The answer to the question is “it depends”. Commonly a combination of 510K approved kits (in Europe known as assays that need to follow IVD-directive 2017/746) and research use only (RUO) kits are used to support the biomarker analysis needed in clinical trials because both types of assays have different strengths and limitations. To select the appropriate kit requires an understanding of these pros and cons in the context of the intended study the assay must support.
510K Approved Assays: Low Variability, Specific Purpose
Having undergone rigorous FDA approval processes, 510k approved kits provide reliable assays that are guaranteed to conform to strict quality system regulations for the specific patient populations, particular sample matrixes, and diagnostic windows for which they are approved. Since these assays are usually established on fully automated clinical analyzers, they offer low inter-lot variability measuring below 5%. Lot-to-lot variability is also minimized because 510K approved kits are manufactured at very high volumes and vendors of such kits are therefore able to tightly control reagent quality.
However, the flip side to this low variability is low flexibility. 510K approved kits are generally established via closed systems and validated for specific parameters that may not fit the patient populations, matrices, or diagnostic window used in your specific study. While it would be ideal to leverage an assay that has already been through stringent FDA review, it is not always feasible to find one that meets the unique needs of a drug development program and the biomarker’s intended use.
RUO Assays: Highly Flexible, Require Validation
Because RUO kits are generally able to be modified, they can be used and validated to support clinical studies in various patient populations and matrices. The process requires making the necessary changes and then performing the appropriate fit-for-purpose (FFP) validation to ensure the biomarker assay is sufficient to support its context of use (COU), or the context in which the data from the assay will be applied.
The tradeoff of greater flexibility is higher variability, which can range from 10% to 25% or more. RUO assays are typically performed in a 96-well plate format with several research-grade reagents added to each well manually, making them inherently more prone to human error and variability than assays set on automated analyzers using highly qualified reagents. Many of these issues come from the fact that RUO kits are made in smaller batches than 510K approved assays – in volumes in the thousands vs. millions – causing more kit lot-to-lot variability as well.
One Size Doesn’t Fit All
The reality is that 510K approved assays can provide a great foundation for some, but not all, biomarker studies. It is also not economically feasible to go through the process of getting every RUO kit 510K approved. However, with the appropriate FFP validation following good bioanalytical laboratory practices, many of the current RUO kits available can be applied to support clinical trials.
At BioAgilytix, we help customers determine the most appropriate assay format for their biomarker studies by first understanding the parameters of their intended clinical trial, particularly related to the biology of their patient population. This helps us ensure upfront that the assay will be relevant for the intended purpose and will in turn guide us to the best kit selection.
The use of 510K approved kits vs. RUO assays is just one topic among many in the field of biomarkers. In our upcoming blog series, we’ll be discussing biomarkers in all of their facets, ranging from biological underpinnings to other contemporary and futuristic topics. In the meantime, you can learn more about our biomarker services here, or schedule a discussion with our scientists to talk through your biomarker needs and how we can support them.