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ESG Chapter 3 Preparatory Activities

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3 Preparatory Activities 
     3.1 Submit Letter of Non-Repudiation Agreement 
     3.2 Obtain Digital Certificate
     3.3 Understand Submission Guidelines 
     3.4 Naming Conventions
     3.5 Detemine Submission Method 
     3.6 Connection Requirements 
     3.7 Help and Information

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 H, 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 J., Digital Signatures.

Table 1: FDA Links to Submission Preparation Guidelines

Center

Link

Center for Biologics Evaluation and Research (CBER)

http://www.fda.gov/BiologicsBloodVaccines
/DevelopmentApprovalProcess/ucm163685.htm

Center for Drug Evaluation and Research (CDER)

http://www.fda.gov/Drugs/DevelopmentApprovalProcess
/FormsSubmissionRequirements/ElectronicSubmissions/default.htm

Center for Devices and Radiological Health (CDRH)

http://www.fda.gov/ForIndustry/FDAeSubmitter/default.htm

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance
/UniqueDeviceIdentification/GlobalUDIDatabaseGUDID/default.htm
(GUDID)

Adverse Event Reporting System (AERS)

http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation
/Surveillance/AdverseDrugEffects/ucm115894.htm

Center for Veterinary Medicine (CVM)

http://www.fda.gov/AnimalVeterinary/DevelopmentApprovalProcess/
ElectronicSubmissions/default.htm

Office of the Commissioner (OC)

http://www.fda.gov/Drugs/DevelopmentApprovalProcess/
FormsSubmissionRequirements/ElectronicSubmissions/default.htm

Center for Tobacco Products

http://www.fda.gov/ForIndustry/FDAeSubmitter/default.htm

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 G., AS2 Header Attributes, for a list of allowed attributes for the different submission types.

Table 2: Electronic Submissions Supported by the FDA ESG

Center

Submissions

CBER

AERS – Adverse Event Reports

AERS Attachments

BLA – Biologics License Application (eCTD and eBLA format)

eCTD – Electronic Common Technical Document

H1N1 Lot Release

IDE – Investigational Device Exemption

IND – Investigational New Drug Application (eCTD and eIND format)

DMF – Drug Master File

Promotional Materials

Lot Distribution Data

510K

EBLA

EDMF

EIDE

EIND

Pilot_Lot_Release

CDISC

SPL_LLD

Pre_IND

VAERS

CDER

AERS – Adverse Event Reports

AERS Attachments

ANDA – Abbreviated New Drug Application

BLA – Biologics License Application (eCTD and eBLA format)

eCTD – Electronic Common Technical Document (includes DMF - Drug Master File)

NDA – New Drug Application (eCTD and eNDA format)

IND – Investigational New Drug Application

EANDA

EBLA

EIND

ENDA

ACA6004_Drug_Samples
 
GDUFA_Facility_Registration

CDRH

Adverse Events

Electronic Submissions

GUDID
 

CFSAN

Biotechnology Final Consultation (Form 3665)

Color Additive Petition (Form 3503)

Color _Master_File (Form 3503)

Food_Contact_Notification (Form 3480)

Food_Contact_Notification_Amendment (Form 3480A)

Food Master File for FCS (Form 3480)

Food_Master_File (Form 3503)

Food_Pilot_Listing

Generally Recognized As Safe Notice (Form 3667)

NDI

New_Protein_Consultation (Form 3666)

Food Additive Petition (Form 3503)

Pre-notification Consultation (Form 3480)

Threshold of Regulation

EON-Payload Files

EON-Notification-Files

CTP

Electronic_Submission

Adverse_Events

CVM

Adverse Events Reports

Electronic Submissions

eSubmitter

OC

SPL - Structured Product Labeling (includes NDC Labeler Code Request, Establishment Registration and Drug Listing)

OOPD**

HUD_Designation_Requests

Orphan_drug_Designation_Requests

GW TEST

CONNECTION TEST*

SIZE TEST*

* These submission types are only supported in the Test environment and are intended solely for testing.

3.4  Naming Conventions

A special consideration applies to the naming convention for files and directories. The following characters are not recommended for use when naming submission files and directories:

/ - forward slash

\ - backslash

: - colon

? - question mark

" - quotation marks

< - less than sign

> - greater than sign

| - vertical bar,

space - If you need to use a space, use_an_underscore_instead or SeparateWordsWithCapitalLetters.

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:

  1. 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.
  2. 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 G., AS2 Header Attributes

*** See Appendix K., 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

FDA ESG Web Interface users need the following:

  • Java Runtime Environment (JRE) 1.6.X, for the browser plug-in files. See JRE Installation Instructions.
  • A web browser: Internet Explorer 6, 7, 8, 9.
  • 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

Preparation/Registration/Policy Questions

Email: esgprep@fda.hhs.gov

Technical Issues with Submissions after becoming a Production System Transaction Partner

Email: esgreg@gnsi.com

Center-specific Submission Guidance

Reference Section 3.3, Understand Submission Guidelines.

 

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