The U.S. FDA has published numerous resources that teams can access to understand the requirements for a submission in electronic Common Technical Document (eCTD) format. It’s in the agency’s best interest to educate sponsors on the requirements, and how the agency receives, accepts, processes, and reviews electronic regulatory submissions. In doing so they minimize the risk of sponsors submitting non-compliant submissions, they reduce the number of technical rejections, and they help R&D teams to better understand review processes and how agency reviewers navigate the submission content, approve new drugs, and monitor data once the drugs/biologics are on the market.
For this same reason, we see FDA representatives at industry conferences and participating in webinars and other events that help promote greater understanding of the requirements. The agency continues to encourage sponsors to reach out, ask questions, and be open to dialog throughout the submission review and approval process. This sets the stage for better communications and more meaningful interactions as the product progresses through the agency’s review and approval cycle. It also encourages new, innovative approaches.
The agency understands that technologies, statistical methods, and trial designs are all continuously evolving. They are open to working with sponsors to explore innovations in science with new techniques, processes, and tools. Through their Technology Modernization Plan and Data Modernization Action Plan, they are strategically focusing on modernizing the use of technology, including computer hardware, software, data, and analytics, to advance FDA’s public health mission.
FDA eCTD Resources
In addition to formal FDA guidances, the agency has published content that provides detailed instructions for key activities in the process of preparing an eCTD submission. These resources cover important topics such as:
The FDA has even created documentation that provides information on how to submit eCTD 4.0 electronic submissions to FDA CDER and CBER, which both Centers are planning to accept sometime in 2023.
If you are new to Regulatory or are preparing for your first eCTD submission, it’s important to know that the eCTD applies to commercial INDS, NDAs, ANDAs and BLAs. This include maintenance submissions to these application types including amendments, supplements, reports, and any master files such as the Drug Master File (DMF) which are considered submissions to an IND, NDA, ANDA or BLA.
Preparing to Use the Electronic Submission Gateway
Electronic submissions are accepted by the FDA through the Electronic Submission Gateway (ESG). The gateway receives submissions, acknowledges receipt, routes the submission to the correct center or office within the FDA, and notifies them of the delivery. To use the gateway, you need an account. There are several steps in the process of obtaining an account, including a testing phase, so you should start well before you intend to submit.
As electronic submissions have evolved, submission data packages have become increasingly important. As noted above, the agency has published technical guides, standards catalogs, and validation rules to help sponsors create compliant data packages. The Clinical Data Interchange Standards Consortium (CDISC) data standards are employed in the eCTD submission for nonclinical and clinical study and analysis data. These include SEND, SDTM and ADaM standards. The FDA has published additional resources and links for these standards on their Study Data Standards Resources page.
The FDAs Data Standards Catalog describes the data and metadata components of the eCTD submission. It lists the current data standards and terminologies that FDA supports and the agency can refuse to receive any electronic submission whose study data does not conform to the standards specified in the catalog. The agency also encourages sponsors and their partners to implement study data standards as early as possible in the product development lifecycle so they are applied in the design, conduct and analysis of studies.
Similar to paper submissions of the past, eCTD submissions to the U.S. FDA must include an application form such as an FDA Form 1571 for INDs or an FDA Form 356h for NDAs. These forms are available as downloadable PDF forms that sponsors can complete electronically and must include in the submission.
Producing Compliant eCTD Output
Depending on the type of submission and the experience of the organization, and whether you are outsourcing submission compilation, publishing, and dispatch, your timelines for preparation will vary. In startups, it is often the case that individuals have electronic submission experience at other companies but have never produced a submission (as a team) at the new company. In these cases, it’s important to start preparing early to ensure that everyone on the team understands their roles and responsibilities, the agreed timelines, and requirements. A bigger picture view helps everyone understand how their contributions impact others on the team and the success of the submission process.
Your Trusted Submission Partner
As you get ready for a submission, keep in mind that updates to the FDA’s standards are always announced in the Federal Register and published on the FDA website. Unfortunately, the requirements are often buried in various guides and guidances. eCTD submissions are complex and require constant attention.
As a trusted submission partner, we keep track of current requirements and are continuously learning about emerging submission requirements and how they impact submission management and publishing processes. Each company is different. Their products, development teams, timelines, and goals vary. We work with each team to understand your submission goals and help you achieve them.
Like the FDA, we have also produced some useful resources to help you in preparation for an eCTD submission.
If you are preparing to submit your first IND, you can listen to our podcast series: Planning Your First IND to learn about budgeting & resources, FDA interactions, and submission planning.
Our Blogs cover an array of submission types such as ad promo, BIMO, and DMFs.
We have also produced a white paper titled, The Key to Finding a Trusted Regulatory Submission Management Partner. In this white paper, we offer insights into how to choose the best regulatory submission partner for your organization.
Contact us to schedule time to talk about your upcoming submission and how we can help streamline the process and ensure you meet your submission goals.