scholarly journals Toward comparability of anti-drug antibody assays: is the amount of anti-drug antibody–reagent complexes at cut-point (CP-ARC) the missing piece?

Bioanalysis ◽  
2020 ◽  
Vol 12 (14) ◽  
pp. 1021-1031
Author(s):  
Gregor Jordan ◽  
Roland F Staack
Keyword(s):  
Bioanalytical Methods ◽  
Assay Development ◽  
Cut Point ◽  
Testing Strategies ◽  
Regulatory Guidelines ◽  
Antibody Assays ◽  
Critical Activity ◽  
Bioanalytical Assay ◽  
Potential Improvement ◽  
Routine Assay

Immunogenicity testing is a mandatory and critical activity during the development of therapeutic proteins. Multiple regulatory guidelines provide clear recommendations on appropriate immunogenicity testing strategies and required bioanalytical assay performances. Unfortunately, it is still generally accepted that a comparison of the immunogenicity of different compounds is not possible due to apparent performance differences of the used bioanalytical methods. In this perspective, we propose the ‘cut-point anti-drug antibody–reagents complex’ (CP-ARC) concept for technical comparability of the bioanalytical methods. The feasibility and implementation in routine assay development is discussed as well as the potential improvement of reporting of bioanalytical immunogenicity data to allow comparison across drugs. Scientific sound comparability of the bioanalytical methods is the first step toward comparability of clinical immunogenicity.

scholarly journals Emerging Technologies and Generic Assays for the Detection of Anti-Drug Antibodies

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Michael A. Partridge ◽  
Shobha Purushothama ◽  
Chinnasamy Elango ◽  
Yanmei Lu
Keyword(s):  
Patient Safety ◽  
Surface Plasmon Resonance ◽  
Drug Development ◽  
Surface Plasmon ◽  
Plasmon Resonance ◽  
Assay Development ◽  
Meso Scale Discovery ◽  
Antibody Assays ◽  
Drug Pharmacokinetics ◽  
Meso Scale

Anti-drug antibodies induced by biologic therapeutics often impact drug pharmacokinetics, pharmacodynamics response, clinical efficacy, and patient safety. It is critical to assess the immunogenicity risk of potential biotherapeutics in producing neutralizing and nonneutralizing anti-drug antibodies, especially in clinical phases of drug development. Different assay methodologies have been used to detect all anti-drug antibodies, including ELISA, radioimmunoassay, surface plasmon resonance, and electrochemiluminescence-based technologies. The most commonly used method is a bridging assay, performed in an ELISA or on the Meso Scale Discovery platform. In this report, we aim to review the emerging new assay technologies that can complement or address challenges associated with the bridging assay format in screening and confirmation of ADAs. We also summarize generic anti-drug antibody assays that do not require drug-specific reagents for nonclinical studies. These generic assays significantly reduce assay development efforts and, therefore, shorten the assay readiness timeline.

scholarly journals Assay concept for detecting anti-drug IgM in human serum samples by using a novel recombinant human IgM positive control

Bioanalysis ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 253-263
Author(s):  
Christian Künzel ◽  
Afsaneh Abdolzade-Bavil ◽  
Alfred M Engel ◽  
Mirko Pleitner ◽  
Eginhard Schick ◽  
...  
Keyword(s):  
Immune Response ◽  
Phase I Trial ◽  
Positive Control ◽  
Assay Development ◽  
Clinical Samples ◽  
Serum Samples ◽  
Assay Sensitivity ◽  
Clinical Phase ◽  
Regulatory Guidelines

Aim: Development and qualification of an easy-to-use ELISA for detection of IgM anti-drug antibodies (ADA) and its use in a clinical Phase I trial. Results & methodology: During the assay development two positive control (PC) approaches, the preparation of a chemically conjugated and a recombinant PC, were pursued. With both PCs, the assay was developed and successfully qualified considering the regulatory guidelines. For a case study, the IgM ADA isotyping assay with the recombinant PC was selected. Different courses and intensities of immune response regarding IgM signals were demonstrated. Conclusion: The easy-to-use ELISA allowed IgM-ADA detection in clinical samples. Conjugated and recombinant IgM PCs were comparable regarding assay sensitivity, precision and suitability.

