Medical Device Link.

Originally Published IVD Technology July 2004

Laboratory Instrumentation

A market demand for workstation consolidation and increased automation led to the development of the Synchron LXi 725 by Beckman Coulter (Fullerton, CA).

Today, diagnostic laboratories face a host of challenging market conditions. Chief among them is a critical labor shortage with no end in sight and an ever-increasing pressure to limit costs. These issues are driving an unprecedented IVD market demand for automated solutions, and manufacturers are responding with new, advanced products. 

In order to integrate all the steps involved in researching and developing a new instrument, companies need to establish a structured and efficient product development process. Such a process should provide a road map for navigating the choices and challenges encountered during development. At the heart of this comprehensive process are key principles that can transform a good idea into a functional, reliable IVD system. 

The product development process also provides continuity for projects that require the manufacturer to perform multiple functions such as marketing, manufacturing, and product support. The process enables a smooth handoff from one discipline to another. 

This article examines the principles behind the product development process, and the role these principles play in the larger context of research, development, and manufacturing. It also illustrates how a standardized process at Beckman Coulter (Fullerton, CA) guided the development and launch of the Synchron LXi 725, a clinical system that combines chemistry and immunoassay testing on one platform. 

Planning and Product Definition 

Table I. The product development process road map (click to enlarge).

The first phase in the development of any new product is the assessement and strategic planning process (see Table I). In this phase, the development team relies on information from several sources, including market research, a preliminary description of the product, a summary of requirements, and a preliminary development plan. 

During this period, the team must generate an organizational structure of personnel required to support the project, as well as create a vision of the finished product. Typically, these steps begin with market research that includes focus groups, customer interviews or questionnaires, an analysis of competitive market pressures, and a review of current market trends. 

This research is then synthesized in a document that outlines the business considerations that have compelled the company to pursue this particular idea at this particular time. 

In addition, the document should enumerate high-level system performance requirements. Even though there will be much that has yet to be determined at this early stage, the company must at least sketch out its preliminary vision for the instrument—its performance characteristics, its proposed cost, and its target release date. Once the finances, strategy, and market overview are set, the team can work on a deeper level of detail. Initially, however, the product must be defined to the point that the team can plan a credible development timeline. 

At this point, many companies become mired in the “fuzzy front end,” a popular term for the beginning of new product development, when both the end goal and the methods for achieving it are not yet fully clarified. This is one of the most critical junctures of the product development cycle, as delays can impact all aspects of the proposed outcome. 

Whenever a cross-functional team is charged with specifying the requirements of a system, including performance, reliability, operability, safety, and similar features, much discussion ensues. Team members may struggle to agree on a common vision and approach. 

By the time a team emerges from the front end, they should do so with a fairly clear product definition. This definition should comprise the overall product scope, major features, performance claims, regulatory requirements, and other limitations and constraints of the final product. At this juncture, the team can determine the true scope of the schedule and budget. 

Also at this point, various layers of the development team become engaged in the process. With the product definition as the blueprint, the team creates detailed documents for each goal that will contribute to the finished product. The product must be defined in sufficient detail to enable the team members from various disciplines to implement the system design with maximum efficiency. 

As documentation of the duties and function of each segment of the team occurs, the interrelationships among the instrument’s features should be thoroughly reviewed. The team should then determine how these features map into the schedule and budget. The team needs to ensure that it can build an effective, reliable system within the parameters it has set forth. A risk management plan is typically created to address the areas that may impact cost, schedule, and performance. 

It is particularly important to highlight the technical requirements at this early stage. The team must describe the overall theory driving the technical approach, and include issues related to hardware or software development. If not thoroughly reviewed, these issues can surface later and impact the progress of the project. 

System and Subsystem Design

System design embraces several key elements. This second phase of instrumentation development involves partitioning the system into subsystems, defining the interface between subsystems, and noting the requirements allocated for each subsystem. Most importantly, the team will identify and create design elements that meet the needs of the customer. 

