e-Reporting mandatory – changing EU legislations

The significant changes are introduced into Pharmacovigilance and Regulatory Affairs business practice to enhance patient safety, increase efficiency and transparency with regard to Pharmacovigilance. The new EU Pharmacovigilance legislation constitutes one of the biggest changes in European drug law since 1995.

As one of the consequences of changing regulations, Marketing Authorisation Holders (MAHs) that maintain products in the European Union, whether centralized, decentralized, Mutual recognition or national are obliged to provide detailed structured data for all human medicinal products authorised in EU/EEA to the Eudravigilance Medicinal Product Dictionary (EVMPD) using new standards; Extended EudraVigilance Product Report Message (XEVPRM) by July 02, 2012 at the latest.

Legal framework and recent developments (2011)

The existing legal framework of Pharmacovigilance for the drugs marketed within the EU is covered under the Regulation (EC) No 726/2004 for centrally authorized medicinal products and EU Directive 2001/83/EC covers the regulations for nationally authorized medicinal products including the products authorized through mutual recognition and decentralized systems.

The latest changes in the Pharmacovigilance regulations issued on December 31, 2010 have brought a significant shift in the existing reporting systems of clinical data post authorization to EudraVigilance.

The enhancement of Eudravigilance by the EMA, to ensure its place as the central database for the EU will help in reducing the duplication and repeated efforts from MAHs to submit their clinical reports to Health agencies.

Amendments to the existing pharmacovigilance regulations

The new legislation on pharmacovigilance brings the following changes:

1. EMA has rebranded the EVMPD (Eudravigilance Medicinal Product Dictionary), which is now called XEVMPD (Extended Eudravigilance Medical Product Dictionary). This is a new version and requires a lot more information than the original requirements. All life sciences organizations will need to oblige to this regulations at the latest by July 02, 2012.

2. Regulation (EU) No 1235/2010 of the European Parliament and of the Council of 15 December 2010 amending, as regards pharmacovigilance of medicinal products for human use, Regulation (EC) No 726/2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency, and Regulation (EC) No 1394/2007 on advanced therapy medicinal products. This Regulation will amend the chapter 3 of Regulation (EC) No 726/2004 and will decrees that the EMA shall set up a list of all medicinal products for human use authorised in the EU, and that MAHs shall, by July 02, 2012 at the latest, electronically submit to the EMA information on all medicinal products for human use authorised or registered in the EU using the format defined by the EMA, and keep it up to date thereafter.

3. Directive 2010/84/EU of the European Parliament and of the Council of 15 December 2010 amending, as regards pharmacovigilance Title IX of Directive 2001/83/EC on the Community code relating to medicinal products for human use. Directive 2010/84/EU to be transposed into national law and will be implemented by July 12, 2012.

EudraVigilance
EudraVigilance was launched by the EMA in December 2001. EudraVigilance stands for European Union Drug Regulating Authorities Pharmacovigilance and is a data processing management system for reporting and evaluating suspected adverse drug reactions (ADRs) during the development and post marketing authorisation approval of medicinal products for human use in the European Economic Area (EEA).

Eudravigilance is one of the main pillars of the European Risk Management Strategy. It is a joint effort between the EMA and National Competent Authorities to strengthen the conduct of Pharmacovigilance in the EEA.

EudraVigilance 2 databases:
The EudraVigilance pools all the data and collects at one place using 2 databases namely:

• The EudraVigilance Clinical Trial Module (EVCTM) to facilitate the electronic reporting of Suspected Unexpected Serious Adverse Reactions (SUSARs) as required by Directive 2001/20/EC.

• The EudraVigilance Post-Authorisation Module (EVPM) designed for post-authorisation ICSRs, Regulation (EC) No 726/2004, Directive 2001/83/EC as amended, and Volume 9A of the "Rules Governing Medicinal Products in the European Union: Pharmacovigilance for medicinal products for human use".

Source Systems for Eudravigilance:
MAHs compiles the data using standard terminology defined in the following Sources:
EudraVigilance Medicinal Product Dictionary (EVMPD)

• Medical Dictionary (MedDRA)

EVMPD and XEVMPD
EVMPD stands for EudraVigilance Medicinal Product Dictionary. EVMPD has been designed to support the collection, reporting, coding and evaluation of medicinal product data in a standardized and structure way.
 
