Regulatory Open Forum

After our intitial stability study has begun (say a 36 month long term and 12 month accelerated), we pull samples annually and place those up at ICH long term conditions for the length of the shelf life determined with the initial study. At this point, our stability chambers are full and the plants are asking if it is a requirement to do the annual pulls.  I have studied every ICH and FDA guidance I can find and I don't see a requirement to do annual studies. And since our change control process is effective, that should catch any changes that would necessitate a new study. 

What are other pharma companies doing to keep stability studies current?  I appreciate the opportunity to benchmark!

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Lisa
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The first place to turn is your initial drug application and determine what ongoing commitment you have made to the agency concerning future stability pulls. 

The FDA has archived its stability guidance in favor of the ICH guidance which might not include the answer to the annual pull question that you are looking for.  In this case, you must look to other countries' guidance concerning annual stability pulls for some sort of direction.

The Eurdalex and PIC/S are very clear on the requirements for an on-going stability program.  You must pull at least one batch per year of product per strength and primary packaging type to be enrolled in the stability program. FDA has been a member of PIC/S since January 1 of this year although I have not seen any move to harmonizing yet.

Annual pulls for stability are required unless you have negotiated an exception or haven't manufactured that strength/primary packaging type within the year.

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RL Johnson RAC
Manager, Global Regulatory Affairs
Denham Springs LA
United States
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Original Message:
Sent: 06-14-2011 11:18
From: Lisa Fischer
Subject: Annual stability sampling/testing


After our intitial stability study has begun (say a 36 month long term and 12 month accelerated), we pull samples annually and place those up at ICH long term conditions for the length of the shelf life determined with the initial study. At this point, our stability chambers are full and the plants are asking if it is a requirement to do the annual pulls.  I have studied every ICH and FDA guidance I can find and I don't see a requirement to do annual studies. And since our change control process is effective, that should catch any changes that would necessitate a new study. 

What are other pharma companies doing to keep stability studies current?  I appreciate the opportunity to benchmark!

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Lisa
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There was a proposal to add this the the CRF 211.166 GMP's (Federal register Vol 61. No 87) in 1996 - but it looks like it never made it.

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Tim Hallberg
Vistakon
Jacksonville GA
United States
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Original Message:
Sent: 06-15-2011 15:37
From: RL Johnson
Subject: Annual stability sampling/testing

The first place to turn is your initial drug application and determine what ongoing commitment you have made to the agency concerning future stability pulls. 

The FDA has archived its stability guidance in favor of the ICH guidance which might not include the answer to the annual pull question that you are looking for.  In this case, you must look to other countries' guidance concerning annual stability pulls for some sort of direction.

The Eurdalex and PIC/S are very clear on the requirements for an on-going stability program.  You must pull at least one batch per year of product per strength and primary packaging type to be enrolled in the stability program. FDA has been a member of PIC/S since January 1 of this year although I have not seen any move to harmonizing yet.

Annual pulls for stability are required unless you have negotiated an exception or haven't manufactured that strength/primary packaging type within the year.

-------------------------------------------
RL Johnson RAC
Manager, Global Regulatory Affairs
Denham Springs LA
United States
-------------------------------------------






Original Message:
Sent: 06-14-2011 11:18
From: Lisa Fischer
Subject: Annual stability sampling/testing


After our intitial stability study has begun (say a 36 month long term and 12 month accelerated), we pull samples annually and place those up at ICH long term conditions for the length of the shelf life determined with the initial study. At this point, our stability chambers are full and the plants are asking if it is a requirement to do the annual pulls.  I have studied every ICH and FDA guidance I can find and I don't see a requirement to do annual studies. And since our change control process is effective, that should catch any changes that would necessitate a new study. 

What are other pharma companies doing to keep stability studies current?  I appreciate the opportunity to benchmark!

-------------------------------------------
Lisa
-------------------------------------------

ICH Q7A Section 11.54 clearly states the annual requirement for drug substance stability.

