Advertisement

Transitioning from development to commercial: risk-based guidance for critical materials management in cell therapies*

  • Author Footnotes
    ⁎⁎ These authors contributed equally to this work.
    Michael Scott
    Footnotes
    ⁎⁎ These authors contributed equally to this work.
    Affiliations
    International Society for Cellular Therapy Process and Product Development Subcommittee, Vancouver, Canada

    BlueRock Therapeutics, Toronto, Canada
    Search for articles by this author
  • Author Footnotes
    ⁎⁎ These authors contributed equally to this work.
    Dominic Clarke
    Correspondence
    Correspondence: Dominic Clarke, PhD, HemaCare Corporation, 8500 Balboa Blvd, Ste 130, Northridge, California 91325, USA.
    Footnotes
    ⁎⁎ These authors contributed equally to this work.
    Affiliations
    International Society for Cellular Therapy Process and Product Development Subcommittee, Vancouver, Canada

    HemaCare Corporation, Northridge, California, USA
    Search for articles by this author
  • Author Footnotes
    ⁎⁎ These authors contributed equally to this work.
    Yonatan Lipsitz
    Footnotes
    ⁎⁎ These authors contributed equally to this work.
    Affiliations
    International Society for Cellular Therapy Process and Product Development Subcommittee, Vancouver, Canada

    Sana Biotechnology, Cambridge, Massachusetts, USA
    Search for articles by this author
  • Harvey Brandwein
    Affiliations
    International Society for Cellular Therapy Process and Product Development Subcommittee, Vancouver, Canada

    Cook Myosite, Indianapolis, Indiana, USA
    Search for articles by this author
  • Julie Allickson
    Affiliations
    International Society for Cellular Therapy Process and Product Development Subcommittee, Vancouver, Canada

    Wake Forest Institute for Regenerative Medicine, Winston-Salem, North Carolina, USA
    Search for articles by this author
  • Dalia Alzebdeh
    Affiliations
    Wake Forest Institute for Regenerative Medicine, Winston-Salem, North Carolina, USA
    Search for articles by this author
  • Sasha Aleksic
    Affiliations
    International Society for Cellular Therapy Process and Product Development Subcommittee, Vancouver, Canada

    Fujifilm Irvine Scientific, Irvine, California, USA
    Search for articles by this author
  • Crystal Kraft
    Affiliations
    International Society for Cellular Therapy Process and Product Development Subcommittee, Vancouver, Canada

    West Pharmaceuticals, Exton, Pennsylvania, USA
    Search for articles by this author
  • Lexan Lhu
    Affiliations
    International Society for Cellular Therapy Process and Product Development Subcommittee, Vancouver, Canada

    PBS Biotech, Camarillo, California, USA
    Search for articles by this author
  • Kenneth Cornetta
    Affiliations
    Indiana University School of Medicine, Indianapolis, Indiana, USA
    Search for articles by this author
  • Author Footnotes
    ⁎ Commissioned by the ISCT Process and Product Development Committee, a Sub Committee of the ISCT Commercialization Committee.
    ⁎⁎ These authors contributed equally to this work.

      Abstract

      A key hurdle to ensuring patient access to cell and gene therapies (CGTs) and continued growth of the industry is the management of raw materials. The combination of rapid growth, individual product and process complexity and limited industry-specific guidance or awareness presents non-obvious risk mitigation challenges for transitioning from development to clinical application. Understanding, assessing and mitigating the varied raw material risks for CGT products during product and clinical development are critical for ensuring smooth transitions into commercialization and for preventing interruption of product supply to patients. This article presents a risk-based approach driven by concerns for patient safety that can help focus and coordinate efforts to address the most critical risk factors. Highlighted are some of the highest risk materials common to the manufacture of many CGTs, including the primary starting material, culture media, reagents and single-use components. Using a hypothetical gene-edited cell therapy as an example, we describe the general manufacturing process and subsequently incorporate the described methodology to perform a sample risk assessment. The practical approach described herein is intended to assist CGT manufacturers and suppliers in actively assessing materials early in development to provide a basic starting point for mitigating risks experienced when translating CGT products for clinical and long-term commercial application.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Cytotherapy
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

      1. Alliance for Regenerative Medicine -Annual Report & Sector Year in Review, https://www.alliancerm.org/sector-report/2019-annual-report/; 2019 [accessed March 2020].

        • Dodson B
        • Levine A
        Challenges in the translation and commercialization of cell therapies.
        BMC Biotechnology. 2015; 15: 1-15
      2. Alliance for Regenerative Medicine - Quarterly Data Report on Gene and Cellular Therapies and the Regenerative Medicine Sector, https://alliancerm.org/wp-content/uploads/2018/04/Q3_2016_Web_Version_FINAL_0.pdf/ 2016 [accessed October 2019].

