Functional design of experiment for potency assay optimization and in-silico simulation.

Bioassay Functional design of experiment In-silico optimization Parameter criticality assessment Potency assay Robustness analysis

Journal

Journal of pharmaceutical and biomedical analysis
ISSN: 1873-264X
Titre abrégé: J Pharm Biomed Anal
Pays: England
ID NLM: 8309336

Informations de publication

Date de publication:
20 Sep 2023
Historique:
received: 11 04 2023
revised: 20 06 2023
accepted: 14 07 2023
medline: 24 7 2023
pubmed: 24 7 2023
entrez: 23 7 2023
Statut: ppublish

Résumé

For biotherapeutic analytics, robust and reliable potency assays are required. Design of experiment (DoE) approaches are used to investigate the impact of multiple assay parameters. Currently, specific assay features (e.g., half effective concentration) are modelled independently from each other. A joint interpretation of several assay features is thus difficult. In our functional DoE approach, we use the functional relationship of the assay features to describe the sigmoidal dose-response curve. With the composed functional form, the direct impact of assay parameters on the dose-response curve shape was modelled. Moreover, a multivariate desirability was defined and used for assay optimization. We believe that functional modelling contributes to understanding the joint influence of assay parameters and helps to design robust biotherapeutic analytics.

Identifiants

pubmed: 37481901
pii: S0731-7085(23)00353-9
doi: 10.1016/j.jpba.2023.115584
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

115584

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Auteurs

Marco Kunzelmann (M)

Analytical Development Biologicals, Boehringer Ingelheim Pharma GmbH & Co KG, Birkendorfer Straße 65, 88397 Biberach an der Riß, Germany. Electronic address: Marco.Kunzelmann@boehringer-ingelheim.com.

Anja Wittmann (A)

Analytical Development Biologicals, Boehringer Ingelheim Pharma GmbH & Co KG, Birkendorfer Straße 65, 88397 Biberach an der Riß, Germany.

Verena Nold (V)

Analytical Development Biologicals, Boehringer Ingelheim Pharma GmbH & Co KG, Birkendorfer Straße 65, 88397 Biberach an der Riß, Germany.

Beate Presser (B)

Analytical Development Biologicals, Boehringer Ingelheim Pharma GmbH & Co KG, Birkendorfer Straße 65, 88397 Biberach an der Riß, Germany.

Jasmin Schreiber (J)

Analytical Development Biologicals, Boehringer Ingelheim Pharma GmbH & Co KG, Birkendorfer Straße 65, 88397 Biberach an der Riß, Germany.

Tanja Gehrig (T)

Analytical Development Biologicals, Boehringer Ingelheim Pharma GmbH & Co KG, Birkendorfer Straße 65, 88397 Biberach an der Riß, Germany.

Sabine Sadlers (S)

Analytical Development Biologicals, Boehringer Ingelheim Pharma GmbH & Co KG, Birkendorfer Straße 65, 88397 Biberach an der Riß, Germany.

Reinhard Scholz (R)

Analytical Development Biologicals, Boehringer Ingelheim Pharma GmbH & Co KG, Birkendorfer Straße 65, 88397 Biberach an der Riß, Germany.

Johannes Solzin (J)

Virus Therapeutics Center, Boehringer Ingelheim Pharma GmbH & Co KG, Birkendorfer Straße 65, 88397 Biberach an der Riß, Germany.

Alexander Berger (A)

Analytical Development Biologicals, Boehringer Ingelheim Pharma GmbH & Co KG, Birkendorfer Straße 65, 88397 Biberach an der Riß, Germany.

Karoline Eppler (K)

Analytical Development Biologicals, Boehringer Ingelheim Pharma GmbH & Co KG, Birkendorfer Straße 65, 88397 Biberach an der Riß, Germany. Electronic address: Karoline.Eppler@boehringer-ingelheim.com.

Classifications MeSH