WAYS Webinar: Ad Promo Submissions: Preparing for the eCTD Mandate

This webinar provides an in-depth exploration of the FDA's eCTD mandate for advertising and promotional (Ad Promo) material submissions, focusing on the transition period leading up to the June 24, 2021, effective date. Presented by Allison Steffen from WAYS Pharmaceutical Services, the session aims to equip life sciences teams with a practical understanding of the final guidance released by the FDA in June 2019. It addresses common challenges and ambiguities, offering a crash course on how to translate the extensive guidance into the required electronic Common Technical Document (eCTD) submission format.

The presentation begins by outlining the historical context of the industry's shift from paper to electronic submissions, driven by the FDA Safety and Innovation Act (FDASIA) of 2012. It then delves into the critical distinction between mandatory and non-mandatory eCTD submission types. Mandatory submissions primarily include final samples of promotional materials submitted via Form FDA 2253 upon first distribution, and pre-submissions for products granted accelerated approval (Subpart H or E). Non-mandatory submissions encompass general correspondence and voluntary draft material reviews, though the webinar strongly encourages adopting eCTD for these for efficiency.

A significant portion of the webinar is dedicated to the practical aspects of eCTD compilation, offering detailed tips and highlighting common pitfalls. Steffen meticulously walks through the structure of Module 1.15, where most Ad Promo materials reside, explaining the required metadata and the specific placement of various documents like the 2253 form, product labeling, clean promotional materials, and annotated versions with supporting references. The session also differentiates between requirements for CDER and CBER products, particularly concerning the 2253 form and draft material submissions. Special attention is given to the rigorous requirements for accelerated approval products, which necessitate pre-review and highly detailed annotated materials and references to guide FDA reviewers. The webinar concludes with actionable advice for the transition period, urging companies to strategize early, train staff, and convert existing applications to the latest eCTD Module 1 version.

Key Takeaways:

• eCTD Mandate for Ad Promo: The FDA's final guidance on electronic Ad Promo submissions, released in June 2019, established a 24-month transition period, making eCTD format mandatory for certain submission types by June 24, 2021.
• Mandatory Submission Types: Final samples of promotional materials submitted under Form FDA 2253 (upon first distribution) and pre-submissions for products under accelerated approval (Subpart H or E) are mandatory in eCTD format.
• Non-Mandatory but Recommended: General correspondence and voluntary draft material submissions are not mandatory in eCTD but adopting the format is highly encouraged for streamlining processes and proactive engagement with the agency.
• Module 1.15 is Key: Approximately 90% of Ad Promo submission content, including cover letters/correspondence and promotional materials, will reside in Module 1.15, with specific subsections for various interaction types and material categories.
• US Module 1 Backbone Version 3.3: All eCTD Ad Promo submissions must utilize version 3.3 of the US Module 1 backbone, which has been in use since 2015 and includes important updates, particularly around Module 1.15.
• No Bundling: Ad Promo submissions cannot be bundled with other NDA or BLA activities (e.g., CMC amendments). Materials for consumers and healthcare professionals must be submitted separately, as should different types of Ad Promo submissions (e.g., correspondence with 2253).
• Specific Form Requirements: For 2253 submissions, the form itself is crucial, requiring details like audience type (professional or consumer), material type, dissemination date, and a unique material ID. CDER only requires the 2253 for final samples, while CBER requires it for both final and draft materials.
• Product Labeling: The current approved product labeling must be submitted with every 2253 sequence, placed in Module 1.14.6, and always marked with the "new" operator, even if cross-referenced.
• Accelerated Approval Products (Subpart H/E): These products require mandatory pre-review of promotional materials before release. Pre-submissions include draft materials for the first 120 days of marketing (before PDUFA date) and subsequent materials (30 days before intended use).
• Required Annotations for Drafts: For accelerated approval pre-submissions and voluntary draft reviews, required annotated versions of promotional materials are needed. Each claim must link directly to an annotated source (label or other references), with specific lines highlighted.
• DTC TV Ads: While not currently mandatory for early submission, it is highly recommended to submit Direct-to-Consumer (DTC) TV ads early for agency review due to their wide reach, even though the 2012 guidance on mandatory 45-day pre-dissemination review has been removed from the final Ad Promo guidance.
• Common FDA Issues: Avoid submitting Form 356h or a cover letter in Module 1.2 or 1.15.1 for 2253s. Ensure the product label is consistently included in 1.14.6. For accelerated products, provide a separate annotated label for each material. External hyperlinks to webpages are not allowed; websites must be included as acceptable file formats in the annotated references section.
• Transition Period Strategy: Companies should define resources, evaluate outsourcing vs. in-house capabilities, get trained on eCTD and Module 1 version 3.3, convert existing NDAs/BLAs to Mod 1 v3.3, and follow submission format history (e.g., amend paper submissions in paper, new submissions in eCTD).

Key Concepts:

• eCTD (electronic Common Technical Document): An electronic format for submitting applications, amendments, supplements, and reports to regulatory authorities, standardized across regions.
• Ad Promo Submissions: Regulatory submissions related to advertising and promotional materials for pharmaceutical products.
• Form FDA 2253: A form used to submit final samples of promotional materials to the FDA at the time of first dissemination.
• Accelerated Approval (Subpart H or E): A regulatory pathway for drugs treating serious conditions with unmet medical needs, allowing approval based on surrogate endpoints, often requiring mandatory pre-review of promotional materials.
• Module 1.15: A specific section within the eCTD Module 1 backbone (US version 3.3) designated for Ad Promo materials and related correspondence.
• Annotated Materials: Promotional materials or references with specific claims or information highlighted and linked to their supporting sources (e.g., product label, journal articles).
• CDER (Center for Drug Evaluation and Research) & CBER (Center for Biologics Evaluation and Research): Two centers within the FDA responsible for regulating drugs and biologics, respectively, with slight differences in Ad Promo submission requirements.

Examples/Case Studies:

• Website vs. Print Ad for Dual Audience: If a material serves both healthcare professionals and consumers, it should be submitted to the audience that will receive the bulk of the information. For a website with separate sections, separate sequences are ideal. For a print ad, if not exclusively for HCPs, it should be submitted as a consumer material.
• Multiple Indications/Review Divisions: If a product has multiple indications falling under different CDER review divisions, it is recommended to keep the Ad Promo submissions for those indications separate.