Regulatory Open Forum

 View Only

  • 1.  Inactive Ingredients Acceptability

    Posted 16-Nov-2013 17:26
    I use the FDA website IIG to confirm the acceptable levels of inactive ingredients for US submissions, however does anyone know where to look for ingredients acceptability for other countries?  I have a global submission and would like to check some formulations for the ROW.

    -------------------------------------------
    Herbert Luther PhD
    VP Reg & Clin Affs
    Somerset NJ
    United States
    -------------------------------------------


  • 2.  RE:Inactive Ingredients Acceptability

    Posted 21-Nov-2013 02:09
    Hi Herbert,

    Most of the countries (African, CIS, Aus/NZ) accept the Type IV DMFs submitted to FDA. 

    EU and ASEAN countries follow the IPEC guidelines for excipients. Please follow the link below:

    http://www.ipec-europe.org/index.asp

    Japan publishes the JPE (Japanese Pharmaceutical Excipients). JPE consists of pharmaceutical excipients not included in Japanese  Pharmacopoeia  as  well  as  those  having  precedent use and often used for the marketable pharmaceutical preparations.

    -------------------------------------------
    Venkatesh Rao
    Senior Consultant
    India
    -------------------------------------------






    Original Message


  • 3.  RE:Inactive Ingredients Acceptability

    Posted 23-Dec-2013 12:04
    Venketesh,

    I'm not sure where you are getting the idea that somehow countries other than the US have any way to utilize US Type IV DMFs in making any type of assessment of the acceptability of an excipient or a level of use.  No one other than the US FDA has any access to any of the information in a Type IV DMF.  You can see a list of what Type IV DMFs are filed in the US on the FDA's website however this list is totally meaningless in determining acceptability of an excipient for a drug use because the fact that there is a DMF on file for an excipient does NOT mean that FDA has ever even looked at this DMF to determine acceptability of an excipient. 

    Just because someone might have a DMF doesn't mean that the excipient has ever been used in an approved drug product in the U.S.  Anyone can file a DMF and not even put any technical or safety information in the DMF to support the use of an excipient since there is no FDA review of a DMF outside of someone referencing the DMF in an actual drug apllication.  Unfortunately, there are many DMFs which exist that have never been referenced in any drug application since some foreign companies file a US DMF to fool companies in other countriues into thinking that their excipient has somehow been approved by FDA which is not the case because it has a DMF.

    Also, I am not sure what the IPEC guidelines have to do with establishing a precedence of use like the IID does in the US.  There is nothing in the IPEC Guidelines for the EU and ASEAN to follow that provides any information regarding what excipients have got a precedence of use in any region or what is considered acceptable by a regulator.  I am one of the founders of IPEC and a past Chair of IPEC Americas and I can assure you that the IPEC guidelines do not provide this type of information.  We do have guidelines that discuss appropriate GMP concepts, and many other topics related to supply chain, QbD and excipient safety but IPEC does not have any information about what excipients and levels are considered acceptable in various countries.

    Regards,
    -------------------------------------------
    David Schoneker
    Dir, Global Regulatory Affairs
    Colorcon
    West Point PA
    United States
    -------------------------------------------






    Original Message


  • 4.  RE:Inactive Ingredients Acceptability

    Posted 05-Dec-2013 03:38
    Herbert,
     
    The IID is the only real database with this type of information except in Japan where you can find a precedence list of excipients with previous approved levels in the Japanese language version of the Japanese Pharmaceutical Excipients Directory (JPED).  This is not the JPE that Venketesh discussed below.  It is a separate book. The JPE is just a a book of monographs like the JP and doesn't contain any precedence information for Japan or approved levels of use.  You will need to look at the Japanese language version of the JPED for this information though since this information is not contained in the English translation of the JPED.  There is not a precedence list of excipients in Europe or in other countries that provides this type of information at this time which makes things difficult.  People do tend to use the IID to provide supportive information however on precedence information in some of the ROW countries where this information doesn't exist.  However, this should only be part of a overall safety argument that a drug company must use to justify their use of an excipient.

    I hope this information is helpful to you.

    Regards,

    -------------------------------------------
    David Schoneker
    Dir, Global Regulatory Affairs
    Colorcon
    West Point PA
    United States
    -------------------------------------------






    Original Message