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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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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. |
format | Online Article Text |
id | pubmed-9965879 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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