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Re: Validation Strategy for NONMEM

From: Jun Shen <jun.shen.ut>
Date: Wed, 22 Oct 2008 09:08:48 -0500

Dear Joachim,

Can you share some of your findings? What system configuration seems to be
optimal (hardware/OS system, compiler, any aiding software)? Thanks.

Jun

On Wed, Oct 22, 2008 at 1:21 AM, <Joachim.Grevel

>
> Dear all,
>
> one of the more useful things we did was an exchange of data files and
> models with a prominent member of our modeling community. This way we
> challenged various aspects of our installation, found some soft spot,
> corrected it, and wrote a document that is worth more than the ink and the
> paper. Yet again, all we did was assuring that our results match those of a
> number of other installations (different compilers, operating systems,
> processors). Furthermore, we got an idea of the comparative speed of our
> installation. These are useful things to have documented when you are a
> system administrator and modeler at the same time.
>
> 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
>
>
>
>
> *"A.J. Rossini" <blindglobe
>
> 10/21/2008 10:41 PM
> To
> Michael.J.Fossler
> cc
> Joachim.Grevel
> Subject
> Re: [NMusers] Validation Strategy for NONMEM
>
>
>
>
> 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
> modeler.
>
> 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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>
>
> --
> 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).
>
> Drink Coffee: Do stupid things faster with more energy!
>
>

Received on Wed Oct 22 2008 - 10:08:48 EDT

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