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  • 1.  Handling of RLD for Bioequivalance Study

    Posted 02-Jan-2018 02:10
    Edited by Rajib Baishnab 02-Jan-2018 02:12
    ​​
    Dear Members,

    We are developing a Product for ANDA submission. Accordingly we have purchased the RLD of that  product to conduct the Bioequivalence study.

    Storage condition of that RLD is given below:

    Store at 20- 25°C (77°F); excursions permitted between 15°C to 30°C (59°F to 86°F)
     
    During transportation of RLD from point of purchase to manufacturing site ,upper alert limit temperature of Data Logger was set at 30°C and lower alert limit was set at  15°C. But as per data obtained from data logger, we found temperature below lower alert limit (15°C) for 1 hour and also found temperature above upper alert limit (30°C) for around 15 Days .High extreme temperature was found 34.4°C and Low extreme temperature was found 14.5°C & Total Trip length was  about 28 Days.
     

    I have gone through the FDA guidance on Handling and Retention of BA and BE Testing Samples but didn't find about anything on excursion of temperature during transportation of RLD.

    Please suggest  if there is any specific FDA guidance for the RLD transportation on temperature & Humidity requirement. Also please suggest whether FDA will raise any query if we submit the above data as the proof of storage during transportation.



    ------------------------------
    Thanks & Best regards

    Rajib Kumar Baishnab
    Manager, Regulatory Affairs
    The ACME Laboratories Ltd.
    Dhamrai, Dhaka-1350, Bangladesh
    Ph: +8801990-407587
    Email: rbaishnab.qo@acmeglobal.com
    ------------------------------
    ​​


  • 2.  RE: Handling of RLD for Bioequivalance Study

    This message was posted by a user wishing to remain anonymous
    Posted 03-Jan-2018 09:31
    This message was posted by a user wishing to remain anonymous

    Hi Rajib- I think you should refer Guidance for Industry E6 Good Clinical Practice: Consolidated Guidance ICH E6

    Generally when Temperature excursions occur:
    -First quarantine the study product from clinical use and investigate the root cause.
    - Always follow available "contingency plan SOP" (company specific)
    -Record all the relevant information.
    -Notify Investigator, sponsor and CRO 
    - Assess the details of the temperature excursion and decide if the product is acceptable for use or it should be returned or destroyed. 
    -Assessment will be based on stability data/ labeling/or information from manufacturer 

    Apart from RLD Drug label, study protocol usually states the conditions/controls under which the study product should be stored in an effort to preserve the quality, strength, purity and identity of the product. If excursions are permissible, this should be described in the study protocol.

    In worst case scenario FDA may point this in 483-Inspection observation(s) that the study drug being stored at temperatures outside of
    the protocol/required range.

    If you still need more information, It would be best to ask the FDA review division (project manager) that is overseeing your application.


  • 3.  RE: Handling of RLD for Bioequivalance Study

    Posted 04-Jan-2018 09:31

    You don't say what the drug is and we know some can be very susceptible to temperature issues while others not (e.g. ice vs salt).  You can do a risk assessment and if this is a drug that is well known to be very stable you may want to proceed.  On the other hand, since the biostudy is a very critical part of your ANDA, perhaps it's just easier to purchase new RLD.

     

    Christopher Smith, CQE, RAC

    President, Coastal Pharmaceutical Consultants, Inc. ®

    7950 Old River Road, Burgaw, NC 28425 USA

    910-259-8877 (land)

    910-789-1232 (mobile)

    chrissmith@coastalpharmaconsultants.com

     






  • 4.  RE: Handling of RLD for Bioequivalance Study

    Posted 06-Jan-2018 23:54

    Thanks a lot to all of you for your kind reply.


    Perhaps The drug is in Oral solid dosage form & is a well-established molecule.


    Can we directly ask NDA holder to send us the stability data of that RLD?

    Please note that we are a generic pharmaceutical company based in Bangladesh.I don't have any idea how to contact the RLD manufacturer.

    Looking forward getting your kind response.



    ------------------------------
    Thanks & Best regards

    Rajib Kumar Baishnab
    Manager, Regulatory Affairs
    The ACME Laboratories Ltd.
    Dhamrai, Dhaka-1350, Bangladesh
    Ph: +8801990-407587
    Email: rbaishnab.qo@acmeglobal.com
    ------------------------------



  • 5.  RE: Handling of RLD for Bioequivalance Study

    Posted 03-Jan-2018 10:10

    I suggest you contact the manufacturer of the RLD.  Many times, sponsors will conduct temperature cycling (freeze/thaw) stability studies which demonstrate that if these types of excursions occur the product is still stable.

    Tom

    Chicago