ESG Chapter 3 Preparatory Activities
ESG User Guide - Table of Contents
Chapter 3 Preparatory Activities
3 Preparatory Activities
There are a number of preparatory activities that need to be completed before beginning the registration process. This section describes these preparatory activities and presents system and protocol issues for FDA ESG users to consider.
3.1 Submit Letter of Non-Repudiation Agreement
A letter of Non-Repudiation Agreement must be submitted to the FDA. Reference Appendix G, Sample Letters of Non-Repudiation Agreement, for letter examples.
The non-repudiation agreement allows the FDA to receive electronically signed submissions in compliance with 21 Code of Federal Regulations (CFR) Part 11.100.
3.2 Obtain Digital Certificate
A digital certificate must be obtained.
Digital certificates ensure private and secure submission of electronic documents. The digital certificate binds together the owner’s name and a pair of electronic keys (a public key and a private key) that can be used to encrypt and sign documents.
Digital certificates can be obtained from either a public or private Certificate Authority (CA). It must be an X.509 version 3 certificate and all data fields in the Issuer and Subject fields must be completed. Reference Appendix C, Digital Certificates for more information on digital certificates.
3.3 Understand Submission Guidelines
Each FDA Center has specific guidelines that must be followed for successful submission. Table 1: FDA Links to Submission Preparation Guidelines below contains links to Center-specific preparation guidelines and contacts. Table 2: Electronic Submissions Supported by the FDA ESG lists electronic submissions supported by the FDA ESG. Important information on the use of digital/electronic signatures on FDA forms can be found in Appendix I, Digital Signatures.
Table 1: FDA Links to Submission Preparation Guidelines
NOTE: Meeting the requirements for using the FDA ESG to route submissions does not mean that these submissions automatically meet FDA Center-specific submission requirements.
For each test submission type, a test submission must be validated by the Center before sending submissions to the Production System.
It is the responsibility of the Transaction Partner to consult the appropriate FDA Center for information on formats, deadlines, and other information or procedures for submissions.
The submission acronyms or names listed in Table 2 below are not to be used as attributes in the submission header. See Table G-1 in Appendix F, AS2 Header Attributes, for a list of allowed attributes for the different submission types.
Table 2: Electronic Submissions Supported by the FDA ESG
| Legend: | |
|---|---|
| (A) | denotes AS2 only. |
| (W) | denotes WebTrader only. |
| (P) | denotes Production environment only. |
| (T) | denotes Test environment only. |
| (NGP) | denotes Not for General Public. |
| (*) | CDRH's only eligible submission categories via the FDA ESG CDRH "Electronic_Submissions" submission type are "Recall Reports of Corrections and Removals" and "Radiological Health Reports and Correspondence". Further, CDRH Premarket submissions should be sent via the CDRH Customer Collaboration Portal. |
| Note: If a WebTrader Display Name or an AS2 Submission Type does not have either the (P) or (T) annotation, then it is allowed in both Production and Test. | |
| Note: If an item does not have the (W) or (A) annotation, then it is allowed in both WebTrader and AS2. | |
| Center | WebTrader Display Name | AS2 Submission Type | Notes |
|---|---|---|---|
| CBER | 510K | 510K | Medical Device Premarket Notification |
| AERS | AERS | Adverse Event Reports (AERS) | |
| AERS Attachments | AERS_ATTACHMENTS | AERS Attachments | |
| AERS_PREMKT_CBER | AERS_PREMKT_CBER | AERS Pre-Market CBER | |
| AERS_ATTACHMENTS_PREMKT_CBER | AERS_ATTACHMENTS_PREMKT_CBER | AERS Attachments for Pre-Market CBER | |
| BEST | BEST | Medical Device Premarket Notification | |
| CDISC | CDISC | Clinical Data Interchange Standards Consortium (CDISC) | |
| EBLA | EBLA | BLA – Biologics License Application (eBLA format) | |
| eDMF | eDMF | DMF – Drug Master File (eDMF format) | |
| EIDE | EIDE | IDE – Investigational Device Exemption (eIDE format) | |
| EIND | EIND | IND – Investigational New Drug Application (eIND format) | |
| EUA | EUA | Emergency Use Authorization (EUA) | |
| H1N1_Lot_Release (A) | Influenza A (H1N1) 2009 Monovalent Vaccines Lot Release | ||
| Lot_Release_Protocol | Lot_Release_Protocol | CBER Lot Release Protocol for Biological Products | |
| NDA | NDA | New Drug Application | |
| PMA | PMA | Premarket Approval Application (PMA) | |
