Re: Validation Strategy for NONMEM

On Tue, Oct 21, 2008 at 9:18 AM, <[EMAIL PROTECTED]> wrote: > > 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.