Medical Device Link.

Originally Published IVD Technology January/February 2004

INSTRUMENTATION DEVELOPMENT

Overcoming the challenges encountered when concurrently developing the essential elements of a lab instrument.

Fred Davis, Stephen Cocks, and Jari Palander

One of the most interesting challenges facing a laboratory instrument development team is creating new automated lab systems built around a novel core technology. This article explores common problems encountered in this type of instrumentation development, and discusses solutions that have been effective for outsourced instrument development and manufacturing service providers. This article also examines the technical and management challenges of developing an automated instrument in parallel with refining chemistry, core technology, and product specifications. Six key strategies are suggested that provide a context for decision making in instrument development projects. These strategies are illustrated with references to project examples.

Primary Elements of an Automated Laboratory System

Developing lab instruments, such as the Peloris dual retort tissue processor by Vision BioSystems (Mount Waverley, Victoria, Australia), involves a number of technical and management issues that must be addressed. (click to enlarge)

As the frontiers of biomedical science expand, lab instrument developers around the world are generating new technologies for processing and analyzing biological samples. At the same time, research and diagnostic laboratories are always searching for better tools with which to conduct tests and do their work. Common ongoing needs include increased efficiency through reduction of effort and expenses, improved usability (by improving operator safety and human factors), and better effectiveness due to enhanced throughput, output quality, repeatability, measurement sensitivity, accuracy, and precision.

In many cases, turning new technologies into automated laboratory systems satisfies this need for better tools. These systems include three primary elements:

• A core technology.
• An automated instrument.
• One or more consumables.

The core technology starts with biological, chemical, and physical processes interacting with or acting on a sample. New science may be added for more effective manipulation or analysis of samples. For example, hydrodynamic steering of parallel laminar fluid flows may be used to control multiple reagents simultaneously interacting with parts of a cell culture. The core technology is then incorporated as processing protocols (e.g., timing, lane width, and positioning, reagent selection for cell culture processing) or subsystems (e.g., pumps, valves, microfluidics chambers housing the cell culture, and laminar flow lanes) within the automated instrument.

The automated instrument is built around the core technology. The supporting instrument hardware handles inputs and outputs, processes samples, and provides an ergonomic and attractive physical interface for the user. Software pulls these elements together, controlling instrument behavior, data management and analysis, and managing interactions with the user.

Consumables vary widely in nature from catalog items, such as molded cuvettes and microscope slides, to custom-made items specifically designed for use with automated instruments. Consumables may also include reagents and their packaging, reaction or processing vessels, and output vessels.

The relative complexity of the consumables versus the instrument is one of the first issues that needs to be considered when taking a new core technology from the instrument developer to the market. For example, in most high-throughput immunoassay systems, simple low-cost consumables are used, and most of the technological complexity is contained in the higher-costing instrument. However, in many point-of-care systems, a greater proportion of the technological complexity is contained in the disposable cartridges, which may contain reagents, sensors, and microfluidic channels. While this increases the consumables cost per test, it reduces the instrument's complexity and cost, making the overall system easier to use.

Concurrent Development Activities

Developing a new automated laboratory system often begins by matching an innovative technology with a series of specific market needs. This process may then generate a plan to develop a new product platform and a family of derivative products. To complete this plan and minimize time to market, the primary core technology, automated instrument, and consumables may all be developed concurrently. Overlapping and parallel development activities for the new system include:

• Product definition and specification (as marketing will always be driven by competition and end-users to refine specifications).
• Instrument development, including designing, building, testing, and refining prototype iterations.
• Further experimental research to optimize core technology performance.
• Reagent development, including chemistry refinement and scale-up for routine production.
• Protocol optimization (e.g., step sequences, volumes, times, and temperatures) by working with the ever-evolving chemistry.
• Design and volume production of physical consumables.
• Product evaluation, verification, and validation testing cycles, with each providing feedback to further development.

Figure 1. Effort versus time for concurrent development activities. (click to enlarge)

Each of these activities is performed by specialist teams and individuals who work together to deliver a lab instrument to the market. The activities occur concurrently, with the level of effort required changing as designs mature during the development life cycle (see Figure 1). This article focuses on the instrument development team's work and how it interacts with the activities of the other teams.

Understanding Market Needs and Critical Requirements

Once an innovative technology is matched with a series of specific market needs, one of the next important steps in instrument development is product definition and specification. This work is typically done by a team that brings together product development, marketing, and end-user experience. This team's activities include visiting laboratories running both manual and automated processes, analyzing competitor systems, interviewing end-users, and running focus group sessions.

