In vitro diagnostic assays play an important role in diagnosing disease, as well as monitoring and managing treatment. They touch nearly every area of patient care, from chemistry and toxicology assays used to monitor the effects of therapeutic drugs or detect drugs of abuse, to immunological tests that detect tumor markers as part of cancer screening diagnosis, to microbiological tests that can detect infectious disease. Nearly every patient will undergo some type of in vitro diagnostic testing during his or her life, highlighting the importance of ensuring the quality and reliability of such tests. Because the impact of assay design and quality on modern healthcare is both significant and far-reaching, it deserves the utmost attention in order to promote good health and provide the best possible patient care.
 [5] |
| The flexible design of strip plates allows them to be used in many types of assays. |
As is the case with so many things, a diagnostic assay is only as good as its individual components. As assay systems grow more complex and technologically sophisticated, the number and types of different components involved continues to increase, encompassing everything from electrical switches to custom-molded plates and other consumables to software used to interpret the results. As a result, identifying and selecting the right components is critical in order to ensure that the finished product performs according to its requirements. This is particularly true in the case of in vitro diagnostics, in which the assay and its results directly affect patient health and wellbeing. When evaluating and selecting assay system components, it is important to balance several factors, including product performance, quality, pricing, flexibility, service, technical support, and environmental impact. Only when each of these considerations is optimized for a particular assay system can the value of the finished product be maximized.
Product Performance
Product performance is nearly always the primary consideration when selecting assay system components. However, depending on the type of component, “product performance” can mean many different things. For example, will the antigens being used bind effectively to the plate that has been selected? Are the chosen reagents optimized for the reaction in question? Are any plastics, such as slides, tubes, or sample containers, chemically compatible with all of the reagents and samples? What is the expected life of any electrical or mechanical components under actual assay usage conditions? Extensive product testing is necessary in order to evaluate and document each component’s performance versus the specification or other assay requirements.
In order to fully assess a component’s performance, purchasing, engineering, R&D, quality control, and production ideally will work together as a team to define and measure performance parameters and targets. In most situations, multiple lots of a given component should be evaluated to measure any variations in performance from lot to lot, in order to ensure that the assay yields consistent, reliable results. For example, when testing a multiwell plate such as those used to perform immunoassays, including enzyme-linked immuno sorbent assay (ELISA; e.g., alkaline phosphatase or horseradish peroxidase), radio immunoassay (RIA), fluorescence immunoassay (FIA; e.g., fluorescein), or luminescence immunoassay (LIA), the binding capacity can be tested using known concentrations of a common antibody such as Immunoglobulin G (IgG). By measuring the binding capacity of each plate using the assay type of interest, the coefficient of variation (CV) can be calculated among sample plates, both within a single lot and among different lots. Once the CV is known, it can be compared to predetermined targets in order to determine the plate’s suitability for a particular assay. In this example, a CV of 5% (for ELISA tests) or 10% (for FIA or LIA tests) typically indicates an acceptable level of variation within a single lot, while a CV of 10% among different lots is usually appropriate. While the target values may vary based on the type of assay or components, a quantitative approach can be used to ensure that product performance is suitable for a given application.
It is also important to understand how each component’s individual performance influences the assay’s final results. In the case of highly sensitive tests, even seemingly small variations can lead to markedly different outcomes. In addition to product performance, other quality parameters should be evaluated as well, including product appearance and condition. Is the component free from cosmetic defects, and does it remain intact under normal usage conditions, without breakage or other damage? For molded components, ensuring dimensional consistency is crucial to promoting optimal performance. Suppliers of high-quality components should also be willing to provide certificates of compliance or other quality certificates to support claims of product performance. Defining and measuring critical product attributes ensures that a given assay will routinely perform exactly as required.
Flexibility
Flexibility can also be an important factor, both for minimizing inventory and ordering costs, as well as allowing for a broader range of potential applications. Products that can be used by more than one type of assay promote this kind of flexibility. For example, choosing a strip plate, in which the plate can be separated into individual strips of eight or 12 wells or even individual wells, instead of using a traditional 96-well plate, makes it possible to subject different strips within a single plate to different test conditions. In diagnostics, this allows greater flexibility in the number of tests and samples used, rather than the more rigidly fixed format of a standard 96-well ELISA plate. Strategically selecting components with an eye toward future flexibility can lead to advantages down the road.
Pricing
Pricing is, in many instances, one of the most important considerations when developing a diagnostic assay. This is particularly true due to the large volume of components typically purchased, and the fact that component costs directly drive the final price of the finished assay kit. In addition to the invoiced price, other product costs should be considered, such as shipping costs and inventory carrying costs. For example, the way in which a component is packaged can affect shipping costs; efficient packaging can minimize shipping charges while preventing costly shipping damage. Manufacturers should also consider the cost of poor quality, including the effort required to manage backorders while waiting for good product to arrive, costs of time spent dealing with defective product, and—perhaps most importantly—lost business due to customer dissatisfaction. Ultimately, the overall value proposition tends to drive the purchasing decision by not simply seeking the lowest price but by negotiating the best possible price for the desired performance level.
