Implementing quality by design for biotech products: Are regulators on track?

Luciani, Francesca; Galluzzo, Sara; Gaggioli, Andrea; Kruse, Nanna Aaby; Venneugues, Pascal; Schneider, Christian K.; Pini, Carlo; Melchiorri, Daniela

doi:10.1080/19420862.2015.1023058

Cited by 32 publications

(20 citation statements)

References 6 publications

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“…One crucial element of QbD is the generation of a Quality Target Product Profile (QTPP) and enhanced process control strategies to assure the product quality (17)(18)(19)(20)(21)(22)(23). These concepts have been debated, discussed, piloted, and reflected in regulatory guidance documents (17)(18)(19)(20)24); however, the implementation and transition to such manufacturing models has been difficult to attain and has not been fully realized.…”

Section: Regulatory Landscape and Mammentioning

confidence: 99%

A View on the Importance of “Multi-Attribute Method” for Measuring Purity of Biopharmaceuticals and Improving Overall Control Strategy

Rogers

Abernathy

Richardson

et al. 2017

AAPS J

124

122

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Abstract.Today, we are experiencing unprecedented growth and innovation within the pharmaceutical industry. Established protein therapeutic modalities, such as recombinant human proteins, monoclonal antibodies (mAbs), and fusion proteins, are being used to treat previously unmet medical needs. Novel therapies such as bispecific T cell engagers (BiTEs), chimeric antigen T cell receptors (CARTs), siRNA, and gene therapies are paving the path towards increasingly personalized medicine. This advancement of new indications and therapeutic modalities is paralleled by development of new analytical technologies and methods that provide enhanced information content in a more efficient manner. Recently, a liquid chromatography-mass spectrometry (LC-MS) multi-attribute method (MAM) has been developed and designed for improved simultaneous detection, identification, quantitation, and quality control (monitoring) of molecular attributes (Rogers et al. MAbs 7(5): 2015). Based on peptide mapping principles, this powerful tool represents a true advancement in testing methodology that can be utilized not only during product characterization, formulation development, stability testing, and development of the manufacturing process, but also as a platform quality control method in dispositioning clinical materials for both innovative biotherapeutics and biosimilars.KEY WORDS: biotherapeutic; mass spectrometry; multi-attribute method; quality by design.To date, multi-attribute method (MAM) has been applied to several early stage clinical programs with different classes of protein therapeutics and compared to current practices. This experience shows that the MAM technology can be utilized for different types of protein therapeutics delivering highly specific and quantitative information, which is invaluable during process development and essential for molecular characterization. Data has also been generated to support its use for release and stability in alignment with Quality by Design (QbD) principles. Utilizing recent advances in the technology, research, and development labs, in industry, has generated convincing data that MAM would be highly beneficial in a cGMP environment. This article will summarize the advantages of MAM relative to conventional product testing approaches. We recommend that MAM, unlike conventional purity methods, be used to specifically monitor and quantify molecular product quality attributes and product/process-related impurities. This increased specificity for attributes with increased relevance to safety and efficacy can lead to better product/process understanding, shorter process and product development timelines, and an improved control strategy by improving specificity of the measurement. MAM OVERVIEWReduced LC-MS-based peptide mapping methods have been used in academia and the industry for several decades. Biopharmaceutical companies are increasingly using quantitative LC-MS-based peptide mapping methods for clinical material characterization, as well as release and stability testing (1-7). Quantit...

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Section: Regulatory Landscape and Mammentioning

confidence: 99%

A View on the Importance of “Multi-Attribute Method” for Measuring Purity of Biopharmaceuticals and Improving Overall Control Strategy

Rogers

Abernathy

Richardson

et al. 2017

AAPS J

124

122

View full text Add to dashboard Cite

show abstract

“…QbD is a framework for process development where scientific principles are used to establish the critical quality attributes (CQAs) of a biopharmaceutical, for example the extent of fucosylation on an N-linked glycan and to understand the critical process parameters which impact these CQAs. The aim of QbD is to establish a 'design space' where manufacturing can operate without affecting the CQAs enabling the process to move without requiring regulatory agency approval [19]. Obviously, if an HTP strategy can be shown to scale authentically then a much greater design space can be explored.…”

Section: Process Developmentmentioning

confidence: 99%

Current advances in the development of high-throughput purification strategies for the generation of therapeutic antibodies

Spooner¹,

Wilkinson²,

Kemp³

2015

Pharmaceutical Bioprocessing

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The demand for therapeutic proteins, and particularly monoclonal antibodies, continues to grow within the biopharmaceutical industry. This is illustrated by the monoclonal antibody Humira ® (adalimumab) having the highest sales of any drug in 2014. With the increasing numbers of biologics entering the market and the emergence of biosimilars and biobetters, costs need to be reduced in order for companies to remain competitive. High-throughput purification can provide the tools to meet the challenge of producing the thousands of potential drug candidates generated in drug discovery while simultaneously providing robust and cost-effective purification strategies in both research and production. In this review, we discuss the many different methodologies and automation technologies that can be employed in high-throughput purification.

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“…Essential for the implementation of QbD are multi-attribute monitoring (MAM) techniques with MS detection to obtain the required in-depth information on structure-function relationships as result of PTMs and the elucidation of the manufacturing attributes that affect the product characteristics [144,145]. However, implementation of MS systems in QC/GMP environments remains controversial in the biopharmaceutical industry, due to the expensive equipment and complicated data analysis [83].…”

Section: Multiple Attribute Monitoring To Enable Quality By Design Mamentioning

confidence: 99%

Glycosylation of biosimilars: Recent advances in analytical characterization and clinical implications

Duivelshof

Jiskoot

Beck

et al. 2019

Analytica Chimica Acta

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License: Article 25fa pilot End User Agreement This publication is distributed under the terms of Article 25fa of the Dutch Copyright Act (Auteurswet) with explicit consent by the author. Dutch law entitles the maker of a short scientific work funded either wholly or partially by Dutch public funds to make that work publicly available for no consideration following a reasonable period of time after the work was first published, provided that clear reference is made to the source of the first publication of the work. This publication is distributed under The Association of Universities in the Netherlands (VSNU) 'Article 25fa implementation' pilot project. In this pilot research outputs of researchers employed by Dutch Universities that comply with the legal requirements of Article 25fa of the Dutch Copyright Act are distributed online and free of cost or other barriers in institutional repositories. Research outputs are distributed six months after their first online publication in the original published version and with proper attribution to the source of the original publication. You are permitted to download and use the publication for personal purposes. All rights remain with the author(s) and/or copyrights owner(s) of this work. Any use of the publication other than authorised under this licence or copyright law is prohibited. If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons.

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Implementing quality by design for biotech products: Are regulators on track?

Abstract: (2015) Implementing quality by design for biotech products: Are regulators on track?, mAbs, 7:3, 451-455,

Cited by 32 publications

References 6 publications

A View on the Importance of “Multi-Attribute Method” for Measuring Purity of Biopharmaceuticals and Improving Overall Control Strategy

A View on the Importance of “Multi-Attribute Method” for Measuring Purity of Biopharmaceuticals and Improving Overall Control Strategy

Current advances in the development of high-throughput purification strategies for the generation of therapeutic antibodies

Glycosylation of biosimilars: Recent advances in analytical characterization and clinical implications

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