Procedure : 2008/0260(COD)
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Document selected : A7-0159/2010

Texts tabled :

A7-0159/2010

Debates :

PV 21/09/2010 - 9
CRE 21/09/2010 - 9

Votes :

PV 22/09/2010 - 5.5
Explanations of votes
Explanations of votes

Texts adopted :

P7_TA(2010)0332

REPORT     ***I
PDF 717kWORD 997k
2 June 2010
PE 430.927v03-00 A7-0159/2010

on the proposal for a directive of the European Parliament and of the Council amending, as regards pharmacovigilance, Directive 2001/83/EC on the Community code relating to medicinal products for human use

(COM(2008)0665 – C6-0514/2008 – 2008/0260(COD))

Committee on the Environment, Public Health and Food Safety

Rapporteur: Linda McAvan

AMENDMENTS
DRAFT EUROPEAN PARLIAMENT LEGISLATIVE RESOLUTION
 EXPLANATORY STATEMENT
 OPINION of the Committee on Industry, Research and Energy
 OPINION of the Committee on the Internal Market and Consumer Protection
 PROCEDURE

DRAFT EUROPEAN PARLIAMENT LEGISLATIVE RESOLUTION

on the proposal for a directive of the European Parliament and of the Council amending, as regards pharmacovigilance, Directive 2001/83/EC on the Community code relating to medicinal products for human use

(COM(2008)0665 – C7-0514/2008 – 2008/0260(COD))

(Ordinary legislative procedure: first reading)

The European Parliament,

–    having regard to the Commission proposal to the European Parliament and the Council (COM(2008)0665),

–    having regard to Article 251(2) and Article 95 of the EC Treaty, pursuant to which the Commission submitted the proposal to Parliament (C7-0514/2008),

–    having regard to the Communication from the Commission to the European Parliament and the Council entitled "Consequences of the entry into force of the Treaty of Lisbon for ongoing interinstitutional decision-making procedures" (COM(2009)0665),

–    having regard to Article 294(3) and Articles 114 and 168(4)(c) of the Treaty on the Functioning of the EU,

–    having regard to the opinion of the European Economic and Social Committee of 10 June 2009(1),

–    having regard to the opinion of the Committee of the Regions of 7 October 2009(2),

–    having regard to Rule 55 of its Rules of Procedure,

–    having regard to the report of the Committee on the Environment, Public Health and Food Safety and the opinions of the Committee on Industry, Research and Energy and the Committee on the Internal Market and Consumer Protection (A7-0159/2010),

1.   Adopts the position at first reading hereinafter set out;

2.   Calls on the Commission to refer the matter to Parliament again if it intends to amend the proposal substantially or replace it with another text;

3.   Instructs its President to forward its position to the Council and the Commission.

Amendment  1

Proposal for a directive – amending act

Citation 2 a (new)

Text proposed by the Commission

Amendment

 

- having regard to the opinion of the European Data Protection Supervisor of 22April 2009(3)

 

OJ C 229, 23.9.2009, p. 19.

Amendment  2

Proposal for a directive – amending act

Recital 5

Text proposed by the Commission

Amendment

(5) For the sake of clarity, the definition of adverse reaction should be amended to ensure that it not only covers noxious and unintended effects derived from the authorised use of a medicinal product at the normal doses, but also medication errors and uses outside the authorised summary of the product characteristics, including the misuse and abuse of the product.

(5) For the sake of clarity, the definition of “medication error” should be introduced, to ensure that preventable non-intentional and inappropriate incidents, resulting in an adverse reaction, derived from the authorised use of a medicinal product at the normal doses, but also those derived from medication errors and from uses outside the authorised summary of the product characteristics, are covered by this Directive.

Amendment  3

Proposal for a directive – amending act

Recital 5 a (new)

Text proposed by the Commission

Amendment

 

(5a) The pollution of waters and soils with pharmaceutical residues is an emerging environmental problem and an emerging public health concern. Measures should be taken to monitor and evaluate adverse environmental effects of medicinal products, including those which impact on public health. The Commission should, based on data received from the European Medicines Agency, the Environment Agency, and Member States, produce a report on the scale of the problem, along with an assessment on whether amendments to EU legislation on medicinal products or to other relevant EU legislation are required.

 

 

Amendment  4

Proposal for a directive – amending act

Recital 6

Text proposed by the Commission

Amendment

(6) The marketing authorisation holder should establish a pharmacovigilance system to ensure the monitoring and supervision of one or more of its authorised medicinal products, recorded in a Pharmacovigilance System Master File permanently accessible for inspection. The competent authorities should undertake the supervision of those systems. A summary of the pharmacovigilance system should be therefore submitted with the marketing authorisation application and include a reference to the site where the Pharmacovigilance System Master File for the medicinal product concerned is maintained and accessible for inspection.

(6) The marketing authorisation holder should establish a pharmacovigilance system to ensure the monitoring and supervision of one or more of its authorised medicinal products, recorded in a Pharmacovigilance System Master File permanently accessible for inspection. The competent authorities should undertake the supervision of those systems. A summary of the pharmacovigilance system should be therefore submitted with the marketing authorisation application and include a reference to the site where the Pharmacovigilance System Master File for the medicinal product concerned is maintained and accessible for inspection by the competent authorities.

Justification

It is the competent authorities who should be able to check the permanent pharmacovigilance file, and this should be clearly stated.

Amendment  5

Proposal for a directive – amending act

Recital 9

Text proposed by the Commission

Amendment

(9) Where a medicinal product is authorized subject to the requirement to conduct a post-authorisation safety study or where there are conditions or restrictions with regard to the safe and effective use of the medicinal product, the medicinal product should be intensively monitored on the market. Patients and healthcare professionals should be encouraged to report all suspect adverse reactions to such medicinal products, and a publicly available list of such medicinal products should be maintained up to date by the European Medicines Agency established by Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (hereinafter referred to as the ‘Agency’).

(9) It is essential that a strengthened system of pharmacovigilance does not lead to the premature granting of market authorisations. However, where a medicinal product is authorized subject to the requirement to conduct a post-authorisation safety study or where there are conditions or restrictions with regard to the safe and effective use of the medicinal product, the medicinal product should be intensively monitored on the market. Patients and healthcare professionals should be encouraged to report all suspected adverse reactions to such medicinal products, identified by a symbol and a corresponding explanatory sentence on the summary of product characteristics on the patient information leaflet, and a publicly available list of such medicinal products should be maintained up to date by the European Medicines Agency established by Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (hereinafter referred to as the ‘Agency’).

Amendment  6

Proposal for a directive – amending act

Recital 10

Text proposed by the Commission

Amendment

(10) In order to make it possible for the healthcare professionals and patients to identify easily the most relevant information about the medicines they use, the summary of the product characteristics and the package leaflet should include a concise section on the key information about the medicinal product and information how to minimize its risks and maximize its benefits.

(10) It is important for healthcare professionals and patients to identify easily the most relevant information about the medicines they use. In order to facilitate such identification, the Commission should review the summary of the product characteristics and the package leaflet within 18 months.

Justification

The rapporteur accepts the majority view that there are problems with the proposed Summary of Essential Information. She will support Compromise Amendment 2a and 2b which delete the Summary of Essential Information on the Summary of Product Characteristics and the Package Information Leaflet, and proposes instead to call on the Commission to come forward with a proposal to revise the package leaflet, and the connected Summary of Product Characteristics.

