taxonomy that was adapted for medical devices from work done by James Reason.³ This taxonomy is described in Annex B of IEC 62366:2007.

The understanding of the taxonomy begins with understanding the definition of the term use error. Use error is defined in IEC 62366 as an “act or omission of an act that results in a different medical device response than intended by the manufacturer or expected by the user.” There is a subtle but important distinction in the choice of the term “use error” over the more commonly used terms of “user error” or “human error.” It recognizes that not all errors arise because of carelessness or inattention on the part of the user. The term is intended to be “blame neutral.” It recognizes that an error may be the direct result of a user interface design that did not properly take into account the capabilities and limitations of the human beings who were required to interact with the medical device.

User actions (or inactions) can be broadly classified into those that are foreseeable and those that are not foreseeable. The interface designer can only deal with those things that are foreseeable. One of the roles of HF engineers in the design process is to apply their knowledge and the tools at their command to identify the ways things can potentially go wrong so that the interface designers can address them. Tools such as cognitive walk-throughs, contextual inquiry, functional and heuristic analyses, rapid prototyping, and testing in simulated environments and in the field help the HF engineer anticipate what the user will do when faced with carrying out a particular task. 

The taxonomy in Figure 1 is based on classifying user actions. However, it can also be used to classify user inaction—the situation where the user should have done something but took no action.

If the user intended to take an action, the result will fall into one of the following three categories.

Figure 1.  (Click here to enlarge) Categories of foreseeable user action. In this figure, an action can result from a user choosing to do something or failing to do something. See Annex C of IEC 62366:2007 for lists of potential use errors and abnormal use or their causes. Nescient is used in the context of a lack of awareness of the adverse consequences of a skill-based action. Source: Figure B.1, Categories of foreseeable user action, from IEC 62366:2007. Copyright IEC, Geneva, Switzerland, and used by the author with permission.

Correct use. This is operation of the medical device in accordance with the instructions for use or in accordance with generally accepted practice for those medical devices provided without instructions for use. In Figure 1, this is shown as “normal use.” However, it is important to remember that a use error can occur while a device is being used as intended. If a user error occurs even though the user is trying to use the device as intended, it is not correct use in this taxonomy.

Abnormal use. This is an intentional act or intentional omission of an act by the user as a result of conduct that is beyond any further reasonable risk control by the manufacturer of the medical device. Typically, abnormal uses are associated with use scenarios where there is no effective risk control measure that can prevent the use scenario. An example would be the use of an automated analyzer without checking calibration in violation of obvious warnings on the screen that calibration is to be checked. This and other examples that are based on actual events that were determined at the time to be instances of abnormal use are provided in Annex C of IEC 62366:2007. These examples were in turn taken from a paper on reporting of use errors prepared by Study Group 2 of the Global Harmonization Task Force (GHTF)⁴. 

Abnormal use is often thought of in terms of a malevolent action or irresponsible use. However, it need not be. Abnormal use is simply using a medical device for a purpose or in a way other than those intended by its manufacturer, often in violation of clear warnings or contraindications. It may or may not have adverse consequences. Abnormal use is not considered a use error because the user understands he or she is using the device in a way not intended by the manufacturer.

Mistake. A mistake is a failure of judgment or the inferential process leading to an incorrect decision about what action to take. Mistakes can arise from applying the wrong operating principles or procedures when making a decision or from nescient error arising from a lack of understanding of the adverse consequence of a particular course of action. Mistakes differ from abnormal use in that with a mistake the results are different than those expected by the user. For example, the user takes a well-intentioned shortcut on procedure, thereby omitting important steps. It is not obvious that the shortcut is hazardous. In the taxonomy shown in Figure 1, a mistake is a type of use error.

If the user did not intend to take a specific action, the result will fall into one of two categories.

Slip. A slip is a failure in the execution of an action sequence. A slip is a potentially observable externalized action not as planned (e.g., a slip of the tongue). For example, the user intends to press one button on a control panel but presses the one next to it instead. That would be a slip in this taxonomy. If the user intended to press the wrong button thinking that it was the correct action to take, it would be a mistake. If the user pressed the wrong button knowing full well that it was the wrong button, then the action would be abnormal use in this taxonomy.

Lapse. A lapse is generally reserved for more covert error forms and often involves a failure of memory, for example, forgetting to do something like cleaning an instrument before using it or confusing the meaning of an alarm signal. Lapses may not manifest themselves in immediately observable behavior because they frequently involved a failure to take a particular action, although they can have an observable effect on the outcome. A lapse may only be apparent to the person who experiences it.

Slips and lapses are errors that result from some failure in execution regardless of whether or not the plan being followed was adequate to achieve the intended purpose.

In the taxonomy in Figure 1, slips, lapses, and mistakes are the elements of use error. Although they may seem very similar on the surface, they arise from different sources. It is important to understand those sources when determining how to deal with them in the design of the user interface.

The following are some examples of use error for which the cause has been classified as a slip, lapse, or mistake.

• The user misreads the value on a glucose meter by interpreting 2.2 to be 22 mg/dL. This is a mistake caused by a display that does not make the decimal point easy to read.

• The user takes an incorrect dose of insulin from an adjustable delivery dose insulin pen after reading the small digital LCD display upside down. This is a mistake because the device design does not give adequate orientation information to properly read the display.

• The user skips a step in loading reagents into a laboratory diagnostic system causing the blood chemistry results not to be produced and error messages to be generated. This is a lapse, because the user omitted a planned item.

• A user is unable to get a blood gas reading from a handheld analyzer, because he or she put the blood sample into the wrong channel on the test cartridge before inserting it into the analyzer. This is a slip due to a reversal in the selection of a target channel for the blood sample.

In a comprehensive risk management process, the manufacturer must identify the hazards connected with the medical device, evaluate the associated risks, and control those risks throughout the medical device’s life cycle. This includes any risks related to the user interface. Applying HFE helps the manufacturer identify potential use errors so that appropriate and effective control measures can be designed. Classifying potential use errors as slips, lapses, or mistakes can provide insight into the ways that these error types may be controlled. Application of this taxonomy provides a lens through which various use-related problems can be viewed.

