scholarly journals Critical reagents for ligand-binding assays: process development methodologies to enable high-quality reagents

Bioanalysis ◽  
2022 ◽  
Author(s):  
Caroline Kittinger ◽  
Jared Delmar ◽  
Lisa Hewitt ◽  
Rebecca Holcomb ◽  
Christopher Jones ◽  
...  

Development of biotherapeutics require pharmacokinetic/pharmacodynamic (PK/PD) and immunogenicity assays that are frequently in a ligand-binding assay (LBA) format. Conjugated critical reagents for LBAs are generated conjugation of the biotherapeutic drug or anti-drug molecule with a label. Since conjugated critical reagent quality impacts LBA performance, control of the generation process is essential. Our perspective is that process development methodologies should be integrated into critical reagent production to understand the impact of conjugation reactions, purification techniques and formulation conditions on the quality of the reagent. In this article, case studies highlight our approach to developing process conditions for different molecular classes of critical reagents including antibodies and a peptide. This development approach can be applied to the generation of future conjugated critical reagents.

Bioanalysis ◽  
2019 ◽  
Vol 11 (19) ◽  
pp. 1787-1798 ◽  
Author(s):  
Susanne Pihl ◽  
Barry WA van der Strate ◽  
Michaela Golob ◽  
Janka Ryding ◽  
Laurent Vermet ◽  
...  

Immunogenicity (ISI) assays are required to measure antidrug antibodies that are generated against biotherapeutic modalities. As for any ligand-binding assays, critical reagents (CR) play a crucial role in immunogenicity assays, as the robustness and reliability of an assay are defined by the quality and long-term availability of these reagents. The current regulatory guidelines do not provide clear directions on how to implement and verify lot-to-lot changes of CR during an assay life cycle, or the acceptance criteria that should be used when implementing new lots of CR. These aspects were extensively discussed within the European Bioanalysis Forum community. In this paper, CR for immunogenicity assays are identified and the minimum requirements for introducing new lots of CR in immunogenicity assays are described.


Author(s):  
Claudio Pulito ◽  
Antonio Cristaudo ◽  
Caterina La Porta ◽  
Stefano Zapperi ◽  
Giovanni Blandino ◽  
...  

Abstract Inflammation response of epithelial mucosa to chemo- radiotherapy cytotoxic effects leads to mucositis, a painful side effect of antineoplastic treatments. About 40% of the patients treated with chemotherapy develop mucositis; this percentage rises to about 90% for head and neck cancer patients (HNC) treated with both chemo- and radiotherapy. 19% of the latter will be hospitalized and will experience a delay in antineoplastic treatment for high-grade mucositis management, resulting in a reduction of the quality of life, a worse prognosis and an increase in patient management costs. Currently, several interventions and prevention guidelines are available, but their effectiveness is uncertain. This review comprehensively describes mucositis, debating the impact of standard chemo-radiotherapy and targeted therapy on mucositis development and pointing out the limits and the benefits of current mucositis treatment strategies and assessment guidelines. Moreover, the review critically examines the feasibility of the existing biomarkers to predict patient risk of developing oral mucositis and their role in early diagnosis. Despite the expression levels of some proteins involved in the inflammation response, such as TNF-α or IL-1β, partially correlate with mucositis process, their presence does not exclude others mucositis-independent inflammation events. This strongly suggests the need to discover biomarkers that specifically feature mucositis process development. Non-coding RNAs might hold this potential.


Bioanalysis ◽  
2020 ◽  
Author(s):  
Renuka Pillutla ◽  
Boris Gorovits ◽  
Carol Gleason ◽  
Jorge Quiroz ◽  
David Christopher ◽  
...  

Historically, ligand-binding assays for pharmacokinetic samples employed duplicate rather than singlet-based analysis. Herein, the Translational and absorption, distribution, metabolism and excretion (ADME) Sciences Leadership Group of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) presents a study aiming to determine the value of duplicate versus singlet-based testing. Based on analysis of data collected from eight organizations for 20 drug candidates representing seven molecular types and four analytical platforms, statistical comparisons of validation and in-study quality controls and study unknown samples demonstrated good agreement across duplicate sets. Simulation models were also used to assess the impact of sample duplicate characteristics on bioequivalence outcomes. Results show that testing in singlet is acceptable for assays with % CV ≤15% between duplicates. Singlet-based approach is proposed as the default for ligand-binding assays while a duplicate-based approach is needed where imprecision and/or inaccuracy impede the validation of the assay.


