E2B reporting with the MHRA: Updated information - January 2008

All marketing authorisation holders (MAHs) are required to successfully test electronic transmission with the MHRA prior to switching from paper to electronic reporting. Testing will be conducted with test reports on a dedicated testing environment at the MHRA. Paper reporting of real reports in fulfilment of reporting obligations should continue in parallel during the testing period. Once testing has been completed to the satisfaction of the MHRA and the MAH, paper reporting can stop and electronic reporting of real reports can begin. It is not intended to have a transition period of parallel paper and electronic reporting of real reports.

Where to find information on the electronic reporting standards
The electronic reporting format that should be used is defined by the International Conference on Harmonisation (ICH) in the ICH E2B(M) standard (the definition of this standard is published on the ICH website (external link). In addition to this standard format, the Medical Dictionary for Regulatory Affairs (MedDRA) medical terminology must be used to code reports. Information on MedDRA and subscription details can be found on the MedDRA MSSO website (external link).

EU regulators and the EMEA have collaborated in the creation of a data processing network and management system called EudraVigilance to support the transmission of electronic ICSRs. Within the UK, market authorisation holders will be expected to submit reports to the MHRA using this network. The network can be considered as a hub and spoke system with the EudraVigilance Gateway as the hub and all EU regulators and MAHs as spokes. Electronic ICSR are routed through the hub to the desired spoke in an automated and secure manner. To use the network, MAHs will need to register with the EudraVigilance gateway and install one of the many software packages that support secure data exchange. The gateway is supported by the EMEA and information on registering and using the gateway can be found on the EMEA website (external link). This site also contains extensive information on the ICH-E2B(M) standard, the EudraVigilance system and links to numerous EU guidance documents on electronic reporting.

Implementation of regulations for small or medium enterprises
After consideration, the MHRA will not be able to provide the ADR ‘conversion’ service, converting paper company ADRs into the electronic format and forwarding this to the EMEA database.  Such companies should use the EMEA EVWEB tool to submit their reports electronically, details of which can be found on the EMEA website (external link). EVWEB supports the full range of two-way electronic communications between regulators and the MAH.

If a MAH is to use the EVWEB tool to submit ICSRs to the MHRA, we anticipate that a truncated period of testing will be required.  This will be just to ensure that the ICSRs meet the MHRA’s specific validation checks and that data fields are completed correctly.

The MHRA is currently in the process of implementing changes to their Sentinel system to allow the smoother and quicker submission of E2B reports to the MHRA. Major Sentinel fixes will be tested during 6 weeks starting late January 2008 to be deployed late March 2008:

Changes that will affect the way in which your company submit E2B reports are:

1. Drug dosage form fields: Files that report this field as text are currently rejected. Changes will be applied to the Sentinel system that will enable this field to be accepted as either text or the codes. Though please note that all exported files (MHRA to Industry) will populate this field using a code. The list of codes and corresponding terms is available:
   › Drug dosage form (E2B element B.4.k.7)
   
   
2. Reporter Qualification: At the present time a reporter qualification is required for every reporter block that has been completed The E2B validation will be amended such that only one reporter qualification is required per case.
3. Study Fields: At the present time the study fields are required to be populated for every reporter block that has been completed. The E2B validation will be amended such that only one study field is required per case.
4. Fatal Outcomes: Currently reports containing multiple fatal outcomes are rejected. Changes will be applied to the Sentinel system to enable the current validation rule to be removed so that more than one fatal outcome can be assigned to each case.
5. ACK error message comment field: This field is currently restricted to 250 characters, and so appears truncated. The Sentinel database will be changed to save around 10000 characters, while the xml field will have a maximum of 2000.
6. MHRA Outbound batch: Currently the MHRA outbound batch sends one ICSR per file. This will be changed such that outbound files are batched by company number (ie for PL 12345/0001 company number is 12345)

All these fixes will be tested during the User Acceptance Testing (UAT) running from January to March 2008.

During this UAT period we will be resuming testing with all companies that we have already started a testing cycle with. If this applies to your company the MHRA will be in contact in due course. After the UAT period there will be a phased deployment of the Sentinel fixes throughout March and April 2008 and testing will begin with all other companies who have previously registered but not completed any testing.

