Ep5 - The Assay is King

MedTech Speed to Data

Focus on The Assay to Improve Overall IVD System Development

Assay performance should be the priority when developing complex cartridge and instrument systems. The Assay is King! As assays are becoming more complex, taking an “inside-out” approach to IVD System Development is optimal for project success.

This approach starts with first defining what the assay needs to do, then figuring out how to automate that process on the cartridge, and only then focusing on what a commercially viable instrument will look like. This leads to reduced costs, shortened timelines, and superior diagnostic performance. Put another way, the assay team should be the customer when architecting and developing IVD Systems—the chemistry should drive the project.

How to implement the inside-out approach

Define the Assay First

The assay is where the magic happens and is where the intellectual property lies. That IP is what drives future acquisitions by global diagnostic players. For example, Roche recently acquired GenMark along with the ePlex system that Key Tech helped develop, to broaden its molecular testing portfolio.

At the end of the day, the instrument serves the cartridge and the cartridge serves the assay. Before starting any product design work, you need to understand whether the chemistry is locked down. Is the benchtop assay working? If not, it may make sense to wait until it is, to avoid costly rework later.

Our CEO and Co-Founder, Jenny Regan, stresses the importance of solidifying assay performance before instrument design:

“Anyone can design a beautiful instrument that doesn’t work. It’s easy to do because it is a tangible milestone for investors and developers alike. The pressure to do that and make something that looks great before doing the nitty-gritty, difficult work of making a working assay is all too easy to fall into.”

Collaborate on Menu Planning Early

It is critical to not only understand the lead assay, but also what other assays are being planned so that both cartridge and instrument can be planned accordingly. Early collaboration with the assay team will ensure that fewer changes and post-market updates need to be made. This approach also affects speed of regulatory approval, since most changes that need to be made to the cartridge or instrument, to support a new assay, will require applying for re-approval.

For example, consider reagent quantity. If your lead assay requires eight reagents, but a few others need ten onboard, you need to ensure that the planned cartridge design takes that extra requirement into account and leaves space for the additional two.

Sample type is another consideration. If the lead assay is going to work with a saliva sample, but a future panel will use a stool or blood sample, you need to ensure the cartridge is designed to be able to handle the future, additional sample types.

De-Risk and Validate Assay Automation Early

Because a working assay is the end goal, it’s critical to get working automated cartridge/instrument prototypes to the assay team early so they can validate that the chemistry is still working, and to design a workflow for their assay. It needs to be easy for the assay team to collect data and interact with these early prototypes.

Often, this means developing test fixtures for each critical step in the assay process. When translating an assay from the bench to the cartridge, there could be steps that only work part of the time on the bench. These must be confirmed to work 100% of the time on the cartridge. Or there could be steps that always work on the bench, but are extremely complex to automate, requiring validation to see if that specific step is even practical in an automated instrument.

At Key Tech, we have a proprietary software platform for hardware interaction, called KeySharp, that allows the assay team to control a prototype instrument while seeing a graphical engineering view of what the cartridge and instrument are doing. With this tool, they have a way to interact with the prototype, adjusting and testing variables, and designing a workflow for their assay.

Constant Collaboration for Real-Time Feedback

The “assay is king” approach requires an ongoing conversation between the engineering team and the assay team, and a consistent feedback loop.

The traditional outside-in approach often creates unnecessary constraints on the assay team by forcing them to operate within an engineered product that was developed without them in mind. If the assay team has tweaked the bench assay to generate a better or quicker result, the design may not be able to support it.

Pivots and updates in the bench assay are commonplace, so constant communication is the only way to anticipate and adapt the development effort in a timely way.

Parallel Development of Cartridge and Instrument

Oftentimes, three teams are working on a project – assay team, cartridge team, and instrument team – which makes efficient development exponentially more difficult. Especially if coordinating across multiple organizations.

On the other hand, parallel cartridge and instrument development by a single interdisciplinary team eliminates conflicting priorities and incentives between vendors. This integrated approach helps your IVD system get to market faster, as both instrument and cartridge are developed under one roof toward a common goal. Ultimately serving the assay, designing the cartridge and instrument in parallel reduces your overall development process time and cost.

Not all design and development firms offer both IVD cartridge and instrument design expertise to support a successful assay. Ben Lane, our Director of Engineering, shares,

“Our claim of integration is truly the case. We have cartridge designers and instrument designers who are literally sitting next to each other and talking to each other all day long.”

In Summary

Assays are becoming more and more complex, and ensuring that platform development actually serves the assay is critical. Placing your assay and engineering teams in constant collaboration and tackling de-risking, menu planning, and validation early in the process will lead to project success.