I think the question of validation is very different from the risk analysis
referenced in the subject line.
On the subject of the FDA accepting open source software. Personally I've
done two sBLA submissions where simulation results were essential aspects
of the filings. Both were approved and during the filings we included both
the results from R as well as the R code (as requested by the FDA).
On Fri, Jun 19, 2020 at 8:41 AM Helmut Sch?tz <helmut.schuetz at bebac.at>
wrote:
> Dear all,
>
> any (!) software used in regulated environments has to be validated.
> Regrettably is is a misconception by many working in the pharmaceutical
> industry that only studies evaluated by SAS are accepted by the FDA.
> See this one-pager https://www.fda.gov/media/109552/download and a
> presentation by the FDA's Paul Schuette at the useR! 2016
> (
>
https://channel9.msdn.com/Events/useR-international-R-User-conference/useR2016/Using-R-in-a-regulatory-environment-FDA-experiences
> ).
> Note that the FDA itself uses R in modeling & simulation.
>
> Contrary to proprietary (off-the-shelf, commercial, you name it)
> software ? where only a black box validation (aka, rubbish in, rubbish
> out) is possible ? open source SW allows ? in principle ? a white box
> validation is possible.
>
> Relying on proprietary SW is not necessarily a good idea ("We payed a
> lot, hence, it will work.") Stephen Senn once told me (given, a good
> while ago) that after an update of SAS, the Welch-test for unequal group
> sizes / variances collapsed into the simple t-test. He called up SAS and
> got the coder on the line. He inspected the source and after a couple of
> minutes replied "Hey, you are right. We screwed up." It took SAS
half a
> year to roll out a corrective patch. What about clinicial studies
> evaluated in the meantime?
>
> We published a couple of papers in a specific field comparing software
> (doi:10.1208/s12248-014-9661-0, doi:10.1208/s12248-014-9704-6,
> doi:10.1208/s12248-020-0427-6). It turned out that one of the commercial
> [sic] SWs tested was seriously flawed. Consequences: Dozens of approved
> drugs taken off the market. The glitch in the software was _partly_
> corrected in 2014 and the vendor stopped marketing it in 2019.
>
> Just by two cents
> Helmut
>
> --
> Ing. Helmut Sch?tz
> BEBAC ? Consultancy Services for
> Bioequivalence and Bioavailability Studies
> Neubaugasse 36/11
> 1070 Vienna, Austria
> T +43 1 2311746
> M +43 699 10792458
> E helmut.schuetz at bebac.at
> W https://bebac.at/
> C https://bebac.at/Contact.htm
> F https://forum.bebac.at/
>
> ______________________________________________
> R-help at r-project.org mailing list -- To UNSUBSCRIBE and more, see
> https://stat.ethz.ch/mailman/listinfo/r-help
> PLEASE do read the posting guide
> http://www.R-project.org/posting-guide.html
> and provide commented, minimal, self-contained, reproducible code.
>
--
John
:wq
[[alternative HTML version deleted]]