Orthogonal Biomarker Validation for In Vitro Diagnostic (IVD) Development
Orthogonal biomarker validation plays a crucial role in developing accurate, clinically relevant, and reliable In Vitro Diagnostic (IVD) assays. Orthogonal validation employs different and diverse methods and platforms to verify and quantify biomarkers to enhance both the robustness and overall reliability of IVDs, leading to more accurate disease detection and evaluation.
Protein Biomarkers in Diagnostics
The advancement of proteomics has revolutionized In Vitro Diagnostics by providing tools for precise and efficient disease diagnosis. Protein biomarker panels coupled with AI algorithms enable accurate disease detection and monitoring, facilitating screening, diagnosis and personalized treatment approaches. This empowers healthcare providers to detect diseases early, monitor progression, adjust therapies, and ultimately enhance patient outcomes while optimizing healthcare delivery. For multiplex protein IVDs, prioritizing and precisely measuring the right biomarkers is pivotal.
Orthogonal Biomarker Validation for accurate IVDs assays
Orthogonal Biomarker Validation relies on using different and independent methods and technologies to verify and quantify biomarkers. By using separate methodologies for quantification in the discovery, validation and development phase, IVD assays reduce method-specific biases and errors and achieve a greater percentage of accuracy. By following this approach, we ensure that the final signal measured by the IVD is not merely noise or an artifact of the methodology, but is instead clinically relevant and reproducible.
Orthogonal biomarker validation employs distinct methods during biomarker development. This includes utilizing platforms like Olink, Somalogic, and Mass Spectrometry for biomarker discovery, followed by separate approaches like bead-based multiplex immunoassays (e.g. Luminex xMAP) for validation to accurately verify and quantify biomarkers.
In clinical diagnostics, the final platform is typically antibody-based (affinity proteomics) for use in diagnostic laboratory settings. Thus, transitioning from high-plex discovery platforms to mid-plex platforms is crucial for the development and manufacturing of In Vitro Diagnostics. Luminex is one of the most widely used platforms for multiplex IVDs due to its regulatory compliance with IVDR and FDA standards, making it a reliable and proven choice for clinical diagnostics.
Key Benefits and Challenges in Orthogonal Validation
Orthogonal biomarker validation contributes to the enhancement of assay accuracy and reliability, yet involves complexities related to method integration and detection limitations. A deeper understanding of these key factors is essential for optimizing diagnostic performance.
Key Benefits:
Orthogonal Validation offers multiple key benefits to assay development. By employing different analytical methods with varying sensitivities, it mitigates misleading interferences and identifies confounding factors early on.
Comparing complementary approaches not only enhances assay robustness, but also significantly reduces false positives and negatives, thereby boosting diagnostic accuracy. Additionally, by delivering clear data at an early stage, Orthogonal Validation shortens development timelines and expedites time-to-market by minimizing the need for repeated testing.
Finally, its ability to reduce the likelihood of assay failures curtails both regulatory setbacks and long-term costs, making Orthogonal Validation a cost-effective strategy for the overall development pipeline.
Challenges:
Integrating various methods for discovery, validation, and development can be technically complex, requiring advanced tools for data analysis and interpretation. Additionally, certain low abundant protein biomarkers may not be validated due to detection limitations of the methods used, leading to the need of modifications in the design.
Protavio’s pipeline | C-PLEX
Protavio has successfully utilized the Luminex xMAP platform with its C-PLEX solution across multiple IVD development projects, demonstrating its efficacy in orthogonal biomarker validation.
By leveraging advanced technologies such as Olink for biomarker discovery, and Luminex with custom monoclonal antibodies for orthogonal validation, Protavio ensures the development of robust multiplex protein IVDs.
This integrated approach not only improves the precision of biomarker identification but also accelerates the pathway to regulatory compliance, enhancing the overall reliability and clinical utility of diagnostic assays.