Amendment  7

Proposal for a directive – amending act

Recital 10 a (new)

Text proposed by the Commission

Amendment

 

(10a) Without any delay, the Commission shall, in collaboration with the Agency, and following consultations with organisations representing patients, consumers, doctors and pharmacists, social health insurers, and Member States and other interested parties, present to the European Parliament and the Council an assessment report regarding the readability of the summaries of product characteristics and the packaging leaflets and their value to the general public and healthcare professionals. Following an analysis of the above data, the Commission shall, if appropriate, put forward proposals to improve the layout and the content of the summaries of product characteristics and of the packaging leaflet to ensure they are a valuable source of information for the general public and healthcare professionals.

Amendment  8

Proposal for a directive – amending act

Recital 13

Text proposed by the Commission

Amendment

(13) With a view to ensuring that the same level of scientific expertise in the area of pharmacovigilance decision-making at both Community and national level, when fulfilling pharmacovigilance tasks the coordination group should be able to rely on the advice of the Pharmacovigilance Risk Assessment Advisory Committee of the Agency.

(13) With a view to ensuring that the same level of scientific expertise in the area of pharmacovigilance decision-making at both Community and national level, when fulfilling pharmacovigilance tasks the coordination group should rely on the recommendation of the Pharmacovigilance Risk Assessment Committee of the Agency.

Justification

The powers of the Pharmacovigilance Risk Assessment Committee (PRAC) should be increased in relation to the coordination group. The coordination group is not a specialist body on pharmacovigilance – its job is to balance overall the risks with benefits. The PRAC should be the only body in charge of pharmacovigilance and risk assessment, in order to avoid undue duplication of roles.

Amendment  9

Proposal for a directive – amending act

Recital 16

Text proposed by the Commission

Amendment

(16) Member States should operate a pharmacovigilance system to collect information useful in the surveillance of medicinal products including information on suspected adverse drug reactions, on misuse, abuse and medication errors, and ensure its quality through the follow up of suspected adverse drug reaction cases.

(16) Member States should operate a pharmacovigilance system to collect information useful in the surveillance of medicinal products including information on suspected adverse drug reactions resulting from normal conditions of use, off-label use, misuse, abuse and medication errors, and ensure its quality through the follow up of suspected adverse drug reaction cases.

Justification

The Commission's proposal is confusing and could be clarified to confirm that the pharmacovigilance system should be used to collect information on all suspected adverse drug reactions - not just those occurring through misuse, abuse and medication errors.

Amendment  10

Proposal for a directive – amending act

Recital 18

Text proposed by the Commission

Amendment

(18) In order to simplify the reporting of suspected adverse reactions the marketing authorisation holders and the Member States should report those reactions only to the Community pharmacovigilance database and data-processing network referred to in Article 57(1)(d) of Regulation (EC) No 726/2004 (hereinafter ‘the Eudravigilance database’).

(18) In order to simplify the reporting of suspected adverse reactions :and to enable Member States to access the same information simultaneously, the marketing authorisation holders and the Member States should report those reactions only to the Community pharmacovigilance database and data-processing network referred to in Article 57(1)(d) of Regulation (EC) No 726/2004 (hereinafter ‘the Eudravigilance database’). The Eudravigilance database should simultaneously and electronically notify the relevant Member States of reports submitted by market authorisation holders. From this perspective, and in order to achieve the objectives referred to above, Member States should not impose any further requirements on marketing authorisation holders in respect of the prompt and regular reporting of suspected adverse reactions. The Eudravigilance database and the national database should be fully interoperable.

 

 

 

 

Justification

Member States should be alerted electronically when Market Authorisation Holders submit reports to Eudravigilance about serious suspected adverse reactions which happen on their territory, as an extra check to ensure that national competent authorities do not miss or overlook this information.

Amendment  11

Proposal for a directive – amending act

Recital 20 a (new)

Text proposed by the Commission

Amendment

 

(20a) Reporting by healthcare professionals should be particularly encouraged in cases where their contribution is essential in order to understand the significance of the adverse reaction and of adverse reactions derived from medication errors. To facilitate this type of reporting and to protect the citizen, access to data contained in patients’ medical files should be accessible to healthcare professionals.

Justification

It is important to emphasise the active role of healthcare professionals in pharmacovigilance reporting. Furthermore, in order to facilitate more accurate identification of potential medication errors resulting in suspect adverse reactions, it is essential that doctors and pharmacists share access to patients’ medical files – while fully respecting the law on privacy and data protection – in a climate of mutual cooperation that has proven results.

Amendment  12

Proposal for a directive – amending act

Recital 22

Text proposed by the Commission

Amendment

(22) Requirements for periodic safety update reports should be proportional to the risks posed by medicinal products. Periodic safety update reporting should therefore be linked to the risk management system for newly authorised medicinal products and routine reporting should not be necessary for generic, well-established use, informed consent, homeopathic, or traditional use registered herbal medicinal products. However, in the interest of public health the authorities should require periodic safety update reports for such products when there is a need to assess their risk or review the adequacy of product information.

(22) Requirements for periodic safety update reports should be proportional to the risks posed by medicinal products. Periodic safety update reporting should therefore be linked to the risk management system for newly authorised medicinal products and routine reporting should be required for generic, well-established use, informed consent, homeopathic, or traditional use registered herbal medicinal products. However, in the interest of public health the authorities should require periodic safety update reports for such products when there is a need to assess their risk or review the adequacy of product information.

Justification

The effects of a medicinal product can vary according to its composition or its method of manufacture, and for this reason all medicinal products should be subject to the publication of periodic safety update reports.

Amendment  13

Proposal for a directive – amending act

Recital 27

Text proposed by the Commission

Amendment

In order to enforce the provisions related to the pharmacovigilance, the Member States should ensure that effective, proportionate and dissuasive penalties are applied to marketing authorisation holders for non-compliance with pharmacovigilance obligations.

In order to enforce the provisions related to pharmacovigilance, the Member States should ensure that effective, proportionate and dissuasive penalties are applied to marketing authorisation holders for non-compliance with pharmacovigilance obligations. If the conditions included in the marketing authorisation are not fulfilled by the given deadline, the national competent authorities should have the power to review the marketing authorisation granted.

Justification

Experience shows that in many cases where companies were required to conduct post-authorisation safety studies they failed to do so. In the case of a highly profitable medicinal product, fines are not always dissuasive, and so the legislation should make clear that Member States also have the possibility of suspending or revoking the market authorisation.

Amendment  14

Proposal for a directive – amending act

Recital 29 a (new)

Text proposed by the Commission

Amendment

 

(29a) This Directive should apply without prejudice to Directive 95/46/EC and Regulation 45/2001/EC on the protection of individuals with regard to the processing of personal data by the Community institutions and bodies and on the free movement of such data. The purpose of safeguarding public health constitutes a substantial public interest which justifies the processing of identifiable health data as long as this is processed only when necessary and the parties involved assess the necessity of processing such data at every stage of the pharmacovigilance process.

Justification

The proposal covers highly sensitive personal information which should be fully protected. However, it should be possible to process personal data within the Eudravigilance system whilst also respecting EU data protection legislation.

Amendment  15

Proposal for a directive – amending act

Article 1 – point 1 – point a

Directive 2001/83/EC

Article 1 – paragraph 11

 

Text proposed by the Commission

Amendment

 

 

“(11) Adverse reaction: A response to a medicinal product which is noxious and unintended.”

“(11) Adverse drug reaction: A response to a medicinal product which is noxious and unintended.”