In this phase, the software design is formalized and validated, and the technology budgets are further defined. At this point, the team should understand the total system reasonably well, and the attention should turn to the subcomponents. Distinct teams will detail the hardware, software, and chemistry modules of the subsystems while paying attention to how these units will interface as a whole. 

At this juncture, the teams will also begin to plan the layout and contents of the operational manual. For some instruments, operational manuals must be printed in multiple languages, and frequently they must be available in both hard-copy and electronic formats. While the final copy for the manual will not be completed during this time, the preliminary work must take place in order to stay on schedule. 

Chemistry process development proceeds in parallel with the subsystem implementation. Prototypes of reagents, calibrators, and controls are developed for pilot tests, and work focuses on optimizing the chemistries for full-scale manufacturing processes.

As the subsystems are finalized, the initial testing begins. During this next phase, the subsystems are validated and detailed reports are created to track performance. This work paves the way for subsystem integration, when the instrument is assembled and readied for full-scale testing. 

Validation 

Figure 1. A formal product development process guided the production of the Synchron LXi 725 by Beckman Coulter, an integrated chemistry and immunoassay system (click to enlarge).

During this third phase, the emphasis turns to validation. The team conducts tests to ensure the system reports the correct results and conforms to customer needs. The final system must meet the attributes captured in the product definition document, and it also must be safe and reliable. 

Evaluation performed in this phase both tests the limits of the system and examines system performance from the perspective of the intended user. Testing volumes and protocols vary to simulate an authentic laboratory environment. Protocol testing can involve multiple types of samples, tests, and calibration intervals. 

Typically, in-house tests are conducted to identify opportunities for improvement, then limited beta tests (i.e. tests performed by customers) begin. During beta tests, an instrument is used in a real laboratory environment, then customers are surveyed regarding their experiences with the system. At the end of this rigorous testing and verification cycle, the elements of the product may need to be fine-tuned or the system may be ready for general release. 

A Case Study

Beckman Coulter used this product development process to develop its Synchron LXi 725 clinical system (see Figure 1). As the impetus for this project, focus groups and interviews with customers validated the need for the analyzer. 

There has been rapid growth of diagnostic analyte utility in the heterogeneous immunoassay market. Diagnostic interpretation of clinical results has been difficult because the many methodologies of testing produce a variety of clinical decision ranges for each analyte. In an effort to simplify clinical interpretation, testing methods have been standardized by using chemiluminescence as the preferred methodology. Therefore, the design team decided to offer standardized results by using chemiluminescence for immunoassay testing as well as spectrophotometry and potentiometry for general chemistry. 

In addition, market research revealed that laboratories face a critical labor shortage, fueling the demand for automated solutions. The ability to do more with less is a top priority for every diagnostic lab. 

Taken together, these market conditions pointed to a trend toward workstation consolidation. Beckman Coulter translated this market need into the concept of the Synchron LXi 725, an analyzer that allows laboratories to conduct their chemistry and immunoassay testing on one instrument. 

The project team encompassed a wide range of individuals, with representatives from research and development, marketing, and manufacturing departments. The program management group oversaw the product definition, development schedule, and system release. The project management group was in charge of the technical integrity of the product, development process, and overall development plan. The functional management group provided the trained staff and the experts in various subjects necessary to execute the plans. 

One of the first challenges faced by the team was the development of a project definition. Marketing research proved that customers would benefit from a consolidated chemistry and immunoassay system. But high-sensitivity immunoassay instruments and general chemistry instruments are two entirely separate entities—at that time, a marriage of the two was considered unconventional. 

As part of creating the product definition, the team had to define the requirements of the system, including performance, reliability, operability, safety, and other features. To stay on schedule, the team focused on what was needed in the new system, as opposed to what it wanted. 

The marketing group organized “needs” and “wants” lists culled from its market research. The team then created a list of boundary conditions, or descriptions of the instrument’s required features. From this, the group proposed 10 concepts for the system, broken down into three families of ideas. 

On one side of the continuum, the team could create a brand-new, fully integrated system—a single workstation that handled both chemistry and immunoassay testing. Though this was an elegant solution, because of a lengthy development time, the time to market would suffer; and due to the newness of the technology, the performance could be compromised.