References 

1. “How Common Are Medical Mistakes?” acessed online at http://www.wrongdiagnosis.com/mistakes/common.htm.

2. “About Human Factors,” accessed online at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Postmarket... (Rockville, MD: U.S. FDA, May 13, 2009).

3. J Reason, Human Error (Cambridge, England: Cambridge University Press, 1990).

4. GHTF SG2N31R8:2003, Global Harmonization Task Force (GHTF), Study Group 2 (SG2), Medical Devices: Post Market Surveillance: Proposal for Reporting of Use Errors with Medical Devices by their Manufacturer or Authorized Representative. 

Charles Sidebottom is the director, coporate standards, for Medtronic Inc. (Minneapolis). He can be reached at charles.sidebottom@medtronic.com.

Pressure-sensitive adhesive tapes for IVD applications

Selecting the proper pressure-sensitive adhesive tape can guarantee product performance and can save production costs of IVD test strips.

IVD test strips and biosensors are used in a range of modern diagnostic applications such as blood glucose monitoring, pregnancy and fertility tests, and infectious disease detection. Such test strips are normally composed of several layers. The state-of-the-art assembly of bonding the different layers is accomplished by either printing heat-seal adhesives or using pressure-sensitive adhesive (PSA) tapes. One single test strip often contains various layers of tapes for laminating and marking. For example, in capillary cell biosensors, a spacer tape defines the height of the capillary cell, which is formed by die- or laser-cutting, while the lid of the capillary is made of another adhesive tape or a hydrophilic film. 

PSA tapes offer diverse advantages for manufacturing IVD test strips and biosensors. They are easier and faster to apply, do not need any heat activation, which might damage the enzyme or other test strip components, and can generate a sufficient and well defined thickness in one step. Therefore, many capillary cell biosensor manufacturers prefer PSA spacer tapes. 

However, if an IVD test strip manufacturer uses an inappropriate adhesive, oozing and adhesive buildup on machine parts during slitting can be an issue.¹ Oozing, or cold flow of the adhesive, can result in numerous problems. For example, if the adhesive oozes out of the edges of the test strips, the strips may stick to each other or the packaging. If the adhesive oozes into a biosensor’s capillary channel, the channel geometry can change, the adhesive might cover and reduce the active enzyme area, or the adhesive could clog the capillary cell’s venting hole. The eventual consequences can be inaccurate test results or defective test strips. Also, adhesive buildup can be an automation challenge for the machine builders and an issue for manufacturers since additional cleaning would be required, causing additional machine downtime and maintenance. 

The compatibility of the adhesive system with the test assay (or other parts of the test strip) and aging stability are thoroughly tested at an early stage in test strip development. Such prerequisites are well known by adhesive and tape manufacturers involved in the IVD industry, and are key considerations during raw material selection, product development, and manufacturing.

In contrast, adhesive buildup and manufacturing efficiency are sometimes tested at later stages in product development (e.g., if a new product is to be produced on a new manufacturing line). The possibility of adhesive buildup and its extent depend on the type and characteristics of the adhesive being used. Mitigating this issue could start with selecting and using PSA tapes at an early stage in test strip development. This article provides background information, study results, and recommendations to consider when testing and selecting PSA tapes for IVD test strips. 

Pressure-Sensitive Adhesives and Tapes for IVDs

In general, four different types of PSAs are used in IVD test strips and biosensors: pure acrylic, modified acrylic, water-based acrylic, and rubber-based adhesives. Pure acrylic adhesives consist of a copolymer, which is made of monomers of different acrylic derivates. Modified acrylic adhesives contain additional resins to increase adhesion. Water-based acrylic adhesives are dispersions, which contain emulgators. Rubber-based adhesives are composed of elastomers/polymers, resins, oil or softeners, and stabilizers.^1-2 

Compatibility of the adhesive with the IVD assay depends on the complexity of the adhesive formulation, or the chemical diversity of the adhesive components. As a general rule, adhesives with less complex formulations and possible impurities have a lower propensity for interactions with test components and thus higher compatibility levels. In addition, a higher number of raw materials increase the risk of subsequent product changes (e.g., if raw material suppliers modify their products). 

Adhesion, the bonding strength of the adhesive to the substrate, and cohesion, the adhesive’s inner strength, are the most important characteristics of an adhesive used in IVD test strips. On one hand, they determine the test strip’s integrity and performance; on the other hand, they safeguard the stability and efficiency of the production process. The adhesive tape must bond to the other layers of the test strip immediately and reliably. The initial and permanent bonding strength depends on not only the adhesive properties but also other factors, such as the substrate materials, their polarity, roughness, and ambient temperature. The bonding strength to the substrate increases after the initial bonding and reaches a plateau over time. Therefore, while the initial adhesion of the PSA tape must be sufficient to guarantee a stable production process and the test strip’s integrity, it does not need to increase further. 

This point is very important when selecting the proper adhesive tape for IVD applications, since adhesion and cohesion evolve in opposite directions and it is expected that the higher the cohesion, the lower the tendency for adhesive buildup.² The cohesive properties of an adhesive depend on the adhesive formulation, the molecular weight of the polymers, and the degree of cross-linking. The higher the molecular weight and the longer the polymer chains, the higher the inter-molecular entanglement and cohesion. Cross-linking, or the forming of bonds between the polymer chains, also increases cohesion. 

sites/www.ivdtechnology.com/files/image/1003/hilfenhaus-tables_big.jpgTable I evaluates and compares the characteristics that determine the compatibility and efficient production of different adhesive types. The comparison reveals that acrylic adhesives offer advantages compared with rubber-based adhesives with respect to compatibility. While the cohesion of rubber-based adhesives is low, pure and modified acrylic adhesives can cover nearly the complete range of the adhesion and cohesion spectrum. Water-based acrylic adhesives with a limited adhesive-cohesive profile are used for special applications, such as inline printing. 