Justification

The term ‘adverse reaction’ should be replaced by the more precise term ‘adverse drug reaction’, which is used by experts and is internationally accepted.

Amendment  16

Proposal for a directive – amending act

Article 1 - point 3

Directive 2001/83/EC

Article 11 - point 3a and subparagraph 3

 

Text proposed by the Commission

Amendment

(a) the following point 3a is inserted:

(a) the following points 3a and 3b are inserted:

3a. a summary of the essential information necessary to use the medicine safely and effectively;

3a. For medicinal products included on the list referred to in Article 23 of Regulation (EC) No 726/2004, the statement, preceded by a black symbol which shall be decided on by means of delegated acts in accordance with Articles 121a, 121b and 121c: “This medicinal product is subject to additional safety monitoring. All suspected adverse reactions should be reported to your doctor, pharmacist, healthcare professional, or to name and web-address, postal address and / or telephone number of the national competent authority.”

(b) the following subparagraph is added:

 

For the purposes of point (3a) of the first subparagraph, for medicinal products included on the list referred to in Article 23 of Regulation (EC) No 726/2004, the summary shall include the statement: “This medicinal product is under intensive monitoring. All suspected adverse reactions should be reported to name and web-address of the national competent authority

3b. For medicinal products not included in the list referred to in Article 23 of Regulation (EC) No 726/2004, the following statement should be included: “All suspected adverse reactions should be reported to your doctor, pharmacist, healthcare professional, or to name and web-address, postal address and/or telephone number of the national competent authority."

Amendment  17

Proposal for a directive – amending act

Article 1 – point 3 a (new)

Directive 2001/83/EC

Article 16c – paragraph 4 – subparagraph 2

 

Text proposed by the Commission

Amendment

 

3a. In Article 16c(4), subparagraph 2 is replaced by the following:

 

The Committee shall consider whether the other criteria for a simplified registration as referred to in Article 16a are fully complied with. If the Committee considers it possible, it shall establish a Community herbal monograph as referred to in Article 16h(3) which shall be complied with by the Member State when taking its final decision.

Justification

The Community procedure to establish monographs is only efficient if the Member States are obliged to follow the Community monographs.

Amendment  18

Proposal for a directive – amending act

Article 1 – point 7

Directive 2001/83/EC

Article 21 – paragraph 3

 

Text proposed by the Commission

Amendment

“3. The national competent authorities shall make publicly available without delay the marketing authorisation together with the summary of the product characteristics and any conditions established in accordance with Articles 21a, 22 and 22a, together with any deadlines for their fulfilment, for each medicinal product which they have authorised.

“3. The national competent authorities shall make publicly available without delay the marketing authorisation together with the package leaflet, summary of the product characteristics and any conditions established in accordance with Articles 21a, 22 and 22a, together with any deadlines for their fulfilment, for each medicinal product which they have authorised.

Justification

In the interest of providing complete and accurate information to the general public, the package leaflet should also be made public when marketing authorisation is granted.

Amendment  19

Proposal for a directive – amending act

Article 1 – point 7

Directive 2001/83/EC

Article 21 – paragraph 4 – subparagraph 2

 

Text proposed by the Commission

Amendment

The national competent authorities shall make publicly accessible without delay the assessment report, together with the reasons for their opinion, after deletion of any information of a commercially confidential nature. The justification shall be provided separately for each indication applied for.

The national competent authorities shall make publicly accessible without delay the final assessment report, together with the reasons for their opinion, after deletion of any information of a commercially confidential nature. The justification shall be provided separately for each indication applied for.

Justification

To keep the public better informed, it is important to specify that the final report will be available for consultation. The technical nature of pharmacovigilance requires many successive stages before a final outcome is reached. It therefore seems appropriate to make the findings publicly available and not the intermediate studies that require subsequent verification. The purpose of this approach is not to cause alarm among the general public about hypotheses that have not yet been proven but rather to provide the information once it has been scientifically approved.

Amendment  20

Proposal for a directive – amending act

Article 1 - point 8

Directive 2001/83/EC

Article 21a

 

Text proposed by the Commission

Amendment

A marketing authorisation may be granted subject to one or more of the following conditions:

In addition to the provisions laid down in Article 19, a marketing authorisation may be granted subject to one or more of the following conditions:

(1) to take certain measures for the safe use of the medicinal product contained in the risk management system;

(1) to take certain measures for the safe use of the medicinal product contained in the risk management system;

(2) to conduct post-authorisation safety studies;

2) to conduct post-authorisation safety studies, or post-authorisation safety and efficacy studies where important questions relating to the efficacy of a product remain, or when scientific advances in the understanding of the disease or in the clinical methodology would significantly change previous efficacy evaluations. For this purpose, the Commission shall provide guidelines.

 

The Commission shall also, based on data received from the Agency and Member States, produce a report focusing on the concept of clinical effectiveness, on studies and data required and on methodologies for assessing it.

(3) to comply with requirements on adverse reaction recording or reporting which are stricter than those referred to in Title IX;

(3) to comply with requirements on adverse reaction recording or reporting which are stricter than those referred to in Title IX;

(4) any other conditions or restrictions with regard to the safe and effective use of the medicinal product.

(4) any other conditions or restrictions with regard to the safe and effective use of the medicinal product.

The marketing authorisation shall lay down deadlines for the fulfilment of the conditions where necessary.

The marketing authorisation shall lay down deadlines for the fulfilment of the conditions. The competent authorities shall have the power and appropriate resources to immediately suspend or revoke the marketing authorisation in the event that the conditions included in the marketing authorisation are not fulfilled by the relevant deadline.

Justification

The compromise doesn't cover amendments 123 - 125, 127 and 128, although these all express concerns about the "added value" of drugs and ability of National Competent Authorities to monitor the efficacy of drugs. By widening the scope of post-authorisation studies, this gives national competent authorities more freedom to determine the kind of study which is most useful. At the moment, most drugs are subject to some kind of PASS as an extra safety precaution. However, although safety monitoring happens throughout the life of a drug, efficacy is only checked once, at the time of authorisation. There should be the possibility to monitor drug efficacy post-authorisation as well - in real world populations and real-life conditions.

Amendment  21

Proposal for a directive – amending act

Article 1 – point 10

Directive 2001/83/EC

Article 22a – paragraph 1

 

Text proposed by the Commission

Amendment

1. After the granting of a marketing authorisation, the national competent authority may require a marketing authorisation holder to conduct a post-authorisation safety study if there are concerns about the risks of an authorised medicinal product. The requirement shall be made in writing, provide a detailed justification and include the objectives and timeframe for submission and conduct of the study.

1. After the granting of a marketing authorisation, the national competent authority may require a marketing authorisation holder to conduct a post-authorisation safety study if there are concerns about the risks of an authorised medicinal product. The requirement shall be made in writing, provide a detailed scientific justification and include the objectives and timeframe for submission and conduct of the study.

Justification

Requests for additional post-authorisation safety studies should be scientifically justified. The Commission’s proposal is not sufficiently clear on this point.

Amendment  22

Proposal for a directive – amending act

Article 1 – point 12 – point b

Directive 2001/83/EC

Article 24– paragraph 3

 

Text proposed by the Commission

Amendment

3. Once renewed, the marketing authorisation shall be valid for an unlimited period, unless the national competent authority decides, on justified grounds relating to pharmacovigilance or to insufficient exposure to the product, to proceed with one additional five-year renewal in accordance with paragraph 2.”

