Quality assessment strategy development and analytical method selection of GMP grade biological drugs for gene and cell therapy

Biological drugs with gene and cell therapy potentials, including natural or rationally created biomacromolecules, recombinant proteins/enzymes, gene-carrying DNA/RNA fragments, oncolytic viruses, plasmid and viral vectors or other gene delivering vehicles with specific therapeutic genes and gene ma...

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Main Authors: Quan-en Yang, Nicole Lee, Nicole Johnson, Jennifer Hong, Jenny (Qinghua) Zhao, Xiulian Sun, Jian Zhang
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:BBA Advances
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Online Access:http://www.sciencedirect.com/science/article/pii/S2667160325000146
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author Quan-en Yang
Nicole Lee
Nicole Johnson
Jennifer Hong
Jenny (Qinghua) Zhao
Xiulian Sun
Jian Zhang
author_facet Quan-en Yang
Nicole Lee
Nicole Johnson
Jennifer Hong
Jenny (Qinghua) Zhao
Xiulian Sun
Jian Zhang
author_sort Quan-en Yang
collection DOAJ
description Biological drugs with gene and cell therapy potentials, including natural or rationally created biomacromolecules, recombinant proteins/enzymes, gene-carrying DNA/RNA fragments, oncolytic viruses, plasmid and viral vectors or other gene delivering vehicles with specific therapeutic genes and gene manipulation tools, and genetically modified and reprogrammed human cells comprise a large fraction of drug development candidates in modern precision and regeneration medicine. These drugs have displayed unique capabilities in treating patients with previously incurable diseases. However, most of the drug preparations have complex multimolecular structures and require specific biomanufacturing systems and many other additional biological active materials for drug synthesis, cell expansion, and production enhancement. Thus, the final products would have to be subjected to sequential extensive purification processes to exclude impurities and to concentrate the drug products after manufacturing. The quality evaluation for each drug product is an individualized process and must be specifically designed and performed according to the characteristics of the drug and its manufacturing and purification methods. Some of the Quality Control (QC) assays may be very costly and time-consuming, frequently with inconsistent test results from batch-to-batch. This review focuses on QC assessment strategy development for common gene and cell therapy drugs which use prokaryotic or eukaryotic cells for manufacturing or cell factories for in vitro expansions, especially for drug identification and concentration determination, impurity detection and quantification, drug potency, stability, and safety evaluations; and discusses some key issues for drug quality assessments in different categories and emphasizes the importance of individualized QC strategy design.
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spelling doaj-art-dbd9c1fbf10e43c0af8636dc96189eaa2025-08-20T02:04:01ZengElsevierBBA Advances2667-16032025-01-01710015110.1016/j.bbadva.2025.100151Quality assessment strategy development and analytical method selection of GMP grade biological drugs for gene and cell therapyQuan-en Yang0Nicole Lee1Nicole Johnson2Jennifer Hong3Jenny (Qinghua) Zhao4Xiulian Sun5Jian Zhang6uBriGene Biosciences, Inc., Germantown, MD, USA; Forecyte Biosciences, Inc., Frederick, MD, USA; Corresponding authors.WZ Biosciences Inc., Rockville, MD, USAForecyte Biosciences, Inc., Frederick, MD, USAVigene Biosciences, Inc., Rockville, MD, USAuBriGene Biosciences, Inc., Germantown, MD, USA; Forecyte Biosciences, Inc., Frederick, MD, USAuBriGene Biosciences, Inc., Germantown, MD, USAWZ Biosciences Inc., Rockville, MD, USA; Corresponding authors.Biological drugs with gene and cell therapy potentials, including natural or rationally created biomacromolecules, recombinant proteins/enzymes, gene-carrying DNA/RNA fragments, oncolytic viruses, plasmid and viral vectors or other gene delivering vehicles with specific therapeutic genes and gene manipulation tools, and genetically modified and reprogrammed human cells comprise a large fraction of drug development candidates in modern precision and regeneration medicine. These drugs have displayed unique capabilities in treating patients with previously incurable diseases. However, most of the drug preparations have complex multimolecular structures and require specific biomanufacturing systems and many other additional biological active materials for drug synthesis, cell expansion, and production enhancement. Thus, the final products would have to be subjected to sequential extensive purification processes to exclude impurities and to concentrate the drug products after manufacturing. The quality evaluation for each drug product is an individualized process and must be specifically designed and performed according to the characteristics of the drug and its manufacturing and purification methods. Some of the Quality Control (QC) assays may be very costly and time-consuming, frequently with inconsistent test results from batch-to-batch. This review focuses on QC assessment strategy development for common gene and cell therapy drugs which use prokaryotic or eukaryotic cells for manufacturing or cell factories for in vitro expansions, especially for drug identification and concentration determination, impurity detection and quantification, drug potency, stability, and safety evaluations; and discusses some key issues for drug quality assessments in different categories and emphasizes the importance of individualized QC strategy design.http://www.sciencedirect.com/science/article/pii/S2667160325000146Biological drug quality assessmentBiosimilarCar-t therapyCell and gene therapyDrug potencyDrug purity analysis
spellingShingle Quan-en Yang
Nicole Lee
Nicole Johnson
Jennifer Hong
Jenny (Qinghua) Zhao
Xiulian Sun
Jian Zhang
Quality assessment strategy development and analytical method selection of GMP grade biological drugs for gene and cell therapy
BBA Advances
Biological drug quality assessment
Biosimilar
Car-t therapy
Cell and gene therapy
Drug potency
Drug purity analysis
title Quality assessment strategy development and analytical method selection of GMP grade biological drugs for gene and cell therapy
title_full Quality assessment strategy development and analytical method selection of GMP grade biological drugs for gene and cell therapy
title_fullStr Quality assessment strategy development and analytical method selection of GMP grade biological drugs for gene and cell therapy
title_full_unstemmed Quality assessment strategy development and analytical method selection of GMP grade biological drugs for gene and cell therapy
title_short Quality assessment strategy development and analytical method selection of GMP grade biological drugs for gene and cell therapy
title_sort quality assessment strategy development and analytical method selection of gmp grade biological drugs for gene and cell therapy
topic Biological drug quality assessment
Biosimilar
Car-t therapy
Cell and gene therapy
Drug potency
Drug purity analysis
url http://www.sciencedirect.com/science/article/pii/S2667160325000146
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