An acid dissociation bridging ELISA for detection of antibodies directed against therapeutic proteins in the presence of antigen

Patton, Aaron; Mullenix, Michael C.; Swanson, Steven J.; Koren, Eugen

doi:10.1016/j.jim.2005.06.014

Cited by 181 publications

(90 citation statements)

References 15 publications

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“…Whether the low-titer ADA presumably masked by the drug interference could have a similar effect on the systemic exposure and the efficacy outcome remains to be elucidated. The development of newer immunogenicity assay technologies less prone to drug interferences (18)(19)(20) will likely address this knowledge gap soon and possibly can further facilitate quantitative evaluations of immunogenicity impact.…”

Section: Discussionmentioning

confidence: 99%

Evaluating and Reporting the Immunogenicity Impacts for Biological Products—a Clinical Pharmacology Perspective

Wang

Hon

et al. 2015

AAPS J

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Abstract. Immunogenicity assessment is important for biological products due to potential impacts of immunogenicity on safety and efficacy. We reviewed the prescribing information and the FDA's clinical pharmacology review of 121 approved biological products for evaluating and reporting of immunogenicity data. Of the 121 products, 89% (n = 108) reported the incidence of immunogenicity and 49% (n = 59) reported immunogenicity impact on efficacy. However, only 26% (n = 31) reported whether the immunogenicity affected pharmacokinetics. A subset of 16 products reported effects of anti-drug antibodies (ADA) on both systemic clearance and efficacy; 8 of 16 products had increased systemic clearance coinciding with reduced efficacy, and 6 of 16 products had no changes in either clearance or efficacy. Factors contributing to infrequent reporting of the ADA effect on exposure and methods for determining the effect of ADA on exposure are summarized. Measuring ADA and drug concentrations concurrently over time enables the evaluation of ADA impact on pharmacokinetics. Within-subject comparison of concentration data (before vs. after ADA formation) is a useful alternative to betweensubject (ADA+ vs. ADA−) comparison when sample size is limited or when the majority of subjects developed ADA. The biological complexity of immune responses presents challenges to quantifying the ADA impact on pharmacokinetics using model-based methods. Our findings support that pharmacokinetic exposure is more sensitive than efficacy endpoints for evaluating ADA effects. A decrease in drug concentration due to formation of ADA during treatment can serve as an early indicator for potential reduced efficacy occurring at a later time.KEY WORDS: clinical pharmacology assessment; immunogenicity data for approved biological products; impact on clinical pharmacokinetics and efficacy; incidence of anti-drug antibodies and neutralizing antibodies.

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Section: Discussionmentioning

confidence: 99%

Evaluating and Reporting the Immunogenicity Impacts for Biological Products—a Clinical Pharmacology Perspective

Wang

Hon

et al. 2015

AAPS J

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“…the drug tolerance level will be higher for samples with higher levels of ADA and lower for samples with lower levels of ADA). Whenever possible, drug interference should be minimized using various strategies, including sample acidification pretreatment, more drug‐tolerant assay formats and platforms, use of competing antibodies or monovalent versions of multivalent BP and longer incubation times 39, 59, 62, 63, 64, 65. However, there are caveats to each of these strategies, as they may dissociate incompletely the immune complexes, may denature and reduce the binding activity of some ADA, may reduce detection of ADA against some epitopes or may increase the level of target interference.…”

Section: Ada Immune Response Assaysmentioning

confidence: 99%

Standardizing terms, definitions and concepts for describing and interpreting unwanted immunogenicity of biopharmaceuticals: recommendations of the Innovative Medicines Initiative ABIRISK consortium

Rup

Pallardy

Sikkema

et al. 2015

Clinical and Experimental Immunology

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SummaryBiopharmaceuticals (BPs) represent a rapidly growing class of approved and investigational drug therapies that is contributing significantly to advancing treatment in multiple disease areas, including inflammatory and autoimmune diseases, genetic deficiencies and cancer. Unfortunately, unwanted immunogenic responses to BPs, in particular those affecting clinical safety or efficacy, remain among the most common negative effects associated with this important class of drugs. To manage and reduce risk of unwanted immunogenicity, diverse communities of clinicians, pharmaceutical industry and academic scientists are involved in: interpretation and management of clinical and biological outcomes of BP immunogenicity, improvement of methods for describing, predicting and mitigating immunogenicity risk and elucidation of underlying causes. Collaboration and alignment of efforts across these communities is made difficult due to lack of agreement on concepts, practices and standardized terms and definitions related to immunogenicity. The Innovative Medicines Initiative (IMI; www.imi-europe.org), ABIRISK consortium [Anti‐Biopharmaceutical (BP) Immunization Prediction and Clinical Relevance to Reduce the Risk; www.abirisk.eu] was formed by leading clinicians, academic scientists and EFPIA (European Federation of Pharmaceutical Industries and Associations) members to elucidate underlying causes, improve methods for immunogenicity prediction and mitigation and establish common definitions around terms and concepts related to immunogenicity. These efforts are expected to facilitate broader collaborations and lead to new guidelines for managing immunogenicity. To support alignment, an overview of concepts behind the set of key terms and definitions adopted to date by ABIRISK is provided herein along with a link to access and download the ABIRISK terms and definitions and provide comments (http://www.abirisk.eu/index_t_and_d.asp).

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“…Finally, to improve the drug tolerance of ADA assays, acid pretreatment is often utilized in both colorimetric ELISA and MSD screening and specificity ADA immunoassay methods (36). Complete understanding of the linker chemistry is essential here, as ADCs may incorporate acidsensitive linkers.…”

Section: Bioanalytical Strategies For Immunogenicity Assessmentmentioning

confidence: 99%

Immunogenicity of Antibody Drug Conjugates: Bioanalytical Methods and Monitoring Strategy for a Novel Therapeutic Modality

Hock

Thudium

Carrasco‐Triguero³

et al. 2014

AAPS J

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Abstract. Immunogenicity (the development of an adaptive immune response reactive with a therapeutic) is a well-described but unwanted facet of biotherapeutic development. There are commonly applied procedures for immunogenicity risk assessment, testing strategies, and bioanalysis. With some modifications, these can be applied to new biotherapeutic modalities. For novel therapies such as antibody-drug conjugates (ADCs), the unique structural components may contribute additional complexities to both immunologic responses and bioanalytical methods. US product inserts (USPIs) for two commercially available ADCs detail the incidence of immunogenicity; however, the body of literature on immunogenicity of ADCs is limited. We recently participated in a conference session on this topic (Annual meeting of the American Association of Pharmaceutical Scientists, held November 2013 in San Antonio, TX, USA. The meeting featured the Symposium: Immunogenicity Assessment for Novel Antibody Drug Conjugates, Nonclinical to Clinical) which prompted an effort to share our perspectives on how immunogenicity risk assessment, testing strategies, and bioanalytical methods can be adapted to reflect the complexity of ADC therapeutics.

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An acid dissociation bridging ELISA for detection of antibodies directed against therapeutic proteins in the presence of antigen

Cited by 181 publications

References 15 publications

Evaluating and Reporting the Immunogenicity Impacts for Biological Products—a Clinical Pharmacology Perspective

Evaluating and Reporting the Immunogenicity Impacts for Biological Products—a Clinical Pharmacology Perspective

Standardizing terms, definitions and concepts for describing and interpreting unwanted immunogenicity of biopharmaceuticals: recommendations of the Innovative Medicines Initiative ABIRISK consortium

Immunogenicity of Antibody Drug Conjugates: Bioanalytical Methods and Monitoring Strategy for a Novel Therapeutic Modality

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