3. Once renewed, the marketing authorisation shall be valid for an unlimited period, unless the competent authority decides, on justified grounds relating to pharmacovigilance, to proceed with one additional five-year renewal in accordance with paragraph 2.”

Justification

The benefits of a harmonised and simplified approach pursued in the current proposal should be preserved. The criterion (d) “insufficient exposure” introduces a degree of uncertainty especially for products, such as orphan drugs, for which exposure is unlikely to ever be sufficient (sufficient exposure is a very difficult threshold/ benchmark to achieve). The new proposal should not regress on improvements introduced by the previous revision of the medicines legislation which aimed at reducing the number of renewal procedures. The original wording regarding the deciding authority should be maintained.

Amendment  23

Proposal for a directive – amending act

Article 1 - point 18

Directive 2001/83/EC

Article 59 -paragraph 1– point aa and subparagraphs 2 and 3

 

Text proposed by the Commission

Amendment

(a) The following point (aa) is inserted:

(a) The following point (aa) is inserted:

(aa) a summary of the essential information necessary to use the medicine safely and effectively;

(aa) For medicinal products included on the list referred to in Article 23 of Regulation (EC) No 726/2004, the following statement shall be included preceded by a black symbol which shall be decided on by means of delegated acts in accordance with Articles 121a, 121b and 121c: “This medicinal product is subject to additional safety monitoring. All suspected adverse reactions should be reported to your doctor, pharmacist, healthcare professional, or to name and web-address, postal address and / or telephone number of the national competent authority.

(b) the following second and third subparagraphs are added:

 

The information referred to in point (aa) of the first subparagraph shall be presented in a box surrounded by a black border. Any new or amended text shall for a period of 1-year be presented in bold text and preceded by the following symbol and text "New information".

 

For medicinal products included on the list referred to in Article 23 of Regulation (EC) No 726/2004, the following additional statement shall be included “This medicinal product is under intensive monitoring. All suspected adverse reactions should be reported to name and web-address of the national competent authority".

For medicinal products not included in the list referred to in Article 23 of Regulation (EC) No 726/2004, the following statement should be included: “All suspected adverse reactions should be reported to your doctor, pharmacist, healthcare professional, or to name, web-address, postal address and/or telephone number of the national competent authority".

Amendment  24

Proposal for a directive – amending act

Article 1 - point 18 a (new)

Directive 2001/83/EC

Article 59 - paragraph 3

 

Text proposed by the Commission

Amendment

 

Article 59(3) is amended as follows:

 

3. Within 18 months of the entry into force of this Directive, the Commission shall present to the European Parliament and the Council an assessment report on how the summary of product characteristics and the package leaflet should meet the needs of patients and healthcare professionals. On the basis of this, the Commission shall issue proposals in order to improve the readability, layout and content of these documents.

3. The package leaflet shall reflect the results of consultations with target patient groups to ensure that it is legible, clear and easy to use.

The package leaflet shall reflect the results of consultations with target patient groups to ensure that it is legible, clear and easy to use.

Justification

The rapporteur accepts the majority view that there are problems with the proposed Summary of Essential Information. She will support Compromise Amendment 2a and 2b which delete the Summary of Essential Information on the Summary of Product Characteristics and the Package Information Leaflet, and proposes instead to call on the Commission to come forward with a proposal to revise the package leaflet, and the connected Summary of Product Characteristics.

Amendment  25

Proposal for a directive – amending act

Article 1 – point 20

Directive 2001/83/EC

Article 65 – point g

 

Text proposed by the Commission

Amendment

 

 

(g) the summary of the essential information necessary to use the medicine safely and effectively provided for in Article 11(3a) and Article 59(1)(aa).”

(g) the Union procedure for defining a procedural timeline, a clear structure and defined roles for all the stakeholders involved, including for the conduct of public hearings.

Justification

The proposed summary of essential information about the safe and effective use of medicines should be rejected since the concept of 'essential information' is misleading and might be misunderstood.

Guidance should be developed to clarify the procedures and timelines for the community procedure, including public hearings.

Amendment  26

Proposal for a directive – amending act

Article 1 – point 20 a (new)

Directive 2001/83/EC

Article 86 – paragraph 2

 

Text proposed by the Commission

Amendment

 

20a. The first indent of Article 86(2) is amended as follows:

 

“– the labelling and the accompanying package leaflets, which are subject to the provisions of Title V, and the summary of the product characteristics, insofar as they are made available to the public independently of the delivery of the medicinal product in unchanged wording and without additional promotional elements,

Justification

The documents approved by the consent authorities (package leaflets and summary of product characteristics) contain important information about the product. It should be made clear that publication of those documents is not be considered as advertising provided that no promotional elements are involved (e.g. a presentation extolling the virtues of the product or inclusion of the documents in supplementary publicity material) and the wording approved by the authorities is used. At the present time this is a subject of legal dispute when, for example, pharmaceutical companies put those documents on their websites (see Case-316/09 concerning the presentation of medicinal products on the Internet, referred to the CJEC by the Bundesgerichtshof for a preliminary ruling by order I ZR 223/06 of 16 July 2009).

Amendment  27

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 101 – paragraph 3

 

Text proposed by the Commission

Amendment

3. Each Member State shall designate a competent authority for the conduct of pharmacovigilance tasks

3. Each Member State shall designate one or more competent authorities for the conduct of pharmacovigilance tasks.

Justification

It should be up to the Member States to have one or more competent authorities responsible for pharmacovigilance. Member States may have different competent authorities for different pharmaceutical products.

Amendment  28

Proposal for a directive – amending act

Article 1 - point 21

Directive 2001/83/EC

Article 102 - paragraph 1- point 1

 

Text proposed by the Commission

Amendment

(1) take all appropriate measures to encourage doctors, pharmacists and other health-care professionals to report suspected adverse reactions to the national competent authority or the marketing authorisation holder;

(1) take all appropriate measures to encourage patients, doctors, pharmacists and other health-care professionals to report suspected adverse reactions to the national competent authority; these measures shall include training for health professionals and a public information campaign for patients. Patients’ and consumer organisations shall be involved in providing information to patients and in developing public information campaigns in cooperation with regulatory bodies.

Justification

Many amendments were tabled to article 102, on spontaneous reporting of ADRs. The rapporteur has incorporated most of the key elements of these amendments into a compromise.

On the last paragraph, she did not include that the reporting of medication errors should be done anonymously (amendment 183), as this could lead to malicious reporting, but has accepted the concept of no-blame reporting.

"Legally privileged" means that the ADR reports would not be presentable in legal proceedings against the health professional involved.

Amendment  29

Proposal for a directive – amending act

Article 1 - point 21

Directive 2001/83/EC

Article 102 - paragraph 1- point 1 a (new)

 

Text proposed by the Commission

Amendment

 

(1a) facilitate direct patient reporting through the provision of alternative reporting formats in addition to web-based formats;

Justification

see justification to am to Article 1 - paragraph 1 - point 1.

Amendment  30

Proposal for a directive – amending act

Article 1 - point 21

Directive 2001/83/EC

Article 102 - paragraph 1- point 2

 

Text proposed by the Commission

Amendment

(2) ensure that adverse reaction reports contain the highest quality information possible;

(2) ensure that adverse reaction reports and databases contain the highest quality information possible;

Justification

see justification to am to Article 1 - paragraph 1 - point 1.

