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Re: 21 CFR Part 11

From: A.J. Rossini <blindglobe>
Date: Wed, 9 May 2007 13:10:39 +0200

Sorry Andreas, not quite right on the technical details, though the
spirit is right on, of course.

At a high level, 21 CFR Part 11 has 2 components: electronic
signatures and audit trails.

With respect to the first, NONMEM isn't relevant.

With respect to the second, submitted results should be done using
such a system, but NONMEM per-say isn't involved except as a black box
within such a system. Replace "NONMEM" with any statistical or data
analysis tool.

What most people really intend to say, technically, is that NONMEM is
GxP-relevant (not 21CFR Part 11 relevant). And hence requiring
qualification as an IT system (not necessarily validation -- it's
basically a programming language, not a simple application, which is
where validation is possible)

And as part of the spirit of those (GxP, i.e. ICH) guidelines, of
course best practices with respect to data analysis should be
followed, work should be reproducible in a temporal neighborhood of
when the initial results were run, and records (data, input, output)
should be kept.

Gosh gillikers.

best,
-tony





On 5/9/07, Andreas Krause <akrause
> Maybe we should put this discussion on a more solid footing, so here are
> some more thoughts:
>
> No software is 21 CFR part 11 compliant per se - not even SAS. What
> matters is that you can show what you did in full detail and reproduce
> it - even 10 years later. So you need to keep (and keep track of) all
> data files, control streams, output files, modifications, and whatever
> it takes to reproduce results. Call it the audit trail.
>
> When it comes to nonmem, in some extreme cases the results vary on
> different hardware or operating systems, sometimes even on the same
> computer using different compilers.
> So in the very least you need to be able to tell what compiler and
> version on what operating system and hardware you used, keeping log file
> and all other output in its original form.
> Simple example: it is not good if the date stamp on your nonmem control
> stream is newer than the date stamp of the log file.
>
> Validation does not mean that you get "correct results" (whatever that
> means), just that your results and the steps you took are reproducible.
> Defining up front what you are going to do is not required (as seems to
> be suggested below).
> On the other hand, being 21 CFR part 11 compliant is mostly relevant for
> submissions, and that frequently means population PK or other analyses
> defined up-front.
>
> One of the problems with nonmem is that software validation includes an
> assessment of how the software was developed and what quality control
> checks were employed. Often includes a developer and vendor audit.
> Usually you have 3 categories towards a full validation, software
> validation, installation qualification, and operational qualification.
> See also http://www.validation-online.net/
>
> Validation can be done, and I once helped getting it done. It is mostly
> paperwork and getting a system in place that everyone uses consistently
> - or that forces people to be compliant.
> There are large systems in place that keep track of everything. These
> systems can be software solutions, operating system-based solutions, or
> databases like PKS where nonmem control streams and output are stored
> where the data sits anyway.
>
> We are sometimes concerned with nonmem validation, and it is certainly a
> topic when it comes to submissions.
> So I hope this sheds more light on the topic.
>
> Andreas
>
>
>
>
>
>
> -----
> Andreas Krause, PhD
> Pharsight Corporation
> Strategic Consulting Services
> http://www.pharsight.com/
>
>
>
>
> ________________________________
>
> From: owner-nmusers
> On Behalf Of David J Garbutt
> Sent: Monday, May 07, 2007 12:01 AM
> To: nonmem
> Cc: NON mem users
> Subject: Re: [NMusers] 21 CFR Part 11
>
>
>
> Hello Steve,
>
> It seems like NONMEM jobs are not part 11 compliant, are
> they? Also, PK analyses are exploratory and cannot be predefined. The
> FDA asks for SAS files and NONMEM works with text files. This also
> makes Part 11 less related.
>
> Thank you,
> Pavel
>
> ----- Original Message -----
> From: Steve Chapel
> Date: Thursday, April 19, 2007 12:07 pm
> Subject: [NMusers] 21 CFR Part 11
> To: nmusers
>
> > I'm looking for the document from the FDA called the "21 CFR
> > Part 11,"
> > which are the regulations for the handling of electronic
> records
> > and
> > signatures required by the FDA.
>
>
>
> Hi,
>
> I have been off-line for a while so I missed this interesting thread.
>
> NONMEM jobs are not compliant in themselves, but can be run in a
> compliant environment. As some one else already mentioned a product I
> will refer you to my paper at the PhUSE 2005 conference. It mentions SAS
> but the environment discussed in that paper covers SAS, S-plus (batch)
> and NONMEM.
>
> The easiest place to get the paper is at lex Janssen's site :
> http://www.lexjansen.com/phuse/2005/as/as09.pdf
>
> Dave
>
> --
> Dave Garbutt
>
> Ingelsteinweg 4d
> CH 4143 Dornach
>
> +41 79 326 8970 (Home: 061 692 6349)
> http://www.mybasel.ch/verkehr_regioplan_karte.cfm?ID=Strassen,14139&Para
> Zoom&Zoom=3000
>
> ________________________________
>
> Peace is made with yesterday's enemies. What is the alternative?
>
> Shimon Peres, Israeli politician
>
>
>
>
>
>


--
best,
-tony

blindglobe
Muttenz, Switzerland.
"Commit early,commit often, and commit in a repository from which we
can easily roll-back your mistakes" (AJR, 4Jan05).
Received on Wed May 09 2007 - 07:10:39 EDT

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