Synchrogenix was well represented at DIA’s Annual Regulatory Submissions, Information, and Document Management (RSIDM) Forum held earlier this month. One of the reasons RSIDM is such a valuable meeting for Regulatory Operations professionals is because it is so well attended by U.S. FDA staff members who participate both as speakers and fellow attendees. We particularly look forward to the “Ask the Regulators” sessions, where FDA representatives answer questions directly from the attendees. Following are highlights from the ‘Ask the Regulators’ sessions.
Highlights from the ‘Ask the Regulators’ Sessions
Addressed by multiple panel members
- It should come as no surprise that government shutdowns negatively impact work at FDA. Although application review and product safety activities are generally funded by user fees, most other activities rely on funding from Congress. Work such as guidance creation, standards development, infrastructure updates, and harmonization efforts are all placed on hold during a government shutdown, thus delaying progress.
- A specific form for DMF submissions is currently under development by FDA, with plans for it to be released for use by the end of the calendar year. FDA will post a Federal Register notice before the form goes live.
- FDA currently plans to transition to eCTD v4 (a.k.a., RPS) with a pilot “sometime” in 2020, followed by full acceptance in 2021.
- One attendee sought guidance from the regulators after explaining that some of their clients do not use an eCTD viewer, but instead review eCTD sequences via a web browser. In doing so, they have trouble accessing the style sheets and displaying the XML correctly. The FDA panel unanimously agreed that the best solution would be for the client to use an eCTD viewer to view their sequences.
- Do you or your clients needs an eCTD viewer? Synchrogenix’s GlobalSubmit WebReview ensures easy anytime, anywhere access to applications. Click here to learn more and to watch a brief product preview.
- The requirement to include program files with ADaM datasets is specific to each review division. You should consult with your RPM to determine if you should provide them in your application
- Synchrogenix recommends that you always provide the program files with ADaM datasets. They should be readily available from your stats vendor, and thus are easy to include in the application with a minimal publishing effort.
Addressed by Valerie Gooding, Regulatory Information Specialist, FDA
- Gooding confirmed that it is acceptable to submit eCTD sequences out of order and that this practice will not result in a rejection of your submissions. However, she cautioned Sponsors to ensure they do not reuse an already-submitted sequence number, as a duplicate sequence number will result in a technical rejection.
- Gooding confirmed that it is acceptable to designate certain blocks of sequence numbers (e.g., the 5,000’s) for OPDP or safety submissions.
- Synchrogenix regularly employs this practice for our clients, especially for those with frequent OPDP or safety submissions.
- Gooding explained two important points related to cross application hyperlinking:
- Such links should be created via the XML backbone
- Sponsors are encouraged to consider the use of cross application hyperlinks to first do a test submission with FDA before employing such links in a real submission
- Gooding discussed the situation where document A is replaced (v2) and thus hyperlinks within document B now point to the old version of document A (v1). In such a case, she stated that FDA does not expect Sponsors to update document B solely to refresh the hyperlinks from document A v1 to document A v2. She noted that the eCTD viewer clearly identifies for reviewers when such a document has been replaced and they are able to navigate themselves to the current version.
- Gooding (re)confirmed that the Append operator should be avoided in favor of the Replace operator.
Addressed by Mark Gray, Senior Project Manager, CBER – FDA
- Gray was asked if CBER would consider issuing pre-assigned application numbers farther in advance than their current practice. He did not have an answer, but promised to investigate the issue. He noted that CBER had problems with numbers being assigned but never used in the past, which may have led to the current practice.
- There are no current plans to implement eCTD for medical device submissions.
- FDA is aware that many literature reference PDFs include security features limiting the publishing work that a Sponsor can perform and thus FDA is forgiving in what they will accept.
- CBER tracks pre-submission correspondence, such as pre-IND meeting correspondence, separately from the IND and assigns them different tracking numbers. When transitioning from pre-submission correspondence to a new IND submission, request a new IND number from CBER (i.e., do not continue using the previously assigned PS number), and begin your IND with sequence 0001.
Addressed by Jonathan Resnick, Project Management Officer, CDER – FDA
- Resnick discussed processing times and delays in receiving CDER’s third acknowledgement from the ESG. He revealed that a frequent cause for delays is when the information on your fillable application form (i.e., Form FDA 356h or 1571) does not match the metadata in your application XML (e.g., sequence number, application number, etc.). In those cases, your sequence cannot be automatically processed and must be held for manual processing. If there are no errors present and your sequence can be automatically processed, the acknowledgements are typically delivered within an hour.
- Approximately 50% of all eCTD sequences received by FDA are using US Regional DTD v3.3. He stated that FDA would like to see all CTD sequences use v3.3, as it offers many benefits including additional submission types, allows for grouped submissions, and it allows FDA to use automation to process sequences upon receipt.
Addressed by Suranjan De, Supervisory Health Science, CDER – FDA
- De addressed the forthcoming change to allow the submission of Individual Case Safety Reports (ICSRs) for INDs via the E2B format instead of via eCTD submissions to the IND. In short, the format offers many advantages, including no requirement for cover letters or 1571s, and the avoidance of submitting duplicate ICSRs across multiple INDs. FDA expects to issue new guidances on this topic by Summer 2019 and to begin accepting ICSRs for INDs in the E2B format by Fall 2019. Initially, compliance will be voluntary, but at some point in the future, it will become mandatory.
Additional Sessions Presented by FDA
Additionally, Ta-Jen Chen, Project Management Officer, CDER – FDA presented a session on the technical rejection criteria for study data. Jonathan Resnick presented a session on eCTD metrics and guidance information. Information from both sessions will be discussed in more detail in future blog posts.