Amendment  31

Proposal for a directive – amending act

Article 1 - point 21

Directive 2001/83/EC

Article 102 - paragraph 1- point 2 a (new)

 

Text proposed by the Commission

Amendment

 

(2a) ensure that the public is given important information in good time on pharmacovigilance concerns relating to the use of a medicinal product through publication on the web portal and through other means of public information as necessary;

Justification

see justification to am to Article 1 - paragraph 1 - point 1.

Amendment  32

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 102 – paragraph 1 – point 3

 

Text proposed by the Commission

Amendment

(3) through the methods of collecting information and where necessary through the follow up of adverse reaction reports, ensure that any biological medicinal product prescribed, dispensed, or sold in their territory which is the subject of an adverse reaction report is identifiable;

(3) ensure that any biological medicinal product prescribed, dispensed, or sold in their territory which is the subject of a report on a suspected adverse reaction is identifiable by, where available, the name of the MAH, the INN, the name of the medicinal product and the batch number, using the standard forms and procedures developed in accordance with Article 25(1) of the Regulation (EC) No 726/2004 and taking due account of the developments within the EudraVigilance system.

 

 

Justification

Accurate identification of the product associated with a suspected adverse event is fundamental to a sound pharmacovigilance system. The Community system will be successful only if the underlying legislative framework ensures accurate reporting of product identity. The present proposal lacks details about how to clearly identify biological medicinal products and creates the risk of 27 different approaches to pharmacovigilance for products generally subject to the centralized authorization procedure. The proposed addition to paragraph (3) of Article 102 seeks to remedy this lack of clarity providing a number of identifiers for biologicals and is linked to an amendment to Art 25 of the Regulation (EC) No 726/2004, which assigns to the European Medicines Agency (EMEA) the task of developing forms for adverse event reporting for biological medicinal products. In addition the amendment is important to ensure that a legal basis is created to request from HCPs and pharmacists requirements relating specifically to the identification of biologics, as far and as many as are available to the HCP, which will contribute to a clear identification of biological medicinal products.

Amendment  33

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 102 – paragraph 2

 

Text proposed by the Commission

Amendment

 

 

For the purposes of point (1) of the first paragraph the Member States may impose specific requirements on doctors, pharmacists and other health-care professionals in respect of the reporting of suspected serious or unexpected adverse reactions.

For the purposes of points (1) and (3)of the first paragraph the Member States may impose specific requirements on doctors, pharmacists and other health-care professionals.

 

Reporting of suspected adverse reactions due to medication errors should be on a 'no blame' basis, and should be legally privileged.

Justification

Accurate identification of the product associated with a suspected adverse event is fundamental to a sound pharmacovigilance system. The Community system will be successful only if the underlying legislative framework ensures accurate reporting of product identity. The present proposal lacks details about how to clearly identify biological medicinal products and creates the risk of 27 different approaches to pharmacovigilance for products generally subject to the centralized authorization procedure. The proposed addition to paragraph (3) of Article 102 seeks to remedy this lack of clarity providing a number of identifiers for biologicals and is linked to an amendment to Art 25 of the Regulation (EC) No 726/2004, which assigns to the European Medicines Agency (EMEA) the task of developing forms for adverse event reporting for biological medicinal products. In addition the amendment is important to ensure that a legal basis is created to request from HCPs and pharmacists requirements relating specifically to the identification of biologics, as far and as many as are available to the HCP, which will contribute to a clear identification of biological medicinal products.

Amendment  34

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 104 – paragraph 2 – subparagraph 2

 

Text proposed by the Commission

Amendment

The marketing authorisation holder shall be required to perform a regular audit of his pharmacovigilance system. He shall place a note concerning the main findings of the audit on the pharmacovigilance system master file and, based on the audit findings, ensure that an appropriate corrective action plan is prepared and followed.

The marketing authorisation holder shall be required to perform a regular audit of his pharmacovigilance system. He shall ensure that an appropriate corrective action plan is prepared and followed.

Justification

Audits are instruments to improve the internal systems of a company. If findings have to be disclosed, this could lead to a tampered audit reports.

Amendment  35

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 104a – paragraph 2 – subparagraph 2

 

Text proposed by the Commission

Amendment

The requirement shall be made in writing, provide a detailed justification, and include the timeframe for submission of the detailed description of the risk-management system.

The requirement shall be made in writing, provide a detailed scientific justification and include the timeframe for submission of the detailed description of the risk-management system.

Justification

Requests for a detailed description of the risk management system should be scientifically justified. The Commission’s proposal is not sufficiently clear on this point.

Amendment  36

Proposal for a directive – amending act

Article 1 - point 21

Directive 2001/83/EC

Article 105 - subparagraph 2

 

Text proposed by the Commission

Amendment

The first paragraph shall not preclude the collection of fees to be paid by marketing authorisation holders for the carrying out of those activities by the national competent authorities.

The first paragraph shall not preclude the collection of fees to be paid by marketing authorisation holders for the carrying out of those activities by the national competent authorities to the extent that their independence is strictly guaranteed.

Justification

The rapporteur can support part of amendments 204 and 205 - that pharmacovigilance can only be financed by fees if the independence of the Agency is guaranteed.

Amendment  37

Proposal for a directive – amending act

Article 1 - point 21

Directive 2001/83/EC

Article 106 - introductory part

 

Text proposed by the Commission

Amendment

Each Member State shall set up and maintain a national medicines safety web-portal which shall be linked to the European medicines safety web-portal established in accordance with Article 26 of Regulation (EC) No 726/2004. By means of the national medicines safety web-portals, the Member States shall make public at least the following:

Each Member State shall set up and maintain a national medicines web-portal, including a dedicated medicine safety web page, which shall be linked to the European medicines web-portal established in accordance with Article 26 of Regulation (EC) No 726/2004. By means of the national medicines safety web-portals, the Member States shall make public at least the following:

Justification

Many colleagues support a greater degree of transparency than is provided for in the Commission's proposal. The rapporteur supports nearly all of these amendments, and, by extension, does not support any attempt to dilute what the Commission proposes should be made public.

The rapporteur supports amendments asking the National Competent Authorities to put the PIL and SPC online for drugs approved in their respective countries, as this is already done in many Member States. She also supports a link to EudraPharm http://eudrapharm.eu/ - where EMA currently publishes the PIL and SPC for centrally authorised products.

This compromise amendment should be read in conjunction with compromise amendment 6 on the Regulation - as article 106 of the Directive sets out what Member States are responsible for publishing on their national web portal, and article 26 of the Regulation sets out what the Agency is responsible for publishing on the (linked) European web portal.

