|February 14, 2014|
Previously published on February 11, 2014
The Electronic Age has changed nearly every aspect of our daily lives, and the day-to-day operations of the U.S. Federal Government are no different. The government is no longer open for business from 9-5, but rather 24 hours a day by virture of electronic media. This 24-hour business day cycle is reflected in a new guidance for industry FDA published earlier this week, titled “Providing Regulatory Submissions in Electronic Format — Receipt Dates.” In that guidance, FDA details not only the Agency’s current policy for assigning receipt dates for Electronic Submission Gateway (“ESG”) (and in-person) submissions (as well as explaining the important distinctions between drug and biologic submissions and receipts), but provides myriad helpful examples of scenarios in which FDA applies that policy and the potential ramifications of submission and receipt date timing. Submission timing is, of course, an important consideration for any drug or biologic company; however, timing is particularly important in Hatch-Waxman World when 180-day generic drug marketing exclusivity is at stake. And in that regard, FDA’s new guidance does not let us down. But we’re getting ahead of ourselves . . . .
FDA’s Receipt Date Guidance first lays down some ground rules and definitions. It identifies the drug and biologic (but not medical device) submissions to which it applies, such as INDs, NDAs, BLA, and ANDAs (including amendments and supplements to them). It also starts out with the basic proposition that “[w]hen FDA receives a submission, the submission is assigned a receipt date.” But that’s important, because the receipt date of a submission has legal and regulatory significance in several contexts. For example, the receipt date of a submission determines the review performance goal date established under the applicable UFA (User Fee Act). Then the guidance goes into the murky territory of “receipt,” “receipt date,” and ANDAs:
It is important to recognize, however, that the “receipt date” as defined under this guidance may . . . differ from the date of “submission” of an ANDA. It is also important to distinguish . . . the “receipt date” as defined under this guidance from the decision by FDA whether or not an ANDA will be “received” within the meaning of the statute and FDA regulations. . . .
FDA regulations set forth criteria for the receipt and initial review of NDAs, BLAs, and ANDAs to determine whether they may be filed (in the case of NDAs and BLAs) or received (in the case of ANDAs) and placed into review. The decision whether or not [an] ANDA may be received depends both on whether appropriate fees have been paid and whether the applications are found to be adequate for review. The receipt date for a premarket application, as described in this guidance, is the date on which an application is deemed to have arrived at FDA. It should not be confused with our subsequent decision to . . . receive an ANDA for review.
With that important distinction explained, FDA states its receipt date policy:
For the purpose of assigning receipt dates, if an electronic submission covered in this guidance arrives via the ESG Monday through Friday, it is deemed to have arrived at FDA on the date and time corresponding to the Official Center Acknowledgment (second acknowledgment) that is automatically sent to the submitter by the ESG. However, except [when a reporting deadline is established in terms of calendar days], if such a submission arrives through the ESG on a weekend, a federal holiday, or another day on which the FDA office that will review the submission is not open for business [(including during a givernment shutdown)], it is deemed to have arrived at FDA on the next day when that office is open for business. If a submission covered in this guidance is submitted in physical media (e.g., paper or CD-ROM), it is deemed to have arrived at FDA on the date on which it arrived physically at the appropriate receiving unit, while open for business, for the FDA center that will review the submission.
In terms of the hours during which FDA can receive a submission, FDA’s receipt date policy translates into the following table (all times Eastern Standard Time/Eastern Daylight Time):
Hours for Receipt of Submission
Postal Service or Private or Commercial Courier
7:00 AM through 6:00 PM
8:00 AM through 4:30 PM
Monday through Friday 12:00 AM to 11:59 PM, excluding federal holidays and days when the FDA office that will review the submission is closed
So, for electronic submissons, FDA is now running on a 24-hour business day clock beginning at midnight. This is different from how FDA had previously counted days. It was not too long ago that electronic submissions made to FDA after 4:30 PM Eastern were considered to have been submitted to FDA on the next business day. Indeed, this is still reflected on at least one FDA webpage:
Q. What is the format of the Official Center Acknowledgement (second acknowledgment)?
A. The Official Center Acknowledgement is a text file that is sent to the sender via the FDA ESG (it is not an email). This text file contains:
1. the original Message ID for the submission;
2. the date/timestamp for when the submission arrived at the Center;
3. a unique identifier (called the CoreID) which the FDA ESG assigns to every submission and uses for reference purposes; and
4. a description of the Center business rules for processing of submissions.
An example of the Official Center Acknowledgement is shown below.
