Regulatory Open Forum

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  • 1.  Long term preclinical tox studies

    Posted 23-May-2019 08:50

    Can non-GMP material be used in these studies? We have "GLP" grade material prepared but want to make sure FDA will accept it before we submit the protocols for FDA comment.

     

    Vincent J. Benn, Ph.D., MBA

     



  • 2.  RE: Long term preclinical tox studies

    Posted 23-May-2019 09:11
    Yes.

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    Glen Park PharmD
    Executive Director, Regulatory Affairs and Quality Assurance
    Jersey City NJ
    United States
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  • 3.  RE: Long term preclinical tox studies

    Posted 23-May-2019 12:28
    In my opinion it is ALWAYS best to use GLP material because as was said in other threads, the level of development dictates the level of requirements for FDA to accept.  Thinking about this logically, you "GLP" material is managed under a defined system of how to make it, what to do with it once it is made, how to store it, how to test and what to test for, etc.  So you are covered with your process.  Since these are preclinical in my mind this is sufficient.​

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    Victor Mencarelli
    Director Regulatory Affairs
    United States
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  • 4.  RE: Long term preclinical tox studies

    Posted 25-May-2019 17:35
    Dear All,

    I think it depends and not "always" to use GLP (non-GMP) materials for a long term tox study is the best practice. For example, if the tox study is planned concurrently with the phase 3 study to support product registration or license application or as a post approval commitment required by the FDA, it is not advisable to use an "old" GLP or non-GMP lot to conduct the chronic long-term tox study because it is not easy to establish CMC analytical comparability (for large molecule) or equivalency (for small molecule) against already established GMP late phase clinical lots. A GMP lot representative to phase 3 and/or commercial batches is highly recommended to avoid risks that analytical comparability cannot be established and the chronic tox study results cannot be utilized to support product registration or satisfy post approval commitment.

    I agree that before phase 1 or concurrently with phase 1, a GLP lot is often recommended for tox studies with exception for some ultra long-term tox study (e.g., =/>2 years, rodent or non-rodent).

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    Gene Zhu
    Independent Consultant
    Basking Ridge NJ
    USA
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