E2B reports: frequently asked questions

E2B R2 is an international standard for transmitting medicine adverse event reports specified by the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).

XML, or Extensible Markup Language, is a markup language that defines rules for structuring documents in a format that can be read by both humans and machines. The structure of XML is based on a grouping of sections and elements that are annotated by start and end tags. Tags are user-friendly phrases used to indicate the data elements contained within the tags. For example, using the E2B R2 format, a patient's date of birth of 19 March 1972 in XML would appear as: <patientbirthdate>19720319</patientbirthdate>.

The preparation of an E2B adverse event report file requires mapping of your internal database to the E2B data set described in the international guidelines for Electronic Transmission of Individual Case Safety Reports Message Specification (ICH ICSR DTD)*. This is available for download on the EudraVigilance or the US Food and Drug Administration websites. 

After your database has been mapped, the data elements must be marked to conform with the specified document type definition (DTD).

The ICH ICSR DTD guideline defines the specific data elements to include for electronic submission of adverse event data, their order, and their interrelationship.

Prior to submission of an E2B R2 file, you will need to set up a connection between your system and the TGA's system. This will require the exchange of technical and contact details as well as applicable digital certificates. Once this connection has been established and tested, E2B R2 files can be electronically submitted system to system using the AS2 transmission protocol.

For further information, refer to the Electronic submission of individual case safety reports - Electronic data interchange for ICSR submission using the E2B R2 format.

The TGA associates adverse event reports from the pharmaceutical industry submitted system to system with a Sponsor record using the AS2 identifier and digital certificates provided by the sender organisation.

An organisation that has multiple Sponsor records with the TGA can choose to have either:

• separate connections established with the TGA for each Sponsor record and adverse events associated with the applicable Sponsor records; or
• one connection established and all adverse events associated with the one Sponsor record.

No. The system has been designed for a single adverse event report per xml file.

There is no limit to the number of xml files that can be submitted from your system to TGA's system.

The system will accept xml files up to 2 megabytes.

Yes. Clinical trial reports can be electronically submitted system to system. The message type for all adverse event reports (including those that occurred in clinical trials) must conform with ICH ICSR DTD guidelines.

Yes. For cases previously provided in the E2B R2 format the follow-up report needs to include the same sender's case safety report unique identifier (A.1.0.1) and worldwide unique case identification number (A.1.10).

For cases previously provided via another method such as email or the online form, the previously issued TGA reference number should be provided in the section 'Other case identifiers in previous transmissions' (A.1.11) of the XML for the updated case. This will assist with the detection and management of duplicates.

No. Electronic submission is only for medicine adverse event reports. Medical device adverse event (incident) reports from sponsors can be submitted via the Sponsors/Manufacturers medical device incident report page.

Sponsors who have submitted an E2B formatted report as an XML file will receive a message delivery notification (MDN) from our system confirming receipt. A standard acknowledgment confirming success or failure of the transmission will be sent after the message is processed. If the submitted report does not load successfully into the TGA's system, the acknowledgment message will include a description of the first error encountered.

If you do not receive an acknowledgement message, please contact psabsystems@health.gov.au and include information on the date/time of your submission.

No. The existing methods for sponsors to submit adverse event reports will continue to be available.

Yes. Sponsors are required to undertake validation testing with the TGA prior to using the E2B system to system functionality. The validation process will be conducted with test reports in a dedicated testing environment at the TGA. Refer to the test scenarios to use the E2B standard.

Your company can register their interest with the TGA by submitting an email to psabsystems@health.gov.au.

The MedDRA LLT should be used for fields such as B.1.8f (Indication) in the ICH M2 EWG - Electronic Transmission of Individual Case Safety Reports Message Specification where only one MedDRA coding level is available.

To meet the validation rules at least one patient characteristic field is required in the xml file to be populated with a value.

If you believe there is a real patient involved but do not have any specific patient characteristics available, you can still report the adverse event by including a value in the Patient Initials B.1.1 field (for example 'UNK').

The TGA prefers that personal information is not included in the case narrative. Information such as patient name, health professional name or health facility name, date of birth and patient identification number, should instead be provided in the sender comments or applicable fields.

The TGA system can receive XML reports that include or do not include a <!DOCTYPE...> comment field. During the on-boarding process, each organisation specifies whether a <!DOCTYPE...> comment field will be used in the XML for the submitted cases.

The acknowledgement message sent by the TGA will include a <!DOCTYPE...> comment field.

The TGA system can support either Unicode Transformation Format (UTF)-8-bit or UTF-16-bit character encoding formats.

During the on-boarding process, each organisation specifies the character encoding format that will be used in the XML for the submitted cases. Once configured, all submitted cases need to be provided in the specified format.

No. Associated documents cannot be submitted using the TGA E2B functionality. All relevant additional documents held by the sender should be specified in the XML (A.1.8.2) and only provided upon request by the TGA. For adverse event reports from the literature, the literature reference must be provided in A.2.2 'Literature reference(s)' and the abstract included in B.5.1 'Case Narrative' if possible.

No. While we strongly recommend our partners use Transport Layer Security (known as SSL) for security reasons, our system can be configured to not require it.

If the TGA E2B functionality is unavailable for a period that affects the sender's ability to meet regulatory reporting timeframes, the sender should submit the ICH E2B(R2) case safety report to the TGA within 2 TGA business days of the gateway becoming available. In reviewing regulatory reporting timeframe compliance, the TGA will consider relevant periods of gateway unavailability.

The TGA will also advise users when the TGA gateway will be unavailable for scheduled maintenance.

No. Sponsors can use the Adverse Event Management System (AEMS) web portal to access adverse event reports from the TGA.

No. The TGA currently only supports the submission of adverse event reports in the E2B R2 format.

At this stage, the TGA does not have a set timeframe for when the service will be extended to include the E2B R3 format.