Frequently Asked Questions (FAQs): Electronic Submissions Program for CBER-Regulated Products

For assistance with questions related to the receipt and processing of regulatory submissions submitted to CBER for regulatory review, please reach out to esubprep@fda.hhs.gov.

Contents

1. Why does Acknowledgement (ACK) 3 take longer than ACK 1 and ACK 2?
2. What is a CBER ACK 3 technical rejection notice?
3. What is the official submission receipt date if I submit on a weekend or holiday?
4. How do I submit my non-eCTD submission via ESG NextGen under one core id number?
5. What file types are acceptable to submit for eCTD publishing?
6. Where can I find eCTD guidance?
7. How long does it take Electronic Submission Gateway (ESG) to deliver my submission to CBER?
8. I have not received a 2nd acknowledgement, who do I contact?
9. I have not received any acknowledgements for my non-eCTD submission. Is this expected?
10. My client has two or more applications under CBER review. Does CBER support cross application hyperlinks?
11. Where should I place Video Files in eCTD?
12. How do I request an eCTD waiver for a type II Drug Master File (DMF)?
13. What sequence number should I start my eCTD pre-submission or original application?
14. Does CBER validate test submissions for ESG NG account approval?
15. Who do I contact with regulatory guidance and submission questions?
16. Where do I submit my single file .xml?

Following are Frequently Asked Questions regarding CBER’s validation and processing of regulatory submissions into CBER for regulatory review.

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1. Why does Acknowledgement (ACK) 3 take longer than ACK 1 and ACK 2?

After delivery via the Electronic Submissions Gateway NextGen (ESG NG), CBER performs validations to ensure the submission is guidance-compliant and accessible before processing it into the Center's repository for regulatory review.

**Please allow 24 hours before contacting esubprep@fda.hhs.gov regarding the receipt of an ACK 3.**

Common causes for the delayed receipt of an ACK 3 include:

• Large volume of submissions in queue
• Submission flagged for manual verification or processing.
• Network or technical issues

More information regarding acknowledgement notifications can be found at Submission Acknowledgements | FDA.

2. What is a CBER ACK 3 technical rejection notice?

CBER generates a technical rejection to notify the submitter that a submission could not be processed in CBER’s repository.

Common causes include:

• A high eCTD validation error see (eCTD Validation Criteria v3.3 or Specification for eCTD 4.0 Validation Criteria)
• Incorrect format for the submission type (i.e. eCTD or non eCTD)
• Incorrect attribute for submission-type or submission-sub-type in the us-regional.xml
• A corrupt or inaccessible file or FDA form within the submission
• Missing supplement number not included on FDA forms 356h, 2252 and 2253

3. What is the official submission receipt date if I submit on a weekend or holiday?

If a submission arrives through the ESG NextGen on a weekend, a federal holiday, or another day on which CBER is not open for business, it is deemed to have arrived at FDA on the next day when that office is open for business.

The ACK 3 receipt will reflect the date the submission was processed into CBER, which may differ from the date that it was submitted.

For more information visit: Providing Regulatory Submissions in Electronic Format--Receipt Date | FDA

4. How do I submit my non-eCTD submission via ESG NextGen under one core id number?

A complete submission must be submitted under one ESG core ID number. Place all documents associated with the submission in a folder and submit by folder via ESG NG.

• Do not submit each document of a submission separately, as this will create multiple core id numbers. CBER does not gather and organize separately submitted documents to make a submission suitable for regulatory review.

5. What file types are acceptabel to submit for eCTD publishing?

Documents should be provided in PDF searchable format. For archival purposes, images and other document types should also be rendered into PDF format and retain searchable text.

• Additional information related to PDF documents is available in the FDA technical specification: See Specifications for File Format Types and FDA Portable Document Format (PDF) Specifications.

6. Where can I find eCTD guidance?

The Electronic Common Technical Document (eCTD) webpage and eCTD Resources webpage are good starting points to identify eCTD related guidance and resources.

7. How long does it take Electronic Submission Gateway (ESG) to deliver my submission to CBER?

The webpage ESG Submission Times provides estimated transaction times for the upload, delivery, and acknowledgements for submissions.

8. I have not received a 2nd acknowledgment, who do I contact?

Acknowledgement 2 is distributed by ESG Next. Please contact esgngsupport@fda.hhs.gov for assistance.

9. I have not received any acknowledgement for my non-eCTD submission. Is this expected?

Yes, CBER does not generate acknowledgements for non-eCTD submission.

10. My client has two or more applications under CBER review. Does CBER support cross application hyperlinks?

No, CBER does not support cross-application hyperlinks. Hyperlinks to sections within the same document are acceptable.

11. Where should I place Video Files in eCTD?

In accordance with the Specifications for File Format Types Using eCTD Specifications, video files should only be submitted in eCTD section “1.15 Promotional material” in support of Promotional Labeling and Advertising Material submissions.

• Contact your CBER Regulatory Project Manager (RPM) or esubprep@fda.hhs.gov, if M1.15 is not the appropriate subject area for your video file.

12. How do I request an eCTD waiver for a type II Drug Master File (DMF)?

Waivers from submitting in eCTD can only be requested for certain Positron Emission Tomography (PET) and certain Type II Drug Master File submissions.

• Review section III of the guidance Providing Regulatory Submissions in Electronic Format-Certain Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications, for information about types of waivers.
• Send email request to esubprep@fda.hhs.gov to request an eCTD waiver from CBER.

13. What sequence number should I start my eCTD pre-submission or original application?

The eCTD sequence number of the original submission should start with 0001. For Investigative New Drug (IND) applications using FDA form 1571, it is not necessary for the IND serial number (0000) and eCTD serial number (0001) to be the same.

See https://www.fda.gov/media/135373/download

14. Does CBER validate test submissions for ESG NG account approval?

CBER does not validate test submissions with the exception of Adverse Events Reporting (AERS) related submission. See Center Submission Types | FDA

15. Who do I contact with regulatory guidance and submission questions?

Topic	Contact
Receipt, validation, and rejection of submissions via ESG NG or email (non-eCTD only)	esubprep@fda.hhs.gov (include the core ID number from ACK 2)
ESG NG account setup, submission loading issues, or missing ACK 2	esgngsupport@fda.hhs.gov
Regulatory review questions (supporting documents, submission types, review process)	industry.biologics@fda.hhs.gov
Consumer questions	cberocod@fda.hhs.gov
Study data and structured data submissions	CBER-edata@fda.hhs.gov

16. Where do I submit my single file .xml?

Use the appropriate FDA portal based on the type of .xml being submitted:

• E2B (R3) XMLs — Submit via the FDA Adverse Event Monitoring System (AEMS), formerly the FDA Adverse Event Reporting System (FAERS). See: FDA Adverse Event Monitoring System (AEMS) – E2B(R3) Standards | FDA
• Structured Product Labeling (SPL) for lot distribution reports — Submit in eCTD Module 3, Section 3.2.R Regional Information. See: Lot Distribution Reports — Electronic Submissions | FDA