Registering for testing
Please note if you have already registered for testing, the MHRA will be in contact from April 2008 onwards regarding your testing slot. Please do not complete a second registration form.

If your company has not yet registered for E2B testing with the MHRA please complete the following information:

• Company name and address
• Company names and company numbers (e.g. XYZ Pharma Ltd, 12345 PL 12345/0001 – the company number is 12345 PL = Product Licence). Please also include the stem number of any clinical trials licences (CTAs) or centralised licences
• Business contact (including name, position, phone, fax and e-mail details)
• Technical contact (including name, position, phone, fax and e-mail details)
• Please specify which level of certification your company is applying for:
• • Full (send and receive ICSRs)
  • Partial (send ICSRs to MHRA only)
  • EVWEB (using web-based form)
  • EVWEB (post production)
• EudraVigilance Gateway ID (testing and production)
• Please provide the name of your database system and version
• Earliest date when available to begin testing
• Preferred date to begin testing
• Is your company fully compliant with E2B?
• Are you ready to accept outbound ICSRs from the MHRA now?
• Do you have access to EVWEB
• If yes, what is your EVWEB User ID (testing and production)
• Once testing has been completed the aim is to switch to production as soon as possible - do you envisage any further delays once testing is complete for both inbound and outbound?

Please complete this information on the following form and e-mail to ICSRtesting@mhra.gsi.gov.uk
› E2B testing registration form (653Kb) 

We will contact you to agree a slot in the testing schedule and a testing plan in due course. Until testing is completed, paper reporting should continue in line with reporting obligations.

To prepare for your testing please ensure that you are able to submit reports following the criteria shown below:

Scenario	Test description
1	An ICSR including details of other drugs, medical history, drug history, narrative and tests
	-Sender must demonstrate that both the structured medical and drug history can be provided for the reports
	- The reports must also contain examples of correctly structured Tests and show the Pharmaceutical forms have been incorporated correctly.
2	A fatal ICSR including cause of death and post mortem details
	- Seriousness death flag must be yes
	- Reaction outcome must be fatal
	- Patient death date should be provided
	- Patient autopsy and patient death cause must be provided
3	A nullification ICSR
	- The nullification flag must be set to Yes
	- The nullification reason must be provided and it must be valid reason to nullify a case
4	A parent-child ICSR
	- The child/foetus must be encoded as the patient
	- The parent's details must be provided in the parent's section
	- It is essential that:
	i) The child (patient) route is entered in B.4.k.8. The drug route of administration must be Transmammary, Transplacental, or Other (if parent is male)
	ii) The parent route is entered in B.4.k.9 and
	iii) That section B.1.10 contains validating parent details (ie initials, age, sex, weight) as well as any relevent parent history/ other details available.
5	A follow-up ICSR to an initial ICSR which has previously been sent
	- Initial report should have the same receipt and receive dates
	- Follow-up report must have the same receive date as the initial but the receipt date must be changed to reflect the new information
	- The worldwide case ID must be identical in both the initial and follow-up reports
6	A follow-up ICSR to an initial ICSR which has previously been sent from an alternative sender (i.e. alternative company or competent authority)
	- This should be a test loading of a case received electronically
	- The worldwide case ID must be preserved by the sender when retransmitting a report to another receiver
7	An ICSR from a study
	- Report type must be "Report from studies"
	- Study type must be "Other studies"
8	An ICSR based on a literature article
	- Literature reference must be provided in Vancouver style
	- Report type can be "Other" for a literature report only if you can not tell from the literature article if it is spontaneous or from a study
9	An ICSR with duplicate details completed
	- 1. To capture all the safety report IDs that has been used in the past to transmit a case between different organisations.
	- 2. To capture all previous paper numbers that have been used in the past, this is to enable the detection of duplicates if a case had previously been sent on paper. e.g. old Yellow card numbers and company CIOMS MFR numbers
10	A SUSAR (if applicable)
	- Report type must be "Report from studies"
	- Study type must be "Clinical trials"
	- Study name must include an example EudraCT number in the correct format e.g  2138383-01#Name of study...
	- Study protocol number must be provided
	- Patient ID must be provided (B.1.1.1d)

