Abstract
In June 2019, the Food and Drug Administration (FDA) issued its final Guidance on submission of advertising and promotional materials to the Office of Prescription Drug Promotion (OPDP) in eCTD format through the electronic gateway. Our goal was to put in place a stepwise plan and clear process to submit these materials in advance of June 2021 when electronic submissions become mandatory. The first step was to test every submission type and every possible iteration, therefore, as issues arose, problems could be easily addressed and resolved. This helped build confidence and achieve a level of comfort in preparing for the first eSubmission. To accomplish this, testing was performed through the gateway including: Form FDA 2253 (and accompanying promotional materials), advisory comments (launch and non-launch), enforcement actions, multiproduct submissions (grouped and ungrouped), and information request responses. The second step was to obtain internal alignment between involved functional areas to pilot a single brand. Finally, after a successful pilot program, eCTD submissions were expanded across all other brands. This paper discusses the stepwise approach taken, considerations for electronic submissions and results for improved efficiencies and cost savings. Implementing a well, laid-out plan, and starting the conversion early, allowed us to be thoughtful in our approach. The steps taken, and the successful outcomes achieved, demonstrate that there is no reason to wait for submitting promotional materials via the FDA gateway.
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Abbreviations
- ANDA:
-
Abbreviated new drug application
- Ad/Promo:
-
Advertising and promotional
- BLA:
-
Biologics license application
- CDER:
-
Center for Drug Evaluation and Research
- CTD:
-
Common technical document
- CRL:
-
Complete Response Letter
- CANDAs:
-
Computer aided new drug applications
- eANDA:
-
Electronic abbreviated new drug applications
- eCTD:
-
Electronic common technical document
- eNDA:
-
Electronic new drug applications
- eSubmission:
-
Electronic submission
- ESG:
-
Electronic submissions gateway
- FDA:
-
Food and Drug Administration
- ICH:
-
International Council on Harmonization
- IND:
-
Investigational new drug
- NDA:
-
New drug application
- OPDP:
-
Office of Prescription Drug Promotion
- PI:
-
Package insert
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Acknowledgements
The authors wish to thank Henrietta Ukwu MD, FACP, FRAPS SVP, Chief Regulatory Officer & Global Head Global Quality & Global Regulatory Affairs at Otsuka Pharmaceutical Development and Commercialization, Inc. for sponsoring this article. We would like to thank Jason Cober from the Office of Prescription Drug Promotion for his support and assistance.
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43441_2020_166_MOESM1_ESM.jpg
(JPG 65 kb) The table below provides an example of the metadata backbone for a single product submission on Form FDA 2253. As noted in the table, the completed Form FDA 2253 resides in eCTD Module 1 under Section 1.1 Forms. Section 1.14.6 contains the current approved PI for the branded product. Section 1.15 houses the Promotional Material where the audience is identified as either Consumer or Professional. Section 1.15.2 denotes the materials for submission as Promotional 2253 and are further characterized in Section 1.15.2.1 by providing the material type, identification and issue date. Section 1.15.2.1.1 house one or more clean (without annotations) copies of the Ad/Promo material(s). Each item in the submission (Form FDA 2253, PI and promotional items) should be designated as “new.”
43441_2020_166_MOESM2_ESM.jpg
(JPG 31 kb) The table provides an example of assigned sequence numbers for grouped submissions. The Multiple Products box on Form FDA 2253 must be checked, and a single NDA number (in this example Product Brand A) listed on the form. The other NDA products will still need to be issued their own sequence number, but these will only be used as placeholders.
43441_2020_166_MOESM3_ESM.jpg
(JPG 74 kb) The table below provides an example of the metadata backbone for Multiple/Grouped Product Submission on Form FDA 2253. Please note that two documents will show under Section 1.1 Forms: the Form FDA 2253 and the other referenced products page. The PI for each product of the grouped submission is placed under Section 1.14.6. Section 1.15 identifies the intended audience. Section 1.15.2.1.1 houses the clean or Final version(s) of Ad/Promo material(s) as described in Appendix A. Alternatively, the PI may be referenced with a hyperlink to a previous submission.
43441_2020_166_MOESM4_ESM.jpg
(JPG 23 kb) The table below provides an example of the metadata backbone for an information request response. FDA may send an information request response letter when further information is needed to explain a specific activity(ies). For example, if the submission is unclear or additional references are needed OPDP may request more information. When responding to an OPDP inquiry, each correspondence should be placed under Section 1.15.1.7 as described. In the example, the request was for a promotional piece intended for a professional audience.
43441_2020_166_MOESM5_ESM.jpg
(JPG 48 kb) The table below provides an example of the metadata backbone for responses to a Warning or Untitled/Enforcement Action Letters. A response to an enforcement action when the FDA has an issue with messages being conveyed can request immediate action. When responding to an OPDP inquiry, each correspondence should be placed under Section 1.15.1.6. It is important to note that this correspondence should not go under a general correspondence section.
43441_2020_166_MOESM6_ESM.jpg
(JPG 97 kb) The table below provides an example of the metadata backbone for Preapproved Launch Materials for Voluntary Request for Advisory Comments. The Cover letter is placed under Section 1.15.1.1 Request for Advisory Comments - launch materials along with all correspondence prior to approval (in this example, the Day 74 Response Letter and CRL). Ad/Promo materials submitted for review are placed under Sections 1.15.2.1.1 (clean) and 1.15.2.1.2 (annotated). Since there is no approved labeling at the pre-approval stage, a draft PI may be submitted. The draft PI both “clean” and “annotated” goes under Section 1.15.2.1.3 under Annotated Labeling Version. Although, the draft PI is listed as Reference 1, the correct location for it should reside under Section 1.15.2.1.3: Annotated-Labeling Version. All other references associated with the promotional pieces are placed under Section 1.15.2.1.4 Annotated References.
43441_2020_166_MOESM7_ESM.jpg
(JPG 182 kb) The table below provides an example of the metadata backbone for Launch Materials for Voluntary Requests for Advisory Comments. The Cover letter (e.g., Voluntary Request for Advisory Comments for Professional Visual Aid) for this submission as well as the product approval letter (e.g., Letter FDA NDA 999999 Approval) are placed under Section 1.15.1.1: Request for Advisory Comments on Launch Materials. Clean copies of Ad/Promo materials under Section 1.15.2.1 where the clean copy resides in Section 1.15.2.1.1 and a copy of the annotated version in Section 1.15.2.1.2. The approved PI both “clean” and “annotated” goes under Section 1.15.2.1.3 under Annotated Labeling Version. Please note that although the annotated PI is listed as Reference 1 (Ref 01), the correct location for this item resides under Section 1.15.2.1.3 as the Annotated-Labeling Version. All other references associated with promotional pieces reside under Section 1.15.2.1.4 as Annotated References.
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Hathaway, J., Hom, K., Reznichenko, B. et al. eSubmission of Promotional Labeling and Advertising Materials via the eCTD FDA Gateway. Ther Innov Regul Sci 54, 1398–1403 (2020). https://doi.org/10.1007/s43441-020-00166-8
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DOI: https://doi.org/10.1007/s43441-020-00166-8