As specification alternatives multiply and the number of ideal features increases, the team needs to consider complex trade-offs between factors such as:

• Product quality, features, functionality, performance, and cost.
• Development time and expenditure, while fitting within budget constraints.
• Level of development and market risk.

Getting the instrument development team involved early in the product definition stage provides highly beneficial input for handling these trade-offs. Ensuring that the development team understands end-user needs is also helpful later, when the developers are making daily design decisions.

Discussing alternative concepts is an effective way to explore relative priorities from a typical user's perspective, and to ensure they are accurately translated into product specifications. Such propositions require preliminary engineering work to generate the concepts and estimate critical decision-making inputs, such as product cost, development expenditure, and time-scale estimates.

For example, in a recent project, a key decision affecting instrument architecture was the nature and location of the graphical display screen, keyboard, and bar code reading input. In this case, marketing and user feedback was obtained by preparing and then reviewing mock-up models, illustrations, and descriptions for a range of concept propositions. Trade-offs were made by discussing the advantages and disadvantages of each option versus associated increments in instrument price.

Product definition can also benefit from a "tight versus loose" approach. Some specifications, such as sensitivity or accuracy, have clear minimum acceptable levels. If the core technology cannot perform to these levels, the product will not be competitive. These specifications are critical to success, and must be tightly monitored and controlled during instrument development.

Figure 2. Touch screen graphical user interface on the Peloris dual retort tissue processor by Vision BioSystems.

Other specifications, such as the details of user interactions with graphical user interfaces, are less clear. For these specifications, a looser, more flexible approach is beneficial, with specification details evolving as understanding of the market improves. Feedback from user trials of early prototypes is invaluable in developing these specification details. A recent example is the Peloris dual retort tissue processor by Vision BioSystems (Mount Waverley, Victoria, Australia) (see Figure 2). A team including marketing, laboratory science, industrial design, and engineering specialists developed the touch screen graphical user interface for this instrument. This team used an iterative approach of generating prototypes, obtaining feedback from user trials, and implementing enhancements to converge on an optimal design.

In addition, urgent technical requirements sometimes get in the way of the very important ones. At the same time, these very important requirements are sometimes neglected, lost among a myriad of less-critical requirements. Capturing and clearly differentiating the critical requirements helps the instrument development team focus on the most important issues. Iterative, early in-field testing by representative users helps reframe and reemphasize the most important issues.

Six Key Strategies

Concurrent development of the core technology, automated instrument, and consumables can save time-to-market and generate a higher-quality product. However, the potential downside is the increased risk of unforeseen delays and rework inefficiencies. Some of the strategies to better manage this risk include:

• Ensuring adequate core technology performance.
• Using a modular system architecture.
• Focusing on value-added innovation.
• Being ready, willing, and able to change.
• Protecting time-to-market.
• Controlling "adequate" versus "excellent."

Ensure Adequate Core Technology Performance

A frequent challenge in developing a lab instrument based on a core technology is that its performance is initially not adequate to meet specifications. Although proof-of-principle feasibility has been established, feasibility testing may be limited in scope to a subset of operating environments or scenarios, or by the maturity of test systems and reagents used. Feasibility testing may also not include protocols still being developed.

It is not always easy to define the level of performance a core technology must deliver at launch. In some cases, performance assessment can be highly subjective or difficult to quantify. Changes in chemistry processes or further developments in the marketplace can raise the bar on critical specifications, such as accuracy or precision. In each of these situations, not being able to meet specifications with the current evolution of a core technology can require a shift in product development strategies and timelines.

The key to managing risk in this area is to establish a series of clear milestones with hard, measurable performance objectives and to be ready to adapt the approach if these milestones are not met. It is also important for the entire team to understand these rules. In the midst of a project, it is easy to be seduced by the promise of being only one more test away from success.

One example involved parallel chemistry refinement and instrument development. The assay involved complex biochemistry in which the effects of the interplay between chemistry and the instrument on sensitivity were not well understood at the outset. Coefficient of variability (CV) metrics were therefore established very early and monitored for all prototype and chemistry evolutions. A clear decision point was defined where, if CV targets were not met by the completion of the alpha prototype instruments, then further instrument design engineering would be put on hold until CV targets were achieved.