DateTime Receipt Generated: 4:25:17,7-22-2005
The date and time stamp contained in this message conveys when (Center name or Programmatic entity) received your submission from the Electronic Submission Gateway. If your submission was received at (Center name or Programmatic entity) after 4:30 PM EST, the official receipt date for the submission is the next government business day.
The now-abandoned 4:30 PM “pencils down” deadline was critical to The Medicines Company winning a court case concerning the availability of a Patent Term Extension (“PTE”) for ANGIOMAX (bivalirudin). As we reported at the time, the district court, in its decision, relied on FDA’s 4:30 PM deadline to justify a next business day interpretation of the PTE statute at 35 U.S.C. § 156. That decision was ultimately incorporated into the PTE statute by Section 37 of the Leahy-Smith America Invents Act.
Although perhaps best saved for another day, we wonder how (if at all) the change from a 4:30 PM deadline to a Midnight deadline for electronic submissions affects previous submissions, and, in particular, 180-day exclusivity-bearing Paragrpah IV certifications. For example, under the old system, if an ANDA sponsor submitted a Paragraph IV certification to a newly issued patent by submitting an amendment to its pending ANDA via FDA’s ESG at 4:35 PM on a given day, and the NDA sponsor submitted information on that patent to FDA on the next day at 2:30 PM, FDA would treat the 4:35 PM EST ANDA amendment to have been submitted to the Agency on the next business day, thereby making it effective. If, however, in this scenario, the ANDA sponsor submitted its Paragraph IV certification amendment to FDA via the Agency’s electronic portal at 4:35 PM on the same day FDA received information on the patent, the Paragraph IV certification would not be considered effective until the next day. This could be one day too late if another ANDA sponsor, for example, submitted its patent certification amendment to FDA via the Agency’s electronic submission portal at 4:23 PM on the same day FDA received information on the patent and the ANDA amendment was processed by FDA’s servers at 4:29 PM.
Although FDA’s Receipt Date Guidance does not address any potential complications arising from the changeover from a 4:30 PM deadline to a Midnight deadline, it does address some interesting ANDA Paragraph IV certification issues. Here’s the set-up:
When an application is submitted electronically, the submission and receipt occur at almost the same time. . . . For most submissions, the distinction between submission and receipt will have no significance. In rare instances, however, the date of submission thus determined may differ from the date of receipt, and certain significance may attach to the date of submission.
It’s those “rare instaces” we’re particularly interested in, because if there’s one thing we’ve learned from Hatch-Waxman, it’s that no scenario is too “left field.” So here are two rather interesting examples of determining receipt date included in an appendix to the guidance:
Example No. 1
Three substantially complete ANDAs are sent to FDA electronically on April 20, all relying on the same reference listed drug and all containing paragraph IV certifications challenging a patent for the reference listed drug. No applicant has previously challenged the patent. Of these three ANDAs, the last to arrive is transmitted to the ESG and that transmission is completed at 11:55 pm EST, but that ANDA does not completely arrive at CDER until 12:01 am EST the next day, April 21, according to the second acknowledgment automatically generated by the ESG. Assuming they pass technical validation, the first two ANDAs will be assigned a receipt date of April 20, and the third will be assigned a receipt date of April 21. In accordance with GDUFA, however, all three ANDAs will be assigned a submission date of April 20 because the transmission of all three to the ESG was completed on April 20. Consistent with the guidance 180-Day Exclusivity When Multiple ANDAs are Submitted on the Same Day, all three applicants are regarded as first applicants and may be eligible for shared 180-day generic drug exclusivity.
Example No. 2
As in the last example, three substantially complete ANDAs are sent to FDA electronically on April 20, all relying on the same reference listed drug and all containing paragraph IV certifications challenging a patent for the reference listed drug. No applicant has previously challenged the patent. The third applicant begins transmission to the ESG at 11:55 pm EST on April 20. Due to a slow connection, transmission to the ESG is not completed until 12:05 am April 21. Assuming they pass technical validation, the first two ANDAs will be assigned a receipt date of April 20, and the third will be assigned a receipt date of April 21 (receipt dates corresponding to the ESG’s second acknowledgment). In accordance with GDUFA, the first two ANDAs will be assigned a submission date of April 20, and the third will be assigned a submission date of April 21, the date on which transmission to the ESG was completed. Consistent with the guidance [in the previous example], the first two applicants are regarded as first applicants and may be eligible for shared 180-day generic drug exclusivity. The third is not.
So how does a potential first applicant ensure that Example No. 1 and not Example No. 2 plays out for itself? FDA has some words to the wise: Applicants are “encouraged to make their submissions with time to spare, taking into account possible unexpected delays in transmission time to the ESG.”