Raphy,
I understand your problem and I'd answer your questions as:
A. Yes. If the assay test required 10 vials, there should be ten vials in the lab.
B. No. If the stability protocol calls for the assay, you have to stay with the assay specifications. If the only assay specification in your reg filing is the release assay of 95-105, that's what you have to use. We often have assay specs at release of 95-105% but 90-110% at stability and I hope you have something similar.
C. Yes. If you are stuck with the 95-105 spec, any value outside that is OOS and needs investigation. You've already explained why a result of 85-115% would be expected, so if you're brave you could say a result 85-115% is OOS but acceptable and not do any additional testing.
I'm assuming the plan was to pool two vials for assay instead of pooling ten. You may want to assay each vial separately so it matches exactly content uniformity. Either way, I think you'll end up with a stability study with several OOS values that will raise eyebrows when submitted and make any shelf life projection very difficult. Since you mentioned testing additional vials as part of an OOS investigation, is there any possibility of using extras and/or canceling time points to get ten vials in the lab? Trying to save money usually results in extra work for somebody and this time that somebody is you. Good luck.
Robert Moore
Dow Pharmaceutical Sciences
-----Original Message-----
From: Pharmaceutical Stability Discussion Group [mailto:[log in to unmask]] On Behalf Of Raphy Bar
Sent: Monday, October 15, 2012 12:09 AM
To: [log in to unmask]
Subject: Re: [PSDGLIST] What specs when a few stability samples are tested?
Claudia and Tony
The point is: the specs of the lyophilisate vials for release are 95 - 105% and when you test 10 lyophilisate vials the average meets the specs with no problem.
The problem is with testing of stability samples: the stability program consists of ONLY 2 vials per timepoint, in this case you can get OOS results because the average is based on only 2 vials. This is not surprising since the specs of the uniformity of content (UOC) test are wider and realistic:
85 -115%.
The question is:
A, Was it wrong to initially set up a stability programs which calls for testing 2 vials (or a few vials) per each timepoint? In other words, the number of stability samples per timepoint ought to be at least 10, irrespective of whether the product is expensive.
B. If you decide to place only a few vials (e.g.2 vials) in the stability program, would you initially set the specs to be different from the release assay specs but identical with those of UOC? In other words: 85 -115%?. If so, how can you evaluate the inherent stability of the drug product if test results are allowed to fluctuate between the wide 85 -115% specs?
C. If you decide to place only a few vials (e.g.2 vials) in the stability program, would you set the specs equal to the release specs (95 - 105%) and treat any result that comes out OOS, as an OOS and do retesting according to an OOS SOP?
Which answer would you follow?
Raphy
_______________________
Raphael (Raphy) Bar, PhD
BR Consulting
http://sites.google.com/site/brconsultraining/
-----Original Message-----
From: Pharmaceutical Stability Discussion Group [mailto:[log in to unmask]] On Behalf Of Claudia Talamona
Sent: Tuesday, October 09, 2012 12:18 PM
To: [log in to unmask]
Subject: Re: [PSDGLIST] What specs when a few stability samples are tested?
We have the same material, and we have an specifications of 90,0-110.0 for assay reesult, and 85,0-115.0 for uniformity of content. But all of this depends on where would you register your product.
Raphy Bar escribió:
> Dear Stabilitarians,
>
>
>
> A sterile drug lyophilisate powder has specifications of 95 -105% of
> Label Claim and 85 - 115% of label claim for Uniformity of Content.
>
>
>
> As we all know, an Assay of main Active refers to an average result
> obtained from either a tested composite material or from at least 10
> individually tested units.
>
>
>
> I would like to ask what specs would you set for a tested stability
> sample which consists of 2 lyophilisate vials? I am referring to a
> stability storage program where only 2 vials of an expensive drug
> product are tested at each timepoint.
>
>
>
> Would you compare each Assay result of each of the two vials against
> the 95 -105% specs? Or against the 85 - 115% specs?
>
> Would you compare the average Assay result of the two vials against
> the 95 -105% specs?
>
> Would you choose other specification values?
>
>
>
>
>
>
>
> Kind Regards!
>
>
>
> Raphy Bar
>
>
>
>
>
> _______________________
>
> Raphael (Raphy) Bar, PhD
>
> BR Consulting
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High quality controlled environmental walk-in rooms and reach-in chambers
Full installation, validation and spare parts also available
Environmental Specialties - http://www.eschambers.com/
Manufacturer of Quality Stability Chambers and
Provider of Complete Validation & Calibration Services
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