The stabilization of B.C.C. Cu in Cu/Nb nanolayered composites

1996 ◽  
Vol 54 ◽  
pp. 228-229
Author(s):  
H. Kung ◽  
A.J. Griffin ◽  
Y.C. Lu ◽  
K.E. Sickafus ◽  
T.E. Mitchell ◽  
...  
Keyword(s):  
Electrical Resistivity ◽  
Layer Thickness ◽  
Volume Fraction ◽  
Ion Beam ◽  
High Strength ◽  
Cross Sectional ◽  
Metastable Structure ◽  
High Resolution Tem ◽  
Potential Improvement ◽  
Two Phases

Materials with compositionally modulated structures have gained much attention recently due to potential improvement in electrical, magnetic and mechanical properties. Specifically, Cu-Nb laminate systems have been extensively studied mainly due to the combination of high strength, and superior thermal and electrical conductivity that can be obtained and optimized for the different applications. The effect of layer thickness on the hardness, residual stress and electrical resistivity has been investigated. In general, increases in hardness and electrical resistivity have been observed with decreasing layer thickness. In addition, reduction in structural scale has caused the formation of a metastable structure which exhibits uniquely different properties. In this study, we report the formation of b.c.c. Cu in highly textured Cu/Nb nanolayers. A series of Cu/Nb nanolayered films, with alternating Cu and Nb layers, were prepared by dc magnetron sputtering onto Si {100} wafers. The nominal total thickness of each layered film was 1 μm. The layer thickness was varied between 1 nm and 500 nm with the volume fraction of the two phases kept constant at 50%. The deposition rates and film densities were determined through a combination of profilometry and ion beam analysis techniques. Cross-sectional transmission electron microscopy (XTEM) was used to examine the structure, phase and grain size distribution of the as-sputtered films. A JEOL 3000F high resolution TEM was used to characterize the microstructure.

“Getting High Resolution Out of A High Voltage Microscope”

1980 ◽  
Vol 38 ◽  
pp. 822-825
Author(s):  
David J. Smith
Keyword(s):  
Electron Microscope ◽  
High Resolution ◽  
High Voltage ◽  
Theoretical Limit ◽  
Voltage Electron ◽  
High Voltage Electron Microscope ◽  
High Voltage Electron ◽  
Technological Advances ◽  
Potential Improvement ◽  
Lower Voltage

The initial attractions of the high voltage electron microscope (HVEM) stemmed mainly from the possibility of considerable increases in electron penetration through thick specimens compared with conventional 100KV microscopes, although the potential improvement in resolution associated with the decrease in election wavelength had been fully appreciated for many years (eg. Cosslett, 1946)1, even if not realizable in practice. Subsequent technological advances enabled the performance of lower voltage machines to be brought closer to the theoretical limit, to be followed in turn by more recent projects which have been successful, eventually, in achieving even higher resolution with dedicated higher voltage instruments such as those at Kyoto (500KV)2, Munich (400KV)3, Ibaraki (1250KV)4 and Cambridge (600KV)5. It does not necessarily follow however that the performance of journal high voltage microscopes can be easily upgraded, retrospectively, to the same level, as will be discussed in detail below.

EINE CHEMISCHE METHODE ZUR BESTIMMUNG VON 16-EPI-ÖSTRIOL IM URIN DES MENSCHEN

1963 ◽  
Vol 44 (1) ◽  
pp. 47-66 ◽  
Author(s):  
W. Nocke ◽  
H. Breuer
Keyword(s):  
Melting Point ◽  
Phosphoric Acid ◽  
Aqueous Alkali ◽  
Percentage Error ◽  
Organic Layer ◽  
Maximum Percentage ◽  
Chemical Determination ◽  
Routine Assay ◽  
Hydrolysis Of

ABSTRACT A method for the chemical determination of 16-epi-oestriol in the urine of nonpregnant women with a qualitative sensitivity of less than 0.5 μg/24 h is described. The separation of 16-epi-oestriol and oestriol is accomplished by converting 16-epi-oestriol into its acetonide, a reaction which is stereoselective for cis-glycols and therefore not undergone by oestriol as a trans-glycol. Following partition between chloroform and aqueous alkali, the acetonide of 16-epi-oestriol is completely separated with the organic layer whereas oestriol as a strong phenol remains in the alkaline phase. 16-epi-oestriol is chromatographed on alumina as the acetonide and determined as a Kober chromogen. This procedure can easily be incorporated into the method of Brown et al. (1957 b) thus making possible the simultaneous routine assay of oestradiol-17β, oestrone, oestriol and 16-epi-oestriol from one sample of urine. The specificity of the method was established by separation of 16-epi-oestriol from nonpregnancy urine as the acetonide, hydrolysis of the acetonide by phosphoric acid, isolation of the free compound by microsublimation and identification by micro melting point, colour reactions and chromatography. The accuracy of the method is given by a mean recovery of 64% for pure crystalline 16-epi-oestriol when added to hydrolysed urine in 5–10 μg amounts. The precision is given by s = 0.24 μg/24 h. For the duplicate determination of 16-epi-oestriol the qualitative sensitivity is 0.44 μg/24 h, the maximum percentage error being ± 100% The quantitative sensitivity (±25% error) is 1.7 μg/24 h.

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