Table I shows only those trends and limitations that are valuable for an initial selection of PSA tapes, and simplifies the view on adhesives. In reality, the adhesive and cohesive properties of all types of adhesives can vary over a broad range. The properties can be adjusted and balanced in various ways, such as the selected monomers and their polarity, the type of polymer, the molecular weight of the polymer, cross-linking, or the utilization of additives (e.g., tackifiers and plasticizers). Testing the level of adhesion is done by conducting peel adhesion on different materials such as steel or polyethylene terephthalate (PET). Cohesion is measured by static shear resistance tests and/or shear deformation tests.^1,3-6 

Tape Characteristics

To assess in detail the buildup of adhesive residue during slitting and to correlate the buildup to PSA tape characteristics, a number of commercially available double-coated tapes used to manufacture IVD test strips were examined. This study focused on PSA tapes with pure and modified acrylic adhesives since they dominate the market for IVD test strips and biosensors. Table II summarizes the characteristics of the different tapes. 

Table II reveals that the peel adhesion on PET varied only slightly for most products, except Tape 4. The results of the peel adhesion studies depend on the type of adhesive, the adhesive coat weight, and the stiffness (or thickness) of the backing material. Therefore, peel adhesion values between two and four N/cm are presumably sufficient in most cases to ensure a stable manufacturing process and product integrity for IVD test strips. (Even if the initial adhesion is too low for a stable process, a slight increase in lamination temperature and pressure can rectify this problem.) This level of peel adhesion can be reached with pure acrylic adhesives, which offer advantages with respect to compatibility. The cohesion properties of pure acrylic adhesives also cover a broad range as verified by the shear study results. Tapes 1 and 2 by tesa SE (Hamburg, Germany), which are based on the same adhesives that are specially designed for IVD test strip applications, show a very high cohesion compared with the other tapes.

The PSA tape properties were also investigated using dynamic mechanical analysis (DMA), which allows the measurement of an adhesive’s viscoelastic properties. Storage modulus G′, loss modulus G″, tan δ (G″/G′), and viscosity were the properties analyzed by DMA. These properties were determined as a function of the temperature (temperature sweep at a constant frequency) or as a function of the frequency (frequency sweep at a constant temperature). DMA enables a general prediction regarding the adhesion properties and the performance of an adhesive in production processes, and is also a useful tool when comparing adhesives. 

Figure 1. Dynamic mechanical analysis of pressure-sensitive tapes used in IVD test strips and biosensors.

Adhesive Residue During Slitting

Figure 1 compares the viscoelasic properties of the different tapes as examined by DMA (tan δ in temperature sweep at a constant frequency of 0.1 rad/s). A good indicator of an adhesive’s cohesion is the tan δ value (G″/G′) at higher temperatures. In general, the lower the tan δ value at higher temperatures, the higher the adhesive’s cohesion. The graphs for tapes 1 and 2 are identical because they were made with the same adhesive, which had a lower tan δ value at temperatures higher than 50° C compared with the other products (see Figure 1). The results of the DMA corresponded with those of the shear studies.

The PSA tapes were tested in slitting trials using a Matrix 2501 Module by Kinematic Automation (Twain Harte, CA). The adhesive buildup from endless slitting runs was determined every 100 meters on a semiquantitative basis. No processing aids, such as knife oil, were used during the trials. The slitting was stopped after either heavy adhesive buildup on the cutting blades or after reaching 600 meters.

Figure 2. Adhesive buildup during slitting with the Kinematic Matrix 2501 Module.

Figure 2 gives an overview of the results, and the photographs in Figure 3 show the adhesive buildup observed in this study.

The results confirmed that the higher the cohesion, the lower the adhesive residue. Surprisingly, the significant increase of the adhesive coat weight in tesa tapes 1 and 2 from 2 × 15 gsm to 2 × 35 gsm did not cause greater adhesive buildup. This result confirmed that the high cohesive strength of the tesa tapes is sufficient to avoid adhesive buildup. In addition, tapes 3 and 4, with a higher adhesive coat weight than tapes 5 and 6, exhibited comparatively lower levels of adhesive buildup. Thus, the study concluded that the cohesive characteristics affect adhesive buildup more than the tape’s adhesive coat weight. 

It is commonly believed that a low adhesive coat weight or a decrease in coat weight reduces the risk and extent of adhesive buildup. However, such an approach to decreasing adhesive coat weight in order to reduce adhesive buildup does not get to the root of the problem (i.e., adhesive formulation) but only optimizes superficially. This approach might even result in additional adhesion-related problems during manufacturing or product-related problems with regard to IVD test strip stability or integrity when applied to challenging or rough surfaces. 

This dilemma and the results of this study showed that the key success factor for a stable and efficient IVD test strip production lies in carefully selecting a PSA tape with well-balanced adhesion and cohesion properties (i.e., an adhesive specially developed for this application). As with any application and final test strip design, the IVD manufacturer must determine the suitability of a specific tape.

Figure 3. Photographs of adhesive buildup observed in this article.

Oozing Tests and Results

The tendency for oozing, or cold flow, is a consequence of the PSA’s viscoelastic behavior. In general, the higher the cohesion, the lower the tendency for cold flow. The tendency for oozing was tested using tapes 2 and 5. The 2.5 × 2.5-cm tape samples were applied to a release liner, loaded with 10 kg weight, and stored at 70° C for 14 days. The microscopic images of the samples after storage show oozing in direct correlation to the adhesive’s cohesion (i.e., very clearly for Tape 5, but almost none for Tape 2) (see Figure 4). In addition, the image of Tape 5 reveals another issue related to oozing during manufacturing: the tape’s contours become indistinct due to the adhesive seeping over the edge. The lack of clarity at the edge of the tape means that the die-cut contours can no longer be used as a register for positioning test strip components during lamination (e.g., when positioning a capillary die-cut onto a bottom film carrying the enzymes and electrodes), and severely affects the reproducibility of manufacturing processes.

Figure 4. Microscopic pictures (100×) of tapes 2 and 5 after oozing tests.

