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Re: Validation Strategy for NONMEM

From: A.J. Rossini <blindglobe>
Date: Tue, 21 Oct 2008 22:41:20 +0200

There is useless validation, and then there is useful validation. The
latter is about making sure your computational results are
reproducible, the former is about making sure that your documentation
can be photocopied. It's sort of the same thing, if you aren't a

Unfortunately, most on this list tend to be modelers.

On Tue, Oct 21, 2008 at 7:37 PM, <Michael.J.Fossler
> After reading this, it is no wonder scientific productivity is at an
> all-time low. Imagine if Marie Curie had to qualify her radium-purifying
> equipment, or if Alexander Fleming had to validate his petri dishes before
> culturing Penecillium. One day scientists are going to push back against
> these IT people, who just make busy work for everyone.
> Joachim.Grevel
> Sent by: owner-nmusers
> 21-Oct-2008 03:18
> To
> nmusers
> cc
> Subject
> Re: [NMusers] Validation Strategy for NONMEM
> Dear Mark,
> I am engaged in this question since the beginning of this year (not finished
> yet), and I am happy to share some basics of my experiences:
> 1. It is important to specify where the data for NONMEM analysis come
> from. If they come from a GCP source and are already QA-ed when they arrive
> at the doorstep of NONMEM then your system will only subject to GCP
> regulation. Otherwise, you also have to comply with GLP.
> 2. There is no way around what is called here a 'Validation Plan' and
> a 'Risk Analysis'. These documents will trigger a slate of other documents
> (in our case here about 15) which describe Installation, Installation
> Validation, Qualification of Users, Modeling Strategy, Review Processes,
> System Life Cycle Management etc.
> 3. We found it useful to differentiate between 'Exploratory Work' and
> 'Submission Work'.
> 4. Before you worry about passing inspection by the FDA, you need to
> worry about passing inspection of your own company QA officers.
> 5. Just installing NONMEM with NMQual does not render you new system
> 'validated' or 'qualified'. Here my apologies to the excellent folks at
> Metrum, but for various reasons, we ended up not using NMQual.
> 6. You have to know what you are trying to build before you concern
> yourself about QA processes. A number of separate installations on PCs
> linked to a file server is a different animal from a server-based
> installation with a grid engine.
> 7. It all takes more time than you think: make generous budgets and
> time lines.
> I hope I helped more than I confused,
> Joachim
> __________________________________________
> Joachim GREVEL, Ph.D.
> MERCK SERONO International S.A.
> Exploratory Medicine
> 1202 Geneva
> Tel: +41.22.414.4751
> Fax: +41.22.414.3059
> Email: joachim.grevel
> "Vilicich, Mark" <Mark.Vilicich
> Sent by: owner-nmusers
> 10/17/2008 10:08 PM
> To
> <nmusers
> cc
> Subject
> [NMusers] Validation Strategy for NONMEM
> Dear All,
> I am interested in perspectives on strategies for "validating" NONMEM. Also,
> experiences from or with the FDA since the FDA is: a key user, customer of
> analysis and auditor of NONMEM use in the industry. Without a large nonmem
> staff here, the challenge I see is in scaling the validation strategy to
> provide the most efficient environment for doing analysis that is defensible
> to both internal and external audits based on the associated GxP risk level.
> Below are the concepts I've cobbled together, though instead of my
> reinventing the wheel I appreciate anything you could share. Any and all
> gems of insight you can share whether it regard the big picture or some
> detailed specifics, IT centric or business process related. You may send
> them back to the listserver or me directly as you feel appropriate.
> Details:
> ~~~~~~~~~~~~~~~~~~~~~~~~~~~
> From searching the archives and other random bits of knowledge on NONMEM,
> part of the validation strategy is to recognize that NONMEM is not to be
> literally validated. NONMEM may be considered more of a development
> environment, optimized for developing specialized forms of complex analysis
> and modeling. As a development platform, an approach could be that NONMEM
> itself is qualified and each specific analysis is validated individually.
> To support establishing a defensible NONMEM environment, I've also read
> discussions on integrating common software development best practices such
> as version control of the "programming" of nonmem, NMQual and other
> commercial and custom tools for capturing all the metadata related to
> running a specific NONMEM job. These themes support defining the state of
> the NONMEM environment and ability to reproduce the outcomes.
> Also, reading in the archives about the differences in the numeric outcomes
> of NONMEM analyses based on the hardware platform, etc. are helpful to know
> up front and to consider in the validation strategy so it is not destined to
> failure if the target environment is multiplatform or otherwise complex.
> Gaps noticed/topics not discussed:
> ~~~~~~~~~~~~~~~~~~~~~~~~~~~
> Is there opportunity in looking at the risk based approached sanctioned by
> the FDA a few years ago that would make the total validation deliverable,
> including both the application and the model development process, more lean
> and targeted at the primary risk targets?
> Does this scientific software environment lend itself to use of modern agile
> software development methodologies that go far beyond basic iterative
> approaches. These methodologies are being used in software development for
> the regulated/GxP industry.
> I've seen the excellent presentation from 2004 that Joga Gobburu from the
> FDA gave, seems like there has been some progression of thought or actions
> on the proposals included there. Any references to follow-up information on
> it would be helpful?
> Regards ,
> Mark Vilicich
> Early Development
> mark.vilicich
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Muttenz, Switzerland.
"Commit early,commit often, and commit in a repository from which we
can easily roll-back your mistakes" (AJR, 4Jan05).

Drink Coffee: Do stupid things faster with more energy!
Received on Tue Oct 21 2008 - 16:41:20 EDT

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