Biotherapeutics have revolutionized the medical space. Today, biologics treat conditions such as inflammatory bowel disease, arthritis, and cancer. However, these biotherapeutics face stiff issues related to immunogenicity. Immunogenicity against therapeutic protein is the primary limiting factor for developing biologics and large molecule drug products. Effects from drug immunogenicity may range from negligible drug reactions to extremely detrimental effects, including death. Therefore, ADA immunogenicity testing becomes crucial for developing biotherapeutic drug products.
Most safety and efficacy data come from pharmacokinetic studies. Hence pharmacokinetic studies are a crucial component of analytical lab testing. However, for immunogenicity testing, recent approaches demonstrate that combining immunogenicity testing services with pharmacokinetic studies is beneficial for drug development studies. Hence the current article explores combining immunogenicity testing services with pharmacokinetic studies to achieve better drug development outcomes.
Combining immunogenicity testing with pharmacokinetic studies
Assessing drug safety and efficacy is a significant factor for the success of preclinical and clinical drug testing. The US FDA has issued several regulatory guidelines for the conduct of in vitro and in vivo studies. Immunogenicity testing services have the expertise to navigate these complexities and address individual ADA study needs and deliver optimal testing results.
Pharmacokinetic studies evaluate the distribution, absorption, metabolism, and excretion characteristics of a biotherapeutic drug. Drug developers employ several PK assay formats, such as a sandwich or direct ELISA, to assess ADA formation. Immunogenicity testing services can develop several PK assays and provide related services such as the development of monoclonal antibodies, selection of antibody pairs, transfer of method, and sample analysis.
Unwanted immunogenicity produces antibodies against the biotherapeutic drug. Anti-drug antibodies mediate unwanted physiological or biological effects by provoking adverse reactions or interacting with therapeutic drug effects.
Immunogenicity testing also involves using anti-drug antibodies as positive controls. Since immunogenicity testing is a complex endeavor, the US FDA recommends a multi-step approach. This method begins with preliminary screening assays to detect negative and positive samples. In the next step, confirmatory assays detect confirmed positives and help remove false positive results. Finally, characterization assays are conducted to assess the neutralization ability of ADA affinity, isotope binding, and titer. Besides, immunogenicity testing services deliver several services, including drug labeling, assay design, transfer of antibodies, and subsequent sample analysis.
Hence combining immunogenicity testing with pharmacokinetic studies can prove beneficial in assessing anti-drug antibodies. One such approach is quantitative systems pharmacology. This model-based approach can predict the impact of anti-drug antibodies on the pharmacokinetic profile of the patient population. This model typically integrates literature-intensive and mechanistic models of immunogenicity with a physiologically based PK model for biotherapeutics. The simulator uses information on the MHC-II affinity of patients to extrapolate data from in vitro assays and bioinformatics to study the PK effects in a specific patient population.
Biotherapeutics and large-molecule drug products will always face the issue of immunogenicity. Therefore, combining immunogenicity testing services with pharmacokinetic studies will prove beneficial for accelerating and achieving better drug development outcomes.