XEVMPD stands for Extended EudraVigilance Medicinal Product Dictionary and it supersedes the EVMPD previous specification effective from July 02, 2012.  The new Eudravigilance medicinal product dictionary (EVMPD version 2.0) has been extended to include the requirements for the collection, reporting, coding and evaluation of Investigational medicinal product (IMP) data as defined in EU directive 2001/20/EC.

EudraVigilance medicinal product dictionary (EVMPD)
The medicinal product dictionary has actually been in existence since 2005 and since then all MAHs have been able to submit basic details of their products to the EMA, either electronically or by manually by entering their data into the EudraVigilance web portal, EVWEB.
 
The EV Medicinal product dictionary consists of three different databases designed to support the collection, standardization, updates, variation and scientific evaluation of authorised medicinal products.

The three different databases are:

1. Product Report Database: is designed to support the data collection and contains the key information related to authorised and development medicinal products whereby the information is provided by the Marketing Authorization holders (MAHs) and sponsors of clinical trials conducted in the EEA.
2. Scientific Product Database: is designed to support data analysis. It implements a hierarchical structure that allows for the classification and grouping of all the medicinal products stored in the EVMPD.
3. Product Index Database: Contains several ‘reporting possibilities’ for one and the same medicinal product.











Data collection process
The entry of the medicinal product information in the EVMPD takes place through EudraVigilance Product report Messages (EVPRMs). EudraVigilance Product Report Messages (EVPRMs) are XML files that allow insertion and maintenance of information in the Product Report Database in a standardized and structured format. The sender of an EVPRM is the formal owner of the data in the EVMPD.

 
The entry of medicinal product information in the product report database can take place in three different ways:







In each of the above mentioned procedures an XML file called EudraVigilance product report message is generated. The EVPRM is the only input the EVMPD accepts.

In view of current scenario, where it will take time for industry to get fully equipped with new legislation’s requirements ESTRI (Electronic standards for Transfer of Regulatory Information) gateway is the most preferred and recommended solution for the industry.

ESTRI is the data exchange service that will support regulatory communication based upon any of the recommended standards.

Marketing Authorization holders can now submit XML schema Definition (XSD) – compliant product information on all the medicinal products authorized and registered in the EU using tools developed in-house by pharmaceutical companies or software vendors via the EudraVigilance Gateway.





Challenge for life sciences industry
With the regulations being revised time to time to harmonize the data submission process worldwide, the pharmaceutical industries are facing a number of crucial business challenges to improve operational excellence in product time-to-market and wide regulatory compliance.

The new legislation means that submitting product data to the EVMPD is no longer voluntary and becomes mandatory from July 02, 2012. Adhering to this new legislation is a significant challenge for many small and medium size organizations.

MAHs, who have electronically submitted information on medicinal products for human use authorised or registered in the Union in accordance with the provisions set out in Volume 9A of The Rules Governing Medicinal Products in the European Union, part III, chapter 11.6 previously, shall update such information in accordance with the format, content and requirements in accordance with Article 57(2), second sub-paragraph of Regulation (EC) No 726/2004, which specifies the format for the electronic submission of information on medicinal products for human use. This new format is referred to as the Extended EudraVigilance Product Report Message (XEVPRM). Marketing Authorization holders shall update the medicinal product information as per XEVPRM that have been previously submitted as per old EVMPD format.

Conclusion
There are significant changes being introduced with the new Pharmacovigilance legislation. A lot of these focus on the use of EudraVigilance as the central European Pharmacovigilance database. With this comes the requirement to ensure accurate updated information. The European Medicines Agency (EMA) has mandated that, from July 02, 2012, life sciences organizations must formally submit the product data to the health authorities in a standardized and structured way.

Pharmaceutical organizations marketing and selling drugs in Europe will have no choice but to abide by July 02, 2012  deadline for implementing these strict new requirements for Pharmacovigilance concerning the collection, reporting, coding and evaluation of medicinal product data, as part of the industry’s latest measures to minimise the impact of adverse reactions to drugs.