+1 (888) 794-0077
« Return

Immunogenicity Assessment for Biologics Development: How to Reduce the Risk of a Clinical Hold

In 2019, the U.S. Food and Drug Administration (FDA) revised its guidance for immunogenicity risk assessment (IRA) of biological therapies. IRA is required to help drug developers and regulatory agencies better understand the potential impact an immune response will or will not have on patients when exposed to the therapeutic. The guidance is important to keep in mind when planning your preclinical and clinical drug development, as failure to adhere could result in barriers that ultimately delay the acceptance of your Investigational New Drug (IND) application, putting your program on clinical hold.

Many aspects of the guidance were revised but in our whitepaper, we highlight the revisions focusing on the following areas:

• Risk assessment

• Statistical approaches to ascertain cut point

• Removal of long-term stability requirement

• Minimal required dilution

Positive control antibodies

• Development of assays to measure neutralizing antibodies

• Strategies for managing pre-existing antibodies

• Updates in documentation requirements


The FDA recommends that immunogenicity risk assessment and rationale should be provided prior to entering first in human (FIH) studies and submitted in conjunction with the IND. Previously, the FDA advised that sponsors should provide a rationale for immunogenicity testing rather than the risk assessment itself. The FDA also provided clarification that test samples during phase 1 and phase 2 studies should use suitable screening, confirmatory assays, and, where necessary, neutralization assays.

Learn more about Large Molecule Bioanalytical services

Established in December 2000, WuXi AppTec provides a broad portfolio of R&D and manufacturing services that enable companies in the pharmaceutical, biotech and medical device industries worldwide to advance discoveries and deliver groundbreaking treatments to patients. With industry-leading capabilities such as R&D and manufacturing for small molecule drugs, cell and gene therapies, and testing for medical devices, WuXi AppTec’s open-access platform is enabling more than 4,000 collaborators from over 30 countries to improve the health of those in need – and to realize our vision that “every drug can be made and every disease can be treated”.

 Follow us on LinkedIn.

Related Articles

The Advantages of LC-MS/MS in Optimizing ADC Bioassays

The Advantages of LC-MS/MS in Optimizing ADC Bioassays

Antibody-drug conjugates (ADCs) are offering hope to cancer patients worldwide. This novel treatment combines the precision targeting of antibodies with the cancer cell-killing power of cytotoxins, delivering treatments directly to tumors and minimizing damage to healthy tissues.