While tied up with clients all day, I just knew Salmon would eventually surface -- and grace us with some expert insight on the Merck "NDA bounced by FDA" news [when I saw the story scroll through my iPhone WSJ app, as I sat locked (helplessly) in a meeting/conference room]. Here is the operative language, from page 46 of Merck's Form 10-Q, this afternoon:
. . . .the FDA recently refused to file the application. The FDA has identified additional manufacturing and stability data that are needed and the Company is assessing the FDA’s response in order to determine a new timetable for filing. . . .
And now, while noting that Larry Husten, over at Cardiobrief had also written earlier today, on the same topic (H/T Marilyn Mann!), I'll turn it over to Salmon, thus:
. . . .The only reason to not file an application is that it's not complete on its face. In other words, there's not even enough information included to review it. Even if prima facie, the studies were negative (or that the sponsor had been told that biomarkers just wouldn't cut it) and the FDA knew the drug had to be turned down eventually they would still file it, and do a review.It's almost unheard of for a big company to not include even adequate information to allow review -- so that it results in a refusal to file. In fact what companies will often do is get the FDA to agree to a submission of the additional data during the review cycle. Of course if it doesn't come in when it was promised the review of this additional info may have to be done in a short time frame and veeeery superficially.
Since the refusal-to-file criteria is a policy that effects the public it should be publicly available somewhere. I'm just too lazy to look for it right now.
Veeery Interesting.
Salmon
November 2, 2009 @ 7:42 PM
Thanks again, Salmon! I'll go look for it now, Salmon -- but it may be that FDA agreed to wait to make this decision public, until Merck could make an SEC filing on the topic, since it is an arguably material development -- in SEC parlance. I will report back.
In the meantime, here is the December 9, 2008 slide on the combo pill, from Whitehouse Station -- and my post on it, from that day:
2 comments:
The FDA doesn't need to withhold information of this sort as they simply don't ever provide any information on NDA filings. It is entirely up to the sponsor when and if they make information regarding filing or review status public. If you recall, I had to infer the approximate filing and PDUFA due dates of asenapine (Saphis) from press reports.
(b) FDA will not publicly disclose the existence of an application or abbreviated application before an approval letter is sent to the applicant under 314.105 or tentative approval letter is sent to the applicant under 314.107, unless the existence of the application or abbreviated application has been previously publicly disclosed or acknowledged.
Sec. 314.430 Availability for public disclosure of data and information in an application or abbreviated application.
(c) If the existence of an unapproved application or abbreviated application has not been publicly disclosed or acknowledged, no data or information in the application or abbreviated application is available for public disclosure.
In the past the criteria for approval of combination products were quite clear. There had to be greater benefit from the combination product (combination of 2 prescription drugs) than from either agent administered separately. However laws and regulations change and on a quick check I can't find this language in the current version of the CFR. In fact the current definition of a combination product on the FDA website is something such as a drug and a device (e.g. autoinjector pen with drug) and does not include 2 drugs. A new product of two drugs however does appear to be a new indication and thus clinical studies may be needed. (You can argue that bioequivalence should be sufficient however this does not take into account drug interactions effecting metabolite profiles which might change toxicitity or efficacy.) I do not see where the old criteria of an increase in efficacy with the combination needs to be fulfilled. However I would need to do much more checking to see what the current regs are.
This is a nuanced issue and a definitive answer would require much more research and information than I have access to.
Salmon
Here's the old guidance on refusal to file.
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM080561.pdf
(Based on my previous comments you can see FDA typically didnt' follow it.)
There are also newer guidances that add additional reasons to refuse to file including failure to pay PDUFA review fees and lack of ability to access electronic files or to be able to navigate electronic files (e.g. links that don't work, lack of tables of contents, inappropriate format for electronic submissions etc.)
Salmon
Post a Comment