By Thomas Christensen
Senior Regulatory Affairs Manager at SynteractHCR, Thomas Christensen, RAC recently spoke about “Lessons Learned for First Time OPDP Submissions, Promotional Material, and Labeling” at DIA Regulatory Submissions, Information, and Document Management Forum in Bethesda, MD. The following is a brief synopsis of his session.
Electronic common technical documents (eCTDs) are already the preferred format to submit regulatory information in many countries, and in May 2017, they became the required standard for submitting New Drug Applications (NDAs), Biologic License Applications (BLAs), Abbreviated New Drug Applications (ANDAs) and Drug Master Files (DMFs) to the FDA. Submissions that do not adhere to the requirements stated in the eCTD Guidance will receive a technical rejection and not be filed.
Therefore, the FDA has updated its eCTD structure to include promotional labeling.
Though the guidance to submit promotional material in eCTD format is not yet final, the change is coming. This requirement to submit promotional material in eCTD will add complexity and more room for error, making it all the more important to prepare for potential challenges.
Whether currently submitting via paper or a hybrid electronic format, submitting advertisements and promotional labeling in eCTD format will require adjustments. Companies that do not already have one will need to apply for an Electronic Submission Gateway (ESG) account, use their own eCTD publishing software or outsource the process.
The FDA Guidance document, “Providing Regulatory Submissions in Electronic and Non-Electronic Format—Promotional Labeling and Advertising Materials for Human Prescription Drugs Guidance for Industry” can help to guide submitters through the Ad/Promo process overall and more specificly the eCTD process, using M1 DTD v3.3 (m1 v2.3).
The FDA Form 2253 “Requests for Advisory Comment Submissions.” form, common to most advertising and promotional labeling submissions, is used differently by the OPDP versus APLB. The OPDP’s Center for Drug Evaluation and Research, or CDER, only requires Form FDA 2253 when final promotional materials are being submitted, for instance. Applicants are required to submit only correspondence and materials for draft to inform this branch. Therefore, when submitting the form to the OPDP the “Draft” or “Final” boxes should NOT be checked.
Conversely, APLB’s Center for Biologics Evaluation and Research, or CBER, requires Form FDA 2253 be submitted for all draft and final submissions. CBER requires use of this form whether the submitter has questions and wants feedback from the FDA or is making a final submission. When submitting to CBER, box 14, titled “For CBER Products Only”, should be checked. Submitters should check the “Final” box on this form only for Final post-marketing submissions to CBER.
Some important XML attributes of Form 2253, of which submitters should make themselves aware, include the following:
The above headings and sub-headings should be specific to the type of material. They will be generated multiple times as new material is submitted and the eCTD hierarchy is created.
Other important considerations in submitting eCTDs for pharmaceutical advertising and promotional materials, include:
Audiences & Indications
As noted, companies should submit consumer- and healthcare professional-directed materials in separate sequences. Additionally, for Form FDA 2253 submissions to the OPDP, if a drug has multiple approved indications that are covered by different reviewers, these should be submitted separately by specific indication if possible.
Include current version of Package Insert with each Ad/Promo submission update leaf title to include date.
The FDA encourages submission of annotated versions of the promotional material(s) cross-referenced to the product labeling and references. Submitters should Include a copy of the current label or reference node. They should also make sure to update the title to be clear it is submitted within the current sequence.
This submission-type should be used for requests for advice-related comments and pre-submissions of revised promotional materials that were previously submitted as “original”. When re-submitting a revised version of draft promotional material, submitters should use the submission-sub-type
Not required for Ad/Promo
The new eCTD submission does not require a Form 356h (or Application to Market a New Drug, Biologic, or An Antibiotic Drug For Human Use), and it does not require a cover letter in module 1.2.
These are just a few of the new processes required as the FDA moves to eCTDs for submitting advertising and promotional materials. Regulatory managers and other submitters, and their organization, need to make time to understand important updates, allow for set up and anticipate complexity of file and submission formats. Early planning can help to build and maintain a knowledge base and ensure smoother processes for initial submissions, and many others to come.
Thomas Christensen, RAC is Senior Regulatory Affairs Manager at SynteractHCR, a full-service contract research organization with a successful two-decade track record supporting biotechnology, medical device and pharmaceutical companies in all phases of clinical development, as well as providing standalone services in biostatistics, safety, medical affairs, and regulatory services support. The company has conducted Phase I-IV studies on six continents and 60 countries, across oncology, immunotherapy, CNS, infectious disease, endocrinology, cardiovascular, respiratory and other therapeutic areas. Thomas Christensen can be reached at Thomas.Christensen@synteracthcr.com.