Posted 18 February 2015
By Michael Mezher
The European Medicines Agency (EMA) released a new document intended to clarify data submission requirements for medicines authorized in the European Economic Area (EEA).
In the document, the agency discusses the current status of its eXtended EudraVigilance Medicinal Product Dictionary (XEVMPD) and talks about planned changes through 2016.
Pharmacovigilance in the EU
Pharmacovigilance is the process of monitoring the use of drugs after they have entered the market. In particular, companies look for side effects or adverse reactions to their products. This information is incredibly important to ensuring patient safety after a product has been approved.
Companies that market pharmaceutical products in the EEA are required to submit pharmacovigilance data to EMA. This goes for all authorized medicinal products, whether they are authorized through national, centralized or decentralized procedures.
To comply with EU pharmacovigilance requirements, companies must develop risk management plans; submit adverse drug reaction (ADR) reports and periodic safety update reports (PSURs); and notify EMA of new or changed marketing authorizations.
The primary legal bases for pharmacovigilance requirements in the EU are found in Article 57 of Regulation (EC) No. 726/2004 and Title IX of Directive 2001/83/EC. In 2010 and 2012, the EU introduced new directives and regulations amending its pharmacovigilance requirements. The amendments were made legally binding throughout the EU in June 2012 with the passage of Regulation (EU) No. 520/2012.
For amendments to Regulation (EC) No. 726/2004 see Regulation (EU) No. 1235/2010 and Regulation (EU) No. 1027/2012.
For amendments to Directive 2001/83/EC see Directive 2010/84/EU and Directive 2012/26/EU.
The amendments were made after a review of the EU’s pharmacovigilance system by the European Commission (EC) in 2005. Following its review, EC said that 197,000 deaths in the EU can be attributed to ADRs each year, citing a total cost to society of €79 billion.
Article 57 Requirements
As amended, Article 57(2) of Regulation (EC) 726/2004 requires EMA to create and maintain a database of all authorized medicinal products for human use. EMA is also required to establish an electronic format for companies to use when submitting their product information to the agency.
The database was called the eXtended EudraVigilance Medicinal Product Dictionary (XEVMDP), after the former EudraVigilance Medicinal Product Dictionary (EVMPD).
Companies were given until 2 July 2012 to submit electronic information to EMA for each of their authorized products using the newly established eXtended EudraVigilance Product Report Message (XEVPRM) format. As of 16 June 2014, companies have been required to actively maintain the information in XEVMPD.
EMA says gathering data in a standardized way provides a number of benefits such as reducing costs, facilitating transparency and simplifying ADR event reporting.
As of 26 January 2015, EMA received data for more than 385,000 products in the new format, and expects the XEVMPD to be completely functional by the end of Q2 2015.
Clarifying XEVPRM and XEVMDP
In an effort to clarify its data submission requirements, EMA has released an explanatory document: Data submission of authorised medicines in the European Union.
The document gives an overview of the data content and governance required under Article 57 and explains the process for completing the submission. The agency also discusses how it approaches controlled terminologies used in the submissions, such as pharmaceutical dose forms and substance names, and directs users to where they can find more information on standard terms.
Quality Control and Completeness
To ensure that the data in the XEVMPD is accurate, EMA hired an external contractor to manually review the data it has received. When the quality control team discovers an error, it contacts the data’s originator for correction. The agency’s goal is to ensure error rates are less than 0.5%, and expects the review to be complete in August 2015.
Additionally, the EU Network Data Board (EUNDP) will be comparing the XEVMPD against the databases maintained by national regulatory authorities to determine if product information is missing from the centralized list.
Even though the XEVPRM format has only been in use for a few years, EMA is already planning to replace it with more internationally accepted standards. The new format will use the International Organization for Standardization (ISO) Identification of Medicinal Product (IDMP) standards, which are currently under development.
EMA says the legal requirements of Article 57 of Regulation (EC) No. 726/2004 will still apply, using ISO IDMP standards. The agency is looking to complete its roadmap for these changes by the end of Q1 2015, while the switch to ISO IMPD is planned for July 2016.