Identifying and Managing Sources of Variability in Cell Therapy Manufacturing and Clinical Trials
Identifying and managing cell therapy variability can be a significant challenge for a company seeking to commercialize a new product. Failure to address this issue can lead to negative consequences such as delayed approval due to unsuccessful clinical investigations, or failed product lots that do...
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Published in | Regenerative engineering and translational medicine Vol. 5; no. 4; pp. 354 - 361 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
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Cham
Springer International Publishing
01.12.2019
Springer Nature B.V |
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Abstract | Identifying and managing cell therapy variability can be a significant challenge for a company seeking to commercialize a new product. Failure to address this issue can lead to negative consequences such as delayed approval due to unsuccessful clinical investigations, or failed product lots that do not meet release criteria. Allogeneic cell therapies can be particularly prone to variability challenges due to the use of variable input material. In order to support the manufacturers of cell therapies, the FDA has identified two primary regulatory pathways (351 vs 361) that reflect the relative risk of the product. In this review, we will discuss criteria that separate the two potential regulatory pathways for cell therapy products in the USA. Also, we will discuss what aspects of manufacturing and clinical trial execution might introduce undesired variability that can derail the path towards licensure and commercialization, along with tools to minimize these potential sources of variability.
ClinicalTrials.gov
Identifier: NCT03347708 and NCT03955315
Lay Summary
Therapies that utilize live cells as the active ingredient, known as cell therapies, are a promising approach to treating many diseases that cannot be addressed with traditional medicines. However, with this great potential comes specific challenges associated with cell therapy, including identifying the appropriate regulatory approval pathway, manufacturing it in a reproducible way, and successfully executing clinical trials. In this review, we describe potential sources of variability that can negatively impact the translation of a cell therapy, and ways to minimize those risks. |
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AbstractList | Identifying and managing cell therapy variability can be a significant challenge for a company seeking to commercialize a new product. Failure to address this issue can lead to negative consequences such as delayed approval due to unsuccessful clinical investigations, or failed product lots that do not meet release criteria. Allogeneic cell therapies can be particularly prone to variability challenges due to the use of variable input material. In order to support the manufacturers of cell therapies, the FDA has identified two primary regulatory pathways (351 vs 361) that reflect the relative risk of the product. In this review, we will discuss criteria that separate the two potential regulatory pathways for cell therapy products in the USA. Also, we will discuss what aspects of manufacturing and clinical trial execution might introduce undesired variability that can derail the path towards licensure and commercialization, along with tools to minimize these potential sources of variability.
ClinicalTrials.gov
Identifier: NCT03347708 and NCT03955315
Lay Summary
Therapies that utilize live cells as the active ingredient, known as cell therapies, are a promising approach to treating many diseases that cannot be addressed with traditional medicines. However, with this great potential comes specific challenges associated with cell therapy, including identifying the appropriate regulatory approval pathway, manufacturing it in a reproducible way, and successfully executing clinical trials. In this review, we describe potential sources of variability that can negatively impact the translation of a cell therapy, and ways to minimize those risks. Identifying and managing cell therapy variability can be a significant challenge for a company seeking to commercialize a new product. Failure to address this issue can lead to negative consequences such as delayed approval due to unsuccessful clinical investigations, or failed product lots that do not meet release criteria. Allogeneic cell therapies can be particularly prone to variability challenges due to the use of variable input material. In order to support the manufacturers of cell therapies, the FDA has identified two primary regulatory pathways (351 vs 361) that reflect the relative risk of the product. In this review, we will discuss criteria that separate the two potential regulatory pathways for cell therapy products in the USA. Also, we will discuss what aspects of manufacturing and clinical trial execution might introduce undesired variability that can derail the path towards licensure and commercialization, along with tools to minimize these potential sources of variability. ClinicalTrials.gov Identifier: NCT03347708 and NCT03955315Lay SummaryTherapies that utilize live cells as the active ingredient, known as cell therapies, are a promising approach to treating many diseases that cannot be addressed with traditional medicines. However, with this great potential comes specific challenges associated with cell therapy, including identifying the appropriate regulatory approval pathway, manufacturing it in a reproducible way, and successfully executing clinical trials. In this review, we describe potential sources of variability that can negatively impact the translation of a cell therapy, and ways to minimize those risks. |
