Addressing eCTDs & New Regulatory Standards for Pharmaceutical Advertising & Promotional Materials

What Sponsors Need to Know: Addressing eCTDs and New Regulatory Standards for Pharmaceutical Advertising and Promotional Materials 

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 will become 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, preparing to submit  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:

• Promotional material audience – submitters will need to indicate if the intended audience is consumer or professional. This is an important field, as for all submissions, consumer-directed promotional materials and healthcare professional-directed materials must be submitted separately.

• Document attributes:

• Promotional material type – submitters will need to indicate how the content is planned to be used. See Module 1 of eCTD using version 3.3 of the us-regional­ backbone file for a full list, but specific examples of what might be entered in this field, include: Promotional 2253 (indicating the form and materials are required from submitter at first publication of marketing and advertising materials) or Request for Advisory Launch (voluntary submission of launch promotional materials for FDA review and comment sent prior to dissemination/publication).

• Material ID –  this is the unique identifier, or attribute, indicating the type of media/delivery method for the promotional material. The material-id attribute may consist of up to 30 alpha and/or numeric characters. Specific entries might contain: audio, book, CD-ROM, direct mail, etc.

• Issue date – this is the date of projected initial distribution; when the promotional-material-doc-type is anticipated to be a final promotional 2253 submission (this should not be submitted in draft types to CBER). This should follow the date format: yyyymmdd (4-digit year, 2-digit month, 2-digit day).

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.

Package Insert

Include current version of Package Insert with each Ad/Promo submission update leaf title to include date.

Annotations

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.

Resubmissions

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 <attribute = resubmission >. They should also use the “replace” operator attribute to replace the previously submitted files with the resubmission’s updated versions.

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. He can be reached at Thomas.Christensen@synteracthcr.com.