        • Orchard-Webb D.
        Progress toward commercial scale and efficiency in cell therapy bioprocessing.
        BioProcess Int. 2016; 14 (s:): 8-17
        • Bravery B
        • Robinson S
        • Burger S
        Making the grade: untangling the myths of raw materials used for the manufacture of cell- and gene-based medicinal products.
        CGT Insights. 2018; 4: 207-225
        • Gilbert A.
        Raw materials in cell therapy: start right early in process development.
        CGT Insights. 2019; 5: 141-146
        • Chalk S
        Raw material variability.
        BioPharm Int. 2014; 27: 1-2
        • Solomon J
        • Csontos L
        • Clarke D
        • Bonyhadi M
        • Zylberberg C
        • et al.
        Current perspectives on the use of ancillary materials for the manufacture of cellular therapies.
        Cytotherapy. 2016; 18: 1-12
        • Ball O
        • Zylberberg C.
        Towards a Common Framework for Defining Ancillary Material Quality across the Development Spectrum.
        Cytotherapy. 2019; 21: 1234-1245
        • Lipsitz YY
        • Timmins NE
        • Zandstra PW
        Quality cell therapy manufacturing by design.
        Nature Biotechnology. 2016; 34: 393-400
        • Magers K.
        Addressing Challenges in Meeting Chemistry, Manufacturing and Control Regulatory Requirements for Gene Therapy Products.
        Cell Gene Ther. Insights. 2019; 5: 1-16
        • Lopez F
        • Di Bartolo C
        • Piazza T
        • Passannanti A
        • Gerlach J
        • Gridelli B
        • Triolo F
        A quality risk management model approach for cell therapy manufacturing.
        Risk Analysis. 2010; 30: 1857-1871
        • Shimoni Y.
        • Srinivasan V.
        • von Gruchalla-Wesierski M.
        A risk-based approach to supplier and raw materials management.
        BioProcess Int. 2015; 13: 10-15
        • Read E.
        Qualification of cellular starting materials for cell-based therapies.
        Cell Gene Ther. Insights. 2019; 5: 177-196
        • Tsokas K
        • McFarland R
        • Burke C
        • Lynch JL
        • Bollenbach T
        • et al.
        Reducing risks and delays in the translation of cell and gene therapy innovations into regulated products.
        NAM Perspectives. National Academy of Medicine, Washington, DC2019https://doi.org/10.31478/201909d
      3. U.S. Food & Drug Administration Warning Letter. Liveyon Labs Inc – MARCS-CMS 588399 – December 05, 2019; 2019; https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/liveyon-labs-inc-588399-12052019.

        • Taylor B
        • Clarke D.
        The Cell Therapy Industry Needs High-Quality Healthy-Donor Material.
        BioProcess Int. 2019; 17: 68
        • Clarke D
        • Taylor B.
        Laying the foundation for successful advanced therapies: bridging the gap.
        European Biopharmaceutical Review. 2019; (Spring:24-28): 24-28
        • Garcia-Gonzalo R
        • Izpisúa Belmonte JC.
        Albumin-Associated Lipids Regulate Human Embryonic Stem Cell Self-Renewal.
        PLoS ONE. 2008; 3: e1384
        • Ieyasu A
        • Ishida R
        • Kimura T
        • Morita M
        • Wilkinson AC
        • Sudo K
        • Nishimura T
        • Ohehara J
        • Tajima Y
        • Lai CY
        • Otsu M
        • Nakamura Y
        • Ema H
        • Nakauchi H
        • Yamazaki S.
        An All-Recombinant Protein-Based Culture System Specifically Identifies Hematopoietic Stem Cell Maintenance Factors.
        Stem Cell Reports. 2017; 8: 500-508
        • International Conference on Harmonisation
        ICH Q5A (R1) Viral Safety Evaluation of Biotechnology Products Derived from Cell lines of Human or.
        Animal Origin. 1999;
        • International Conference on Harmonisation
        ICH Q5D Derivation and Characterisation of Cell Substrates Used for Production of.
        Biotechnological/Biological Products. 1997;
        • Van der loo J
        • Wright J.
        Progress and Challenges in Viral Vector Manufacturing.
        Human Mol. Genetics. 2016; 25: R42-R52
      4. U.S. Food & Drug Administration. Testing of Retroviral Vector-Based Human Gene Therapy Products for Replication Competent Retrovirus During Product Manufacture and Patient Follow-up Draft Guidance of Industry, https://www.fda.gov/regulatory-information/search-fda-guidance-documents/testing-retroviral-vector-based-human-gene-therapy-products-replication-competent-retrovirus-during; 2020 [accessed March 2020].

        • van der Loo JC
        • Wright JF.
        Progress and challenges in viral vector manufacturing.
        Hum Mol Genet. 2016; 25: R42-R52
      5. ISO/TS 20399-1:2018 Biotechnology—Ancillary materials present during the production of cellular therapeutic products—Part 1: General requirements, https://www.iso.org/obp/ui#iso:std:iso:ts:20399:-1:ed-1:v1:en/; 2018 [accessed March 2020].

        • Ding W
        • Madsen G
        • Mahajan E
        • O'Connor S
        • Wong K.
        Standardized extractables testing protocol for single-use systems in biomanufacturing.
        Pharmaceutical Engineering. 2014; 34: 74-85
        • Ruprecht V
        • Monzo P
        • Ravasio A
        • Yue Z
        • Makhija E
        • Olivier Strale P
        • et al.
        How cells respond to environmental cues—insights from bio-functionalized substrates.
        Journal of Cell Science. 2017; 130: 51-60
        • Vollrath I.
        • Matheas R
        • Sediq AS
        • Jere D
        • Jorg S
        • Huwyler J
        • et al.
        Subvisible particulate contamination in cell therapy products—can we distinguish?.
        Journal of Pharmaceutical Sciences. 2020; 109: 216-219