| Pre_IND | PRE_IND | Pre Investigational New Drug Application | |
| Promotional_Materials | Promotional_Materials | Promotional Materials | |
| QSUBS | QSUBS | Q-Submissions | |
| SEND_PILOT (T) | SEND_PILOT (T) | ||
| SPL_LDD | SPL_LDD | Structured Product Labeling (SPL) Lot Distribution Database (LDD) | |
| VAERS | VAERS | Vaccine Adverse Event Reporting System (VAERS) | |
| CDER | ACA6004_Drug_Samples | ACA6004_Drug_Samples | Affordable Care Act (ACA) Section 6004 Certain Drug Sample Information |
| AERS | AERS | Adverse Event Reports (AERS) | |
| AERS Attachments | AERS_ATTACHMENTS | AERS Attachments | |
| AERS IND (T) | AERS_IND (T) | AERS for Investigational New Drug Application | |
| AERS Attachment IND (T) | AERS_ATTACHMENTS_IND (T) | AERS Attachments for Investigational New Drug Application | |
| AERS_PREMKT (T) | AERS_PREMKT (T) | AERS Pre-Market | |
| AERS_Attachments_PREMKT (T) | AERS_Attachments_PREMKT (T) | AERS Pre-Market Attachments | |
| AERS_PREMKT_CDER | AERS_PREMKT_CDER | AERS Pre-Market for CDER | |
| AERS_ATTACHMENTS_PREMKT_CDER | AERS_ATTACHMENTS_PREMKT_CDER | AERS Pre-Market Attachments for CDER | |
| ECTD | ECTD | Filing Options:
|
|
| ECTD WAIVED | ECTD_WAIVED | Electronic Common Technical Document (eCTD) Waived | |
| EDMF TYPEIII | EDMF_TYPEIII | Electronic Drug Master Files (eDMF) Type III Packaging Material | |
| EIND | EIND | Electronic Investigational New Drug Application (eIND format) | |
| FFU-PILOT (T) | FFU-PILOT (T) | Focus-Forming Units (FFU) pilot submissions | |
| GDUFA_Facility_Registration | GDUFA_Facility_Registration | Generic Drug User Fee Amendments (GDUFA) Facility Registration | |
| PFC | PFC | Pre-Submission Facility Correspondence (PFC) | |
| POR Large Molecule Documents | POR_Large_Molecule_Docs | Pre-Operational Reports (POR) for Large Molecules | |
| Voluntary_Direct_AEs (W) | Voluntary Direct Adverse Events | ||
| CDRH | Adverse Events | Adverse_Events | CDRH Adverse Events |
| Electronic_Submissions (*) | Electronic_Submissions (*) | Electronic Submissions | |
| GUDID | GUDID | Global Unique Device Identification Database (GUDID) | |
| HFP (formerly CFSAN) | DSR_Adverse_Events (A) | CFSAN DSR Adverse Events | |
| EON-Payload-Files (P) | EON-Payload-Files (P) | CFSAN Emergency Operations Network (EON) Payload Files | |
| Food_Pilot_Listing (P) | Food_Pilot_Listing (P) | CFSAN Voluntary Food Pilot Program | |
| Form3479 | Form3479 | Food Contact Substance Formulation Notification (Form 3479) | |
| Form3480 | Form3480 | Filing Options:
|
|
| Form3480A | Form3480A | Food Contact Notification Amendment (Form 3480A) | |
| Form3503 | Form3503 | Filing Options:
|
|
| Form3665 | Form3665 | Biotechnology Final Consultation (Form 3665) | |
| Form3666 | Form3666 | New Protein Consultation (Form 3666) | |
| Form3667 | Form3667 | Generally Recognized As Safe Notice (Form 3667) | |
| NDI (P) | NDI (P) | New Dietary Ingredients (NDI) | |
| Threshold_of_Regulation | Threshold_of_Regulation | ||
| CTP | Adverse_Events (A) | CTP's Adverse Events | |
| Electronic_Submission | Electronic_Submission | Electronic Submission | |
| CVM | Adverse_Events_Reports | Adverse_Events_Reports | CVM's Adverse Events |
| eSubmitter | eSubmitter | ||
| Manage Form | Electronic_Submissions | Electronic Submissions | |
| CVM-VDD | eSubmitter (T) | eSubmitter (T) | CVM VDD's Electronic Submissions |
| GWTEST | ConnectTest (T) | ConnectTest (T) | To test the connectivity for submissions and receipts / notifications. Not more than 1GB to 50GB submissions. |
| SizeTest (T) | SizeTest (T) | To test the size of submissions. | |
| HC | Transaction | Transaction | FAQ Language Options: |
| MWP | MWP_Report (A, NGP) | Microwell Plate Report | |
| OC | SPL | SPL | Structured Product Labeling (SPL) includes NDC Labeler Code Request, Establishment Registration, and Drug Listing |
| OCAC | OCAC | Postmarket Cosmetics - Office of Cosmetics and Colors | |
| OOPD | HUD_Designation_Requests (T) | HUD_Designation_Requests (T) | |
| Orphan_drug_Designation_Requests (T) | Orphan_drug_Designation_Requests (T) | ||
| OPQ | 704a4_Pharma_Inspection_Records (W) | ||
| ORA | Document_Requests (W) | ||
| POR Small Molecule Documents | POR_Small_Molecule_Docs | Pre-Operational Reports (POR) for Small Molecules |
3.4 Naming Conventions
ESG recommends using only letters, numbers, spaces, and underscores when naming files, directories and digital certificates. The following characters are not recommended when naming files, directories and digital certificates: forward/back slash, colon, question mark, quotation marks, less/greater than sign, vertical bar, and pound/hash sign.