Component Selection
When selecting assay system components, it is important to decide which type of sales channel can best meet the requirements. In some situations, it may be better to work directly with the manufacturer, while in others, purchasing through a distributor may be the better choice. Each option carries its own advantages. While buying directly from the manufacturer can sometimes yield lower pricing, a distributor may offer value-added services that a manufacturer cannot, such as maintaining inventory to facilitate a just-in-time approach to stocking levels, or holding inventory in multiple locations. Sourcing components through a distributor can also allow supplier consolidation by offering a wide variety of components produced by a broad array of different manufacturers, which can help reduce order costs. On the other hand, in addition to resulting in potentially lower pricing, working directly with the manufacturer may facilitate product customization when needed, allowing assay performance to be optimized. In either case, there may also be a choice between the personal service of a local supplier and the global reach and resources of a large, multinational corporation. Choosing the type of supplier that best fits the specific needs will help ensure that the purchasing process runs efficiently and cost effectively.
 [6] |
| Selecting the ideal component is an involved process |
Another consideration when choosing a component source is the supplier’s level of technical knowledge and expertise. Ideally, the supplier should be able to assist with questions regarding the suitability of a particular component for a given assay, and help address even highly technical inquiries regarding its components. Knowledgeable and experienced suppliers can also be a tremendous asset when trying to troubleshoot problems with an assay, offering suggestions to help pinpoint and address the root cause. Finding a component supplier that has experience with a specific assay and employs experts in that discipline, such as PhDs in closely related fields or other experienced scientists, provides a significant advantage. Working with a component source that has an in-house lab to assist with optimizing reactions or problem solving is also of great benefit, as it can provide hands-on assistance, try different techniques, and provide continuous feedback. Supplier Web sites can also be a valuable technical resource and should be evaluated for both content and ease of use. On the whole, a technically knowledgeable supplier functions as a true partner in the assay development process.
Environmental Considerations
It is worth considering the potential environmental impact of different component choices. What steps is the manufacturer taking to minimize its products’ environmental impact and promote sustainable practices? Areas to investigate include energy efficiency and waste reduction. For example, component manufacturers may use lower wattage or motion-activated lights in their facilities to help reduce energy consumption, or they may have a program in place to routinely replace older equipment with newer, more-efficient models. To reduce waste, they may have minimized packaging and chosen to use recycled and recyclable materials where possible, or they may recycle scrap from their manufacturing processes. As companies implement increasingly ambitious strategies to lessen their impact on the environment, there are more ways to promote sustainability through component choices than ever before.
Market Trends
It is also wise to keep abreast of market trends and their potential impact on the product. For example, there has been an ongoing trend toward miniaturization of assays. Tests which were once performed in test tubes transitioned to 96-well plates, which are now being replaced in some applications by 384-well plates. Each successive shift has minimized the amount of antigen and reagent required to perform each assay while increasing throughput by allowing a greater number of assays to be performed in the same amount of time. In the future, further shifts may take place away from multiwell plates altogether and toward significantly smaller formats such as microarrays. Microarrays consist of hundreds or thousands of microscopic spots printed on a substrate, each containing tiny amounts of the substance of interest (such as DNA fragments or proteins). This allows researchers to examine a small number of samples for thousands of different parameters, or conversely, examine a large number of samples at once for a few substances of interest. Being aware of market trends can help prevent being stuck with old, unwanted inventory when the market shifts to other products and technologies.
Another market trend to be aware of is the significant increase in demand for in vitro diagnostic tests projected to occur over the next several years. Fortunately, because the healthcare industry has traditionally been recession-proof, this growth is expected despite the current adverse economic conditions. A number of factors are driving this increased demand. The U.S. clinical diagnostic laboratory market is projected to grow by ninety percent by 2017, driven by an expanding range of available tests, an aging population, and increased awareness of and diagnosis rate for a number of conditions, including allergies and other autoimmune disorders. Recently, the American Academy of Allergy Asthma & Immunology found that “the prevalence of food allergy among children under the age of 18 increased 18% percent from 1997 to 2007.” Because colorimetric (including ELISA) and fluorometric assays are frequently used to diagnose a broad range of allergies, a continued rise in allergy rates will drive increased demand for in vitro diagnostic assays.
Finding Balance
Optimizing the components that make up an in vitro diagnostic assay involves balancing a number of different factors, from pricing, to service, to environmental impact. As each affects the finished product either directly or indirectly, careful attention to each will ensure the best possible assay performance, resulting in the highest standard of care for patients.
Amy McGhee is a product manager at Greiner Bio-One North America (Monroe, NC). She can be reached at amy.mcghee@gbo.com [7].