Regulatory Open Forum

Dear RAPS community,

     I would very much appreciate it if someone can point me to some specific examples where a drug approved through the 505(j) or 505(b)(2) pathway has a longer expiration date than that of the reference drug.  Thank you

First, I do not believe regulatory submissions for the 505(j) or 505(b)(2) pathways are made public. Second, in my experience, the expiration date is typically based on each manufacturers own bench data. So, when a manufacturer shows their specific degradation profile (I.e. CMC purity, identity, strength, etc. as required) based on accelerated and real time aging studies (also, as required), then, the label should reflect the tested and true expiration date for the specific product labeled (whether shorter or longer than the RLD).

Dear RAPS community,

     I would very much appreciate it if someone can point me to some specific examples where a drug approved through the 505(j) or 505(b)(2) pathway has a longer expiration date than that of the reference drug.  Thank you

I agree with Joy.  The expiration dating of the generic product is based on the actual real-time stability data generated by the generic manufacturer.  You can have a longer or shorter expiry period than the RLD.  The dating is determined by stability testing and also marketing strategy (even if the product is very stable, there may be other reasons to not extend the expiration dating).  

First, I do not believe regulatory submissions for the 505(j) or 505(b)(2) pathways are made public. Second, in my experience, the expiration date is typically based on each manufacturers own bench data. So, when a manufacturer shows their specific degradation profile (I.e. CMC purity, identity, strength, etc. as required) based on accelerated and real time aging studies (also, as required), then, the label should reflect the tested and true expiration date for the specific product labeled (whether shorter or longer than the RLD).

Dear RAPS community,

     I would very much appreciate it if someone can point me to some specific examples where a drug approved through the 505(j) or 505(b)(2) pathway has a longer expiration date than that of the reference drug.  Thank you

Hi Joy and Lisa,

     Thank you so much for the replies, much appreciated.  I can not agree with you more than the expiry period of a drug can, in principle, be longer or shorter than that of the RLD.  I was looking for specific examples when it is longer.  I have no experience with the generic industry, but have read reviews of at least some of the 505(b)(2) in the public domain in their redacted form.  An example of such reviews is the first drug mentioned in this article.  If expiry periods are often redacted, perhaps people are willing to share such info for older drugs that have little commercial values now?

   I have a further question for you if you don't mind: someone who has very significant CMC experience told me that  the agency grants shelf-life 2x the long-term data, up to 24 months, regardless of the availability of accelerated data or sound statistical analysis for an ANDA.  Is this your understanding too?  This is contradictory to everything I know about ICH Q1E, and definitely not true for a 505(b)<o:p></o:p>

    Thanks again.

I agree with Joy.  The expiration dating of the generic product is based on the actual real-time stability data generated by the generic manufacturer.  You can have a longer or shorter expiry period than the RLD.  The dating is determined by stability testing and also marketing strategy (even if the product is very stable, there may be other reasons to not extend the expiration dating).  

First, I do not believe regulatory submissions for the 505(j) or 505(b)(2) pathways are made public. Second, in my experience, the expiration date is typically based on each manufacturers own bench data. So, when a manufacturer shows their specific degradation profile (I.e. CMC purity, identity, strength, etc. as required) based on accelerated and real time aging studies (also, as required), then, the label should reflect the tested and true expiration date for the specific product labeled (whether shorter or longer than the RLD).

Dear RAPS community,

     I would very much appreciate it if someone can point me to some specific examples where a drug approved through the 505(j) or 505(b)(2) pathway has a longer expiration date than that of the reference drug.  Thank you

Hi Joy and Lisa,

     Thank you so much for the replies, much appreciated.  I can not agree with you more than the expiry period of a drug can, in principle, be longer or shorter than that of the RLD.  I was looking for specific examples when it is longer.  I have no experience with the generic industry, but have read reviews of at least some of the 505(b)(2) in the public domain in their redacted form.  An example of such reviews is the first drug mentioned in this article.  If expiry periods are often redacted, perhaps people are willing to share such info for older drugs that have little commercial values now?

   I have a further question for you if you don't mind: someone who has very significant CMC experience told me that  the agency grants shelf-life 2x the long-term data, up to 24 months, regardless of the availability of accelerated data or sound statistical analysis for an ANDA.  Is this your understanding too?  This is contradictory to everything I know about ICH Q1E, and definitely not true for a 505(b)<o:p></o:p>

    Thanks again.

I agree with Joy.  The expiration dating of the generic product is based on the actual real-time stability data generated by the generic manufacturer.  You can have a longer or shorter expiry period than the RLD.  The dating is determined by stability testing and also marketing strategy (even if the product is very stable, there may be other reasons to not extend the expiration dating).  

First, I do not believe regulatory submissions for the 505(j) or 505(b)(2) pathways are made public. Second, in my experience, the expiration date is typically based on each manufacturers own bench data. So, when a manufacturer shows their specific degradation profile (I.e. CMC purity, identity, strength, etc. as required) based on accelerated and real time aging studies (also, as required), then, the label should reflect the tested and true expiration date for the specific product labeled (whether shorter or longer than the RLD).

Dear RAPS community,

     I would very much appreciate it if someone can point me to some specific examples where a drug approved through the 505(j) or 505(b)(2) pathway has a longer expiration date than that of the reference drug.  Thank you

Hi Anon,

I have focused my regulatory work to the generic industry, so I can address the ANDA side.  I do not have examples of where a generic and RLD expiry periods differ, nor have I ever needed that information.  Also, there is little to no information published about a generic approval package (505(j) pathway), no approval letters or labeling.  Just that an ANDA was approved.

