Re: Validation Strategy for NONMEM

On Wed, Oct 22, 2008 at 1:21 AM, <[EMAIL PROTECTED]> wrote: > > 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: [EMAIL PROTECTED] > > > > > *"A.J. Rossini" <[EMAIL PROTECTED]>* > > 10/21/2008 10:41 PM > To > [EMAIL PROTECTED] > cc > [EMAIL PROTECTED], [email protected] > 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, <[EMAIL PROTECTED]> wrote: > > > > 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. > > > > > > > > [EMAIL PROTECTED] > > Sent by: [EMAIL PROTECTED] > > > > 21-Oct-2008 03:18 > > > > > > To > > [email protected] > > 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: [EMAIL PROTECTED] > > > > > > > > "Vilicich, Mark" <[EMAIL PROTECTED]> > > Sent by: [EMAIL PROTECTED] > > > > 10/17/2008 10:08 PM > > > > To > > <[email protected]> > > 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 > > [EMAIL PROTECTED] > > > > ________________________________ > > > > This message and any attachment are confidential, may be privileged or > > otherwise protected from disclosure and are intended only for use by the > > addressee(s) named herein. If you are not the intended recipient, you > must > > not copy this message or attachment or disclose the contents to any other > > person. If you have received this transmission in error, please notify > the > > sender immediately and delete the message and any attachment from your > > system.