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November 2017

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Subject:
From:
Bob Friedel <[log in to unmask]>
Reply To:
Pharmaceutical Stability Discussion Group <[log in to unmask]>
Date:
Tue, 28 Nov 2017 14:48:23 -0500
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“…it appears that the results of the 16 temps may have been AVERAGED TO MEET THE NECESSARY CRITERIA.”  

You also noted that you [normally] “do not average temp readings for our other environmental stability chambers validation studies…” 

Until qualified as legitimate or not, this sticks out like a sore thumb and raises a QA red flag. The verbiage “to meet” immediately got my attention and reminds me of the days of “testing into compliance” with Barr vs U.S.: 

https://www.fda.gov/Drugs/DevelopmentApprovalProcess/Manufacturing/ucm212214.htm

Conversely, maybe you can average temperature data from environmental chambers in regards to CYCLED temperature studies vs. CONSTANT temperature units?  I don’t know off the top of my head.  Any guidance from FDA and/or ICH?  

First Question:  Was there a provision in the Equipment Qualification protocol to allow for “averaging” the CYCLED temperature data?  If NO, then the Operational Qualification (OQ) (i.e., “the chamber is running empty”) was not followed as written and an investigation should be initiated before proceeding any further.  In other words, don’t dig the hole any deeper.

I would think that the “study clock" starts (i.e., for whichever cycle) when all of the thermocouples are within the pre-defined +/- 2 degree mark.  I would contact the manufacturer and verify if the environmental chamber is actually capable of meeting the specifications outlined in your OQ.  Second, can the unit meet those criteria in “automatic” operation mode versus “manual” operation mode, as you [obviously] can’t have someone sitting there flipping the switches back and forth!  Finally, I noticed that there was no provision to account for the door of the chamber being opened/closed during the study.  Not sure if that is an issue or not?  If yes, then factor that potential challenge into the revised protocol too.

Bob

  

> On Nov 27, 2017, at 4:18 PM, Eric Hammang <[log in to unmask]> wrote:
> 
> Hello All,
> 
> It has been recommended we update the validation protocol and studies for a stability chamber that will begin being used for a cycling study.
> The program has 4 phases and takes 8 hours to complete before beginning again. It holds at -3C° for 3 hours, ramp to 40C° in 1 hour, holds 40C° for 3 hours, ramp to -3C° in 1 hour, and repeat.
> 
> In review of our last study, we used 16 thermocouples placed methodically and consistently throughout a 40sq. ft. walk-in chamber and I am finding that the 1 hour ramp period for both warming or cooling (plus a 15 minute stabilization period written into the protocol) was still not enough time to get all thermocouples ±2C° of specified temperature. At the time the study was conducted it appears the results of the 16 temps may have been averaged to meet the necessary criteria. We do not average temp readings for our other constant environment stability chambers validation studies and am unable to find any reference indicating it is ok for cycling validation studies.
> 
> The data indicates that some thermocouples took a total of 45 minutes into the 3 hour holding period after the 1 hour ramp period ended for stabilization within that ±2C°.
> 
> Does anyone have experience dealing with a similar scenario? I am seeking guidance for what type of language to use that offers an appropriate defense if scrutinized.
> 
> I am unable to change the cycling program times or temperatures. Also, the controller is working as intended with the input received from the thermocouple and it is capable of ramping faster when needed. For example, it took about 33 minutes to cool from 55C° to -3C° when being checked in a manual operation mode.
> 
> In these instances the chamber is running empty. We will also be simulating an approximate load of between 60-70% of the space in separate studies.
> 
> Any help is much appreciated.
> 
> Kind regards,
> 
> Eric Hammang
> 
> 
> 
> =================================
> The nature of this service is to provide a medium for communication.  The specific statements and endorsements of individuals participating in the discussions are not necessarily those of The Microbiology Network, Inc., the PSDG, or the sponsors of the list.
> 
> ------------------
> The PSDGList (http://microbiol.org/psdglist.htm) is operated from The Microbiology Network (http://www.microbiol.org) and supported by our sponsors as a service to the scientific community.   Please take a second to visit our sponsors' web sites and say thank you for their support of this service.
> 
> ScienTek - http://www.iStability.com/
>   Provides iStability® - Web browser based software for stability management,
>   reporting, testing/data management, statistical data analysis, and more.
> 
> Avista Pharma Solutions - http://www.avistapharma.com/
>   Comprehensive testing and CMC services organization
>   Analytical and Microbiology support to early stage API and drug product development and manufacturing.
> 
> BahnsonEnvironmental Specialties - http://www.eschambers.com/
>   Manufacturer of Quality Stability Chambers, Warm & Cold Rooms, Freezers and
>   Ultra Low Storage Chambers with Complete Validation, Maintenance & Calibration
> 
> Cincinnati Sub-Zero - http://www.cszindustrial.com/
>    Provides a large selection of environmental chambers from benchtop, reach in to walk-in
>    rooms along with chambers for freeze/thaw, temperature cycling applications.



=================================
The nature of this service is to provide a medium for communication.  The specific statements and endorsements of individuals participating in the discussions are not necessarily those of The Microbiology Network, Inc., the PSDG, or the sponsors of the list.

------------------
The PSDGList (http://microbiol.org/psdglist.htm) is operated from The Microbiology Network (http://www.microbiol.org) and supported by our sponsors as a service to the scientific community.   Please take a second to visit our sponsors' web sites and say thank you for their support of this service.

ScienTek - http://www.iStability.com/
   Provides iStability® - Web browser based software for stability management,
   reporting, testing/data management, statistical data analysis, and more.

Avista Pharma Solutions - http://www.avistapharma.com/
   Comprehensive testing and CMC services organization
   Analytical and Microbiology support to early stage API and drug product development and manufacturing.

BahnsonEnvironmental Specialties - http://www.eschambers.com/
   Manufacturer of Quality Stability Chambers, Warm & Cold Rooms, Freezers and
   Ultra Low Storage Chambers with Complete Validation, Maintenance & Calibration

Cincinnati Sub-Zero - http://www.cszindustrial.com/
    Provides a large selection of environmental chambers from benchtop, reach in to walk-in
    rooms along with chambers for freeze/thaw, temperature cycling applications.

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