Conclusion

The selection of adhesive tapes is a critical step in developing new IVD test strips. This selection should be based on product design-related properties, such as compatibility, stability, thickness tolerances, etc., but must also consider manufacturing-related characteristics. In this respect, while adhesion is obviously the first characteristic to be considered, cohesive characteristics are sometimes neglected during the initial selection stage. The result is that a series of optimization cycles with changes in the tools, the process, or even the adhesive tape are required to reduce adhesive buildup or oozing. Under the pressure of a tight product launch schedule, such changes can become an adhesive nightmare. 

Selecting the right tape with the right adhesive at an early stage in IVD test strip development reduces time-to-market and provides the basis for a stable and efficient production. The balance between adhesive and cohesive characteristics and customized tape designs is a key success factor. Pure acrylic adhesives offer an adhesion level sufficient for most test strip substrates and advantages with respect to cohesion (i.e., a lower risk of adhesive buildup). In addition, they offer advantages with respect to compatibility. 
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References

1. D Satas, Handbook of Pressure Sensitive Adhesive Technology, 3rd ed. (Warwick, NY: Sata Associates, 1999), 121-138 for cold flow, 139-152 for test methods, 444-514 for acrylic PSAs.

2. I Benedek, Development in Pressure-Sensitive Products, 2nd ed. (Boca Raton, FL: CRC Press, 2006), 5-49 for PSA overview, 274-309 for adhesion vs. cohesion/shear.

3. PSTC 101/AFERA 4001/DIN EN 1939, “Test Methods for Peel Adhesion.”

4. PSTC 107/AFERA 5012/DIN EN 1943, “Test Methods for Cohesion/Shear Resistance.”

5. W Karmann, R Brummer , B Lühmann, A B Kummer, S Godersky, L Müller, G de Roton, and G Westphal, Patent DE10042289A1, March 14, 2002.

6. A B Kummer, “Trends in Medical Adhesive Development,” FEICA World Adhesives Conference, Barcelona, Spain, 2000. 

Peter Hilfenhaus, PhD, is product manager for health markets at tesa SE (Hamburg, Germany). He can be reached at peter.hilfenhaus@tesa.com.

Ingo Neubert, PhD, is laboratory manager for health markets at tesa SE (Hamburg, Germany). He can be reached at ingo.neubert@tesa.com.

Ted Meigs is cofounder of Kinematic Automation (Sonora, CA). He can be reached at tmeigs@kinematic.com.

A report by Kalorama Information (New York), “The Worldwide Market for In Vitro Diagnostic Tests,” concluded that the future for immunoassays is a mixed bag. In the clinical laboratory, mature assays will show moderate growth while emerging assays will fuel most of the growth in this IVD segment.

However, all immunoassays will have to pass the test of medical research to demonstrate their contributions to improving patient outcomes. For example, increased knowledge of disease physiology derived from molecular biology and human genome studies will enhance the position of analytes used in chronic conditions such as cardiovascular disease, autoimmune disorders, and diabetes. The function of genes is measured by the presence of tangible products, such as proteins of every size and molecular structure. Thus, immunoassays combined with DNA probe studies will have an important place in post-genomic medicine.

For point-of-care (POC) immunoassays, the future outlook is both good and bad. Since the early 1990s, patient self-testing has grown in popularity. Test kits are now readily available for pregnancy, blood pressure, drugs of abuse, H. pylori, blood glucose, cholesterol, cancer, and HIV. Predictions are that patient self-testing will skyrocket because of rising consumer expectations, technological innovations, and the surge of consumer activism in healthcare. Furthermore, pharmacies, retail outlets, and physician offices are establishing their positions for patient wellness screening. Under these conditions, the expectation is that both patient POC self-testing and professional POC testing will grow at 20-25% per year.

But in the professional setting, outside the hospital, most POC immunoassays do not meet the quality standards offered by lab-based tests. Furthermore, the thought is that new tests and assay technologies are too expensive. Faster, more sensitive, more user-friendly, and less expensive tests may produce better market penetration. Nonetheless, as the cost of POC devices have become more affordable and healthcare organizations have constructed data management infrastructures, POC testing has also become an attractive operational and economical alternative to traditional laboratory-based testing in various situations, including physician office testing, homecare, and in-hospital care.

Editor’s note: IVD Technology’s blog, IVDT Insight is now online at ivdtechnology.com/blog. Written and produced by the editors of IVD Technology, IVDT Insight analyzes the latest breaking headlines, offers informed commentary on industry topics, and provides a forum for our readers’ opinions and feedback. You can also stay up-to-date on the latest “Breaking Industry News” that is updated daily by accessing IVD Technology’s homepage at ivdtechnology.com. In addition, IVD Technology launched its online “Ask the Experts” program. If you have a question related to IVD development and manufacturing that you would like to ask our experts, please visit ivdt.canon-experts.com. 

Richard Park

richard.park@cancom.com

For diagnostics manufacturers, entering into a contract with the military can be very lucrative and worthwhile; however, it is not for the faint of heart. From initial discussions to production of the final product, the process is very involved and can take years. 

To learn more about what a diagnostic company can expect when forging a relationship with the military or with local first-responder teams, IVD Technology editor Richard Park spoke with Matt Scullion, business development director at Idaho Technology, a pathogen identification and DNA analysis company (Salt Lake City). In this interview, Scullion talks about the peculiarities of working with the U.S. military, Idaho Technology’s experiences in the nonclinical diagnostics arena, and the evolution of the real-time PCR platform.

IVD Technology: How did Idaho Technology first get involved with working in the area of nonclinical diagnostics and developing technologies for the biodefense military testing market?

Matt Scullion: We started a small biotech company. It was a bootstrap company, and it was a spinoff from the University of Utah. This was back in the early 90s; we’re actually in our twentieth year now.

It was very-high-speed PCR that evolved into the LightCycler technology. The military had bought some of the high-speed PCR machines that became real-time PCR machines, and they liked them a lot. The military came to us and said, these are great and all, but when we strap into planes and want to take the machines into these kind of rough environments and bounce them around and transport them all over, they rattle to pieces.

So they asked us to make a rugged version of our LightCycler. This occurred in the mid- to late 90s and with a small amount of money from the U.S. Air Force. We launched a military-specific real-time thermal cycler based on our LightCycler technology.

