The US Food and Drug Administration (FDA) has issued final guidance, Guidance for Industry: Immunogenicity Assessment for Therapeutic Protein Products, to assist manufacturers and clinical investigators involved in the development of therapeutic protein products for human use. In the document, the FDA outlines and recommends adoption of a risk-based approach to evaluating and mitigating immune responses to or adverse immunologically related responses associated with therapeutic protein products that affect their safety and efficacy.
In the guidance, the FDA outlines that any given approach to assessing and mitigating immunogenicity is determined on a case-by-case basis and should take into consideration the risk assessment the agency describes. For the purposes of the guidance, immunogenicity is defined as the propensity of the therapeutic protein product to generate immune responses to itself and to related proteins or to induce immunologically related adverse clinical events.
This guidance describes major clinical consequences of immune responses to therapeutic protein products and offers recommendations for risk mitigation in the clinical phase of development. It also describes product- and patient-specific factors that can affect the immunogenicity of therapeutic protein products. For each factor, recommendations are made for sponsors and investigators that may help them reduce the likelihood that these products will generate an immune response
Although this guidance focuses on therapeutic protein products, the FDA said that the scientific principles may also apply to related products and biological entities, such as peptides. The guidance does not cover products, such as vaccines, which are intended to induce a specific immune response to prevent or treat a disease or condition.