Regulatory Open Forum

 View Only

  • 1.  ANDA Post Approval Filing strategy to reduce the tablet weight

    This message was posted by a user wishing to remain anonymous
    Posted 23-Oct-2017 11:24
    This message was posted by a user wishing to remain anonymous

    Hi Everyone,

    ​My company is planning to change the formulation of an approved ANDA (tablets) to reduce the tablets weight to 35-40% by reducing the excipient quantity or if possible eliminate an excipient . No change in the active, facility, specs etc...

    We believe a PAS can be filed, however, have the below concerns : 
    1. Post commercialization products from both formulation (different sized tablets could be in the market until the expiration of the previous and it may cause patient confusion, We may able to propose different NDC? But FDA may not allow a new NDC for the same NDC/strength/pack?
     2. Number of exhibit/stability batches needed One or three?
    3. Do we need to repeat BE - both invitro and invivo? 

    Appreciate your suggestions/comments
    Thanks
     


  • 2.  RE: ANDA Post Approval Filing strategy to reduce the tablet weight

    Posted 23-Oct-2017 16:29
    Hi,

    Yes you are correct this will be filed as a PAS application to FDA.

    1) Yes you can request for a new NDC number: See CFR 207.35 bullet 6 21 CFR 207.35 
    2) If Significant body of information available:
    One batch with three months accelerated stability data reported in supplement; one batch on long-term stability data reported in annual report.
    If Significant body of information not available:
    Up to three batches with three months accelerated stability data reported in supplement; one batch on long-term stability data reported in annual report.
    3) Bioequivalence study may be waived with an acceptable in vivo/in vitro correlation has been verified.

    Hope this helps

    ------------------------------
    Shahid Hussain
    MCPHS University
    Allston MA
    United States
    ------------------------------

    Original Message


  • 3.  RE: ANDA Post Approval Filing strategy to reduce the tablet weight

    Posted 24-Oct-2017 10:18
    Hello, your post approval changes have more to do with the tablet components of the product, as your target Active Pharmaceutical Ingredient will be the same. You need to make that clear to the FDA. You will need to prove your dissolution/disintegration, hardness, friability and all other current quality attributes of the tablet have not changed.  If they have, then you have another issue all together.

    You will need a substantial body of evidence to define that the tablet quality attributes are identical and then you may provide support to the FDA and make recommendations for how you wish to proceed. This may be a PAS, but you may discuss with the FDA why you believe the product could be a CBE30.

    You must have three stability batches, with at least one long-term data to submit, all with accelerated data and demonstrate or correlate comparability of the quality attributes to the existing product that the tablets are equivalent. You must discuss with FDA why you think bioequivalency is not needed or why it is needed.

    You definitely need to discuss with the FDA what you define is different about the tablet/product, any concerns about the difference and what your company knows about the difference, what your company plans to do about the difference (the comparative stability, quality characteristics, the difference in size, why bioequivalence is not needed, or why it is needed, ect.) and your eventual conclusion on what you believe is required for your submission to the FDA. You already are thinking about a new NDC number and this is appropriate as the tablet will look almost half the size. Changing ingredients is always difficult to establish an effect, so you need to be prepared with knowledge that your product is equivalent to the comparator tablet/product in the approved ANDA.

    ------------------------------
    Dean Murphy
    VP Regulatory and QA
    NeuroTrauma Sciences, LLC
    Alpharetta, GA
    USA
    ------------------------------

    Original Message


  • 4.  RE: ANDA Post Approval Filing strategy to reduce the tablet weight

    Posted 24-Oct-2017 11:15

    Here are my thoughts:

    1. I would recommend a new NDC.  FDA will likely require a new NDC anyway. At my previous company we changed from a non-scored tablet to a scored tablet and tried using the same NDC, but at the 11th hour FDA said we had to change NDC's since tablets had different appearance – this caused a lot of headaches having to change NDCs so late in the process. FDA also requested we add a banner to the outer package (carton) for 6 months highlighting the new scored tablet.  They may expect the same in your case since the tablets will have a different size.
    2. I assume your product is an IR tablet so suggest you refer to the SUPAC-IR Guidance.  Whether you have a Significant Body of Information available may dictate whether you need 1 vs 3 batches.  Appears you fall into a Level 3 change.
    3. I would expect a BE study would be required since you are making significant changes in the formulation.

     

    Tom

    Chicago




    Original Message


  • 5.  RE: ANDA Post Approval Filing strategy to reduce the tablet weight

    Posted 25-Oct-2017 11:28
    1) Assign new product code (different formulation) and eventually its new NDC. If proposed change is not approved/accepted, you may carry on with current formulation without unnecessary change controls for this product.

    2) Its level 3 change as per SUPAC guidance as your excipient level is vary more than 10%. Total tablet weight is reduced to 35%-40% and the tablet CQA including size, weight, thickness, hardness may change from the approved application.
               A) If you have same CQA  specification within your approved application than 1 batch ACC and 1 batch RT.
               B) If you have different CQA specification from your approved application than 3 batch ACC and 1 batch RT.

    3)       A) If you have same CQA  specification within your approved application than only in-vitro and compare with approved dissolution data.
               B) If you have different CQA specification from your approved application than in-vitro and compare with approved dissolution data and prove IVIVC with new formulation else repeat bio-study.

    ------------------------------
    Gaurang Bhavsar, MS, RAC
    Scientist-II, R&D and RA
    Sunrise Pharmaceutical, Inc.
    Rahway, NJ 07065
    USA
    ------------------------------

    Original Message


Related Content