A Survey of Applications of Biological Products for Drug Interference of Immunogenicity Assays

• Published in: Pharmaceutical research 2012-12, Vol.29 (12), p.3384-3392
• Main Authors: Wang, Yow-Ming C., Fang, Lanyan, Zhou, Lin, Wang, Jie, Ahn, Hae-Young
• Format: Article
• Language: English
• Subjects: Antibodies - immunology; Antibody Formation - drug effects; Biochemistry; Biological and medical sciences; Biological products; Biological Products - immunology; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Drug Hypersensitivity - immunology; Drug Tolerance; Drug-Related Side Effects and Adverse Reactions; General pharmacology; Humans; Immunoassay; Immunologic Techniques - methods; Medical Law; Medical sciences; Medical tests; Pharmaceutical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Pharmacology/Toxicology; Pharmacy; Research Paper; Side effects
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-012-0833-2

Purpose Biological drugs in circulation can interfere with anti-drug antibody (ADA) assays and cause false ADA negatives. We surveyed the applications of biological products approved by FDA during 2005–2011 for prevalence of drug interferences and proposed approaches to address this issue scientifically. Methods The immunogenicity assay drug tolerance, steady-state drug concentrations, and immunogenicity rates were reviewed for 26 BLA/NDA and 2 sBLA. Results Many FDA approved biologics had higher steady-state drug concentrations than the drug tolerance of ADA assays, by 1.2- to 800-fold. Reported immunogenicity rates may be negatively impacted. Some sponsors triaged immunogenicity samples according to the drug tolerance, leaving some samples un-assayed or reporting them as inconclusive ADA; but these samples were interpreted as ADA− for calculating immunogenicity rates. Conclusions Implementation of ADA assays that can tolerate therapeutic drug concentrations is imperative. Given drug interferences, we propose in this paper the following practices: (i) to measure drug concentrations in ADA samples, (ii) to explicitly list all ADA status, including inconclusive ADA and un-assayed samples, (iii) to calculate population immunogenicity rates based on only subjects with confirmed ADA+ and ADA−, and (iv) to make available ADA assay specifics relevant to the use of ADA data in disease management.