Amendment  38

Proposal for a directive – amending act

Article 1 - point 21

Directive 2001/83/EC

Article 106 - point 1

 

Text proposed by the Commission

Amendment

(1) risk management systems for medicinal products authorised in accordance with this Directive;

(1) risk management systems and a user-friendly summary of these systems, for medicinal products authorised in accordance with this Directive;

Justification

see justification to Article 106 - introductory part

Amendment  39

Proposal for a directive – amending act

Article 1 - point 21

Directive 2001/83/EC

Article 106 - point 1 a (new)

 

Text proposed by the Commission

Amendment

 

(1a) the most up-to-date electronic version of the leaflets of the medicines available on the national market in the national language (and where applicable the link to the Agency's EudraPharm database);

Justification

see justification to Article 106 - introductory part

Amendment  40

Proposal for a directive – amending act

Article 1 - point 21

Directive 2001/83/EC

Article 106 - point 1 b (new)

 

Text proposed by the Commission

Amendment

 

(1b) for each medicinal product which Member States have authorised, the most up-to-date electronic version of the summary of the product characteristics and any conditions established in accordance with Articles 21a, 22 and 22a, together with any deadlines for their fulfilment;;

Justification

see justification to Article 106 - introductory part

Amendment  41

Proposal for a directive – amending act

Article 1 - point 21

Directive 2001/83/EC

Article 106 - point 1 c (new)

 

Text proposed by the Commission

Amendment

 

(1c) assessment reports for medicinal products authorised in accordance with this Directive (and where applicable the link to the EPAR summary);

Justification

see justification to Article 106 - introductory part

Amendment  42

Proposal for a directive – amending act

Article 1 - point 21

Directive 2001/83/EC

Article 106 - point 2

 

Text proposed by the Commission

Amendment

(2) the list of medicinal products under intensive monitoring referred to in Article 23 of Regulation (EC) No 726/2004;

(2) the list of medicinal products referred to in Article 23 of Regulation (EC) No 726/2004;

Justification

see justification to Article 106 - introductory part

Amendment  43

Proposal for a directive – amending act

Article 1 - point 21

Directive 2001/83/EC

Article 106 - point 3

 

Text proposed by the Commission

Amendment

(3) web-based structured forms for the reporting of suspected adverse reactions by healthcare professionals and patients based on the forms referred to in Article 25 of Regulation (EC) No 726/2004.

(3) structured forms for the reporting of suspected adverse reactions by healthcare professionals and patients based on the forms referred to in Article 25 of Regulation (EC) No 726/2004.

Justification

see justification to Article 106 - introductory part

Amendment  44

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 107 – paragraph 2

 

Text proposed by the Commission

Amendment

2. The marketing authorisation holder may not refuse reports of suspected adverse reactions received electronically from patients and health-care professionals.

2. The marketing authorisation holder may not refuse reports of suspected adverse reactions received electronically or by any other appropriate means from health-care professionals.

Justification

It is important not to prevent the reporting of adverse reactions by creating technological barriers. Some people do not necessarily have access to the Internet or have difficulty using it.

Amendment  45

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 107 – paragraph 2 a (new)

 

Text proposed by the Commission

Amendment

 

2a. Unless justifiable on grounds related to pharmacovigilance, individual Member States shall not impose any additional reporting requirements on marketing authorisation holders.

Justification

One of the objectives of the Commission’s proposal, and as stated in recital 5 of the Regulation, is that no additional national requirements result from its implementation. Additional national requirements require lots of resources and time for both authorities and marketing authorisation holders and may even disable harmonised signal detection.

Amendment  46

Proposal for a directive – amending act

Article 1 - point 21

Directive 2001/83/EC

Article 107 - paragraph 3 - subparagraph 1

 

Text proposed by the Commission

Amendment

3. Marketing authorisation holders shall be required to submit electronically to the database and data-processing network referred to in Article 24 of Regulation (EC) No 726/2004 (hereinafter referred to as ‘the Eudravigilance database’) information on all serious suspected adverse reactions that occur in the Community and in third countries within 15 days following the receipt of the report or, in the absence of a report, following the day on which the holder concerned gained knowledge of the event.

3. Marketing authorisation holders shall be required to submit electronically to the database and data-processing network referred to in Article 24 of Regulation (EC) No 726/2004 (hereinafter referred to as ‘the Eudravigilance database’) information on all serious suspected adverse reactions that occur in the Community and in third countries within 15 days following the receipt of the report or, in the absence of a report, following the day on which the holder concerned gained knowledge of the event. A system shall be established to simultaneously notify the relevant Member States of these submitted reports.

Justification

Member States should be alerted electronically when Market Authorisation Holders submit reports to Eudravigilance about serious suspected adverse reactions which happen on their territory, as an extra check to ensure that national competent authorities do not miss or overlook this information.

Amendment  47

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 107 – paragraph 3 – subparagraph 2

 

Text proposed by the Commission

Amendment

Marketing authorisation holders shall be required to submit electronically to the Eudravigilance database information on all non-serious suspected adverse reactions that occur in the Community, within 90 days following the receipt of the report or, in the absence of a report, following the day on which the holder concerned gained knowledge of the event.

Marketing authorisation holders shall be required to submit electronically to the Eudravigilance database information on all non-serious suspected adverse reactions that occur in the Community, within 90 days following the receipt of the report or, in the absence of a report, following the day on which the holder concerned gained knowledge of the event. Marketing authorisation holders of medicines authorised on the basis of Article 10a and holders of registrations for medicinal products referred to in Articles 14 to 16a shall be exempted from the above requirement.

Justification

The proposed new requirement for pharmaceutical companies to report all non serious suspected adverse reactions (including non-medically confirmed consumer reports) will have a massive impact on the workload of both the industry and regulatory authorities since the majority of cases are non-serious unconfirmed consumer reports. Apart from the huge drain of pharmacovigilance resources, collection of such data will not add any value from a public health perspective for old medicines; it may on the contrary impair detection of potential new safety signals.

Amendment  48

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 107a – paragraph 1 – subparagraph 1

 

Text proposed by the Commission

Amendment

The Member States shall record all suspected adverse reactions that occur in their territory which are brought to their attention from healthcare professionals and patients.

The Member States shall record all suspected adverse reactions that occur in their territory which are brought to their attention from healthcare professionals. Concerning suspected adverse reactions reported by patients, Member States may decide whether those are reported directly or via healthcare professionals.

Justification

Patients might not be experienced enough to discriminate effectively between symptoms connected to an individual medicinal products or a disease. Taking this into consideration it is feared that the system may be overwhelmed with reports of minor symptoms and unclear cases resulting in the situation that signals of new adverse drug reactions might be lost in the “noise” of patient reports. It is therefore proposed to encourage patients to contact health care professionals and ask them to help report suspected adverse drug reactions. The decision concerning direct reporting by patients or reporting via health care professionals should be up to the Member States as the situation is already now different within the EU.

Amendment  49

Proposal for a directive – amending act

Article 1 - point 21

Directive 2001/83/EC

Article 107a - paragraph 1 - subparagraph 2

 

Text proposed by the Commission

Amendment

 

 

Member States shall ensure that reports of such reactions are submitted by means of the national medicines safety web-portals.

Member States shall ensure that reports of such reactions may be submitted by means of the national medicines safety web-portals, or by any other appropriate means.

Justification

This change brings the article into line with amendments 11, 12 & 14. It must be possible for patients to submit reports electronically, however the provision of other formats should not be prevented. It is the responsibility of the Member State to put the report into an electronic format compatible with Eudravigilance.

Amendment  50

Proposal for a directive – amending act

Article 1 - point 21

Directive 2001/83/EC

Article 107e - paragraph 3

 

Text proposed by the Commission

Amendment

3. At its next meeting following the end of the period for comments by the marketing authorisation holder referred to in paragraph 2, the Pharmacovigilance Risk Assessment Advisory Committee shall adopt the assessment report with or without changes, taking into account any comments submitted in accordance with that paragraph.

3. At its next meeting following the end of the period for comments by the marketing authorisation holder referred to in paragraph 2, the Pharmacovigilance Risk Assessment Committee shall adopt the assessment report with or without changes, taking into account any comments submitted in accordance with that paragraph.

 

It shall formulate a recommendation for the coordination group on the basis of the assessment report.

