A comparative multi-tiered immunogenicity assessment of biosimilar pegylated filgrastim: validation of methods for clinical assessment of INTP5.
Expert Opin Biol Ther
; 22(2): 321-330, 2022 Feb.
Article
em En
| MEDLINE
| ID: mdl-34794342
ABSTRACT
BACKGROUND AND OBJECTIVE:
Validated and highly sensitive assays are required for comparative assessment of immunogenicity of biosimilars. For INTP5, a biosimilar pegylated filgrastim, the immunogenicity assessment included tiers that allowed for assessment of antibodies against the PEG and the Filgrastim moieties for comparative clinical immunogenicity assessment.METHODS:
Electrochemiluminescence immunoassay (ECLIA) was used for Screening, Specificity, and Titer assays for detecting anti-drug antibodies (ADAs) and cell-based method for neutralizing ADAs. The methods were validated to enable use of same methods irrespective of biosimilar or reference arms.RESULTS:
The ADA and cell-based assay for neutralizing antibody detection were validated with a sensitivity capable of detecting binding Anti-Pegfilgrastim antibody at ~40 ng/mL and Neutralizing antibody at ~380 ng/mL and used for a comparative immunogenicity study. Of 194 subjects, 10 subjects had confirmed positive anti-drug-antibody in the biosimilar arm and 9 in the reference arm. None of the subjects were detected with neutralizing anti-drug antibodies.CONCLUSION:
This work demonstrates the application of a rigorous approach toward validation of assays for immunogenicity studies for biosimilars. Highly sensitive, precise, and robust assays were used to conclude comparable low incidences of anti-drug antibodies in both biosimilar and innovator arms of the clinical study for Pegfilgrastim.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Medicamentos Biossimilares
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article