Does Idaho Technology have a relatively longstanding relationship with the U.S. military in terms of developing various testing technologies?

Yes. When the military develops a product on its own, it’s an extremely long process. The development cycle can usually take somewhere from 7 to 10 years. It’s all part of the long acquisition process that the military has. It’s very involved, and it can take years writing specifications and documents and going through the initial testing and evaluation, down to selecting the companies that have potentially useful technologies. Then they send out requests for information, and they keep narrowing their list down until they come to a company or number of companies that can provide them the products that they need, or products close to what they need.

They can award the contract to one or two companies, and those firms develop products to meet the military specifications. Then, finally, after a long, long process, they get to the actual production. That’s quite a long process and it’s a bit different from your standard commercial process where you go and ask the market what they want, or you do research into what the market needs and build around those needs, and then use traditional sales channels to move your products. The military is two-sided. They want the products that they want in terms of rugged military-type devices, but they also need clinical diagnostics just like any hospital in the United States.

The military has more than 3 million troops out there that they need to keep healthy, and it’s not all military hardware that they’re keeping them healthy with—it’s mostly standard, commercial, off-the-shelf products that they buy.

There is not a very big commercial market for biodefense or biowarfare technology, so the military actually sends out the specifications for what they want and they ask companies to build to those. We happen to have some unique products that fit into what they wanted to do, and we competed for the contracts that we have. And we’ve been very successful there, but it’s also a very niche market spot.

How exactly did the military contact Idaho Technology?

There are different routes that they have taken to contact us. In the case of the original one, they directly contacted us and wrote up a small program around our LightCycler technology because it happened to be the fastest real-time PCR technology available at that time. We built a rugged version—just a rugged box for them that they could transport around. We did some software modifications to make it a little easier to use. We also freeze-dried the reagents so that they didn’t need refrigerator freezing, which makes a big difference for the military. But initially they had scientists and development labs that had used our original equipment. So they thought it would be a great thing to have a more military version of it.

Are the biodefense and military testing technologies that Idaho Technology is working on adopted from other previously developed technologies? If so, how did Idaho Technology adopt the technologies to be used for biodefense military testing purposes?

They all stemmed from previous technologies, more or less. Real-time PCR, the LightCycler—that’s where our original technology for the military stemmed from. Later on, as the technology has changed and evolved, the military likes to make things extremely easy to use and very simple.

Much of the evolution of these products—this goes for most lab products in general—start out in the lab and then become automated and much simpler to use. The military wants the same thing, but it also relies on existing technology that’s available.

In the late 90s, there was real-time PCR, and you still needed to be a lab technician to use it, but we did make some military-specific adjustments to our lab kit that made it easier for them to use. But it was still a lab kit that required a lab technician.

As these things have progressed, and the military has seen where the technology is going, they’ve requested that we make simpler systems that are easier for soldiers to use. So we developed a real-time PCR platform called the Razor for first responders and special forces.

They don’t need to be lab techs. They don’t need to do a lot of sample manipulation. They simply take a sample with a syringe, pop it into a cartridge, and the cartridge pulls in the sample and automatically does the analysis for them.

That’s kind of the direction we’re going in with most of our technologies in general. It’s ease of use, less human interaction. But from the beginning, it’s all usually technologies that are already in existence. We just adopted them over to the military’s needs, which are ruggedness and the ability to target and identify bugs that aren’t very common and are more specific to biowarfare.

How do you go about making military-specific adjustments?

 Military personnel have to take their instruments into some pretty rugged environments over which you don’t always have temperature control or humidity control. You can’t always control having a roof over your head. You may not necessarily have power. They’re faced with logistics challenges that you don’t have in a standard lab.

On top of all that, they move their equipment around frequently so it’s got to be able to be dropped and handle vibration. If the device is being used on a ship, for example, it must be able to run with some vibration and rocking. The military has some pretty long documents with miles and miles of specifications.

How do you go about making the equipment simpler to use for military personnel?

They actually have training programs for lab technicians in the military, and each branch has medical technicians for the medical labs. But you also have these forward-operating bases and much more rugged areas where this equipment is deployed, and some of these medics and other folks don’t have a high level of lab training.

We do have to make these things simpler and simpler. The military is also very rigorous about their training and giving equipment to people with the requisite training. So the simpler you can make these systems, the easier it is for the military to train their personnel, and the easier it is to use.

When it comes to biowarfare detection, it’s not something they do everyday. So the systems have to be simple enough or self-guiding enough that someone can pick it up after not using it for six months or a year, and be able to turn it on and run a test.

It’s a difficult job of doing what they call “soldier proofing” these systems to make them simple, rugged, and easy to use.

What exactly is the process involved in developing biodefense military diagnostics? Do you as a company identify specific pathogens and develop completely new technologies for those agents, or do you adopt current technologies to detect those specific agents?

We generally use existing technologies, and most of our base is real-time PCR or some derivative of that—melting curve technology or melting curve analysis post-PCR. With the military, it’s more a matter of handling unusual pathogens that are not very commonly occurring—things like anthrax, Ebola, smallpox. These are things we take for granted since we’ll never see an outbreak of them in most places in the United States. They are extremely rare diseases, which doesn’t necessarily make the creation or development of the test difficult. What’s difficult is getting a hold of the pathogens for testing and then actually devising a clinical trial through FDA that the agency would find acceptable. The rate of these diseases per year in the human population is so low that it’s really hard to find enough positive samples to obtain a representative statistical sample that we can take to FDA.

What are the primary challenges involved in developing biodefense military diagnostics, and how do IVD companies overcome these challenges? You just mentioned finding samples. Is finding proper and sufficient samples one of the main challenges?

Yes, absolutely. For some of these diseases, they occur so infrequently that you’ve got to design special trials around them and move to spiking samples or animal models to complete the trials. You also have to go to specialized facilities. You need biosafety laboratories that can handle anthrax and some of these other bad pathogens and have the clearances to do it.

