On 12th May 2015, European Medicines Agency (EMA) released official notification of their new service, MLM (Medical Literature Monitoring). EMA has published the list of active substances and a reference to the journals that will be covered by this new service. This service will start with a limited number (50 active molecules) of active substances on 1 July 2015 and will be fully rolled out in September 2015. EMA will use following journals/reference databases:
- EBSCO, this covers wide variety of resources, with main focus on use of
– Medline Plus
– International Pharmaceutical Abstracts (IPA)
– The Allied and the Complementary Medicine Database (AMED)
Summary of this new service:
What: Medical literature is an important source of information on suspected adverse reactions reported on medicines.
It is being provided as a service to industry which, for the active substances and literature covered by the EMA activities, will no longer be obliged to enter the information on suspected adverse reactions into EudraVigilance. Individual cases of suspected adverse reactions found in the literature will be made available to marketing-authorization holders (MAH) so they can include them in their safety databases and meet their reporting obligations outside the European Economic Area.
A total of 400 active substance groups will be monitored by EMA, in particular substances that are contained in a high number of medicinal products, and over 4,000 companies will benefit.
As of 1 July 2015, the service will cover the top 50 chemical active substance groups (ID 1 to ID 50) which are listed in the notification. Companies with medicines containing one of these active substances will benefit from the EMA service from 1 July and will need to adapt their processes by that date. All the other substances, including the herbal active substances that are listed, will be included in the EMA service as of September 2015.
The dedicated webpage will also be regularly updated.
Why: This initiative aims to improve the safety monitoring of medicines by enhancing the quality and consistency of data reported in EudraVigilance. Monitoring of medical literature and the entry of relevant information into EudraVigilance will be carried out by EMA in order to:
- Enhance the efficiency of adverse reactions reporting;
- Provide a simplification for the pharmaceutical industry;
- Improve data quality by reducing the number of duplicates;
- Contribute to resource savings for the pharmaceutical industry; and
- Support signal detection activities by national competent authorities and marketing-authorization holder
How: The following steps would need to be followed –
- ICSRs resulting from the MLM service refer to the selected medical literature subject to monitoring by the Agency and the identified reports of suspected adverse reactions to medicinal products containing active substances identified as part of the scope of the Agency’s activities
- ICSRs resulting from the MLM service are transmitted electronically to EudraVigilance
- ICSRs resulting from the MLM service are transmitted electronically via the EudraVigilance Gateway to NCAs in EEA Member States in accordance with the reporting requirements of ICSRs applicable during the interim period
- ICSRs resulting from the MLM service are made available for download by the MAHs (EudraVigilance download area or EVWEB). This refers to ICSRs of suspected serious adverse reactions occurring within and outside the EEA and non-serious adverse reactions from within the EEA
- Concerned MAHs can download the ICSRs resulting from the MLM service in XML format in compliance with the “Note for guidance: EudraVigilance Human – Processing of safety messages and individual case safety reports (ICSRs)” (EMA/H/20665/04/Final Rev. 2)
Following steps would no longer be required effective 01-Jul-2015:
- Member States should not re-submit the ICSRs resulting from the MLM service to EudraVigilance.
- Member States should no longer forward/provide the ICSRs resulting from the MLM service to the concerned MAHs, since MAHs can download those ICSRs from the EudraVigilance Download Area
- Concerned MAHs should not re-submit the ICSRs resulting from the MLM service to EudraVigilance (suspected serious adverse reactions from outside the EEA)
- Concerned MAHs should no longer forward/provide the ICSRs resulting from the MLM service to the concerned NCA(s) in the EEA
Impact for the MAH:
This does not replace the literature search that is currently performed. For a global organization, there would not be any change needed in the way search strings are set-up. Only change would be, not to submit the ICSRs present in the MLM with in EU/EEA. Other regulatory requirements and criteria remain same for FDA and other regulatory agencies.
Some technical preparations are needed.
MAH WEB Trader user:
- Access to EVWEB environment (no changes for users already registered in the EVWEB environment)
- The existent requirements and browser restrictions for EVWEB apply (preferable IE 8)
EudraVigilance download area for MAHs: Test and production environment
- System configured to accept ICSRs with the Sender identifier “MLMSERVICE”
In addition, EMA have organized series of online question and answer sessions next two as per below mentioned dates and time (UK time),
- Monday 8 June 2015 from 10:00-11:00 am
Monday 15 June 2015 from 09:30-11:00 am
Expressions of interest to participate in the Q&A sessions should be sent to email@example.com.
This is indeed a good initiative from EMA and is the first of its kind. As per EMA, this will help over 4000 pharma organizations in the long run. It aims to improve the safety monitoring of medicines by enhancing the quality and consistency of data reported in EudraVigilance and to support signal detection activities by NCA (National Competent Authorities) and MAHs. EMA mentioned that it will send updates on the implementation of its medical literature monitoring service to the qualified persons for pharmacovigilance as well as to pharmaceutical industry organizations. Most of the organizations might have already received this information, either directly or via their QPPVs in EU.
EMA website has a detailed guideline, guidance document, a training video, a document detailing the inclusion and exclusion criteria, user manual etc. We will try to bring more light on the processes and challenges, through details of the process at EMA, will this bring efficiency and simplification, what if the same article is processed before it is available at MLM etc., in our next blog on this topic. While there are clear-cut benefits to MAHs, especially within EEA, it would also be good to see how this evolves in the long term.