The MHRA has previously incorporated further UK specific validation checks in addition to those in the ICH standard. As a result of the changes to Sentinel as outlined above, these additional validations have been updated and are detailed below:

E2B Element	E2B Field name	Sentinel Field name	Validation
A1.1	primarysourcecountry	Country of Origin (Case Attributes)	Mandatory field for all cases.
A.2.1.4	qualification	Reporter Qualification (Reporter tab)	At least one required for each case
B1.2.2a	patientonsetage	Age (Patient tab)	Age cannot be greater than 120 years
B.1.3	patientweight	Weight (Patient tab)	Not to be greater than 500kg
B.1.4	patientheight	Height (Patient tab)	Not to be greater than 300 cm
B.1.7.1c	patientmedicalstartdate	Start Date (Relevant Medical History - Patient tab)	Date is not greater than today’s/report’s date
B.1.7.1f	patientmedicalenddate	End Date (Relevant Medical History - Patient tab)	Date is not greater than today’s/report’s date
B.1.8c	patientdrugstartdate	Start Date (Past Drug History - Patient tab)	Date is not greater than today’s/report’s date
B.1.8e	patientdrugenddate	End Date (Past Drug History - Patient tab)	Date is not greater than today’s/report’s date
B.1.9.1b	patientdeathdate	Date of Death (Fatal Tab)	Date is not greater than today’s/report’s date or less than any drug start date
B.1.10.7.1c	parentmedicalstartdate	Episode start date (Parent - Medical History)	Date is not greater than today’s/report’s date
B.1.10.7.1f	parentmedicalenddate	Episode stop date (Parent - Medical History)	Date is not greater than today’s/report’s date
B.1.10.8c	parentdrugstartdate	Start Date (Relevant Past Drug History – parent)	Date is not greater than today’s/report’s date
B.1.10.8e	parentdrugenddate	End Date (Relevant Past Drug History – parent)	Date is not greater than today’s/report’s date
B.2.i.8	reactionoutcome	Outcome (Reaction Details page)	All outcomes should be populated. If the outcome is unknown this field should be populated with 'unknown' and not left blank
B.3.1b	testdate	Test Date (Test tab)	Date is not greater than today’s/report’s date
N/A	All dates	All dates	If partial dates are received the following will apply for validation
			- If no day is specified, it will be assumed that it is the 1st of the month when validating.
			- If no month is specified if will be assumed that it is 01/mm/yyyy when validating.
B.4.k.2.1 B.4.k.4.1	MA Number		The Product name and MA Number field will be validated to ensure that they match in the Sentinel database. If the specific product and the MA number given do not match, the MA number will be ignored. Companies should be advised to report at the SP level, and if this is not possible, at the PBG level.
	Drug Name (Drug Details page)
B.4.k.7	drugdosageform	Pharmaceutical Form	The pharmaceutical form can be reported using both the text and code format. However the terms / codes will need to be selected from the table available on the MHRA website only

All other data elements not specified in the table are as defined in the ICH E2B(M) standard.

Please be aware that it is the MHRAs intention to reduce the number of paper ASPRs . Therefore if your company is currently unable to receive electronic ICSRs via E2B from the MHRA then you will need to register to receive ASPRs in pdf form via the portal. More information regarding the portal and collection of ASPRs and for information on how to register can be found in our Anonymised Single Patient Reports section.

For further information please see our Questions and answers on E2B reporting section.

Who are the key contacts in the MHRA for E2B reporting?

For technical assistance please contact:
Phil Tregunno  020 7084 2696  phil.tregunno@mhra.gsi.gov.uk
Paul Barrow   020 7084 2655  paul.barrow@mhra.gsi.gov.uk
Rebecca Webb 020 7084 2275 rebecca.webb@mhra.gsi.gov.uk

Please e-mail ASPR Portal enquiries to ASPRenquiry@mhra.gsi.gov.uk