 

 

 

This amendment concerns the whole text

Justification

See amendment 3. The powers of the Pharmacovigilance Risk Assessment Committee (PRAC) should be increased in relation to the coordination group. The coordination group is not a specialist body on pharmacovigilance – its job is to balance overall the risks with benefits. The PRAC should be the only body in charge of pharmacovigilance and risk assessment, in order to avoid undue duplication of roles.

Amendment  51

Proposal for a directive – amending act

Article 1 - point 21

Directive 2001/83/EC

Article 107g - paragraph 1

 

Text proposed by the Commission

Amendment

1. In the case of a single assessment of periodic safety update reports concerning more than one marketing authorisation in accordance with Article 107e(1) which does not include any marketing authorisation granted in accordance with Regulation (EC) No 726/2004, the coordination group shall, within 30 days of receipt of the report of the Pharmacovigilance Risk Assessment Advisory Committee, consider the report and adopt an opinion on the maintenance, variation, suspension or revocation of the marketing authorisations concerned, including a timetable for the implementation of the opinion.

1. In the case of a single assessment of periodic safety update reports concerning more than one marketing authorisation in accordance with Article 107e(1) which does not include any marketing authorisation granted in accordance with Regulation (EC) No 726/2004, the coordination group shall, within 30 days of receipt of the recommendation of the Pharmacovigilance Risk Assessment Committee, adopt an opinion on the maintenance, variation, suspension or revocation of the marketing authorisations concerned, including a timetable for the implementation of the opinion. Before adopting such a decision, the coordination group shall allow the marketing authorisation holders concerned to submit written or verbal explanations within the required time-limits, which must be specified. The opinion shall be published immediately, indicating any minority views.

Justification

The opinion of the PRAC should carry more weight with the coordination group and with the CHMP, who should only be able to overturn the PRAC's recommendation if they justify their decision on the grounds of science and public health.

Amendment  52

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 107 g – paragraph 2 - subparagraph 2

 

Text proposed by the Commission

Amendment

 

 

If an opinion by consensus cannot be adopted, the majority opinion shall be forwarded to the Commission which shall apply the procedure laid down in Articles 33 and 34..

 

If an opinion by consensus cannot be adopted, the majority opinion shall be forwarded to the Commission which shall apply the procedure laid down in Articles 33 and 34.. The stages of the procedure described in Article 32(4) may be applied.

 

 

Justification

The final decisions must be adopted in a consistent manner, following the same pattern as the other regulatory procedures, while bearing in mind the urgent nature of the issues that may need to be dealt with.

Amendment  53

Proposal for a directive – amending act

Article 1 - point 21

Directive 2001/83/EC

Article 107g - paragraph 3

 

Text proposed by the Commission

Amendment

3. In the case of a single assessment of periodic safety update reports concerning more than one marketing authorisation in accordance with Article 107e(1) which includes at least one marketing authorisation granted in accordance with the procedure of Regulation (EC) No 726/2004, the Committee for Medicinal Products for Human Use shall, within 30 days of receipt of the report of the Pharmacovigilance Risk Assessment Advisory Committee, consider the report and adopt an opinion on the maintenance, variation, suspension or revocation of the marketing authorisations concerned.

3. In the case of a single assessment of periodic safety update reports concerning more than one marketing authorisation in accordance with Article 107e(1) which includes at least one marketing authorisation granted in accordance with the procedure of Regulation (EC) No 726/2004, the Committee for Medicinal Products for Human Use shall, within 30 days of receipt of the recommendation of the Pharmacovigilance Risk Assessment Committee, adopt an opinion on the maintenance, variation, suspension or revocation of the marketing authorisations concerned. The stages of the procedure described in Article 9(2) of Regulation (EC) No 726/2004 may be applied.

 

The Committee for Medicinal Products for Human Use shall adopt an opinion which differs from the recommendation of the Pharmacovigilance Risk Assessment Committee, only if there exist strong scientific and public health grounds for doing so. The Committee for Medicinal Products for Human Use shall explain these grounds in a justification to be annexed to its opinion.

Justification

see justification to Article 107g - paragraph 1.

Amendment  54

Proposal for a directive – amending act

Article 1 - point 21

Directive 2001/83/EC

Section 2 a (new) to be inserted before Article 107h

 

Text proposed by the Commission

Amendment

 

Section 2a

 

Signal Detection

 

 

Justification

Section 2 of the proposal is entitled "Periodic safety update reports", however Article 107h is not concerned with PSURs. Instead, it sets out the procedure for detecting and assessing signals from the Eudravigilance database, which is a crucial stage in the pharmacovigilance system. To avoid confusion, this article should have its own, appropriately named section.

Amendment  55

Proposal for a directive – amending act

Article 1 - point 21

Directive 2001/83/EC

Section 3 - heading

 

Text proposed by the Commission

Amendment

Community procedure

Urgent Union procedure

Justification

This section describes the procedure for immediate information sharing and coordination if one Member State uncovers a serious safety concern and acts - or considers acting - to unilaterally revoke or suspend a market authorisation. The proposed title, "Community procedure", does not reflect the urgency of the procedure and is confusing in the context of centralised and decentralised authorisation procedures for medicines.

Amendment  56

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 107 i – paragraph 1

 

Text proposed by the Commission

Amendment

1. A Member State shall initiate the procedure under this section, by informing the other Member States, the Agency and the Commission, in any of the following cases:

1. A Member State shall initiate the procedure under this section, by informing the other Member States, the Agency, the Commission and the marketing authorisation holders potentially affected, in any of the following cases:

(a) it considers suspending or revoking of a marketing authorisation;

(a) it considers, in the light of the outcome of the assessment of pharmacovigilance data, one of the following regulatory measures:

 

– suspending or revoking a marketing authorisation;

(b) it considers prohibiting the supply of a medicinal product;

prohibiting the supply of a medicinal product;

(c) it considers refusing the renewal of a marketing authorisation;

refusing the renewal of a marketing authorisation;

(d) it is informed by the marketing authorisation holder that, on the basis of safety concerns, he has interrupted the placing on the market of a medicinal product or withdrawn a marketing authorisation, or that he intends to do so;

(b) it is informed by the marketing authorisation holder that, on the basis of safety concerns, he has interrupted the placing on the market of a medicinal product or withdrawn a marketing authorisation, or that he intends to do so;

(e) it considers that new contraindications, a reduction in the recommended dose, or a restriction to the indications is necessary;

 

(f) it has conducted a pharmacovigilance inspection and found serious deficiencies.

(c) it has conducted a pharmacovigilance inspection and found serious deficiencies.

Justification

The marketing authorisation holder must be able to be informed very quickly once the procedure has been initiated so that he can assemble the evidence and information needed for the swift conduct of the procedure. Since cases requiring a review or restriction of a marketing authorisation are covered by Article 31 of Directive 2001/81/EC, any confusion and red tape created by having dual procedures must be avoided.

Amendment  57

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 107k – paragraph 1 – subparagraph 1

 

Text proposed by the Commission

Amendment

1. Following the information referred to in Article 107i(1), the Agency shall publicly announce the initiation of the procedure by means of the European medicines safety web-portal.

1. Following the information referred to in Article 107i(1), the Agency shall notify the concerned marketing authorisation holders and publicly announce the initiation of the procedure by means of the European medicines web-portal.

Amendment  58

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 107 k – paragraph 2 – subparagraph 1

 

Text proposed by the Commission

Amendment

2. The Pharmacovigilance Risk Assessment Advisory Committee shall assess the matter which has been submitted. For the purposes of that assessment, it may hold a public hearing.

