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  • 1.  IND - CMC -stability - mAb -

    This message was posted by a user wishing to remain anonymous
    Posted 02-Dec-2021 14:26
    This message was posted by a user wishing to remain anonymous

    Hi,

    Our product is a mAb. For initial IND submission, we included 1-month stability data for the clinical batch. What type of testing is a must?

    Is potency testing for 1 -month time point a must?
    Is sterility testing for 1 - month time point a must?
    Is sub-visible particulate testing for 1 - month time point a must?


  • 2.  RE: IND - CMC -stability - mAb -

    Posted 05-Dec-2021 13:05
    Hi Anon -

    You indicate that you submitted stability data in the original IND. Regardless, you should refer to ICH Q5C, which states (my emphasis) " the manufacturer should propose a stability-indicating profile that provides assurance that changes in the identity, purity and potency of the product will be detected." If you can't say that for each parameter you mention, that is an issue.

    ------------------------------
    Glen Park PharmD
    Vice President, Regulatory Affairs and Quality Assurance
    New York NY
    United States
    ------------------------------

    Original Message


  • 3.  RE: IND - CMC -stability - mAb -

    This message was posted by a user wishing to remain anonymous
    Posted 08-Dec-2021 10:18
    This message was posted by a user wishing to remain anonymous

    Hi Anon,

    For a parenteral mAb, here is an acceptable strategy I've used for the long-term storage condition (X indicates when tests are performed):

    Test

    Time Point (Months)

    Release

    1

    3

    6

    9

    12

    Visible Appearance

    X

    X

    X

    X

    X

    X

    Particles (Visible and Sub-Visible)

    X

    X

    X

    X

    X

    X

    Osmolality

    X

    X

    X

    X

    X

    X

    pH

    X

    X

    X

    X

    X

    X

    Purity

    X

    X

    X

    X

    X

    X

    Potency

    X

    X

    X

    X

    X

    X

    Protein concentration

    X

    X

    X

    X

    X

    X

    Excipients

    X

    X

    X

    X

    X

    X

    Extractable Volume

    X

    -

    -

    -

    -

    X

    Endotoxin

    X

    -

    -

    -

    -

    X

    Sterility

    X

    -

    -

    -

    -

    X

    Potency is a must at any timepoint (unless you have multiple orthogonal methods and one can be positioned as 'stability indicating'). Sterility is generally only required at beginning and end of the stability program (this is covered in ICH Q5C). Lately FDA has been very interested in sub-visible particulate testing for mAbs, presumably as an indicator of aggregation, so I expect that to be a requirement at every time point as well.

    Cheers,
    Anon
    Original Message


  • 4.  RE: IND - CMC -stability - mAb -

    This message was posted by a user wishing to remain anonymous
    Posted 09-Dec-2021 11:15
    This message was posted by a user wishing to remain anonymous

    Thank you! Speaking about the potency, should we do both ELISA binding and ADCC cell-based assay, or is ELISA binding alone enough for phase I stability testing?
    Original Message


  • 5.  RE: IND - CMC -stability - mAb -

    This message was posted by a user wishing to remain anonymous
    Posted 09-Dec-2021 23:41
    This message was posted by a user wishing to remain anonymous

    ADCC question is a drug development related! Assuming you are developing NBE (mab) at phase 1, don't you and your nonclinical/clin pharm or even management want to know or characterize this new baby about its functionality at this stage before you further invest in expensive clinical trials? FDA for phase 1 stage especially for a NBE, would focus on safety both clinical and CMC but I don't think its their job to help you with drug development or precisely functionality of your NBE (mab). The other question are more RA CMC related but not this one!
    Original Message


  • 6.  RE: IND - CMC -stability - mAb -

    Posted 10-Dec-2021 12:17
    Agree with the above Anon's response regarding drug development versus pure RA related issues/questions! Whether the FDA requires or not, as a drug development company and especially if this is a NBE-New biological Entity mab at phase 1, I'd perform both ELISA and ADCC to characterize this NBE (that the preclinical/nonclincal responses are in line with the clinical evaluation) at FIH phase 1 stage. Once these two are assessed during clinical evaluation regarding mab performance, the FDA may allow you not to do it routinely once the product is approved. Good luck!
    I agree that the CMC potency test/method and other CMC related tests as pointed out by another Anon's response are appropriate and belong to CMC section. Also I'd suggest that you consult your clin pharm function regarding ELISA and ADCC.

    ------------------------------
    GRSAOnline
    ------------------------------

    Original Message


  • 7.  RE: IND - CMC -stability - mAb -

    This message was posted by a user wishing to remain anonymous
    Posted 09-Dec-2021 23:41
    This message was posted by a user wishing to remain anonymous

    Hi Anon,

    For mAb potency an ELISA will probably be sufficient in Phase 1 stability testing, though be prepared for a request from FDA (particularly DAVP, which sounds like your review division) to develop a more 'mechanistic' cell-based assay as soon as possible thereafter, if it hasn't been requested already. 

    Cheers,
    Anon
    Original Message


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