2010 ◽  
Vol 139-141 ◽  
pp. 567-570
Author(s):  
Li Hong Zhao ◽  
Zheng Yi Ren ◽  
Shu Yong Jiang ◽  
Nan Yang

Impact line is one of important factors to affect the shape accuracy and surface quality of auto body panel design and manufacture. It is difficult to study because of the complexity shape of auto body panels. The system of test analysis on impact line is established by analyzing the shapes and forming processes of auto-body panels, of which based on hyperboloid shallow shells. The criterion and research technique of impact line are introduced. Extensive experiment results, which show the effects of forming process conditions, such as blank holding force, draw bead arrangement, and lubrication on impact line, are achieved. It can be concluded that the draw bead arrangement significantly influence the impact line, the displacement of impact line is different with difference of blank holding force and the friction coefficient.


2015 ◽  
Vol 51 (41) ◽  
pp. 8618-8621 ◽  
Author(s):  
Mayako Michino ◽  
R. Benjamin Free ◽  
Trevor B. Doyle ◽  
David R. Sibley ◽  
Lei Shi

To understand the structural basis for the Na+-sensitivity of ligand binding to dopamine D2-like receptors, using computational analysis in combination with binding assays, we identified interactions critical in propagating the impact of Na+on receptor conformations and on the ligand-binding site.


2021 ◽  
Vol 72 (4) ◽  
pp. 347-352
Author(s):  
Ahad Furugi ◽  
Fatih Yapici

Optimization of process conditions in oriented strand board (OSB) manufacturing is a very important issue for both reducing cost and improving the quality of panels. Taguchi experimental design technique was applied to determination and optimization of the most influential controlling parameters of OSB panels such as press condition (pressure-time-temperature) and the ratio of adhesive parameters on modulus of elasticity (MOE). The value of the MOE is one of the very important mechanical properties of OSB panels. For this purpose, several experiments were conducted according to Taguchi L27 orthogonal design. The signal-to-noise (S/N) and the analysis of variance (ANOVA) were used to find the optimum levels and to indicate the impact of the controlling parameters on MOE. A verification test was also performed to prove the effectiveness of Taguchi technique. Since the predicted and the measured values were very close to each other, it was concluded that the Taguchi method was very successful in the optimization of effective parameters in OSB’s manufacturing.


Nafta-Gaz ◽  
2020 ◽  
Vol 76 (11) ◽  
pp. 837-837
Author(s):  
Anna Huszał ◽  
◽  
Albert Albert ◽  

Proper and systematic control of the odorization process is a basic condition for ensuring public safety in the distribution and use of gaseous fuels and for the continuity of the process. Maintaining a constant level of gas odorization requires gas network operators to constantly monitor the odorizing process. The control is carried out, among others by measuring the concentration of odorant in the gas. This is an important and inseparable element of controlling the degree of odorization of gaseous fuels, aimed at controlling the operation of odorizing devices by verifying the dose of odorizing agent or controlling the composition of gaseous fuel at any point of the gas distribution network. The correctness of uninterrupted control of the degree of gas odorization depends on the availability and quality of measuring instruments. The only process chromatographic analyzer intended for continuous measurement of the odorant concentration in gaseous fuels used on a national scale is the ANAT-M analyzer. Since this device works under process conditions, not supervised by an analyst, it is extremely important to recognize the restrictions on the correctness of its indications resulting from the presence of certain compounds in the gas. The article presents the analysis of observations and results of analyzes regarding the impact of selected sulfur compounds and other components of high-methane natural gas on the response of the THT detector currently used in ANAT-M analyzers. The significance of this influence for the quality of obtained THT concentration measurement results was determined. Gases containing sulfur compounds that may be present in the network gas, such as hydrogen sulfide, methyl mercaptan, dimethyl sulfide, as well as network gas containing the addition of LNG and biogas gases were tested. The obtained test results were analyzed in terms of determining the magnitude of the impact of the tested parameters on the precision of measurements performed with the ANAT-M analyzer.


Author(s):  
W. de Jong ◽  
J. Andries ◽  
K. R. G. Hein

In the framework of a multi-national European Joule project, experimental research and modeling concerning co-gasification of biomass and coal in a bubbling pressurized fluidized bed reactor is performed. The impact of fuel characteristics (biomass type, mixing ratio) and process conditions (pressure, temperature, gas residence time, air-fuel ratio and air-steam ratio) on the performance of the gasifier (carbon conversion, fuel gas composition, non-steady state behaviour) was studied experimentally and theoretically. Pelletized straw and miscanthus were used as biomass fuels. The process development unit has a maximum thermal capacity of 1.5 MW and was operated at pressures up to 10 bar and bed temperatures in the range of 650 °C–900 °C. The bed zone of the reactor is 2 m high with a diameter of 0.4 m and is followed by an adiabatic freeboard, approximately 4 m high with a diameter of 0.5 m. Time-averaged as well as time-dependent characteristics of the fuel gas were determined experimentally. The results will be compared with the gas turbine requirements provided by a gas turbine manufacturer, one of the partners in the project. The evaluation of the results will ultimately be used to implement and test an adequate control strategy for the pressurized fluidized bed gasifier integrated with a gas turbine combustion chamber.


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