Some of these bugs are controlled in terms of who’s allowed to handle them and even have them in their stocks. But the facilities and people that you need to do these tests are pretty specialized people and you don’t have them everywhere. So you have to go places like the Army or the Air Force to get these tested on their special biosafety level 3 and 4 facilities. That’s a huge challenge. Finding real clinical samples of people who have these rare diseases and are presenting with anthrax or plague is another huge challenge. So designing a clinical trial around such small numbers, or artificially spiking these things, is a challenge.

It is something you have got to work hand in hand with FDA to work through, to figure out how you can create and make a trial that’s representative of what you’d expect to see in the real world if one of these things were intentionally released and you had to actually use these for future diagnostic purposes.

I presume the military is fairly willing to provide you with hard-to-find samples. But what about nonmilitary sources of such samples? How open are they to providing and sharing samples for your R&D purposes?

Most people are pretty receptive to it since this is often work that’s sponsored by the military. We go through military labs often. Other times we go to foreign countries that might have a prevalence of Q fever or one of these other exotic diseases or pathogens. If there is a certain rate of them within the country, then we can find clinical isolates that occur frequently during the year.

Some of our clinical trials actually happen outside of the United States. But, especially for these military systems, we always work in conjunction with the U.S. government because they are often sponsoring the development and clearance of these tests. It’s still a challenge, though. Most folks who work with these pathogens are, on a day-to-day basis, generally research types, or they are researchers connected to some clinical facility.

But because these trials don’t happen frequently, they are often very eager to help us with doing that clinical and future diagnostic test for some of these “orphan” pathogens because they just aren’t very frequently seen.

You mentioned working with FDA, and I presume it has something to do with devising clinical trials. Is such a collaboration truly necessary, since the devices that Idaho Technology is developing are primarily for military purposes and the company is under military contract to develop them? Or is it because the plan is to eventually commercialize these products outside of the military sphere and make them available to others, such as first responders—police departments, fire departments, and others?

We are currently developing many more commercially tracked IVD products in our film-array systems for respiratory disease panels and sepsis panels. We have a wing of our company that’s dedicated now to developing IVD-commercial-specific products.

In terms of the military products, we have permission to share them with U.S. federal government agencies. So outside the DOD, U.S. federal government agencies are allowed to purchase these IVDs for use in events such as the anthrax attacks of 2001. So it is open for use to first responders and public health for doing IVDs if they need the kits. 

Prior to 1991 and Gulf War Syndrome, I think the military took a turn in their own policy and went the route of wanting to have all their clinical diagnostics as well as their therapeutics, like vaccines—anthrax vaccine and the other vaccines that they’re developing for these exotic agents—to be FDA-cleared.

I think they found that it’s just not acceptable to use experimental technology or “for research use only” techniques on troops just because they’re in the military. So they had a bit of a policy change in the mid 90s, but it has shifted everything that is clinical in use or used on troops for healthcare or diagnostics. Be it biowarfare or day-to-day use, it is all FDA cleared. 

I think the idea that the military gets a so-called “free pass” is an old philosophy that is still lingering a little bit, but in fact, our JBAIDS (Joint Biologic Agent Identification and Diagnostic System) instrument was the first FDA-cleared military device that they’d ever done in in vitro diagnostics. So we may have helped them turn that corner, but I believe they had that policy change in the mid-90s to make sure that they weren’t doing experiments on soldiers anymore.

Have biodefense military diagnostics been developed for all the major pathogens, and which agents are Idaho Technology and other IVD companies still working on and developing diagnostics for?

Not all of those pathogens have diagnostics built around them. Some of them require PMAs—premarket authorization—which is a little more expensive and much more difficult to get through FDA.

Some of the other pathogens, such as smallpox, are just so difficult to get a hold of that the thought of doing an FDA clearance is a little bit daunting. So we have a short subset of what we do have cleared. They are much more accepted, traditional biowarfare pathogens that have a higher rate of natural occurrence—things like Q Fever.

We’re going through clinical trials now, and I believe we have a couple more slated, but they’re also finding some emerging infectious diseases that are also a big concern to the military, such as influenza and the swine flu. So we’ve been taking the CDC assays and transferring them over to military platforms and doing the bridging studies and getting FDA clearance to use them on our platform.

There is a list of important biowarfare pathgoens we have developed environmental tests to detect.  We examine that list and prioritize our FDA clearance efforts using multiple criteria including what is possible to get through FDA without doing a PMA.

From what you know and understand, what sort of effort is the military trying to make to determine what other bugs or pathogens that are out there could be weaponized? How are they engaging companies like Idaho Technology to stay on top of it and develop technologies for testing purposes?

That’s an interesting and somewhat complicated question. The government as a whole has a policy on how to deal with emerging infectious diseases and enhanced and modified pathogens. 

With emerging infectious diseases, such as SARS, for example, sequencing came in as a key technology to identify what the pathogen was in the first place. Type it out, and then you can develop in vitro diagnostic tests once you have sequenced it.

Rapid sequencing is useful and powerful in identifying emerging infectious disease, but it is not fast enough or cost-effective enough for day-to-day in vitro diagnostics They aid in identification of these modified and genetically engineered bugs or bugs that have been engineered to be resistant to such therapeutics as antibiotics.

But it’s a difficult challenge, and they certainly have infrastructure in place to deal with that, but the intelligence community gathers data from their sources. You know they collect samples and isolates from all over the world to archive and get a database for sequence information. Then anything new that might pop up—they’ve got great tools these days for sequencing new pathogens very, very quickly.

That trickles down to a company like us that designs, tests, and can quickly turn around and manufacture products and get them through FDA as fast as possible. Even FDA has mechanisms for emergency-use authorization for emerging infectious disease like what we saw with the swine flu.

There’ve been a number of tests that have gone through FDA clearance for emergency use authorization very, very quickly. So there are mechanisms in place to deal with these things. They’re never ideal. Nothing happens overnight, but the process has gotten quite good and quite fast, and the infrastructure is there to deal with this as a much more high-level public health response rather than local researchers doing their own little research-use or home-brew tests anymore.

Looking toward the future, what efforts will Idaho Technology continue to make in order to develop biodefense military diagnostics that are better and faster? Furthermore, do the military’s demanding specifications include rapid testing as well? 

