Electronic Regulatory Submission and Review (ERSR)
Welcome to the Center for Drug Evaluation and Research's Electronic Regulatory Submissions and Review (ERSR) web page. This page provides information about the electronic submission of regulatory information to the Center and the review of it by CDER staff. Additional guidance documents, when available in draft or final form, will be added to this page.
- All CDER Guidances on Electronic Submissions
- General Considerations
- Requesting a Pre-Assigned Application Number
- Abbreviated New Drug Applications (ANDAs)
- Annual Reports for New Drug Applications (NDAs)
- Carcinogenicity Data
- Providing Digital Electrocardiogram (ECG) Data
- Electronic Common Technical Document (eCTD)
- Drug Master File
- Investigational New Drug Applications (INDs)
- Launch Material and Other Submissions to the Division of Drug Marketing, Advertising, and Communications (DDMAC)
- New Drug Applications (NDAs)
- Postmarketing Adverse Events Reporting
- Structured Product Labeling (SPL)
- Information Packages for Meetings
Submission of Electronic Documents (6/7/2004)
- Send all electronic submissions (except ANDAs) to:
5901-B Ammendale Road
Beltsville, MD 20705
- Send ANDA submissions to:
7500 Standish Place, E-150
Rockville, MD 20855
- Electronic Document Room (EDR)
- Secure Electronic Mail and the FDA Electronic Submissions Gateway
- Division Files System (DFS)
- Reviewer Training
- Portable Document File Format (PDF)
- SAS Transport File Format
- Technical Assistance
- Recent Presentations
- Other ERSR Links
- CDER and the Center for Biologics Evaluation and Research (CBER) have co-published a guidance document called Guidance for Industry: Providing Regulatory Submissions in Electronic Format - General Considerations (PDF - 288KB). This document provides general information about the electronic submissions process.
- Note: In the general considerations guidance, we recommend the following: Digital Tape - Digital Equipment Corp. DLT 20/40 and 10/20 GB format using OPENVMS with VMS backup or NT server 4.0 with NT backup or backup exec."
Since the release of this guidance, there have been some changes in CDER. First, we are currently not able to accept tapes using OPENVMS with VMS backup. Second, we are able to use 35/70 DLT tapes. We are not, however, able to handle 40/80 DLT tapes. We are working on an update to this guidance and plan to add this information accordingly. (Posted 3/1/2001)
Since the above posting on March 1, 2001, CDER is now able to handle 40/80 DLT tapes though we prefer 35/70. CDER cannot process DLT tapes that have been prepared using the backup applet included with the Windows 2000 operating system. It is recommended that systems running Windows 2000 use backup exec to produce the DLT transport tape for CDER. (Posted 9/28/01).
- For more information on ERSR guidance documents, please contact Randy Levin at firstname.lastname@example.org.
- Information on electronic datasets that accompany an ANDA submission:
You may now submit ANDAs in electronic format in place of paper. We have placed the ANDA on public docket 92S-0251 as a submission acceptable in electronic format as allowed under 21 CFR Part 11. It should be noted that Part 11 requires that datasets provided in electronic format and used in the review process meet the requirements for archiving, i.e., protection of those records to enable their accurate and ready retrieval throughout the records retention period.
Electronic datasets, including those accompanying a paper submission cannot be considered as official and used to support the application if they are submitted in a file format that is not archivable. As FDA and industry progress in meeting the goals of use of electronic submissions, compliance with electronic submission regulations will be expected. Typically, electronic datasets accompany an ANDA application to support the review of bioequivalence studies. With the implementation of the guidance for industry Providing Regulatory Submissions in Electronic Format – ANDAs (June 2002), the submission of these dataset records for use in the review should be in archivable format. At this time, the archival dataset format is SAS Transport. (Posted 7/15/2002)
- Guidance for Industry: Providing Regulatory Submissions in Electronic Format - General Considerations (PDF - 288KB)
- Please refer to: Providing Regulatory Submissions in Electronic Format - Human Pharmaceutical Product Applications and Related Submissions (PDF - 133KB).