The requirement for annual drug product batches was in the 1998 draft stability guidance and in the 2003 draft drug product cmc guidance, both of which have been withdrawn. A colleague of mine asked an FDA representative about the requirement and was told that the Agency considered it a requirement of 21 CFR 211.166(b) and that it is also considered a cGMP requirement. Additionally it has become industry practice and that it would be considered a cGMP violation not to place at least one new batch on stability annually.

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Beverly Lewis RAC
Lewis CMC Consulting Inc
Nags Head NC
United States
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Original Message:
Sent: 06-15-2011 15:37
From: RL Johnson
Subject: Annual stability sampling/testing

The first place to turn is your initial drug application and determine what ongoing commitment you have made to the agency concerning future stability pulls. 

The FDA has archived its stability guidance in favor of the ICH guidance which might not include the answer to the annual pull question that you are looking for.  In this case, you must look to other countries' guidance concerning annual stability pulls for some sort of direction.

The Eurdalex and PIC/S are very clear on the requirements for an on-going stability program.  You must pull at least one batch per year of product per strength and primary packaging type to be enrolled in the stability program. FDA has been a member of PIC/S since January 1 of this year although I have not seen any move to harmonizing yet.

Annual pulls for stability are required unless you have negotiated an exception or haven't manufactured that strength/primary packaging type within the year.

-------------------------------------------
RL Johnson RAC
Manager, Global Regulatory Affairs
Denham Springs LA
United States
-------------------------------------------






Original Message:
Sent: 06-14-2011 11:18
From: Lisa Fischer
Subject: Annual stability sampling/testing


After our intitial stability study has begun (say a 36 month long term and 12 month accelerated), we pull samples annually and place those up at ICH long term conditions for the length of the shelf life determined with the initial study. At this point, our stability chambers are full and the plants are asking if it is a requirement to do the annual pulls.  I have studied every ICH and FDA guidance I can find and I don't see a requirement to do annual studies. And since our change control process is effective, that should catch any changes that would necessitate a new study. 

What are other pharma companies doing to keep stability studies current?  I appreciate the opportunity to benchmark!

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Lisa
-------------------------------------------

In PIC/S GMP Section 6.29 requires the annual pull of stability testing.

Also, in your marketing application, it is standard to submit a commitment of performing ongoing stability program and also stability study protocol.  You should check your submission package on whether you have submit such commitment.  Any changes in the stability study protocol must be submitted to FDA for review.

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Julia Lin
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Original Message:
Sent: 06-14-2011 11:18
From: Lisa Fischer
Subject: Annual stability sampling/testing


After our intitial stability study has begun (say a 36 month long term and 12 month accelerated), we pull samples annually and place those up at ICH long term conditions for the length of the shelf life determined with the initial study. At this point, our stability chambers are full and the plants are asking if it is a requirement to do the annual pulls.  I have studied every ICH and FDA guidance I can find and I don't see a requirement to do annual studies. And since our change control process is effective, that should catch any changes that would necessitate a new study. 

What are other pharma companies doing to keep stability studies current?  I appreciate the opportunity to benchmark!

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Lisa
-------------------------------------------

We are an IVD company, but I think there is application.  For established products, our policy is to test one lot per year at beginning, interem and expiry.  There may not be prescriptive guidance, but a quality system would require that stability is monitored (up to the company to determine frequency).  Opinions to the contrary will surely follow if there is anything documented to the contrary!



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Sarah Parsons RAC
Regulatory Affairs Manager
Ortho-Clinical Diagnostics
Rochester NY
United States
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Original Message:
Sent: 06-14-2011 11:18
From: Lisa Fischer
Subject: Annual stability sampling/testing


After our intitial stability study has begun (say a 36 month long term and 12 month accelerated), we pull samples annually and place those up at ICH long term conditions for the length of the shelf life determined with the initial study. At this point, our stability chambers are full and the plants are asking if it is a requirement to do the annual pulls.  I have studied every ICH and FDA guidance I can find and I don't see a requirement to do annual studies. And since our change control process is effective, that should catch any changes that would necessitate a new study. 

What are other pharma companies doing to keep stability studies current?  I appreciate the opportunity to benchmark!

-------------------------------------------
Lisa
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