Regulatory Open Forum

This message was posted by a user wishing to remain anonymous

​Hi everyone.

I think I am losing my mind here.  I remember back several years ago looking through something from FDA that showed the parameters for setting specifications for active ingredient content in a topical drug product.  I also seem to remember that FDA had accepted generally (subject to verification of the manufacturing process) that a specification using the nominal amount of the active ingredient is the midpoint of the specification and then there was a +/-10% allowance (so if the nominal level is 2% then the specification range for acceptance would be 1.8-2.2%).  I believe this was mainly based on the potential variability in the assay and the preparation of the samples but it also might simply be a bit of variation in getting the active ingredient fully from its packaging into the production vessel.

Does anyone else remember this or can anyone share insight on where that +/-10% might have come from?  I am being asked for a reference for that guidance for setting specification values and I cannot for the life of me find the document any more either in my files or on FDA's website.  Thanks!

Hi,
Setting specifications is based on your data that you have generated before arriving at final specifications. Based 'n'  of batches then you derive SD+/<g class="gr_ gr_289 gr-alert gr_gramm gr_inline_cards gr_run_anim Style multiReplace" id="289" data-gr-id="289">- .</g> The whole process is your basis document for setting specifications.International Conference on Harmonization (ICH) Q6 defines specifications as "a list of tests, references to analytical procedures, and appropriate acceptance criteria which are numerical limits, ranges, or other criteria for the tests described

Regards
Subba Raju BV 

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Venkata Subba Raju Balaraju PhD
AGM- Regulatory
Hyderabad
India
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Original Message:
Sent: 10-Aug-2018 16:08
From: Anonymous Member
Subject: Setting Specifications

This message was posted by a user wishing to remain anonymous

​Hi everyone.

I think I am losing my mind here.  I remember back several years ago looking through something from FDA that showed the parameters for setting specifications for active ingredient content in a topical drug product.  I also seem to remember that FDA had accepted generally (subject to verification of the manufacturing process) that a specification using the nominal amount of the active ingredient is the midpoint of the specification and then there was a +/-10% allowance (so if the nominal level is 2% then the specification range for acceptance would be 1.8-2.2%).  I believe this was mainly based on the potential variability in the assay and the preparation of the samples but it also might simply be a bit of variation in getting the active ingredient fully from its packaging into the production vessel.

Does anyone else remember this or can anyone share insight on where that +/-10% might have come from?  I am being asked for a reference for that guidance for setting specification values and I cannot for the life of me find the document any more either in my files or on FDA's website.  Thanks!

10% absolute reference as attached.

Blend Uniformity Draft guidance 2003, that has been already withdrawn.

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

Original Message:
Sent: 10-Aug-2018 16:08
From: Anonymous Member
Subject: Setting Specifications

This message was posted by a user wishing to remain anonymous

​Hi everyone.

I think I am losing my mind here.  I remember back several years ago looking through something from FDA that showed the parameters for setting specifications for active ingredient content in a topical drug product.  I also seem to remember that FDA had accepted generally (subject to verification of the manufacturing process) that a specification using the nominal amount of the active ingredient is the midpoint of the specification and then there was a +/-10% allowance (so if the nominal level is 2% then the specification range for acceptance would be 1.8-2.2%).  I believe this was mainly based on the potential variability in the assay and the preparation of the samples but it also might simply be a bit of variation in getting the active ingredient fully from its packaging into the production vessel.

Does anyone else remember this or can anyone share insight on where that +/-10% might have come from?  I am being asked for a reference for that guidance for setting specification values and I cannot for the life of me find the document any more either in my files or on FDA's website.  Thanks!