- An example of a SAS transport file for carcinogenicity data set is available. This is a self-extracting ZIP file that will be loaded to your C drive. If you download this file, the path to the example is: C:\WINDOWS\TEMP\example\N123456\pharmtox\datasets\101.
For more information on carcinogenicity data, please contact Karl Lin at email@example.com.
FDA is interested in having access to ECG waveform data collected during the course of "definitive" studies on drug effects on ventricular repolarization and annotated for interval measurements. The basis for this interest is described in detail in the concept paper, "The Clinical Evaluation of QT Interval Prolongation and Proarrhythmic Potential for Non-antiarrhythmic Drugs," jointly authored by the U.S. and Canadian regulatory authorities and discussed at a joint FDA/DIA meeting in January 2003.
In 2004, FDA announced its intent to accept annotated ECG waveform data in electronic format (XML) following the Health Level Seven (HL7) Annotated ECG Waveform Data Standard (aECG) accredited by the American National Standards Institute. You can find more detailed information on the aECG message standard and supporting materials by visiting the HL7 Version 3 ECG page and following the "Link to ECG Annotation Message Review Material." To facilitate access to the aECG data, FDA has entered into a Cooperative Research and Development Agreement (CRADA) with Mortara Instruments to develop and implement a digital data warehouse to collect, store, and archive aECG data from controlled clinical trials. FDA reviewers have access to this data warehouse to support their assessment of the risk of new drugs.
You can upload data to the warehouse for FDA access at the Mortara ECG Warehouse. For questions, contact the project manager in the appropriate review division.
- Refer to the Guidance for Industry: Providing Regulatory Submissions in Electronic Format - Human Pharmaceutical Product Applications and Related Submissions (PDF - 133KB) for information on the submission of electronic DMFs.
- For more information on electronic submissions for DMF, please contact CDER at firstname.lastname@example.org. General DMF questions may be sent to email@example.com.
- On March 26, 2002, FDA published final guidance on the submission of INDs in electronic format to the Center for Biologics Evaluation and Research (CBER) (PDF - 80KB). Once the IND submission to CBER is posted on public docket 92S-0251, we will be capable of accepting INDs submitted to CBER in electronic format without paper copies. At this time, we are not extending this to INDs submitted to CDER.
The electronic IND guidance leverages the current BLA/NDA guidances and the experience set from CBER's eIND pilot program. This guidance features PDF tables of contents, roadmap files, and a folder structure that enables the reviewer to easily access and review documents. We expect the experience of receiving the IND applications and amendments with or without media, featuring an electronic signature, as well as the review of these electronic INDs submissions to help the FDA further other electronic submission initiatives.
In the future, we plan on upgrading the electronic IND filing and review process to include the use of XML-based technology. We are currently working toward accepting the electronic common technical document using XML for marketing applications and will build on this to accept XML-based electronic INDs. Once this is completed, we will then issue draft guidance that incorporates the XML-based technology for all INDs including those submitted to CDER. We hope to have XML specifications for electronic INDs available in 2003.
- Federal Register notice for the public meeting to discuss the cumulative table of contents for the IND. Optional format: PDF. (Posted 12/29/2000)
Launch Material and Other Submissions to the Division of Drug Marketing, Advertising, and Communications (DDMAC)
- Draft Guidance: Providing Regulatory Submissions in Electronic Format - Prescription Drug Advertising and Promotional Labeling (PDF - 28KB) (Issued 1/2001, Posted 1/30/2001)
- Guidance for Industry: Providing Regulatory Submissions in Electronic Format - General Considerations (PDF - 288KB). (Issued 1/1999, Posted 1/27/1999)
- MaPP 7600.7 (PDF - 19KB) Processing an Electronic New Drug Application (Issued 5/31/2000, Posted 6/5/2000)
- Sample Electronic NDA Submission
Voluntary Electronic Submissions
- Postmarketing Expedited and Periodic ICSRs Memoranda to Docket 92S-0251 that allows for voluntary electronic submission of all postmarketing individual case safety reports, whether expedited or periodic, in electronic format in place of paper.