On the other end of the spectrum was an instrument with very little integration. Though it would be a simpler option and would save development time, customers might not have seen the long-term value of such a product, particularly if it did not offer a single user interface. 

To determine the best system concept, team members considered customer needs as well as their own resources. Then, the team scored each idea in a variety of qualifiers such as time to market, technical difficulty, regulatory impact, and development costs. 

By using these evaluation tools, and by strictly adhering to program management processes, the group emerged from the fuzzy front end in three months, with a clear vision of its end goal.

The selected design was inspired by two existing Beckman Coulter systems, the Synchron LX20 Pro clinical analyzer and the Access 2 immunoassay system. Rather than create a new instrument from scratch, the team opted to combine these systems, with which the company and its customers were already familiar, on one platform with automation and data management components to link them together. This would allow them to leverage existing technologies and avoid a costly and lengthy ground-up development approach.

Building the System 

Figure 2. Closed-tube sampling and aliquotting remove manual processes.

As the team moved into the development and manufacturing stage, the principles of the product development process played a critical role, particularly since the group was integrating two distinct instruments, each with its own group of technical experts. 

The Synchron LX20 Pro chemistry analyzer alone contains more than 500,000 lines of software code, and the Access 2 immunoassay system incorporates as many as 250,000 lines of code. To bridge the differences between the systems, the team implemented a closed-tube aliquotter module (CTA). 

The CTA offered a form of automation scaled to a level that suits more- modest-sized laboratories (see Figure 2). With this solution, operators could set a sample tube in the CTA, then the system automatically aspirates a portion of the sample into an aliquot tube for immunoassay testing. Next, the primary tube is routed to the chemistry side. This parallel-processing capability was one of the top requirements identified as part of the team’s boundary conditions.

Another challenge during the product development was balancing the testing throughput between the two systems. Too often, when manufacturers combine instruments on one platform, it slows the overall efficiency of the combined system. The team needed to strike the right balance between routine performance and efficient throughput, and it needed to maintain the ability to run stat tests at any time. 

Reliance on the product development process helped overcome these challenges. The team turned to documents created early in the development cycle to revisit customer requirements and market data. From the market research, the team knew that its typical customer shouldered a heavy workload, and team members were able to define the typical test mix for customers in a 24-hour period. 

With this input, the team entered the verification and validation phase. Here, it ran a number of simulated tests, each with a different approach to throughput. By taking the needs of different laboratories into account, the group arrived at an effective balance between throughput and capabilities. These exercises not only improved the design of the system, but they also allowed team members to develop protocols that could be used during the beta tests. 

David Heibel is director of product management, lab systems, and routine testing at Beckman Coulter (Fullerton,  CA). He can be contacted at dcheibel@beckman.com.

In the final phases of testing, the beta tests were run by a small pool of customers, including industry opinion leaders and early adopters of the new system. During this phase, the team validated that the features offered on the Synchron LXi 725 were indeed important to customers. 

The data gathered in the beta tests helped inform the launch strategy. Beckman Coulter targeted laboratories worldwide with the message that the Synchron LXi 725 could lower costs, speed turnaround time, and—above all—help laboratories do more with less. Customers responded, and orders for the Synchron LXi 725 climbed. 

Conclusion

At its height, the project at Beckman Coulter involved more than 80 individuals with a diverse range of skills. During the development cycle, the team’s strict approach to program management allowed it to manage this large, complex undertaking. In the end, the company met its design objective, delivering a system that offered both standardized immunoassay testing and general chemistry testing.

The journey from concept to finished product is never easy, and distractions, challenges, and roadblocks arise in every phase of the development cycle. But by adhering to the principles of a structured product development process, teams can break daunting projects into manageable phases and create a common vision that pulls disparate functions into one integrated effort. 

With this type of disciplined approach, manufacturers can continue to respond with timely solutions that elevate laboratory efficiency, productivity, and patient care to new levels.  

Copyright ©2004 IVD Technology