Use a Modular System Architecture

Figure 3. Innovation collocated in duplicated staining modules in the Bond X instrument by Vision BioSystems. (click to enlarge)

Another strategy for managing parallel core technology and instrument development is to collocate as much of the technology as possible in a single module or subsystem. In developing the Bond X instrument by Vision BioSystems, the instrument architecture was subdivided into modules, and a specialist team was dedicated to optimizing the module containing the core technology. This module was then duplicated into three adjacent components in order to scale the instrument's size to match capacity requirements (see Figure 3). The instrument architecture was designed to have minimum coupling in the physical interfaces and functional interactions between the core technology module and the rest of the instrument. This minimized the likelihood of changes in the core technology affecting the overall system design, and reduced the risk of rework. Minimizing the coupling also allowed those teams focused on developing supporting infrastructure (e.g., control electronics, software, chassis, covers, bulk reagent handling) to progress up to a point at full speed, largely unaffected by core technology–driven changes.

One specific benefit of using the modular approach is that individual teams can be established and staffed with specialists and the right skills mix. Those team members best at managing and delivering on innovation are dedicated to the core technology. Those with strong detailed design skills focus on the supporting subsystems and on designing for cost reduction. This modular approach enables the teams to utilize their strengths and focus on a smaller number of clear and achievable objectives.

Another benefit of the modular approach is the ability to incorporate pre-existing proprietary or off-the-shelf (OTS) modules into the design. These OTS modules can significantly reduce the development effort by providing the agility to change development direction when needed, and reduce risk in non-core areas since the reuse modules have already been tested and characterized. When developing with reuse modules, the following issues should be considered:

• Favor modular, industry-standard instrument architectures that have become reusable components.
• Choose reuse development targets carefully by picking Pareto items, and those that may be reused often and solve key technical risks (e.g., capacitive liquid level sensing for a sampling probe), first.
• Base the module interfaces on industry standards where possible.
• Document the design almost as if it were a commercial OTS item.
• Establish a reuse library and appoint a librarian to ensure that the library grows and stays organized.
• Where possible, do not preclude the possibility of customizing a reuse module (e.g., define the reusable module as a stepper motor drive circuit, adaptable to various circuit boards that accommodate other components and have different physical dimensions).

Focus on Value-Added Innovation

In addition to focusing on higher-risk innovation areas, another area for design focus should be features and functions that add strong value to the lab instrument. This can be demonstrated by some simple mathematics. Choices in apportioning development effort and attention to competing product functions can be made objectively by calculating the net present value (NPV) on design effort invested versus benefits delivered and expected returns. Recognizing the preliminary nature of many of the assumptions made, especially in predicting increases in sales volumes and pricing, it can be helpful to use upper and lower bounds at least to discriminate between the clear winners and losers.

An example of this trade-off decision making can be seen in the development of a sample preparation instrument that considered the options of designing a custom robot or integrating an OTS solution. Relative development costs were considered, such as the cost of a custom module versus the cost of OTS sourcing for a given annual instrument volume, together with risks and time-to-market drivers. From this analysis, it was clear that integrating the OTS solution made sense financially. OTS integration also made sense practically, as it increased the level of innovation effort available to focus on solving problems that truly added value to the overall instrument life cycle.

Figure 4. Two retorts provide higher capacity in the Peloris tissue processor by Vision BioSystems. (click to enlarge)

The focus on value-added is also illustrated by the decision to incorporate two processing retorts in the Peloris tissue processor by Vision BioSystems (see Figure 4). Large histopathology laboratories need instruments that provide a high throughput tissue processing capacity, and the flexibility to start batches at different times during the day. Traditionally, this need has been met by employing several independent tissue processors, each with a single processing retort. However, incorporating two independently controllable processing retorts in one instrument is a better match for the needs of these high-end users.

Be Ready, Willing, and Able to Change

Developing brand new instrument platforms is quite unlike developing a next-generation, reverse engineered, or "me-too" product. It requires a high degree of flexibility and adaptability to changes in specifications and design. Detailed requirements associated with the new technology approach are not always clear until users have conducted tests on relatively mature prototypes. Hence, experienced laboratorians may be employed to perform representative chemistry testing in-house in order to gather feedback as early as possible and before prototypes are mature enough to leave the in-house wet labs. As in-house and in-field testing progresses, unforeseen problems may emerge. Addressing these problems can require unplanned changes in the design, sometimes of a fundamental nature. A major challenge for the development team is to decide whether these problems can be overcome with small incremental changes to the current design, or whether more-significant and radical new design options need to be explored. This requires judgment, experience, and the willingness to change.