The military definitely has a different view of nonclinical tests. They’re more environmental tests. They want to know if something has been released in the environment or if the troops have been exposed to something.

The faster they know, the faster they can treat them. You can’t wait 2 or 3 days for a culture to come back before you start treating someone. By that time, it may be too late to actually get effective treatment before the pathogen will kill them.

Developing these rapid diagnostics as well as environmental tests is pretty important for the military. The quick turnaround is also important because they have detectors out there that will alarm when they see a biologic cloud or something unusual blowing through the air—in which case, the troops will put on their protective gear and will stay in it until someone can test one of the air samples and say that it is a false alarm. The faster you can get those troops out of that hot, cumbersome, protective gear, the better the troops are going to do their jobs. 

The military does have specific requirements because they work in environments and conditions that we don’t see typically in the United States’ civilian society. They give us specifications for developing systems and turnaround time. Historically, the desire for turnaround of real-time PCR assay for the Department of Defense is 30 minutes. We in turn aim to design systems that will meet that target. On our new, more-automated systems, we incorporate sample prep and all the multilevel PCR and run analysis. It’s all done in less than an hour, and we’re even trying to push that to get closer to that 30-minute mark that we like.

Is Idaho Technology involved in developing technologies for other areas in nonclinical testing, such as agriculture, food, environmental, et cetera? How does Idaho Technology parlay its biodefense military technologies and experiences into developing other nonclinical or even clinical diagnostic technologies?

We have an entire food testing division, so we leverage our high-speed, easy-to-use test formats to test for things like salmonella and E. coli and Listeria, and various food matrices.

The food testing market has its own regulatory agencies and its own challenges with all different types of foods, but we draw on our military testing background experience. The commercial sector also wants things that are easy to use. They want things that are very robust, and if they move a machine around, they don’t want to have to recalibrate it and go through all of the standard steps that less-robust systems might require to get them operating again.

But we do apply that to our food industry. We also have a life science division. That’s where we vet a lot of these technologies before we move them into the military or commercial space to make sure that they’re robust enough and easy enough to use.

We start them in the research market where scientists are much more likely to be able to use them, and if we decide they’re going to be robust enough for the research market, we move them into the food testing, military, and clinical diagnostic markets.

What we’ve learned from our military users is that ease of use is a big thing. The less an operator has to be involved in the operation of the system, the less likely it is that human error will come into play in the final results.

So ease of use, ease of use, ease of use. The easier you can make it, the happier people are with your equipment. It’s kind of the way of the world, but we’ve taken our cues from the military on that point. If we can make our systems extremely easy to use, clinicians and lab folks are going to like them better.

So would you say that Idaho Technologies has a rather easy flow of information and experiences that are shared among disciplines, whether you’re dealing with biodefense military testing, or food testing, or life sciences?

Absolutely. We are a small company. We’re currently about 250 people, but we all draw from the same R&D and engineering resources, and we all draw from these common technology systems and platforms. We have a lot of people working on our defense systems who end up finishing one project there and then moving over to food or moving over to clinical diagnostics.

But our in vitro diagnostic group draws on all of that experience from our military history and our in vitro diagnostic experience with the military. So all of our commercial products that are tracking through FDA clearance and in vitro diagnostics are drawing from the same in vitro diagnostic expertise and knowledge that we use for our military products.

We’re just not a very big company. We aren’t so segmented that all our divisions don’t talk to each other.

To what extent has Idaho Technology been engaged with or been in contact with first responders like local police departments and fire departments and so forth who would, I imagine, be particularly interested in either developing or acquiring various technologies that you’ve developed for the military?

We are very heavily involved in marketing and selling to first responders from police to fire and hazardous-materials fire groups. They’re one of our key customers for these products. It’s a fairly niche product. Outside of the military, that is our customer base.

We usually have a military version that’s specific to the U.S. DOD and a commercial version of the same instrument that we sell to first responders and police. But it’s the same technology and often the same pathogens that we’re targeting. They are part of our core market for military and defense products.

Do the local first responders like police departments, fire departments, and hazmat teams have their own specific needs that they are looking for that may be a little different than what’s already in place for the military?

The military definitely has its own specifications and restrictions on what they’ve paid for us to develop. We usually maintain a certain level of rights and control over the end products so that we are able to sell to the first-responder market. It’s such a small, niche marketplace. We’ve done very, very well in that marketplace, but at the same time, some of these systems that we developed for very niche customers in the U.S. military don’t employ a very high program level or sell in very large volumes. But we still have to keep these instruments supported and sustained for years to come. 

They realize that if they’re not going to buy hundreds of these pieces of equipment then we have to be able to commercialize the products and sell them to the first-responder marketplace. Their requirement times often overlap. Even though the firemen aren’t traveling from country to country, they do bounce around a lot in their trucks and they do have to travel to sites to respond to instances and hoaxes such as what we saw in 2001 with the anthrax scare.

There were thousands and thousands of hoaxes out there—people just putting white powder in envelopes.  Addressing those incidents required equipment and protective gear similar to what the military uses. 

They’ve got many of the same challenges of moving around and needing equipment that’s very, very rugged and very, very easy to use because they have more tasks to do than just biowarfare detection. Most of the time what they’re doing is putting out fires or responding to gas spills—things like that.

What future challenges do you foresee in developing biodefense and military diagnostics? What are your overall views and impressions of the nonclinical diagnostics market?

One ever-present challenge of working with the military is the long procurement process. The acquisition process of the U.S. DOD is a long, drawn-out process. So we want to stay quite ahead of the curve in development for what the military is going to need, and anticipate their needs.

Doing that is not easy, however, because the procurement cycle is so long that they could be writing specifications and designing programs around technology that eventually they’re going to buy, say, in seven years. Guessing whether that technology is going to be obsolete in the same amount of time is a gamble. That’s a tough issue with biotechnology—it does move pretty quickly.

In terms of my impressions of the nonclinical diagnostic market, it certainly is a more difficult marketplace to identify specific niche markets within which you can have a profitable product. The clinical diagnostic market has a lot of money—that’s why so much competition exists there.

