COM(2021)0497
EUR-Lex

The Commission presents a report on the national and European Medicines Agency experience regarding the list of medicines for human use subject to additional monitoring.

Regulation (EC) No 726/2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and Directive 2001/83/EC on the Community code relating to medicinal products for human use provide the EU legal framework for pharmacovigilance for medicinal products for human use. The provisions on pharmacovigilance were amended in 2010 and 2012.

Additional monitoring

The 2010 revision introduced additional monitoring for certain medicines and a mandatory scope of new biological medicines or those containing a new active substance. The medicines which are subject to additional monitoring are identified by the inclusion of a ‘black symbol’ (a black inverted triangle) in the product information. In 2012, the mandatory scope was extended to include medicines with certain post authorisation obligations.

This report is based on a joint report of the Heads of Medicines Agencies (HMA) and EMA and gives an overview of the experience in the three years after the introduction of the black triangle in 2013.

Main findings

The report noted, inter alia , that:

- both more time and more communication are needed to raise the awareness of AM [additional monitoring], as well as the need for adverse drug reaction (ADR) reporting in general. The EMA survey results suggest that knowledge of AM is higher in some groups than others and that these data could be used to target the messaging and intensity of communications;

- the EudraVigilance analysis investigating the effect of additional monitoring status on reporting of ADRs was not conclusive and the known disparate influences on ADR reporting raise doubts as to whether a longer period and larger product sample would enable the detection of an impact of AM on ADR reporting and signal detection, if such an effects exists;

- the inclusion of imposed post authorisation safety study (PASS) as a mandatory trigger for additional monitoring leads to large numbers of established products being included in the list and is of limited value;

- additional monitoring status being at product level combined with the inclusion of imposed PASS as a mandatory trigger for additional monitoring were highlighted as major issues with the additional monitoring concept. This is because of the resulting misunderstanding among patients and health care professionals, due to situations when several products containing the same active substance have different AM status. Most examples of this inconsistency could be resolved by removing imposed PASS as a mandatory trigger of additional monitoring status;

- the Pharmacovigilance Risk Assessment Committee (PRAC) would support reconsideration of the scope of additional monitoring, particularly the mandatory inclusion of products subject to imposed PASS.

Recommendations

On the basis of these findings, the report made the following recommendations.

Recommendation 1

Member States and EMA are encouraged to continue promoting ADR reporting and sharing their experience to further develop best practices.

Recommendation 2

The evidence does not allow a conclusion on the impact of additional monitoring on the reporting or detection of adverse events. It is recommended to continue to monitor the impact to strengthen the evidence base for future review of the scheme.

Recommendation 3

Competent authorities are invited to continue to collect data regarding the implementation of additional monitoring to allow at a later stage further assessment of the understanding of additional monitoring and its impact with respect to medicines with the same active substance, as well as experience concerning medicines with an imposed PASS.

COM(2019)0591
EUR-Lex

The Commission presented a report on pharmacovigilance related activities of Member States and the European Medicines Agency (EMA) concerning medicinal products for human use (2012 – 2014).

The EU legal framework of pharmacovigilance for medicinal products for human use is provided for in Regulation (EC) No 726/2004 and Directive 2001/83/EC . The legislation was amended in 2010 and 2012 .

Pharmacovigilance, as defined by the World Health Organisation (WHO), is ‘the science and activities relating to the detection, assessment, understanding and prevention of adverse effects or any other drug-related problem’.

This report and the accompanying Staff Working Document describe the activities of the EU’s networked and collaborative system for monitoring and controlling the safety of human medicines and is focused on activities since the start of operation of new legislation in 2012 until the end of 2014, but also includes information on some tasks and processes initiated up to July 2015.

The main conclusions of the report are as follows:

Strong collaboration between the European regulatory authorities : the medicines regulatory authorities in 31 European Economic Area (EEA) countries, the EMA and the European Commission closely collaborate and work in partnership as a network to discuss and deal swiftly with any emerging problem in the interest of patients' access to safe and efficacious medicines. The ability to take quick and robust regulatory action was enhanced through the legislation by :

the creation of the Pharmacovigilance Risk Assessment Committee; strengthening of the Co-ordination group for Mutual recognition and Decentralised procedures – human; the introduction of new procedures to fast-track decision-making when public health is at risk.

Continuing and future development of the network : over the period of the report and beyond, the pharmacovigilance network is focusing on training to develop understanding of pharmacovigilance and regulatory science to enable sharing of best practice, improving the efficiency and effectiveness of the processes, and building capacity.

