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  • 1.  CMC - Drug substance and Drug product description (appearance)

    This message was posted by a user wishing to remain anonymous
    Posted 13-Jun-2022 09:41
    This message was posted by a user wishing to remain anonymous

    Hello, community,

    We are producing mAb drugs for phase I studies.
    The Description/Appearance specification for DS is "colorless to slightly yellow/brown solution."
    The Description/Appearance specification for DP is "colorless to slightly yellow/brown solution; essentially free of visible particles"

    My questions are:

    1) Are these specifications make sense? Should we separate the "essentially free of visible particles" from Description/Appearance? Because the "essentially free of visible particles" is determined by inspecting all vials after aseptic filling?

    2) I understand that the method to determine the Appearance is "Visual." Our current SOP uses Light Box, but I think the method is more suitable for detecting visible particles. Color seems to be subjective. How do you determine Description/Appearance? What essential information shall be in the SOP?

    Thank you.


  • 2.  RE: CMC - Drug substance and Drug product description (appearance)

    Posted 15-Jun-2022 16:12
    Edited by Michael Koivula 15-Jun-2022 16:12
    The descriptions are not atypical. There should be an appropriate justification as to why this Clarity and range of Color is suitable.

    (1) The visual test for presence of visible particulate is a test that is required for parenteral drug products. For U.S. - see USP <1>

    (2)The Appearance test is subjective. Each evaluation (color, clarity, visible particulate) should employ a suitable control to be used as a comparator (control).

    (Also see other recent reply to Anonymous)


  • 3.  RE: CMC - Drug substance and Drug product description (appearance)

    Posted 24-Jun-2022 13:15
    We usually have separate tests listed on the specification for Appearance and Visible Particles. That doesn't preclude you from assessing them in the same test.

    For the appearance, we use the Ph.Eur. test and standards, so the specification will be something like "Not more colored than reference standard BY3". In the description, such as appears in the label, we will use something like what you state: "colorless to slightly yellow/brown".

    Note that the EU at least also requires a clarity specification for parenterals (eg, clear to slightly opaque), which is tested against a defined set of standards in the Ph.Eur. (eg, reference suspension III).

    ------------------------------
    Rachel Thornton
    Associate Director
    Smyrna GA
    United States
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    Original Message


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