Public companies, especially banks and financial services firms, are well-accustomed to online filings; they have been a fact of life for many years. Not so for drug and medical device makers that will soon face new electronic submission requirements from the Food and Drug Administration.
With a flurry of new rules and guidance in recent months, the FDA has set the stage for an overhaul of how it accepts submissions for new drugs and medical devices, adverse event reports, the pre-approval of advertising and marketing materials, and other such filings.
It isn’t so much that the FDA is just now getting into the electronic submissions game. Since 2008 it has encouraged drug companies to submit new drug applications, biologic license applications, and other filings electronically using its Electronic Submissions Gateway portal. Submissions have long been accepted using Electronic Common Technical Document (eCTD) specifications, a standard created to harmonize and streamline submissions to multiple regulators.
Few but the largest drug companies, however, have availed themselves of the opportunity, and for good reason: The FDA never made electronic submissions mandatory. Many companies still rely on paper submissions.
Congress stepped in with the Food and Drug Administration Safety and Innovation Act of 2012, wherein it demanded mandatory electronic submissions. Although the FDA tinkered around the edges of the mandate since that time (no timeline was mandated), the legislative demands are now coming to pass.
The electronic submission of post-marketing adverse event reports became a reality on June 10. Beginning Aug. 14, medical device manufacturers and importers must submit medical device reports electronically. Final guidance issued in May sets the stage for most drug submissions, including new drug applications and biologics license applications; they will be submitted electronically by May 2017. Commercial investigational new drug applications face the same requirement by May 2018. The FDA has also issued new draft guidance on submission protocols for promotional, labeling, and advertising materials for prescription drugs.
“When you read some of the rationales of why the government is doing this, it is partially because setting standards will allow them to better meet their timelines and it will make reviews a lot easier.”
Leslie Tector, Partner, Quarles & Brady
It’s a lot to digest for drug and device makers and time will tell how difficult compliance might be. “The pains might be more or less depending on the size of the company and the capabilities you have,” says David Graham, a member of the products and professional liability practice group for the law firm Dykema. “For larger, more sophisticated companies, they may have plenty of resources to make sure this is all correct, but not every drug company out there is a Pfizer or Merck.”
There may be some advantages for regulator and issuers alike as the FDA moves away from the time-consuming practice of written submissions. “It could make the review process more efficient,” says Leslie Tector, a partner with the law firm Quarles & Brady’s health law practice group. “When you read some of the rationales of why the government is doing this, it is partially because setting standards will allow them to better meet their timelines and it will make reviews a lot easier.” Manufacturers, meanwhile, might appreciate the ability to submit essentially the same electronic form to multiple regulators at once.
Prepping and Filing
Even without the Congressional push, the FDA would likely have championed electronic filings anyway, says Dale Cooke, an FDA expert at the firm PhillyCooke Consulting. “The FDA wants to move as much as possible to electronic filings and there are just as many benefits to doing so for sponsors as the agency,” he says. “The eCTD format for submissions to regulatory authorities around the world has already been adopted by some companies for new drug applications and biologics license applications. Now, they will also have to use that same basic platform for their advertising and promotional positions.”
A bigger headache will be for companies that have ignored the eCTD format altogether until now. “Even if you are a company that has a very well-oiled machine for eCDT publishing for other aspects of your company, when you move your advertising/promotion group into it, there are definitely going to be some challenges,” Cooke says. “You will have people who are dealing with very different types of submissions.”
As for the guidance issued so far by the FDA, it is lengthy, complex, and likely to cause more than a little frustration.
THE PROCESS FOR DEVICE E-FILING
The following is from a “questions and answers” document released by the Food and Drug Administration eMDR (Electronic Medical Device Reporting).
What do I need to do to start submitting MDRs electronically to FDA?
To submit MDRs electronically, you will need to set up a Web Trader Account and then submit test data that is successfully processed through the ESG before you receive a production account to use for your MDR submissions. Here is the process for beginning to file eMDRs:
Request a web trader account from the ESG.
Submit a letter of non-repudiation to FDA.
Obtain a personal digital certificate.
Submit Test Data
Prepare a test eMDR (a mock report and not an actual adverse event report) containing the information specified in the appropriate section of 21 CFR Part 803: 803.32 for user facilities, 803.42 for importers, or 803.52 for manufacturers.
Receive a production account from the ESG. CDRH will notify ESG to provide you with the production account once you have completed successful testing.
Use the production account to send your actual eMDRs to FDA.
You can choose from two options to create your eMDR submission:
There are two options for filing eMDRs:
The eSubmitter program is a free, downloadable application that allows users to create one report at a time. With eSubmitter, the user manually enters the required MDR information into the eSubmitter program. The eSubmitter program allows the user to print a copy of the submitted report(s) and allows the attachment of labeling or other documents to the initial report or to a supplemental or follow-up report.
Health Level Seven Individual Case Safety Reporting
This option provides the capability to create and submit eMDRs either individually or in batches (containing multiple individual reports in a single submission). Entities who choose this option are encouraged to develop systems that can save or print the resultant report and that can encode attachments into their eMDRs.
The imminent confusion, Cooke says, stems from Congress only authorizing the FDA to demand some submissions (or elements of submissions) electronically—so the FDA had to create guidance where some parts were mandatory, other parts not. “There are places where the FDA specifies that you must do X and other areas where it says, ‘We would really like you to do X and encourage it.’ Figuring out some of those things is going to be challenging.”
The FDA’s advice for companies with electronic filing on the horizon: Start now by registering for an Electronic Submission Gateway (ESG) account and sending test submissions. Those tests may have to wait a bit. For device manufacturers readying themselves for the new requirement, they can give things a test drive starting on June 29.
Given the free filing tools the FDA offers for use with its ESG, companies may be able to keep costs manageable (and third-party filing agents abound for those willing to spend for the convenience). Complexity is likely to be the bigger worry.
Filers will need to confirm that their submission has the right structure needed to fit the electronic map the FDA will have at the receiving end, so all data fields match and the submission is accepted, Graham says. “The various labeling and post-market surveillance reports have to match up and go to the right place. From a compliance standpoint, you don’t want the FDA thinking that you haven’t done your full market surveillance report–reporting on adverse events and things like that–just because the data didn’t match up.”
“In the beginning the compliance department or regulatory professionals at these companies are going to be responsible for making sure the new method works, that they are in compliance, or finding out why it doesn’t and they are not,” Graham says. “It’s about getting the right identifiers and certificates and electronic signature elements correct from the start and then making sure the people in the various places that prepare reports know how to submit them.”
An important reminder: Other than the filing method, neither deadlines, expectations, nor the required scientific data changes.
Cooke’s advice is that firms understand the nuance to their filings and how different interests within the company may need to use the same reporting tools differently. Get all of those details right, establish what information you are going to collect, prepare how you are going to present the information, and develop the processes and procedures needed to make sure that everything works.