Note: Directories and sub-directories cannot begin with the "." (dot) character
3.5 Determine Submission Method
There are two options for sending FDA ESG submissions:
- FDA ESG Web Interface – The FDA ESG Web Interface sends submissions via Hyper Text Transfer Protocol Secure (HTTPS) through a web browser according to Applicability Statement 2 (AS2) standards.
- Applicability Statement 2 (AS2) Gateway-to-Gateway – An electronic submission protocol that uses HTTP/HTTPS for communications.
Determining the best of these options for your organization will be influenced by the types of submissions to be transmitted, infrastructure capabilities, and business requirements.
One or more of these options can be selected to submit electronic documents to the FDA. However, a separate registration will be required for each option selected.
Considerations for each option are shown in Table 3 below.
Table 3: Considerations for Submission Protocol Choice
| FDA ESG Web Interface | AS2 Gateway-to-Gateway |
|
|---|---|---|
| Cost | None | High setup and support costs |
| Setup | Minimal | Need to install and configure Gateway |
| User-friendly web interface | Yes | No |
| Submission types supported | All, including AERS reports | All, including AERS reports |
| Long-term support by FDA | Yes | Yes |
| Preparation of multi-file submissions * | Occurs automatically | Multi-file submissions need to be archived and compressed using a tar and gzip utility prior to submission |
| Custom attributes for submission routing ** | Automatically adds custom attributes to the AS2 header | Need to add custom attributes to the AS2 header |
| Routing IDs *** | N/A |
Need to add routing IDs to the AS2 header |
| Integration to backend systems | No |
Can be automated |
|
Tracking of submission activity by Transaction Partner |
Manual tracking | Can be automated |
| Automation of submission process | No | Yes |
* See Appendix B, Creating .tar Files and Compressing Files for Submission
** See Appendix F, AS2 Header Attributes
*** See Appendix J, AS2 Routing IDs
A factor that determines how quickly a submission can be sent to the FDA ESG is the Transaction Partner’s network connection to the Internet. Table 4 lists the maximum transmission rates for a variety of network connections and the optimal time it would take to send a 1 GB submission.
Table 4: Transmission Rates for Network Connections and Optimal Times for Transmission
| Network Connection | Max. Transmission Rate (Mbps) | Time (min) |
|---|---|---|
| T1 | 1.54 | 83 |
| T2 | 6.31 | 21 |
| T3 | 44.7 |
3 |
| OC1 | 51.8 | 2.5 |
| OC3 | 155.4 | 0.8 |
| T4 | 274.8 | 0.5 |
| OC12 | 621.6 | 0.2 |
Mbps = Megabits per sec.
1 GB (Gigabyte) = 8,590 Megabits
Actual times will be greater than those listed in the table due to factors such as network configuration and the amount of traffic coming in and going out through the line. For example, submissions sent in the middle of the day typically take 1.5 – 2 times longer to send than those sent after business hours. Pilot testing with selected Industry Transaction Partners has shown that it takes approximately 24 hrs for submissions 15 GB to 25 GB in total size to be transmitted and processed by the FDA ESG. These companies had T3 network connections or better. FDA recommends that submissions of this size be sent overnight, starting at 4:30 PM EST, in order for the submission to be received by the target Center before the end of the next business day.
During the testing process, Transaction Partners who will be sending submissions larger than 1 GB in total size will be asked to send a 7.5 GB test submission. This test will allow Transaction Partners to identify and resolve network limitations that will impact the speed of delivery.
3.6 Connection Requirements
For FDA ESG Web Interface users, submissions may be viewed from most systems that have Internet access. In order to send submissions, a system must have the following:
- An Operating System of Windows 7 or above.
- Any of the following browsers: Internet Explorer 11 or above, Mozilla Firefox, or Google Chrome. For Internet Explorer, Compatibility Mode may be set by going to Internet Options, selecting Compatibility View Settings and adding fda.gov. Organizations that have an IT staff may also use Enterprise Mode if accessing WebTrader with Internet Explorer 11.
- Note: FDA has tested the new WebTrader with Windows 2007 R2, IE 11 (11.0.9600.18665), Firefox (53.0.2), Chrome (58.0.3029.110)
- Hard disk: space of at least three times the size of the submission.
- A high-speed internet connection.
Gateway-to-Gateway users need the following:
- A high-speed internet connection.
- An AS2 compliant Gateway product,
- Hard disk space of at least three times the size of the submission.
3.7 Help and Information
There are resources that can be contacted if you need assistance with various aspects of the submission process. These are provided in the table below.
Table 5: Submission Process Aspects and Help and Information Contacts
| Submission Process Aspect | Contact |
|---|---|
|
ESG Account Registration |
Email: ESGHelpDesk@fda.hhs.gov |
| Technical Issues with Submissions after becoming a Production System Transaction Partner | Email: ESGHelpDesk@fda.hhs.gov |
| Center-specific Submission Guidance | Reference Section 3.3, Understand Submission Guidelines. |