Protect Time-to-Market

Achieving schedule milestones in any instrument development is critical. With the uncertainties intrinsic in parallel core technology development, risk mitigation strategies are essential to protect time-to-market.

A recent project employed an effective strategy that ordered functional and size redundancies for each prototype iteration. A risk assessment concluded that in order to implement a function, the size of a component might need to be larger than envisioned during the design planning stage. To mitigate this risk, initial prototypes were made larger in appropriate areas, based on the principle that it is easier to reduce size later when the design matures. Recognizing that this approach can achieve earlier market entry, but with a higher-cost product, some companies will deliberately plan a fast-following Mark 2 instrument.

Another common tactic used to minimize time-to-market is to move forward with the design, procurement, and building of the next prototype iteration before the testing of the previous iteration is completed. This can compress schedules, but at the risk of the cost of potential rework. These decisions must be based on well-thought-out plans, with all risks and ramifications carefully considered.

During the early phases of instrument development, the turnaround time for software changes is also a key risk. Identifying the need for a software change, documenting it, and getting the code modified, built, tested, and released can take a significant amount of time. To maximize flexibility and responsiveness, rapid prototyping tools can be used, allowing development engineers to optimize the instrument control algorithms with minimal turnaround delays, and then subsequently proceed to detailed design.

Another schedule-consuming issue is when two parallel streams of activity reach a deadlock. For example, team A cannot progress until team B advances, and vice versa. It is necessary to monitor continually for deadlock situations and seek quick resolutions.

Control 'Adequate' versus 'Excellent'

A final challenge toward the end of the instrument development process is knowing when enough is enough for first-generation launch. Categories for product features provide a useful framework for considering this matter.¹ Some product features are categorized as "delighters." These features delight because they deliver benefits that the user was not expecting. As user trials with prototypes progress, options for additional delighters are regularly identified.

These delighters represent both an opportunity and a risk. Including these additional delighters in prelaunch design updates can be very beneficial, increasing early product sales and differentiating the new product from competitors. However, the risk is that late introduction into the design may extend timelines due to additional verification testing, and may introduce unplanned delays due to unforeseen problems caused by the design changes. A balanced approach is needed. In some cases, including new delighters is acceptable. In other cases, the best option is to leave delighter ideas for consideration for next-generation derivatives and line extensions.

Other features have been categorized as one-dimensional, where users derive progressively more benefit and are more pleased as the performance or quantity of the feature increases. In the case of one-dimensional features, a little more development time could have been spent in pursuit of perfection. The law of diminishing returns usually applies though, with more time and effort being needed to achieve smaller gains in performance. This is another area in which the goals need to be clearly set and communicated to the team. Once the acceptable goals have been verified, it is time to launch. If the goals are too ambitious, it may be worthwhile to reevaluate them in exchange for the benefits of an earlier first-generation product launch.

Conclusion

This article has discussed a series of risk-management-based strategies for concurrent instrument, consumables, and core-technology development. These strategies represent some current best practices in delivering successful project outcomes. The strategies have evolved from lessons learned from many projects during the last 15 years. They help in anticipating and responding appropriately to the challenges that arise during the complex work of IVD instrumentation development. More importantly, these strategies are not static. They will continue to evolve as each new project experience is added to the mix.

Making the right judgment calls on the balance of technology maturity, development gates, and time-to-market is not easy. Getting it wrong will mean excessive design rework and development time and expenditure overrun. Getting it correct will deliver a more successful product to market earlier. These strategies provide a context for the implementation of projects. Other ingredients include an effective quality system and the right mix of experience. Having these components in place will pay off in better decision making throughout the instrument development life cycle and ultimately in getting successful products to market faster.

Reference

1. D Walden et al., "Kano's Methods for Understanding Customer-Defined Quality," Center for Quality of Management Journal 2, no. 4, (1993): 2–36.

Fred Davis, PhD, is director of instrument development, Stephen Cocks is a senior systems engineer, and Jari Palander is vice president of business development at Invetech (Melbourne, Victoria, Australia), a contract biomedical instrument development and manufacturing firm. They can be reached at fred.davis@invetech.com.au, stephen.cocks@invetech.com.au, and jari.palander@invetech.com.au, respectively.

Copyright ©2004 IVD Technology