In the nonclinical-diagnostics marketplace, margins are much thinner, and it’s a much more difficult market to sell into because it just doesn’t have as much money. The plus side of that, though, is that the regulatory hurdles are much lower. So there is a lower barrier to entry than what exists in clinical diagnostics.

Why do you suppose the regulatory hurdles are lower for the nonclinical diagnostics market?

For food testing, there is a testing group it turns to called the Association of Official Analytical Chemists, and its requirements are fairly strict and fairly high. So the food market has a higher regulatory bar to clear.

The margins on food are quite small, so the cost per test must be very, very low. That’s the challenge in that market space. The veterinary market space and the agriculture market space are two more-difficult areas because, again, it’s all a matter of how much money these people have to spend on testing.

There’s not a ton of money in those areas. The research market is much, much bigger, but you also see much more competition there. But when you’re a small company like us, you have to identify a certain niche and go after that niche because you have to be much more surgical about your marketing and identifying who your customers are.

There is not as much money in nonclinical diagnostics as there is in clinical. So to be successful, you have to be very good, and your marketing and sales have to be very good.

Do you have any additional comments?

I just want to reiterate that with commercial products, specifications for them should be based on market research. But the military develops specifications based on their own internal process of identifying products that they need to have made specifically for them, and then writing their own specifications.

It’s a much more drawn-out, long process that definitely results in having the newest technology to hand to soldiers. But challenges are the nature of the beast with these large, bureaucratic systems—especially the military—as they require things that civilians just don’t need. 

Matt Scullion is currently business development director at Idaho Technology Inc. (Salt Lake City) and is responsible for program development, new technologies and market development for ITI. During his time with Idaho Technology, he has been an R&D scientist, a sales manager, a customer support and training specialist, and a marketing manager for applied systems. He can be reached at matts@idahotech.com

One need only peruse issues of IVD Technology magazine from the last decade to appreciate the tremendous development and advancement of biotechnology-based IVDs. Although regulators such as FDA have instituted forward-leaning policies and programs such as FDA’s Critical Path Initiative to facilitate medical product development, implementation of these programs has been uneven. One area badly in need of more focused and enlightened regulation is point-of-care test (POCT) IVDs; in particular, physician office laboratory (POL)–type IVDs. The promise of POCT devices is that test results can be obtained quickly so that appropriate medical care can be administered to patients without delay.  With the emergence of portable test instrument technologies, realization of the benefits of POCT can now occur in a wide range of settings that are in close proximity to the patient. The challenge to manufacturers, of course, is to develop POCT IVDs that are at least as high quality and reliable as their clinical laboratory counterparts. This aspect is understandably the salient focus of the FDA premarket review process.

Unlike other types of IVDs, POL devices often must undergo a two-tiered regulatory scheme that can impose additional barriers and disincentives to the manufacturers. Many POL IVDs must satisfy not only FDA regulatory requirements, but, for marketing purposes, CLIA waiver requirements as well. Typically a POL IVD that can be shown to perform as well as its clinical laboratory counterpart when evaluated in a POL setting is usually acceptable to FDA and is cleared or approved as being safe and effective for use in this setting. However, since many POLs wish to avoid being subject to full-blown CLIA requirements, their decision to use an FDA-cleared POL IVD is often contingent on the device being CLIA waived. Consequently, many sponsors of FDA-cleared POL IVDs must return to FDA and seek a CLIA waiver for their device, which consumes considerably more time and cost. Moreover, unlike the FDA premarket review (typically the 510(k) process), through which the overwhelming majority of new IVDs of all types are cleared (and FDA rejection is the exception), the premise of the CLIA waiver review process is that the waived device should be an exception and the waiver not routinely granted. In effect, an FDA-cleared POL IVD may not be readily available if CLIA waiver is not also granted. 

Although FDA has done a credible job of providing waiver guidance to the IVD industry, the threshold for demonstrating POL IVD accuracy and reliability to obtain CLIA waiver often significantly exceeds FDA 510(k) requirements, thus leading to a highly uncertain waiver review end point. Unfortunately, a safe and effective POL IVD as determined by FDA through the 510(k) process may not be usable given the CLIA waiver burden. Although FDA’s premarket submission review and CLIA waiver processes focus on different aspects of test validation and use, there is clear linkage regarding their particular effect on the commercial usability of POL IVDs. 

One of the primary concerns leading to CLIA in 1988 was the poor quality of testing evidenced in POLs. To address this concern, CLIA required that any facility, including POLs, performing clinical testing would be subject to the same testing standards unless the facility obtained a Certificate of Waiver, which meant that the facility could only deploy waived tests. Thus, in order for a test to be used in a waived CLIA facility, the test would need to “employ methodologies that are so simple and accurate as to render the likelihood of erroneous results negligible; or pose no reasonable risk of harm to the patient if the test is performed incorrectly.” Although FDA has granted waiver for a variety of POL IVDs, it is still exceedingly difficult for a new POL IVD that has obtained 510(k) clearance to also obtain CLIA waiver despite the POL IVD sponsor’s attempt to design “simple and accurate” tests. 

CMS surveys over the last two decades have shown that the quality of testing in POLs, even when the tests being used are waived, is still at best uneven. If, as Congress intended, the quality of testing performed in a POL environment were comparable to testing performed in other testing environments, then why would any test have to be waived in order for it to be used in most POLs? Admittedly, however, if the waived category were eliminated, then POLs would be forced to comply with current CLIA requirements for non-waived tests—which arguably would be highly resisted by most POLs. Clearly, resolution of this situation is difficult and may require Congress to act by amending CLIA. Nevertheless, the process of enabling access to new POL IVDs would be much less burdensome if a single FDA clearance would suffice. 

Thomas M. Tsakeris is president of Devices and Diagnostics Consulting Group. He can be reached at ddcgi@comcast.net. 

Leah R. Kendall is a senior associate in Epstein Becker Green's healthcare and life sciences practice in the firm's Washington, DC office. Leah works regularly with IVD clients, assisting them with FDA and other healthcare regulatory issues throughout the product lifecycle. She can be reached at lkendall@ebglaw.com.