The European pharmacovigilance network represents an example of successful co-operation at the European level, to the benefit of EU citizens. The networked system allows participants to share in the best available expertise and evidence and co-ordinate the regulatory actions, producing more efficient and consistent outcomes for everybody.

The regulatory tools made available under the revised legislation represent an increasingly proactive approach to medicines safety. These tools comprise the following:

risk management planning : Pharmacovigilance Risk Assessment Committee (PRAC) reviewed 48 risk management plans (RMPs) in July–December 2012, 637 in 2013 and 597 in 2014. The Member States, collectively, received around 3 500 (2012), 7 500 (2013), and 9 000 (2014) RMPs for nationally authorised medicines; post-authorisation studies : between July 2012 and December 2014, PRAC reviewed protocols for 38 imposed non-interventional post authorisation safety studies (PASSs); signal detection and management at EU level : analysing reports of suspected side effects to identify signals. Some 193 unique signals were evaluated by PRAC between September 2012 and December 2014; periodic safety update reports : routine benefit-risk monitoring of medicines via periodic safety update reports (PSURs) and maintaining the list (EURD list) of schedules for submitting PSURs; inspections : carrying out inspections to ensure company pharmacovigilance systems comply with good pharmacovigilance practice.

The regulatory tools are complemented by improvements in regulatory action and communication when safety concerns are identified.

Increased transparency : mechanisms have been put in place to ensure that accurate safety information reaches the EU public in a timely manner. Engagement of key stakeholders such as patients and healthcare professionals is embedded in the system including through patient reporting of suspected side effects.

For the future, deepening involvement is foreseen, including the holding of public hearings for critical safety issues.

Improving service systems : work is proceeding on the infrastructure needed to support further development of the system, and to simplify and streamline existing processes where possible so that the regulatory burden is minimised for all stakeholders. Work concerns:

delivery of the medical literature monitoring service of the new EudraVigilance system , of the PSUR repository; full use of EU product database (provided for by Article 57) of all authorised medicines (both centrally and nationally authorised) in the EU with information on over 580 000 medicines from nearly 4 300 marketing authorisation holders.

Work continues to complete the development and implementation of other systems such as centralised ADR reporting through the EudraVigilance database. Ongoing research in the field of regulatory science, such as the research supported through the EU Research Framework Programmes, will also support future improvements.

COM(2016)0498
EUR-Lex

EUR-Lex
SWD(2016)0284

The Commission presented a report on the exercise of the delegation of powers conferred on the Commission pursuant to:

Directive 2001/83/EC of the European Parliament and of the Council on the Community code relating to medicinal products for human use; Regulation (EC) No 726/2004 of the European Parliament and of the Council laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency.

Delegation of power : pursuant to the aforementioned texts, the power to adopt delegated acts is conferred on the Commission for five years from January 2011. The Commission is required to report on its exercise of those powers at the latest six months before the end of this period.

Regulation (EC) No 726/2004 , as amended by Regulation (EU) No 1235/2010 , empowered the Commission to adopt delegated acts on post-authorisation efficacy studies (Article 10b).

Exercise delegated powers : to date, the Commission has exercised the delegated powers provided for by Regulation (EC) No 726/2004.

Under this Regulation, it may be necessary in specific situations to complement the data available at the time a medicinal product was granted marketing authorisation with additional information on its efficacy, to address concerns that could not be resolved before the authorisation was granted.

Under Article 10b of the Regulation, the Commission is empowered to specify the situations in which post-authorisation efficacy studies may be required.

Following the consultation with the Expert Group formed by the Pharmaceutical Committee, the Commission adopted the Delegated Regulation (EU) No 357/2014 and notified the European Parliament and the Council of it. Neither institution objected to the delegated act. The Commission Delegated Regulation was published in the Official Journal and entered into force on 30 April 2014.

In conclusion, the Commission considered that the delegated powers conferred by Article 10b of Regulation (EC) No 726/2004, as amended by Regulation (EU) No 1235/2010, should remain in force .

COM(2015)0138
EUR-Lex

C(2012)9279

C(2012)5562

LEGISLATIVE ACT : Commission Regulation 507/2006/EC on the conditional marketing authorisation for medicinal products for human use falling within the scope of Regulation 726/2004/EC of the European Parliament and of the Council.

CONTENT : t his Regulation lays down rules on the granting of a marketing authorisation subject to specific obligations in accordance with Article 14(7) of Regulation 726/2004/EC ("conditional marketing authorisation").

