Questions and answers on E2B reporting

1. What is the status of the MHRA for electronic reporting? How many companies are they in production with and how many are testing? Currently there are two companies who are sending E2B electronic files (inbound) to the MHRA and two companies receiving these files from the MHRA (outbound).

Testing has revealed inconsistencies between the implementation of the E2B specification by the EMEA and that of the MHRA.  The problem appears to be caused by some areas of ambiguity in the E2B standard.  The MHRA are in correspondence with the EMEA in order to understand how the EMEA have implemented E2B both in respect of the specification and validation requirements. The MHRA will then endeavour to ensure that the specification implemented by the MHRA is compatible with the EMEA. Where it is identified that a specific requirement will compromise the quality of the MHRA Sentinel system, then a work around will be developed. A good example of this is the potential for multiple fatal outcomes for a single case report. Since this does compromise the quality of Sentinel by affecting our signal detection programmes, the MHRA have developed a work around which maintains the quality of Sentinel but does not invalidate the incoming report from Industry. It will also allow for the forwarding on of this report to the EMEA and other companies as required. The Company will be informed as to how this case is held in Sentinel and therefore how it will appear on cumulative reports such as the Drug Analysis Print.
 
In addition to the companies already in production, we are currently testing with 13 companies and 3 more are scheduled. The MHRA have received many expressions of interest to test transmission from industry. These are currently being reviewed in line with a number of proposed technical changes to Sentinel.
 
2. Are there any specific business rules required by the MHRA for electronic reporting?
Yes - please see the table below. The majority of the validation rules below refer to data quality. The MHRA are however aware of a number of issues with E2B elements for example A.2.1.4 (reporter qualification). We are working to implement a technical solution in Sentinel to remove this validation rule.  An issue identified with multiple fatal outcomes has been addressed in question 1 above and will also be removed as a validation rule once these technical changes have been implemented.

E2B Element	E2B Field name	Sentinel Field name	Validation
	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 all cases
B1.2.2a	patientonsetage	Age (Patient tab)	Age can not 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 Medicial 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)	At least one outcome to be recorded. Additionally, if the outcome ‘Fatal’ is recorded against any of the reactions, one of the following fields on the Fatal tab should be populated; Reported Cause of Death (at least one term)(B.1.9.2.b) or Post Mortem Cause of Death (at least one term)(B.1.9.4b). We are investigating removing the fatal outcome validation rule
B.3.1b	testdate	Test Date (Test tab)	Date is not greater than today's/report's date

3. What are the testing requirements for the MHRA?  Are there any written instructions published by the MHRA to help companies with testing?  Where can they be found?
Yes there are testing requirements and as stated in question 3 above they are currently under review to ensure compatibility with the EMEA requirements. These requirements are sent to companies once they have registered their intention to test with the MHRA. 

4. What is the timeframe required for companies to complete the testing phase with the MHRA?  What happens if testing and remediation is not completed by this set timeframe?
Companies will be scheduled a 2 week slot, within which it should be possible to complete the testing required for certification. If a testing slot is overrun, additional 2 week slots will be scheduled by the MHRA. Whilst we cannot guarantee that it will be sequential we will endeavour to ensure continuity.
 
5. How will the testing timeslots be agreed and communicated with individual companies and how much notice will be given?
At present the notice is approximately one month and we are reviewing this in order to improve the testing schedule. Our intention is to give companies as much notice as possible.
 
6. What is the turn-around time for MHRA to review test submissions?
We intend to complete as many testing cycles as possible in the scheduled period of 2 weeks.  The aim is to provide a rapid turnaround of feedback, usually within 48 hours.
 
7. Are there any mandatory timelines set by the MHRA for companies to be able to receive ASPRs electronically? 
At present there are no timelines mandated. At the MHRA/ABPI E2B e-reporting facilitation group meeting it was stated that some companies found it more complex to receive than send reports. We are aware of potential issues and are working with companies to facilitate this changeover.

8. Can companies receive ASPRs from the MHRA using the EVWEB? 
Yes, however before the MHRA activates this facility for a specific company it would be necessary to give consideration to the volume of ICSRs which would be received.  Contact shelley.gandhi@mhra.gsi.gov.uk if your company wishes to receive ASPRs via this method. 
 
9. What is the process for sending literature cases in to the MHRA electronically? 
Once the initial electronic ICSR for a literature report has been sent to the MHRA and acknowledgement received, the article should be e-mailed on an Adobe PDF format to literature@mhra.gsi.gov.uk along with the worldwide unique ID.

10. What is the MedDRA version currently being used by the MHRA? What is the plan for future upgrades? 
The MHRA has recently upgraded to MedDRA 10.0, and has developed a process to ensure that subsequent versions will be uploaded in coordination with companies and regulatory authorities

11. What are stem numbers (company numbers) and how should they be communicated to the MHRA?
The company ‘stem’ numbers are taken from the marketing authorisation number. For example: the company number is 12345 for PL 12345/0001.  Companies may hold several of these and it is important that all of them are provided. These should be supplied when registering to test electronic reporting with the MHRA.  They will be confirmed with the company once a test slot has been agreed.  If your company holds EU licences, please provide all current granted EU licences to the MHRA when registering.
 