- Descriptive Information of Periodic Reports Memorandum to Docket 92S-0251 that allows for voluntary electronic submission of the descriptive information of postmarketing periodic adverse experience reports in electronic format in place of paper.
- Draft Guidance for industry: Providing Regulatory Submissions in Electronic Format – Postmarketing Individual Case Safety Reports (PDF - 107KB)
- Guidance for industry: E2BM Data Elements for Transmission of Individual Case Safety Reports (PDF - 58KB)
- “Periodic safety update reports” section of the guidance for industry Providing Regulatory Submissions in Electronic Format - Human Pharmaceutical Product Applications and Related Submissions (PDF - 133KB) (provides information on submitting the descriptive information of periodic adverse drug experience reports in an electronic format)
- Specifications for Preparing and Submitting Electronic ICSRs and ICSR Attachments [PDF]
- Organizing the Electronic Submission
- Data Elements and Electronic Transport Format for Electronic Submissions
- Preparing SGML Files
- Preparing XML Files
- SGML and XML Files – Specifications for Populating Specific Elements of an ICSR Electronic Format for ICSR Attachments
- SGML and XML File format and character set information [PDF]
- M2 Electronic Transmission of Individual Case Safety Report Message Specification [PDF]
- SGML DTD [PDF]
- XML DTD [PDF]
- Transmitting Electronic ICSRs and ICSR Attachments on Physical Media [PDF]
- Acknowledgment Messages and Formats
- After receipt of a submission into the ESG, an ESG message delivery notice (MDN) will be returned to the sender. We will then load the ICSRs into the AERS database. For submissions sent via the ESG, an automated acknowledgment message will be returned to the sender via the ESG. The acknowledgment message will be in SGML or XML format. The acknowledgment files will be created with a file extension “.ack”. For production submissions, the value for “messagesenderidentifier” element will be “ZZFDA”. For test submissions, the value for “messagesenderidentifier” element will be “ZZFDATST”.
The acknowledgment messages will give the sender the status of each report in the transmission. Refer to the following attachments for the appropriate acknowledgment formats:
Submit comments and queries on these specifications to the AERS Electronic Submission Coordinator at firstname.lastname@example.org.
- Adverse Event Reporting System (AERS). A program permitting electronic submission of individual case safety reports by applicants, manufacturers, packers, and distributors for marketed drug and biological products, including therapeutic vaccines, but excluding prophylactic vaccines, whole blood and components of whole blood. The electronic submission format follows the International Conference on Harmonization (ICH) standards. For more information on the ICH, please contact Gary Gensinger at email@example.com.
- For information on FDA’s intention to require electronic submission of postmarketing safety reports, see 63 FR 59746, Advanced Notice of Proposed Rulemaking (ANPRM) for Electronic Reporting of Postmarketing Adverse Drug Reactions, published on November 5, 1998.
Related Web Sites
- FDA’s Electronic Submission Gateway (ESG)
- CDER’s guidance page
- FDA’s AERS Electronic Submissions Web Site
- Check for the system status of ESG or AERS
- Public Law 109-462, Dietary Supplement and Nonprescription Drug Consumer Protection Act
- The EDR is an extension of the central document room. We perform a check on each submission sent to the EDR for file formats used and integrity of bookmarks and hypertext links.
- NDA Conformance Check List (2/22/2000)
- Electronic mail is in widespread use within CDER and industry. Secure email between CDER and industry is useful for informal communications when confidential information maybe included in the message (for example trade secrets or patient information). Secure email should not be used for formal regulatory submissions (for example NDAs, INDs, amendments and supplements).
