Building Teamwork into Your Strategic Cell Therapy Assay Development

By Charles Kivolowitz

Anyone who’s in assay development knows this is a team sport. Anyone in development for more than a few minutes knows that sometimes individual teams pull in different directions according to their narrow definitions of success. This problem is well understood in business but takes on its flavor in the rapidly developing and relatively young field of Cell Therapy. This organizational siloing risks not only bankruptcy but also incurring significant human costs as eligible patients die waiting for treatment.

Silo Failure in Therapeutic Development

Synthesizing an example from my field observations in Cell Therapy that highlights the pernicious effect of siloing, we begin with a great idea in the hands of the R&D team. They thoroughly develop a comprehensive screening panel that delivers critical phenotyping and expression data. Their delighted leadership orders the assay transferred to the translational team. Unfortunately, the R&D and Translational teams have never met, are completely unaware of their differing needs, and are unable to share mutually valuable data between teams. The translational team receives the assay from R&D and begins working to prepare it for the scale, regulatory, and manufacturing needs down the development pipeline. Too bad they didn’t know that the R&D team had already extensively characterized the reagents used, pressure tested the most variable steps of the process, and defined success criteria based on the full library of tested candidates. 

This archetypal silo failure has significantly slowed many teams' progress and inflated the overall cost to the organization. It is also extremely difficult to track the impact of these kinds of silo failures unless someone within the organization has access to both the general data/work performed by these teams and the high-level financials. After all, R&D’s reagent budget is separate from Translation; who’s to know that they both just spent large sums of money and time buying the same reagents for the same experiments? Fortunately, it doesn’t have to be this way and there are great lessons to be learned from the assay development process itself. 

Path to the Ideal State

As Sun Tzu noted, “Victorious warriors win first and then go to war while defeated warriors go to war first and then seek to win”.

So too with assay development. Successful organizations define their development process first and then go to the bench while unsuccessful organizations go to the bench and then develop their process. This strategic understanding has been incorporated by the most able teams I’ve worked with and appears similar across different teams and companies. In the ideal state, directors and executives in each domain of the development pipeline routinely interact and have strong relationships in addition to general knowledge about the work performed by other groups in line. This knowledge usually radiates outward from each director into the processes immediately before and after their unit, but care is also taken to make sure that those leading at the beginning and end of the entire development process have at least some familiarity with each other. When done well, this leads to the effective communication of critical assays between teams to future-proof each step, reduce rework, and streamline operations. 

Tactical Versus Strategic Assay Development 

After seeing so many underperforming and over performing teams in the wild, I have come to think of the assay development processes in terms of Tactical and Strategic development. Tactical assay development focuses solely on its domain and is driven by segmented or poorly integrated commercial organizations. It’s readily apparent to those observing the interactions between the teams wherein, for example, Analytical Development laments the terrible state of the notes they’ve received and has no idea why 15 of the 25 parameters in the assay are there at all. So too can one easily observe process development and manufacturing teams shaking their fists in frustration upon receiving a 10 parameter assay that they somehow must squeeze down to 5.

Strategic assay development, conversely, brings together all the stakeholders involved in the lifecycle of the assay from the outset. In this environment, Manufacturing has already communicated that they need a 5-parameter assay for release testing due to regulatory and cost concerns. The R&D team integrates this need into their plans and ensures that the early-stage assay is built around a 5-parameter core they extensively characterize. The Analytical development team is aware of both the additional parameters used in R&D and the need for a slim panel for manufacturing purposes and works with Process Development to create a streamlined translation that clearly explains which parameters are critical, which are removed, and at which stage, and also why each is occurring. In this environment, the assay reaches manufacturing having built on the hard work of each of the upstream groups with minimal duplication of effort such that, should regulatory come back down the line with additional assay needs, the organization can immediately track and recall the work already performed rather than starting from scratch. 

Nested Contexts of Use 

Fortunately, the path to strategic assay development runs through the assay development literature itself in the form of Context of Use. H62, the Clinical and Laboratory Standards Institute bible of Flow Cytometry assay validation defines Context of Use as a 

“complete and precise statement that describes the appropriate use of the biomarker assay and how the validated assay is allowed to be used. The COU statement is based on the endpoint to which the assay has been qualified or validated (ie, exploratory, secondary, or primary). During drug development and regulatory review, the COU statement also describes important criteria regarding the circumstances under which the biomarker is qualified.”  

When used appropriately within assay validation, the COU defines the scope and outputs needed from the development team. It also serves to clearly and explicitly state why the assay is being developed and for what environment (examples can be found on this FDA website). Applying this type of explicit clarity to the assay lifecycle; a strategic development process is one where each unit has a clearly stated COU written to not only govern the assay(s) developed in their hands but also the overall process and aims of their unit. Each unit must be familiar with the COUs governing their up and downstream neighbors. Zooming out, the executive(s) overseeing this entire process should take pains to organize each of the COUs into a nested COU that provides the structured “why” and specific aims of each unit to the entire organization. 

Performing this exercise from the outset yields numerous benefits to the team. First, it forces the mid- and senior-level leadership to interact intellectually to write the specific COUs, enabling them also to share the particular flavors of their unit with peers to also share the particular flavors of their unit with peers. Secondly, it provides a forum for addressing experimental needs, philosophical differences, and pressures across the company. Thirdly, it enhances the development of junior leadership and bench-level operators by clearly understandingproviding a clear understanding of why their work matters and how it fits into the bigger picture of the organization’s aims. 

Final Takeaway 

Understanding where your company falls in the spectrum of tactical to strategic development approachesBy understanding where your company falls in the spectrum of tactical to strategic development approaches, you can more effectively overcome obstacles, organize teams, build a collaborative culture, and optimize your drug (and assay) development. Applying the idea of Context of Use statements to the overall development lifecycle will also break down silos and reduce the cost - in time and money - to develop badly needed therapies for the most pressing ailments.