Gene And Cell Therapy Products Community

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  • 1.  Increasing use of DMSO in CAR-T formulations

    Community Leadership
    Posted 08-21-2023 22:01

    The Excipients Community recently had a knowledge exchange and the topic of DMSO in parental formulations brought up by @Robert Strickley.  It is an excipient in 7 commercial products since 2017 at concentrations at 5% or greater for an intravenous infusion. There is no maximum IV infusion listed in the FDA Inactive Ingredients Database. Can anyone comment about using DMSO in these formulations?

    Year

    Product

    Route of Administration

    % DMSO Injected

    Amount of DMSO Injected

    Application

    2017

    Yescarta®

    IV infusion

    5.0%

    ~ 3.4 mL

    CAR-T therapy

    2017

    KYMRIAH™

    IV infusion

    7.5%

    ~ 2.2-11 mL

    CAR-T therapy

    2020

    Tecartus

    IV infusion

    5.0%

    ~ 3.4 mL

    CAR-T therapy

    2021

    BREYANZI

    IV infusion

    6.0%

    CAR-T therapy

    2021

    Abecma®

    IV infusion

    5.0%

    CAR-T therapy

    2022

    Skysona®

    IV infusion

    5.0%

    ~ 2.0 mL

    CAR-T therapy

    2023

    Omisirge®

    IV infusion

    10%

    ~ 3.5 mL

    CAR-T therapy

    Thank you from the inquiring minds in the Excipients Community!



    ------------------------------
    Allison Radwick Ph.D.
    Sr Regulatory & Policy Comms Mgr
    USP
    Rockville MD
    [email protected]

    Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
    ------------------------------


  • 2.  RE: Increasing use of DMSO in CAR-T formulations

    Community Leadership
    Posted 08-22-2023 15:22

    I am probably stating the obvious (too bad I couldn't join the discussion)!

    The source is a cryoprotectant (containing DMSO) for the CAR T drug product (frozen). 

    The actual percentage in the infusion might differ depending on how the infusion solution is prepared from the DP.



    ------------------------------
    Tapan Das, Ph.D., FAAPS
    Bristol Myers Squibb


    Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer
    ------------------------------



  • 3.  RE: Increasing use of DMSO in CAR-T formulations

    Community Leadership
    Posted 08-24-2023 09:44

    Thank you @Tapan Das!  We did discuss that DMSO was used as a cryoprotectant and we would have loved to have you in the discussion.  @Robert Strickley noted the trend of using DMSO started in 2017 and that DMSO is not used in all CAR-T therapies.  We also talked about the limited number of parenteral DMSO suppliers. 

    Gvoke was also approved in 2019 (see below) and MEKINIST (trametinib) tablets for oral use has 0.5635 trametinib dimethyl sulfoxide equivalent to 0.5 mg of trametinib nonsolvated parent. 

    2019

    Gvoke

    Subcutaneous

    95%

    0.2 mL

    Pre-filled syringe

    Auto-injector

    I will add this topic to the next GCTP CMC Subteam meeting. If anyone would like to join the GCTP CMC Subteam, let me know!

    Allison



    ------------------------------
    Allison Radwick Ph.D.
    Sr Regulatory & Policy Comms Mgr
    USP
    Rockville MD
    [email protected]

    Disclaimer: Opinions expressed are solely my own and do not express the views or opinions of my employer.
    ------------------------------