Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Jun 15;4(6):547-555.
doi: 10.1017/cts.2020.493.

Regulatory and strategic considerations for addressing immunogenicity and related responses in biopharmaceutical development programs

Tyler C Vandivort  1 , David B Horton  1 , Steven B Johnson  2
Affiliations
Review

Regulatory and strategic considerations for addressing immunogenicity and related responses in biopharmaceutical development programs

Tyler C Vandivort et al. J Clin Transl Sci. .

Abstract

The last three decades have seen the biotherapeutic drug market evolve from promising concept to market dominance in a range of clinical indications. This growth has been spurred by the success of established drug classes like monoclonal antibodies, but also by the introduction of biosimilars, and more recently, multiple novel cell and gene therapies. Biotherapeutic drug development presents many unique challenges, but unintended immune responses are among the most common reasons for program attrition. Anti-drug antibodies can impact the safety and efficacy of drug products, and related immune responses, like the cytokine release syndrome that occurred in the infamous TGN-1412 clinical trial, can be challenging to predict with nonclinical models. For this reason, it is important that development programs proceed with a scientifically grounded and measured approach to these responses. This process begins at the discovery stage with the application of "quality by design," continues into the clinic with the development of quality assays and management strategies, and culminates in the effective presentation of this information in regulatory documents. This review provides an overview of some of the key strategic and regulatory considerations for biotherapeutics as they pertain to immunogenicity and related responses.

Keywords: Regulatory science; anti-drug antibodies; biotherapeutics; drug development; immunogenicity.

PubMed Disclaimer

Figures

Fig. 1.
Fig. 1.
Factors that influence immune responses.
See this image and copyright information in PMC

References

    1. Wan H. An overall comparison of small molecules and large biologics in ADME testing. ADMET & DMPK 2016; 4(1): 1–22.
    1. Dimitrov DS. Therapeutic proteins. Methods in Molecular Biology 2012; 899: 1–26. - PMC - PubMed
    1. The Alliance for Regenerative Medicine. Available Products [Internet]. (https://alliancerm.org/available-products/).
    1. Office of Tissues and Advanced Therapies. Approved cellular and gene therapy products [Internet], 2019. (https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-produ...).
    1. US Food and Drug Administration (FDA). FDA Statement: Statement from FDA Commissioner Scott Gottlieb, M.D. and Peter Marks, M.D., Ph.D., Director of the Center for Biologics Evaluation and Research on new policies to advance development of safe and effective cell and gene therapies [Internet], 2019. (https://www.fda.gov/news-events/press-announcements/statement-fda-commis...).