12. What are the Gateway IDs for the MHRA Test and Production Gateways?
Production:   MHRAUK
Test:   MHRAUKTEST

13. What information should be included in Receiver section (A.3.2.1 to A.3.2.3L) of an E2B submission

receivertype	Regulatory Authority
receiverorganization	MHRA
receiverdepartment	Pharmacovigilance
receivertitle	Mr
receivergivenname	Mick
receivermiddlename
receiverfamilyname	Foy
receiverstreetaddress	15-2 Market Towers, 1 Nine Elms Lane, Market Towers
receivercity	London
receiverstate
receiverpostcode	SW8 5NQ
receivercountrycode	UK
receivertel	0207 084 2039
receivertelcountrycode	44
receiverfaxccountrycode	44
receiverfax	0207 084 2060
messagerreceiveridentifier	Test: MHRAUKTEST Production: MHRAUK

14. What is the MHRA portal?
The MHRA Portal is a website providing a secure means of transmitting and receiving documents between industry and the MHRA.  It was initially developed for submission of licensing applications.  More information can be found in the Portal section on the MHRA website.

15. If companies are not able to receive ASPRs electronically are there any interim solutions for receipt of ASPRs?
The MHRA Portal is now being used as an interim measure to send ASPRs to Industry until a fully compliant E2B system is available. Existing MAHs that are already registered with the Portal are being moved over to receive ASPRs via the Portal.  Those companies who are not registered will continue to receive hardcopy ASPRs via post until they have registered. It may be possible for companies who are in production with EVWEB to receive ASPRs via EVWEB - please see question 8.
 
16. How can companies register to use the MHRA portal? 
For more information please visit the Anonymised Single Patient Reports section.

This information has also been published in MAIL 159 (Jan/Feb 2007).p10.
 
17. What are the timelines for when this Interim ASPRs solution will be implemented by the MHRA? 
The project has been rolled out to companies who are registered on the MHRA portal and all other companies will be moved over to receive ASPRs via this route once they have registered and training is complete.
 
18. How will users be trained? What supporting instruction will be provided for the use of the portal? 
Companies already trained in the portal will require minimal training and this will be provided by an emailed presentation. For new registrations a one-to-one telephone training session will be provided and a PowerPoint presentation provided for backup.

19. How do you delete single ASPRs?
Step by step guidance will be provided via an emailed PowerPoint presentation.

20. What if no ASPRs can be found in my portal workspace?
Please contact the portal helpdesk on portal.manager@mhra.gsi.gov.uk or 020 7084 3100

21. Who do I contact for portal login or permission issues?
Please contact the portal helpdesk on portal.manager@mhra.gsi.gov.uk or 020 7084 3100

22. Should EU and non-EU cases be sent to the MHRA directly or will they be accessed via the EudraVigilance Data Warehouse?
The MHRA considers that once the EudraVigilance Data Warehouse and Analysis System is fully functional, competent authorities will access reports not occurring in their territory directly from the EudraVigilance database.  Until this time however the MHRA will continue to operate the current system.

23. Should companies continue to parallel report UK reports to the EMEA?
MAHs who have been parallel reporting UK reports to the EMEA EudraVigilance system as a voluntary interim measure can stop this arrangement since the MHRA has been sending these reports to the EMEA since June 2006.

24. Are there any guidelines by the MHRA for disaster recovery and contingency plans to instruct companies on actions if systems fail to submit cases electronically?
The MHRA has disaster recovery and business continuity procedures in place. During a recent test of these procedures the recovery of the cyclone server was successfully tested.  In the event of a catastrophic event it has been shown that the Sentinel system together with the data can be recovered within 48 hours from the start of the process. In such a situation companies reporting electronically would be advised and an allowance of additional time for compliance reporting agreed.  It is assumed that companies have disaster recovery and business continuity procedures tested and in place.

25. On what basis are ASPRs distributed to companies?
The MHRA currently distributes ASPRs for all serious ADRs (CIOMS criteria or internally considered medically significant dictionary terms) to all companies that hold a license for an active substance reported as suspect within that ADR.  If a brand name is reported, all companies holding a licence for an active substance which is a constituent of the drug brand will receive an ASPR for that ADR.

We are aware that some ASPRs have been incorrectly distributed (including production of some duplicate ASPRs), and are developing technical solutions to resolve these problems.

26. Who are the key contacts in the MHRA for E2B reporting and ASPR Portal enquiries and what are the working hours at the MHRA (for contact purposes)? 
Support is available at the MHRA from 09:00-1700. Voicemail will be available.

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 
 
ICSRtesting@mhra.gsi.gov.uk to register for E2B testing with the MHRA
ICSRInformation@mhra.gsi.gov.uk for enquiries regarding electronic reporting
 
ASPRenquiry@mhra.gsi.gov.uk for enquiries specifically regarding ASPRs

Portal helpdesk for general queries regarding the portal, such as workspaces and user login or permission problems
020 7084 3100, portal.manager@mhra.gsi.gov.uk