Over the past 20 years biologics have transformed the treatment landscape worldwide for patients with malignancy and other chronic diseases. As biologics patents are approaching expiry, several biosimilars are being developed for treatment.
These biosimilars are structurally complex, induce immune response and result in production of ADA. Immunogenicity is only the natural response to fight against any “foreign entrant” into body. However, for the pharma industry this response is totally unwanted (except in few cases like vaccines).
Assessment of immunogenicity to the protein therapeutics, therefore, becomes an integral part of drug development program as these may affect safety, efficacy and bioavailability of the drug. The strategy for assessing immunogenicity is a risk-based approach which need to be evaluated with adverse events and need to be tested by well-considered assay strategy.
At Cliantha Research, the Immunoanalytics Lab has analytical expertise to perform immunogenicity assays using tiered approach. The current regulatory guideline recommends ‘’fit for purpose’’ risk-based assay strategy. Samples are initially screened for binding antibody; presumptive positive results are then confirmed in a confirmatory assay which are further characterized in a quasi-quantitative assay. Screening assays, also known as binding antibody assays, are used to detect antibodies that bind to the therapeutic protein product. The specificity of ADA for the therapeutic protein product is usually established by competition with a therapeutic protein in a confirmatory assay. 3ADAs are characterized further using titration and neutralization assays.
The most common and first approach is to use ELISA based ligand binding assay which offers quick development time, high throughput and low cost. Cliantha Research follows USFDA & EMA guidelines for Immunogenicity assessment and offers 21CFR part 11 compliance systems, end to end SOP driven validations, sample analysis and regulated bioanalytical services.
Cell Culture Lab at Cliantha Research is well equipped to perform cell based neutralizing antibody assay as per recent regulatory guidelines. In contrast to ligand binding assay formats, cell-based bioassays are more complex, sensitive, time consuming and costly. However, since cell-based assay demonstrate functional response, they are usually preferred by the regulatory.
As bioanalytical platforms for detecting unwanted immune responses against protein therapeutics continue to advance, sponsors and CRO(s) need to stay abreast of the regulatory development in order to accurately interpret the risk of immune response to protein therapeutics.
References:
- Comparative Immunogenicity assessment of Biosimilars, Thomas Schreitmuller et all, Future Oncol, 2019 15(3), 319-329
- Ligand Binding Assays: Development, Validation and implementation in the Drug Development Arena. Edited by Masood Khan and John W A Findlay, Chapter 8.
- Immunogenicity Testing of Therapeutic Protein Products — Developing and Validating Assays for Anti-Drug Antibody Detection, Guidance for Industry, USFDA, Jan 2019
DR. SHAIFALI GUPTA
Sr. Director, Clinical & Large Molecule Lab
sgupta@cliantha.com