Re: 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. Merck Serono does not accept liability for any omissions or errors in this message which may arise as a result of E-Mail-transmission or for damages resulting from any unauthorized changes of the content of this message and any attachment thereto. If verification is required, please request a hard-copy version. Merck Serono does not guarantee that this message is free of viruses and does not accept liability for any damages caused by any virus transmitted therewith.