We look forward to attending the annual WRIB conference every year – it is a staple event for our industry and provides an invaluable opportunity to collaborate with and learn from colleagues, sponsors, and regulatory authorities that are actively shaping the future of bioanalysis.
Our scientific team was able to host several presentations as well as participate in a number of discussions surrounding the latest topics of interest in biomarkers, immunogenicity, and regulatory standards. We wanted to share some of the valuable insights we gained and communicate their significance by recapping our key takeaways below:
Reiterating the Need for Context of Use & Fit-for-Purpose Method Development
The topics of context of use (COU) and fit-for-purpose (FFP) resurfaced at the 13th annual WRIB in lively discussions, reiterating the importance of these concepts in biomarker assay development and validation. Because the biomarker assay procedure needs to adequately meet the goals of the investigation, emphasis was placed on establishing the biomarker’s COU early in the biomarker validation process. This will help to ensure that the assay is constructed in a way that its resulting measurements are suitable for the study’s specific objectives and the biomarker’s intended purpose.
In my own presentation entitled “Understanding of the Biology of Biomarkers for Successful BAV”, I also emphasized that the COU should be directly related to and supported by the FFP process, which has been thoroughly summarized by Lee et al. (2006). This paper states that the FFP status of a biomarker method is deemed acceptable if the assay is capable of discriminating changes that are statistically significant from the intra- and inter-subject variation associated with the biomarker.
Remember, Biology Matters
The benefits of defining COU and FFP expectations were made particularly clear when discussing the fact that biomarkers are endogenous molecules and therefore their measurement often fluctuates with variability in physiology, disease biology, pathology, treatment administered, and environmental factors. Given these realities, the acceptance criteria and expectations for assays used in the analytical validation of biomarkers must take into consideration the type of molecules being measured and the context in which the biomarker is being applied in the drug development process and in regulatory decision making.
As I noted in my session, there is no clear “textbook” for biomarker validation. You won’t yet find one single guidance or universal standard that can be applied to all biomarker work, and that means we need to apply scientific ingenuity instead to set appropriate acceptance criteria in line with study expectations and to account for the unique variabilities that biomarkers create.
Upholding the Long-Term Integrity of Critical Reagents
Several sessions at WRIB highlighted the growing focus on critical reagent lifecycle management. It was noted that functional assessment of the reagent alone is not enough. These are essential assay components with unique characteristics and inherent variability that can affect assay performance, and the programs they are used in can span years as the drug matures through development to commercialization. Therefore critical reagents need to be carefully managed throughout their entire lifecycle, from production to characterization, documentation, storage, and periodic recharacterization as needed to ensure structural integrity and stability are appropriately upheld through the stages of development.
Determining Cut Points in ADA Studies
Another area of focus in this year’s WRIB discussions was around the determination of cut points for ADA assays, and the need to exclude pre-existing antibodies during this evaluation. Natural antibodies may be present in treatment-naïve subjects due to previous exposure to similar or related structures or due to the presence of product-related compounds such excipients or impurities/contaminants. These pre-existing antibodies need to be considered when calculating the assay cut point. While the removal of outliers has been discussed multiple times over the years, it was highlighted that to ensure appropriate statistical power, sometimes more than 50 samples are needed for this analysis.
We thank everyone who attended WRIB for being part of these engaging conversations and for the opportunity to share our collective insights to advance our common goal: improving global health.
If you would like to hear more about BioAgilytix’s perspective on these and other important topics in bioanalysis today, feel free to reach out to me to continue the conversation.