- Formal regulatory submissions can be securely submitted to CDER via the FDA Electronic Submissions Gateway (ESG). For more information on the FDA ESG see: http://www.fda.gov/esg/default.htm
- For more information on establishing a Secure Electronic mail link with CDER, contact Wendy Lee at: wendy.lee@ fda.hhs.gov
- DFS is the cornerstone of the Administrative Management of Files (AMF) initiative. It provides document management, tracking, archiving, and electronic signature capabilities for internally generated review documents. It also provides search and retrieval capabilities for final versions of internally generated review documents.
- DFS is being developed incrementally. The first phase focuses on building an electronic repository for final review documents and for capturing signature information. The review documents tracked and saved by DFS are associated with regulatory submissions in the Centerwide Oracle Management Information System (COMIS). Future phases of DFS will include an update of COMIS assignments when the author signs the review in DFS. Reviewers use DFS to check in final review documents, to route them for sign off, to sign off on them electronically, to automatically store review documents in the electronic repository, and to find and view documents stored in the DFS electronic repository.
- The DFS is a graphical user interface (GUI) software application that has the look and feel of most Windows-based applications. DFS uses standard Windows features, such as icons, drop-down menus, buttons, scroll bars, and dialog boxes.
- Electronic Submissions Training (EST). Instructs reviewers on how to search for a specific NDA via the Electronic Document Room (EDR) Intranet site and to map the drive path of the folder. Acrobat Exchange is then used to open, navigate, view, follow links, create electronic notes, and copy and paste text, tables, and graphics into other applications from a sample electronic NDA.
- Electronic Data Analysis Training (EDAT). Instructs reviewers on how to access NDA data in SAS Transport format via the Electronic Document Room (EDR) and to convert the files to formats that can be used with a variety of software packages. NEDAT incorporates the use of the SAS System Viewer, Stat/Transfer, and JMP to convert the data and perform basic analysis. Additional introduction to JMP courses are also available that discuss analysis of adverse events, exposure, efficacy, lab, and demographic data.
- Creating Portable Document Format Reviewer Documents. Instructs reviewers on how to create a Portable Document Format (PDF) version of a review document that maintains the formatting of the original MS Word document. Instruction covers fonts, paragraph, page, and section formatting needed prior to converting an MS Word review document to the PDF archiving standard used in the Division Files System (DFS). Adobe Acrobat 4.0 is then used to convert the document to PDF and to open, view, and enhance the PDF review document.
- JMP. An introduction to JMP teaches reviewers how to use JMP to review electronic data. Users learn how to use a variety of JMP functions to analyze electronic data, with a specific focus on adverse event, laboratory, exposure, and efficacy data. Basic functions of summary tables, graphs, statistical tests, and the formula calculator are covered. The course is taught in the computer lab with hands-on instruction. Prior completion of the NDA Electronic Data Analysis Training (NEDAT) course and/or familiarity with electronic datasets is recommended. Although primarily geared toward the clinical reviewer, the course provides useful instruction for reviewers of all disciplines.
- The Agency established the Electronic Submissions Public Docket number 92-0251 to provide a permanent location for a list of the Agency units that are prepared to receive electronic submissions, as well as a list of the specific types of regulatory records that can be accepted in electronic format (62 FR 13467, March 20, 1997).
- PDF is an open format developed by Adobe Systems. Additional information is available at http://www.adobe.com.
- We are able to archive data sets in SAS XPORT transport format, also called version 5 SAS transport format. This is an open, published file format developed by SAS Institute. For additional information, see the SAS Institute's Standards for Electronic Submissions and SAS XPORT transport format web site.
- For more general information regarding the preparation of submissions in electronic format, please contact the Electronic Submissions Coordinator at firstname.lastname@example.org.
- CDER Electronic Records; Electronic Signature Regulations. This page provides links to pertinent Code of Federal Regulations and Federal Register documents.
- ERSR Agency Charter. Federal Register - Electronic Records; Electronic Signatures, Final Rule, March 20, 1997.