US regulators have released yet another guidance document on electronic submissions-the US Food and Drug Administration's (FDA) third in the span of a week-this time on receipt dates for drug applications submitted electronically.
In 2012, the Food and Drug Administration Safety and Innovation Act (FDASIA) was passed into law, and with it a provision mandating that all applications submitted under Section 505(b)/(i)/(j) or 351(a)/(k)-that is, any new drug, investigational drug, generic drug, biologic drug or biosimilar drug-would need to be submitted electronically in a format specified by FDA.
Instead of releasing just one guidance covering all aspects of the electronic submission process, FDA has instead proposed a series of guidance documents covering single issues.
For example, a draft guidance released on 6 February 2014 calls for industry to use only FDA-approved formats when submitting study data, or else risk having their applications rejected. And a "roadmap" guidance released earlier in the week provided a general outline of how FDA expects to update the guidance documents in the future.
The latest guidance is intended to answer a small yet critically important question: How are receipt dates calculated for electronic submissions?
While seemingly small in nature, the importance of the answer is due to how many of FDA's regulations require submissions by a certain date before or after an action. Investigational New Drug (IND) applications must be submitted a certain number of days in advance of the start of a clinical trial; adverse event reports a certain number of days after an unexpected event; and first-to-file designations give generic drug producers 180 days of exclusivity.
So while at worst a miscalculation might cost a day or two, that day or two could be the difference between compliance and noncompliance, and even hundreds of millions of dollars in extra revenue.
Submitted vs. Received
Where this gets tricky is that there are regulatory distinctions between a company's submission of an application and FDA's receipt of that application. For example, during the 2013 government shutdown, companies could submit applications to the agency, but FDA did not receive them until it reopened for business.
Something is therefore deemed to be "submitted" when FDA has successfully received the electronic submission in its electronic submission gateway (ESG). For example, if a company submits an application on a Sunday, FDA may not formally receive it until a Monday. The data of submission for regulatory purposes would therefore be a Monday. FDA also acknowledged that in rare circumstances, a delay between a company sending a submission and FDA receiving it may occur. This could have a meaningful impact if an application was sent at the very end of the day, making FDA's day of receipt the day after it was submitted.
In addition, FDA may refuse to file an application if the corresponding fees have not been paid. To again reference the government shutdown of 2013, the following scenario occurred:
If a company had paid its user fees, FDA was legally able to accept and process the company's subsequent application.
If a company had not paid its user fees, FDA could not collect the user fee (its authority to collect them had lapsed), and therefore could not file the application since the fee had not yet been paid.
However, the receipt date is separate from the filing date. The former is deemed to be the day on which an application arrived at FDA; the latter is the day on which FDA accepts a document for review and associated review timelines begin.
The guidance document goes on to elaborate on the specifics of the submission process. Under the new electronic submission system, FDA will accept submissions from 12:00 am on Monday through 11:59 pm EST on Friday. It will be closed on Saturday and Sunday.
The nuances of FDA's process are also evident in the guidance. In addition to an initial receipt by the ESG, FDA also has a second receipt notice generated by the receiving center (CDER or CBER). For instances in which the ESG receipt is on one day, and the Center acknowledgement is on the next, FDA will use the ESG's submission date unless it was sent to the incorrect Center through sponsor error, it said.
Likewise, all technically deficient submissions will not be deemed "submitted" until they are fixed, FDA said. This includes examples like the presence of a computer virus, file format incompatibility, damaged media or inaccurate metadata. Sponsors will be responsible for correcting deficiencies and resubmitting to FDA, the guidance said.
If those deficiencies are not corrected within the current user fee cycle (usually by 1 October of a given year), the sponsor will be responsible for paying the adjusted user fee for the next fiscal year as well.
The index of the guidance contains many specific examples that may be experienced by industry.
Providing Regulatory Submissions in Electronic Format - Receipt Dates