Today Eisai Inc. issued a press release entitled "Eisai Announces Extension of FDA Review of Drug Application for Investigational Agent Eribulin Mesylate". The company sites the reason for the extension is "a result of the agency classifying recent responses to questions regarding the chemistry, manufacturing and controls (CMC) section of the NDA as a major amendment to the NDA."
Last month in the post "What is a PDUFA Date?" I laid out the basics behind a PDUFA date and noted that the date is a target date for the FDA to make a decision about a new drug application (NDA) and whether or not the product is approved or there is need for some further work (which results in a Complete Response Letter). It was mentioned in that post that the FDA can, and sometimes does, announce a decision prior to a PDUFA date.
But what about moving the PDUFA date itself? Yep, the FDA can and sometimes does move a PDUFA date, though it is relatively rare. The FDA has a piece on it in the Manual of Policies and Procedures – MAPP 6010.8. Unfortunately, it is not available in English, it is written in beaucratese. I will do my best to translate.
The FDA can move the PDUFA date when there is a "major amendment" made to an NDA which can be because the FDA has requested certain information (a solicited amendment) or because the sponsor of the compound submits an amendment because there is new data that has to go into the application, such as results from a study (an unsolicited amendment). In the case of Eisai, it was due to the former situation.
Examples that serve as the basis for a "major amendment" is information about (i) protocol deviations and the impact that they might have had on study outcomes; (ii) that provides clarification about a manufacturing site; (iii) data inadvertently left out of the final study report; (iv) there is new validation data and analyses; (v) updated data from a previously reported study.
Just because there is a major amendment doesn't mean that the PDUFA date will have to be extended, it just means that it can. If the major amendment is submitted early in the review cycle then the division overseeing the application may not choose to extend the date. If however, the information is submitted to the FDA within 90 days of the PDUFA date, then the original PDUFA date will be extended.
It would be too convenient and too easy if this were spelled out in one document and if there is one, I couldn't find it. But there is also a guidance on the topic that gives some other details not contained in the MAPP. The guidance, which was updated in June 2008, provides a complex formula for figuring out the time of an extension based on when the amendment is submitted, however, in every single example that I could find through a Google Search on the topic, the period of the extension was 3 months from the original 10-month PDUFA date.
And so closes the latest little Tutorial from Eye on FDA. Comments providing further illumination are most welcome because I'm sure there is an expert on this out there somewhere!