Editor’s Note: This post is the second of three coinciding with GlobalSubmit’s 3-part Module 1 Education webinar series.
The number of submissions the FDA receives annually outstrips that of similar agencies worldwide by a comfortable margin. That number is expected to grow, which will require modernization of technology and processes on each side of the submission gateway.
On the horizon is the mandate to submit all drug applications, with few exceptions, in electronic format. More immediately, implementation of a new Module 1 will also generate a spike in electronic Advertising and Promotional submissions, as both the Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) can now receive Ad Promo materials in eCTD format.
In CY2014 CDER received just shy of 47,000 FDA 2253 submissions which translates to roughly 80,000 materials. As of June 15, 2015, all eCTD Ad Promo submissions to CDER OPDP must use the new M1 specifications. Paper format and the old M1 specifications are permissible when submitting to CBER.
The M1 initiative, specifically the updated guidelines for Ad Promo submissions, is an example of the FDA gently nudging sponsors to adopt practices that will benefit industry as a whole. The draft guidance on the Ad Promo topic states “the Agency is currently able to process, review, and archive electronic formats in eCTD and firms are strongly encouraged to make such submissions electronically.”
Submitting video, audio and images as DVD media by mail in an age of such impressive computing power at low cost is much too tedious for sponsor and Agency.
By updating the specification, updating the technology, and encouraging a rethinking of internal processes, the FDA is moving toward a more modern business reality.
Updating the Specification
Adding more descriptive metadata to section 1.15 will help reviewers better identify Ad Promo materials, improve system automation, and facilitate recording keeping.
The most noticeable addition is Audience Type – a sponsor must now specify whether promotional materials are directed to a consumer or professional audience. Determining whether materials should be classified as consumer or professional is not always straightforward.
For example, websites with distinct sections for healthcare professionals and consumers should be divided into two separate submissions. However, if a website doesn’t split consumer and professional into distinct content areas and is not solely intended for healthcare professionals, the entire website would be considered a consumer submission.
Read the guidance closely if your consumer vs. professional choice isn’t abundantly clear.
As we move deeper into the TOC, subsection 1.15.2 asks for Promotional Material Document Type, Material Type, Material ID, and Issue Date. Extra granularity will help the Agency tag, view, and archive the materials it receives.
Updating the Technology
Submissions using the new M1 specifications will be accepted by the FDA starting June 15, 2015, but they’re optional unless you want to submit promotional and labeling materials in eCTD to OPDP, as you read earlier, or take advantage of grouped submissions.
No retirement date has been announced for us-regional DTD v2.02, and the timeline of Regulated Product Submissions (RPS) makes it likely that the new M1 specifications will be a bridge rather than a permanent fixture.
In this sense, M1 is much more an opportunity to modernize than a mandate. The first step is to evaluate your current systems for readiness. Has your vendor invested in technology to comply with the M1 specifications, and when will the technology be ready? Developing a comfort level with the systems you’ll use for eCTD publishing, validation, and a review is crucial to starting down this path.
Publishing systems will have to account for the new metadata being collected for M1 when applications or sequences are built, and be able to support creation of grouped submissions.
In order to accept submissions using the new M1, the FDA had to update validation criteria to account for Ad Promo and grouped submissions. Does your system accurately identify new validation errors that could lead to rejection?
The FDA has publically stated that M1 will create a learning curve as review software has been updated. Internally the Agency conducted training sessions to prepare its reviewers for the change.
On the review side there are two major questions:
1. Does your review tool provide visibility as to which submissions are grouped?
2. Can you easily see the entire group of submissions supporting a regulatory activity?
A look at GlobalSubmit’s eCTD publishing software reveals a double icon folder to indicate a grouped submission and a view dedicated to all submissions tied to a decision, i.e., a regulatory activity.
Rethinking Internal Processes
Adopting the new M1 specifications presents a number of potential advantages for sponsors, including
- Electronic submission of Ad Promo materials using the ESG
- Apply 1 sequence to many applications using grouped submissions
- Harmonize, streamline internal processes
As noted in the previous section, first conduct an assessment of the viability of your software systems for publishing, viewing, and validating.
Next you’ll have to assess whether or not using new M1 specifications for Ad Promo and grouped submissions aligns with your organization’s business objectives. There are many points you’ll need to consider.
How is your organization currently completing Ad Promo submissions and in what format?
- Regulatory Operations department is responsible for Ad Promo submissions in addition to all eCTD-related tasks
- Department solely dedicated to Ad Promo submissions
- Outsourcing to a single vendor
- Outsourcing to multiple vendors
If you’re working on Ad Promo submissions internally, your workflow for document creation and review will likely change if you adopt to the new M1 specifications. SOPs would have to be rewritten or revised.
Comparison of Submitting Ad Promo in Paper vs. eCTD
Transitioning from paper to electronic submissions, as is the case for moving to eCTD generally, requires acquisition or application of different skill sets internally. Publishers would need additional training. Again, your workflow, including archival processes, would need to be updated.
What Advantages Would you Realize?
Preparing Ad Promo submissions would not require as much rote, manual effort. There would be no counting of hard paper copies and burning media to discs.
Your organization could also take advantage of the convenience and visibility afforded when performing Lifecycle operations in eCTD. Here are a number of scenarios taken directly from the Ad Promo guidance document.
A video file included in a paper or non-eCTD format 2253 submission does not play. When filing in paper, a sponsor is required to submit the entire 2253 again if part of the original submission is rejected.
If the 2253 submission is filed in eCTD format, a sponsor can simply file an amendment that includes materials that were missing or previously rejected.
For resubmissions, use the “replace” operator attribute to replace the previously submitted files with the resubmission updated files. When resubmitting only part of the original submission, the operator for the correspondence file should be “new.”
Withdrawals should be submitted using the “delete” operator attribute on all leaves that are affected by the withdrawal request. The operator for the correspondence file should be “new.”
When submitting in paper, two paper hard copies of the withdrawal request are required for both CDER and CBER.
Outsourcing Ad Promo Submissions
Finally, maintaining a unique sequence number when outsourcing Ad Promo submissions or working with a partner firm could present a challenge when using the new M1 specifications. Duplicate sequence numbers will result in a rejection.
The Agency recommends assigning a block of numbers to a particular vendor (e.g., start promotional submissions with sequence 5000).
It’s important to note that each company must be using the same DTD version.