Evaluation of a generic immunoassay with drug tolerance to detect immune complexes in serum samples from cynomolgus monkeys after administration of human antibodies

Stubenrauch, Kay; Wessels, Uwe; Essig, Ulrich; Vogel, Rudolf; Schleypen, Julia

doi:10.1016/j.jpba.2009.12.029

Cited by 50 publications

(35 citation statements)

References 9 publications

(12 reference statements)

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“…It is recommended in cases where drug tolerance is poor resulting in ADA assays with significant drug interference, the sponsor should provide the totality of the data and demonstrate a good faith effort to develop a drugtolerant assay by considering exploring acid dissociation, acid-capture-elution (ACE), solid-phase extraction with acid dissociation (SPEAD), precipitation and acid method (PANDA) [33] or an alternative assay format [34,35]. However, if acid dissociation is used, there is a risk of denaturing ADA due to pH treatment, or the potential to release the soluble target from the therapeutic:target complex [36].…”

Section: Drug Tolerancementioning

confidence: 99%

2017 White Paper on Recent Issues in Bioanalysis: A Global Perspective on Immunogenicity Guidelines & Biomarker Assay Performance (Part 3 – Lba: Immunogenicity, Biomarkers and PK Assays)

et al. 2017

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The 2017 11th Workshop on Recent Issues in Bioanalysis took place in Los Angeles/Universal City, California, on 3–7 April 2017 with participation of close to 750 professionals from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations and regulatory agencies worldwide. WRIB was once again a 5-day, week-long event – a full immersion week of bioanalysis, biomarkers and immunogenicity. As usual, it was specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest including both small- and large-molecule analysis involving LC–MS, hybrid ligand-binding assay (LBA)/LC–MS and LBA approaches. This 2017 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2017 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 3) covers the recommendations for large-molecule bioanalysis, biomarkers and immunogenicity using LBA. Part 1 (LC–MS for small molecules, peptides and small molecule biomarkers) and Part 2 (hybrid LBA/LC–MS for biotherapeutics and regulatory agencies’ inputs) are published in volume 9 of Bioanalysis, issues 22 and 23 (2017), respectively.

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Section: Drug Tolerancementioning

confidence: 99%

2017 White Paper on Recent Issues in Bioanalysis: A Global Perspective on Immunogenicity Guidelines & Biomarker Assay Performance (Part 3 – Lba: Immunogenicity, Biomarkers and PK Assays)

et al. 2017

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“…Most methods rely on the disruption of the immune complex so that the ADA (or in some cases, soluble target) can be "free" to be captured by an assay reagent(s) (3,(13)(14)(15)(16)(17)(18). Alternatively, a generic ADA assay able to detect ADA-drug complexes formed in vivo, has been described by Stubenrauch et al (19).…”

Section: Disruption Methodsmentioning

confidence: 99%

Theoretical Considerations and Practical Approaches to Address the Effect of Anti-drug Antibody (ADA) on Quantification of Biotherapeutics in Circulation

Kelley

Ahene

Gorovits

et al. 2013

AAPS J

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Abstract. Continuous improvement in bioanalytical method development is desired in order to ensure the quality of the data and to better support pharmacokinetic (PK) and safety studies of biotherapeutics. One area that has been getting increasing attention recently is in the assessment of "free" and "total" analyte and the impact of the assay format on those assessments. To compliment these considerations, the authors provide a critical review of available literature and prospectively explore methods to mitigate the potential impact of anti-drug antibody on PK assay measurement. This challenge is of particular interest and importance since biotherapeutic drugs often elicit an immune response, and thus may have a direct impact on quantification of the drug for its PK and safety evaluations.

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“…With traditional ADA immunoassay, only drug-free or partially drug-free ADA can be detected, and the presence of high drug levels in study samples can interfere with the detection of ADA, especially in bridging assay formats. Drug tolerance which is generally defined as the maximal amount of free drug in the samples that still allows detection of ADA at an acceptable sensitivity, may be improved using various approaches including the use of excess spiked drug to create and detect drug-ADA complexes rather than free ADA [18][19][20][21]. LC/MS has been used to assess ADA in the presence of excess protein therapeutic in support of clinical programs addressing the safety and tolerability of human growth hormone analogues [21].…”

Section: Introductionmentioning

confidence: 99%

Detection of cynomolgus monkey anti-protein XYZ antibody using immunocapture-LC/MS

Roos¹,

Chen²,

Vesapogu³

et al. 2016

J Appl Bioanal

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Although enzyme-linked immunosorbent assays and electrochemiluminescence (ECL) immunoassays are the most widely used platform for ADA detection, they may be compromised by drug interference. We describe here an alternate, free of drug interference, immunocapture-LC/MS methodology for detecting anti-protein XYZ antibody in cynomolgus monkey plasma. In our approach, ADA-protein XYZ complexes are captured by a mouse monoclonal anti-drug antibody on streptavidin magnetic beads and separated from monkey plasma by a magnet. After elution, ADA are digested with trypsin and detected by LC/MS using a surrogate peptide common to monkey IgG subclasses 1-4. The immunocapture-LC/MS assay was applied to support a toxicology study and results were in close agreement with those from a modified ECL immunoassay. To our knowledge, this is the first application of using LC/MS for monkey ADA detection.

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Evaluation of a generic immunoassay with drug tolerance to detect immune complexes in serum samples from cynomolgus monkeys after administration of human antibodies

Cited by 50 publications

References 9 publications

2017 White Paper on Recent Issues in Bioanalysis: A Global Perspective on Immunogenicity Guidelines & Biomarker Assay Performance (Part 3 – Lba: Immunogenicity, Biomarkers and PK Assays)

2017 White Paper on Recent Issues in Bioanalysis: A Global Perspective on Immunogenicity Guidelines & Biomarker Assay Performance (Part 3 – Lba: Immunogenicity, Biomarkers and PK Assays)

Theoretical Considerations and Practical Approaches to Address the Effect of Anti-drug Antibody (ADA) on Quantification of Biotherapeutics in Circulation

Detection of cynomolgus monkey anti-protein XYZ antibody using immunocapture-LC/MS

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