In the case of certain categories of medicinal products, in order to meet unmet medical needs of patients and in the interests of public health, it may be necessary to grant marketing authorisations on the basis of less complete data than is normally the case and subject to specific obligations.

This Regulation applies to medicinal products for human use that fall under Article 3(1) and (2) of Regulation 726/2004/EC and belong to one of the following categories:

- medicinal products which aim at the treatment, the prevention or the medical diagnosis of seriously debilitating diseases or life-threatening diseases;

- medicinal products to be used in emergency situations, in response to public health threats duly recognised either by the World Health Organisation or by the Community in the framework of Decision 2119/98/EC;

- medicinal products designated as orphan medicinal products in accordance with Article 3 of Regulation 141/2000/EC.

ENTRY INTO FORCE: 02/04/2006.

32006R0507
OJ L 092 30.03.2006, p. 0006-0009

ACT : Commission Regulation 2049/2005/EC laying down, pursuant to Regulation 726/2004/EC of the European Parliament and of the Council, rules regarding the payment of fees to, and the receipt of administrative assistance from, the European Medicines Agency by micro, small and medium-sized enterprises.

CONTENT : Regulation 726/2004/EC provides that the revenue of the European Medicines Agency must consist of a contribution from the Community and fees paid by companies, and states that the situation of micro, small and medium-sized enterprises (SMEs) has to be considered separately. This Regulation establishes the circumstances in which, by derogation from the relevant provisions of Regulation 297/95/EC, SMEs may pay reduced fees, defer payment of fees, or receive administrative assistance when submitting applications under Regulation 726/2004/EC to the Agency. The Regulation applies both to applications concerning medicinal products for human use and to applications concerning veterinary medicinal products.

Fee deferrals and reductions: The payment of certain fees is deferred until the notification of the final decision on the marketing authorisation is issued, or the application is withdrawn:

- the fee for an application for a marketing authorisation of a medicinal product;

- the fee for inspections undertaken for the purpose of assessing a marketing authorisation application for a medicinal product.

These fees are payable within 45 days of the date of the notification of the final decision on the marketing authorisation, or within 45 days of the date of the notification of withdrawal of the application.

The Regulation makes provision for a conditional fee exemption, where an application for marketing authorisation is submitted for a medicinal product on which scientific advice has already been given by the Agency. The fee payable to the Agency for the examination of that application will be due only if a marketing authorisation is granted.

Fee reductions:

- in the case of inspections a 90 % reduction to the inspection fee;

- in the case of scientific advice a 90 % reduction to the scientific advice fee;

- in the case of scientific services a 90 % reduction to the scientific service fee;

- scientific advice and scientific services for designated orphan medicinal products as referred to in Regulation 141/2000/EC shall be provided free of charge;

- a 90 % reduction to the full and additional maximum residue limits (MRL) fees, as referred to in Regulation 297/95/EC;

- there are provisions on multiple fee reductions.

SME Office: The Executive Director of the Agency shall set up dedicated administrative structures and specific procedures for the establishment of an SME Office, which will have the following tasks:

- to give advice to applicants on the administrative and procedural steps necessary to comply with the requirements laid down in Regulation 726/2004/EC;

- to ensure the appropriate monitoring of all requests and applications submitted by the same applicant and related to a particular medicinal product;

- to organise workshops and training sessions for applicants on the administrative and procedural steps necessary to comply with the requirements laid down in Regulation 726/2004/EC.

The Agency will publish a detailed User Guide on the administrative and procedural aspects of the provisions laid down in Regulation 726/2004/EC, which are of particular relevance for SMEs.

ENTRY INTO FORCE : 16/12/2005. The Regulation shall not apply to valid applications pending at the date of its entry into force.

32005R2049
OJ L 329 16.12.2005, p. 0004-0007

Regulation 2004/726
OJ L 136 30.04.2004, p. 0001-0033

COM(2004)0124
EUR-Lex

T5-0576/2003
OJ C 091 15.04.2004, p. 0133-0253 E

T5-0576/2003

Debate in Parliament

A5-0425/2003

A5-0425/2003

SEC(2003)1082
EUR-Lex

10949/2/2003
OJ C 297 09.12.2003, p. 0001-0040 E

10949/2/2003

12155/1/2003

COM(2002)0735
EUR-Lex

COM(2002)0735
EUR-Lex

2470

T5-0504/2002
OJ C 300 11.12.2003, p. 0166-0308 E

T5-0504/2002

Debate in Parliament

A5-0330/2002

A5-0330/2002

CES1007/2002

2440

EUR-Lex
COM(2001)0404

EUR-Lex
COM(2001)0404