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Quality by Design (QbD) Approach for a Nanoparticulate Imiquimod Formulation as an Investigational Medicinal Product

The present article exemplifies the application of the concept of quality by design (QbD) for the systematic development of a nanoparticulate imiquimod (IMQ) emulsion gel formulation as an investigational medicinal product (IMP) for evaluation in an academic phase-I/II clinical trial for the treatme...

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Autores principales: Pielenhofer, Jonas, Meiser, Sophie Luise, Gogoll, Karsten, Ciciliani, Anna-Maria, Denny, Mark, Klak, Michael, Lang, Berenice M., Staubach, Petra, Grabbe, Stephan, Schild, Hansjörg, Radsak, Markus P., Spahn-Langguth, Hilde, Langguth, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9965879/
https://www.ncbi.nlm.nih.gov/pubmed/36839835
http://dx.doi.org/10.3390/pharmaceutics15020514
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author Pielenhofer, Jonas
Meiser, Sophie Luise
Gogoll, Karsten
Ciciliani, Anna-Maria
Denny, Mark
Klak, Michael
Lang, Berenice M.
Staubach, Petra
Grabbe, Stephan
Schild, Hansjörg
Radsak, Markus P.
Spahn-Langguth, Hilde
Langguth, Peter
author_facet Pielenhofer, Jonas
Meiser, Sophie Luise
Gogoll, Karsten
Ciciliani, Anna-Maria
Denny, Mark
Klak, Michael
Lang, Berenice M.
Staubach, Petra
Grabbe, Stephan
Schild, Hansjörg
Radsak, Markus P.
Spahn-Langguth, Hilde
Langguth, Peter
author_sort Pielenhofer, Jonas
collection PubMed
description The present article exemplifies the application of the concept of quality by design (QbD) for the systematic development of a nanoparticulate imiquimod (IMQ) emulsion gel formulation as an investigational medicinal product (IMP) for evaluation in an academic phase-I/II clinical trial for the treatment of actinic keratosis (AK) against the comparator Aldara (EudraCT: 2015-002203-28). The design of the QbD elements of a quality target product profile (QTPP) enables the identification of the critical quality attributes (CQAs) of the drug product as the content of IMQ, the particle-size distribution, the pH, the rheological properties, the permeation rate and the chemical, physical and microbiological stability. Critical material attributes (CMAs) and critical process parameters (CPPs) are identified by using a risk-based approach in an Ishikawa diagram and in a risk-estimation matrix. In this study, the identified CPPs of the wet media ball-milling process’s milling time and milling speed are evaluated in a central composite design of experiments (DoEs) approach, revealing criticality for both factors for the resulting mean particle size, while only the milling time is significantly affecting the polydispersity. To achieve a mean particle size in the range of 300–400 nm with a minimal PdI, the optimal process conditions are found to be 650 rpm for 135 min. Validating the model reveals a good correlation between the predicted and observed values. Adequate control strategies were implemented for intermediate products as in-process controls (IPCs) and quality control (QC) tests of the identified CQAs. The IPC and QC data from 13 “IMI-Gel” batches manufactured in adherence to good manufacturing practice (GMP) reveal consistent quality with minimal batch-to-batch variability.
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spelling pubmed-99658792023-02-26 Quality by Design (QbD) Approach for a Nanoparticulate Imiquimod Formulation as an Investigational Medicinal Product Pielenhofer, Jonas Meiser, Sophie Luise Gogoll, Karsten Ciciliani, Anna-Maria Denny, Mark Klak, Michael Lang, Berenice M. Staubach, Petra Grabbe, Stephan Schild, Hansjörg Radsak, Markus P. Spahn-Langguth, Hilde Langguth, Peter Pharmaceutics Article The present article exemplifies the application of the concept of quality by design (QbD) for the systematic development of a nanoparticulate imiquimod (IMQ) emulsion gel formulation as an investigational medicinal product (IMP) for evaluation in an academic phase-I/II clinical trial for the treatment of actinic keratosis (AK) against the comparator Aldara (EudraCT: 2015-002203-28). The design of the QbD elements of a quality target product profile (QTPP) enables the identification of the critical quality attributes (CQAs) of the drug product as the content of IMQ, the particle-size distribution, the pH, the rheological properties, the permeation rate and the chemical, physical and microbiological stability. Critical material attributes (CMAs) and critical process parameters (CPPs) are identified by using a risk-based approach in an Ishikawa diagram and in a risk-estimation matrix. In this study, the identified CPPs of the wet media ball-milling process’s milling time and milling speed are evaluated in a central composite design of experiments (DoEs) approach, revealing criticality for both factors for the resulting mean particle size, while only the milling time is significantly affecting the polydispersity. To achieve a mean particle size in the range of 300–400 nm with a minimal PdI, the optimal process conditions are found to be 650 rpm for 135 min. Validating the model reveals a good correlation between the predicted and observed values. Adequate control strategies were implemented for intermediate products as in-process controls (IPCs) and quality control (QC) tests of the identified CQAs. The IPC and QC data from 13 “IMI-Gel” batches manufactured in adherence to good manufacturing practice (GMP) reveal consistent quality with minimal batch-to-batch variability. MDPI 2023-02-03 /pmc/articles/PMC9965879/ /pubmed/36839835 http://dx.doi.org/10.3390/pharmaceutics15020514 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pielenhofer, Jonas
Meiser, Sophie Luise
Gogoll, Karsten
Ciciliani, Anna-Maria
Denny, Mark
Klak, Michael
Lang, Berenice M.
Staubach, Petra
Grabbe, Stephan
Schild, Hansjörg
Radsak, Markus P.
Spahn-Langguth, Hilde
Langguth, Peter
Quality by Design (QbD) Approach for a Nanoparticulate Imiquimod Formulation as an Investigational Medicinal Product
title Quality by Design (QbD) Approach for a Nanoparticulate Imiquimod Formulation as an Investigational Medicinal Product
title_full Quality by Design (QbD) Approach for a Nanoparticulate Imiquimod Formulation as an Investigational Medicinal Product
title_fullStr Quality by Design (QbD) Approach for a Nanoparticulate Imiquimod Formulation as an Investigational Medicinal Product
title_full_unstemmed Quality by Design (QbD) Approach for a Nanoparticulate Imiquimod Formulation as an Investigational Medicinal Product
title_short Quality by Design (QbD) Approach for a Nanoparticulate Imiquimod Formulation as an Investigational Medicinal Product
title_sort quality by design (qbd) approach for a nanoparticulate imiquimod formulation as an investigational medicinal product
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9965879/
https://www.ncbi.nlm.nih.gov/pubmed/36839835
http://dx.doi.org/10.3390/pharmaceutics15020514
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