Author | Rodriguez-Granrose, Daniel Flanagan, Flagg Simpson, Katie Foley, Kevin T. Silverman, Lara Ionescu Saxon, Lindsey Hart |
Author_xml | – sequence: 1 givenname: Lara Ionescu orcidid: 0000-0002-7497-847X surname: Silverman fullname: Silverman, Lara Ionescu email: lara@discgenics.com organization: DiscGenics, Inc., Department of Neurosurgery, University of Tennessee Health Science Center – sequence: 2 givenname: Flagg surname: Flanagan fullname: Flanagan, Flagg organization: DiscGenics, Inc – sequence: 3 givenname: Daniel surname: Rodriguez-Granrose fullname: Rodriguez-Granrose, Daniel organization: DiscGenics, Inc., Department of Biochemistry and Molecular Biology, University of Miami – sequence: 4 givenname: Katie surname: Simpson fullname: Simpson, Katie organization: DiscGenics, Inc – sequence: 5 givenname: Lindsey Hart surname: Saxon fullname: Saxon, Lindsey Hart organization: DiscGenics, Inc – sequence: 6 givenname: Kevin T. surname: Foley fullname: Foley, Kevin T. organization: DiscGenics, Inc., Department of Neurosurgery, University of Tennessee Health Science Center, Semmes-Murphey Clinic |
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Cites_doi | 10.1038/nbt.3525 10.1155/2012/970752 10.1016/j.spinee.2010.03.032 10.4103/HMJ.HMJ_85_18 10.1016/j.jcyt.2016.11.011 10.1016/j.biomaterials.2015.10.065 |
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Copyright | The Author(s) 2019 The Author(s) 2019. This work is published under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. |
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References | Guidance for industry: current good tissue practice (CGTP) and Additional Requirements for Manufacturers of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps). US Department of Health and Human Services Food and drug Administration Center for Biologics Evaluation and Research Center for devices and radiological health Office of Combination Products. December 2011; https://www.fda.gov/media/82724/download. Accessed 17 July 2019. DagenaisSTriccoACHaldemanSSynthesis of recommendations for the assessment and management of low back pain from recent clinical practice guidelinesSpine J201010651452910.1016/j.spinee.2010.03.032 FDA. https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/approved-cellular-and-gene-therapy-products. Accessed July 24, 2019. LipsitzYYTimminsNEZandstraPWQuality cell therapy manufacturing by designNat Biotechnol20163443934001:CAS:528:DC%2BC28Xlsl2hu74%3D10.1038/nbt.3525 Regulatory considerations for human cells, tissues, and cellular and tissue- based products: minimal manipulation and homologous use, Guidance for industry and Food and Drug Administration staff. US Department of Health and Human Services Food and drug Administration Center for Biologics Evaluation and Research Center for devices and radiological health Office of Combination Products. December 2017; https://www.fda.gov/media/109176/download. Accessed 17 July 2019. BurnoufTStrunkDKohMBSchallmoserKHuman platelet lysate: replacing fetal bovine serum as a gold standard for human cell propagation?Biomaterials2016763713871:CAS:528:DC%2BC2MXhslCmurzO10.1016/j.biomaterials.2015.10.065 KarnieliOFriednerOMAllicksonJGZhangNJungSFiorentiniDAbrahamEEakerSSYongKChanAGriffithsSWehnAKOhSKarnieliOA consensus introduction to serum replacements and serum-free media for cellular therapiesCytotherapy.20171921551691:CAS:528:DC%2BC28XitFKrtrnM10.1016/j.jcyt.2016.11.011 TaherFEssigDLeblDRLumbar degenerative disc disease: current and future concepts of diagnosis and managementAdv Orthop2012201297075210.1155/2012/970752 Q1 2019 Data report Alliance for regenerative medicine. 2019. https://alliancerm.org/publication/q1-2019-data-report/. Accessed July 17 2019. H Serhan. Advancements in the treatment of degenerative disc disease. Hamdan Med J 2018;11:175–183. 129_CR9 T Burnouf (129_CR7) 2016; 76 O Karnieli (129_CR8) 2017; 19 129_CR1 YY Lipsitz (129_CR6) 2016; 34 129_CR5 129_CR4 F Taher (129_CR10) 2012; 2012 129_CR2 S Dagenais (129_CR3) 2010; 10 |
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SubjectTerms | Biomaterials Biomedical Engineering and Bioengineering Chemistry and Materials Science Clinical trials Commercialization Forum on Regenerative Medicine Manufacturing Materials Science Regenerative Medicine/Tissue Engineering Regulatory approval Therapy Variability |
Title | Identifying and Managing Sources of Variability in Cell Therapy Manufacturing and Clinical Trials |
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