If you are working with both NDA and ANDA products, please keep in mind that the ANDA review and approval process is different.  In some instances, significantly different. 

An ANDA can be submitted with 6 month CRT and ACC stability data.  During the review process, you will update your ANDA with additional CRT stability data.  It is true that OGD has stated they will grant up to 2x the CRT stability data as the expiry.  In reality, you will likely have 18-24 months data available by approval.  Unless you have a reason (failures), the ANDA will be granted 24 months.  A longer expiry will require real-time data covering the extended period.

Hi Joy and Lisa,

     Thank you so much for the replies, much appreciated.  I can not agree with you more than the expiry period of a drug can, in principle, be longer or shorter than that of the RLD.  I was looking for specific examples when it is longer.  I have no experience with the generic industry, but have read reviews of at least some of the 505(b)(2) in the public domain in their redacted form.  An example of such reviews is the first drug mentioned in this article.  If expiry periods are often redacted, perhaps people are willing to share such info for older drugs that have little commercial values now?

   I have a further question for you if you don't mind: someone who has very significant CMC experience told me that  the agency grants shelf-life 2x the long-term data, up to 24 months, regardless of the availability of accelerated data or sound statistical analysis for an ANDA.  Is this your understanding too?  This is contradictory to everything I know about ICH Q1E, and definitely not true for a 505(b)<o:p></o:p>

    Thanks again.

Original Message:
Sent: 12-Feb-2023 14:23
From: Lisa Apolis
Subject: Precedent: longer expiration date than the RLD

I agree with Joy.  The expiration dating of the generic product is based on the actual real-time stability data generated by the generic manufacturer.  You can have a longer or shorter expiry period than the RLD.  The dating is determined by stability testing and also marketing strategy (even if the product is very stable, there may be other reasons to not extend the expiration dating).  

First, I do not believe regulatory submissions for the 505(j) or 505(b)(2) pathways are made public. Second, in my experience, the expiration date is typically based on each manufacturers own bench data. So, when a manufacturer shows their specific degradation profile (I.e. CMC purity, identity, strength, etc. as required) based on accelerated and real time aging studies (also, as required), then, the label should reflect the tested and true expiration date for the specific product labeled (whether shorter or longer than the RLD).

Dear RAPS community,

     I would very much appreciate it if someone can point me to some specific examples where a drug approved through the 505(j) or 505(b)(2) pathway has a longer expiration date than that of the reference drug.  Thank you

Hi Joy and Lisa,

    Thank you so much for the replies, much appreciated.

    Just to make sure I understand your comments correctly:

    1) If the 6-month accelerated data are mandatory for an ANDA, then the 2x shelf-life up to 24 months is entirely consistent with ICH Q1E

    2) If, on the contrary, accelerated data are not absolutely required, then a sponsor can submit 12-month RT data only and get a 24-month shelf-life, provided it commits to providing the 24-month RT data when they become available?

     3) If hypothetically, a sponsor has 18-month RT time and 6-month accelerated data at the time of ANDA submission, the OGD will grant only 24-months shelf-life because RT data are required for expiry period beyond 24 months?

     Thank you again for your insights

Anon

Hi Anon,

I have focused my regulatory work to the generic industry, so I can address the ANDA side.  I do not have examples of where a generic and RLD expiry periods differ, nor have I ever needed that information.  Also, there is little to no information published about a generic approval package (505(j) pathway), no approval letters or labeling.  Just that an ANDA was approved.

If you are working with both NDA and ANDA products, please keep in mind that the ANDA review and approval process is different.  In some instances, significantly different. 

An ANDA can be submitted with 6 month CRT and ACC stability data.  During the review process, you will update your ANDA with additional CRT stability data.  It is true that OGD has stated they will grant up to 2x the CRT stability data as the expiry.  In reality, you will likely have 18-24 months data available by approval.  Unless you have a reason (failures), the ANDA will be granted 24 months.  A longer expiry will require real-time data covering the extended period.

Hi Joy and Lisa,

     Thank you so much for the replies, much appreciated.  I can not agree with you more than the expiry period of a drug can, in principle, be longer or shorter than that of the RLD.  I was looking for specific examples when it is longer.  I have no experience with the generic industry, but have read reviews of at least some of the 505(b)(2) in the public domain in their redacted form.  An example of such reviews is the first drug mentioned in this article.  If expiry periods are often redacted, perhaps people are willing to share such info for older drugs that have little commercial values now?

   I have a further question for you if you don't mind: someone who has very significant CMC experience told me that  the agency grants shelf-life 2x the long-term data, up to 24 months, regardless of the availability of accelerated data or sound statistical analysis for an ANDA.  Is this your understanding too?  This is contradictory to everything I know about ICH Q1E, and definitely not true for a 505(b)<o:p></o:p>

    Thanks again.

I agree with Joy.  The expiration dating of the generic product is based on the actual real-time stability data generated by the generic manufacturer.  You can have a longer or shorter expiry period than the RLD.  The dating is determined by stability testing and also marketing strategy (even if the product is very stable, there may be other reasons to not extend the expiration dating).  

First, I do not believe regulatory submissions for the 505(j) or 505(b)(2) pathways are made public. Second, in my experience, the expiration date is typically based on each manufacturers own bench data. So, when a manufacturer shows their specific degradation profile (I.e. CMC purity, identity, strength, etc. as required) based on accelerated and real time aging studies (also, as required), then, the label should reflect the tested and true expiration date for the specific product labeled (whether shorter or longer than the RLD).

Dear RAPS community,

     I would very much appreciate it if someone can point me to some specific examples where a drug approved through the 505(j) or 505(b)(2) pathway has a longer expiration date than that of the reference drug.  Thank you