Application and Interpretation of Data

The consequences of an immune response to biological therapeutics are diverse, and often range from a transient appearance of antibodies without any clinical 

The positive control is the sole basis for verifying whether the ADA assay developed is appropriate for its intended purpose, even though this control may not completely reflect the characteristics of the antibodies elicited in vivo. Thus, as a biological therapeutic moves through the clinical development process, it is important to periodically compare the specificity of this control to confirmed positive clinical samples and determine its relevancy to what was observed in the clinic. Pooling of clinical samples to improve or modify the positive-control preparation may be necessary to reflect these new ADA specificities. While this new control will require assay re-validation, the resulting positive control will lead to a more robust assay. 

The decision on which type of method to use for the ADA screening/confirmation assays will depend upon the structure of the drug and conclusions from the risk assessment. The most common and first approach is to use an ELISA-based LBA method, which offers quick development times, high throughput, and low cost. However, more complex method platforms (possibly more sensitive) such as, ECL or SPR assays may need to be developed if the ELISA platform does not meet the program s needs. While not commonly used, RIPA methods can provide many of the positive attributes of the ELISA with increased sensitivity. 

While the procedures and the parameters evaluated during the validation for each ADA method may be different, each of them must be able to distinguish a positive from a negative response in a complex milieu. Without appropriately validated anti-drug antibody assays, the relevance of ADA on safety and efficacy in the context of nonclinical and clinical studies cannot be determined. 

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NACE Pubhcation 35201 (latest revision), Technical Report on the Application and Interpretation of Data from External Coupons Used in the Evaluation of CathodicaUy Protected Metallic Structures (Houston, TX NACE). 

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