2. The Pharmacovigilance Risk Assessment Committee shall assess the matter which has been submitted. For the purposes of that assessment, it may hold a public hearing, if objective criteria are met on the basis of scientific data, taking account of the effectiveness and benefits of the product concerned and of earlier risk/benefit assessments conducted by the Committee for Medicinal Products for Human Use or the coordination group in accordance with the procedure for granting marketing authorisations laid down in Article 107l, which must involve the rapporteur of the Committee for Medicinal Products for Human Use on the product in question, or the rapporteur of the coordination group. The Agency, in consultation with the parties concerned, shall draw up guidelines on the organisation and conduct of public hearings.

Justification

The holding of public hearings by the Committee is a relevant tool provided that they are conducted properly and take account not just of the risks but also of the benefits of the product(s) concerned, so that discussions on the subject are credible and objective. The main aim is to protect the patient’s wellbeing and to compare the risks and benefits of a medicinal product in the light of all the information provided.

Amendment  59

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 107 k – paragraph 3 – introductory part

 

Text proposed by the Commission

Amendment

3. Within 60 days of the information submitted, the Pharmacovigilance Risk Assessment Advisory Committee shall make a recommendation, stating the reasons on which it is based. The recommendation shall be any or a combination of the following:

3. Within 60 days of the information submitted, the Pharmacovigilance Risk Assessment Advisory Committee shall make a recommendation, stating the reasons on which it is based, and taking account of the benefits of the medicinal product as assessed by the Committee for Medicinal Products for Human Use or the coordination group in accordance with the procedure for granting marketing authorisations laid down in Article 107l. The recommendation shall be any or a combination of the following:

Justification

The holding of public hearings by the Committee is a relevant tool provided that they are conducted properly and take account not just of the risks but also of the benefits of the product(s) concerned, so that discussions on the subject are credible and objective. The main aim is to protect the patient’s wellbeing and to compare the risks and benefits of a medicinal product in the light of all the information provided.

Amendment  60

Proposal for a directive – amending act

Article 1 - point 21

Directive 2001/83/EC

Article 107 l - paragraph 1

 

Text proposed by the Commission

Amendment

1. Where the scope of the procedure, as determined in accordance with Article 107i(2), does not include any marketing authorisation granted in accordance with the procedure of Regulation (EC) No 726/2004, the coordination group shall, within 30 days of the recommendation of the Pharmacovigilance Risk Assessment Advisory Committee, consider the recommendation and adopt an opinion on the maintenance, variation, suspension, revocation or refusal of the renewal of the marketing authorisations concerned, including a timetable for the implementation of the opinion.

1. Where the scope of the procedure, as determined in accordance with Article 107i(2), does not include any marketing authorisation granted in accordance with the procedure of Regulation (EC) No 726/2004, the coordination group shall act in accordance with Article 107g(1).

Justification

The principle that the CHMP and the coordination group should have to justify why their opinion differs from the recommendation of the PRAC should also apply to assessments carried out under the Urgent Community Procedure.

Amendment  61

Proposal for a directive – amending act

Article 1 - point 21

Directive 2001/83/EC

Article 107 l - paragraph 3

 

Text proposed by the Commission

Amendment

3. Where the scope of the procedure, as determined in accordance with Article 107i(2), includes at least one marketing authorisation granted in accordance with the procedure of Regulation (EC) No 726/2004, the Committee for Medicinal Products for Human Use shall, within 30 days of the recommendation of the Pharmacovigilance Risk Assessment Advisory Committee, consider the recommendation and adopt an opinion on the maintenance, variation, suspension, revocation or refusal of the renewal of the marketing authorisations concerned.

3. Where the scope of the procedure, as determined in accordance with Article 107i(2), includes at least one marketing authorisation granted in accordance with the procedure of Regulation (EC) No 726/2004, the Committee for Medicinal Products for Human Use shall act in accordance with Article 107g(3).

Justification

see justification to Article 107l - paragraph 1.

Amendment  62

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 107 m

 

Text proposed by the Commission

Amendment

The Agency shall make public the recommendations, opinions and decisions referred to in Articles 107b to 107l by means of the European medicines safety web-portal.

The Agency shall make public the final conclusions (recommendations, opinions and final decisions) referred to in Articles 107b to 107l by means of the European medicines web-portal.

Justification

The information to be published on this web-portal must be comprehensive but not complex.

Amendment  63

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 107 n – paragraph 1

 

Text proposed by the Commission

Amendment

1. This Chapter shall apply to non-interventional post-authorisation safety studies which are initiated, managed or financed by the marketing authorisation holder, voluntarily or following a requirement in accordance with Articles 21a or 22a, and which involve the

collection of data from patients or health-care professionals.

1. The procedures laid down in Articles 107o to 107r shall apply to non-interventional post-authorisation safety studies which are initiated, managed or financed by the marketing authorisation holder, voluntarily or following a requirement in accordance with Articles 21a or 22a, and which involve the

collection of data from patients or health-care professionals.

Justification

It is unrealistic to oblige the new Pharmacovigilance Risk Assessment Advisory Committee (PRAAC) to review all post-authorisation safety studies (PASS) before they are conducted.

The requirement of prior authorisation of all such studies by the PRAAC, as stipulated in the legislative proposal, would apply to an extremely large number of studies, including, for example :

- Studies conducted by independent researchers partly financed by the pharmaceutical industry

- Studies in which safety is only a secondary purpose (e.g. pharmaco-economic studies), which would fall within the definition of PASS in the legislative proposal (Article 1, point 15).

We consider that it is important to have a monitoring system for this type of study that ensures, as required by point 2 of the same article, that the purpose is scientific and not promotional.

For this task, however, monitoring at the level of the Member States would be more efficient, since it would avoiding blocking the PRAAC, as well as more appropriate, since the promotional activities of the pharmaceutical industry usually focus on the health services of the individual Member States. Moreover, many Member State have already acquired considerable experience in monitoring such studies. In Spain, for example, legislation that has been in force for several years provides that studies of this type, undertaken voluntarily by pharmaceutical laboratories, require prior authorisation by the health authorities of the autonomous regional communities.

Amendment  64

Proposal for a directive – amending act

Article 1 - point 21

Directive 2001/83/EC

Article 108 - introductory sentence

 

Text proposed by the Commission

Amendment

Following consultation with the Agency ,Member States and interested parties, the Commission shall adopt and make public guidelines on good pharmacovigilance practice for medicinal products authorised in accordance with Article 6(1)in the following areas:

Following appropriate consultations, the Commission shall adopt, by means of delegated acts in accordance with Article 121a and subject to the conditions of Articles 121b and 121c, and make public, guidelines on good pharmacovigilance practice for medicinal products authorised in accordance with Article 6(1) in the following areas:

Amendment  65

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 108 – paragraph 1 – point 5

 

Text proposed by the Commission

Amendment

(5) the format of electronic reporting of adverse reactions by Member states and marketing authorization holders;

(5) the format of electronic reporting of adverse reactions by Member states and marketing authorization holders, including the presentation of the collected information. The collected information must distinguish adverse reactions due to overdose, misuse, abuse, medication errors, and adverse reactions occurring in the course of studies with the medicinal product or after occupational exposure;

Justification

To enable an appropriate assessment and follow up, competent authorities must be able to distinguish between the different adverse reactions because it will lead to a different follow-up (additional warnings, contra-indications, suspension of marketing authorisation etc…).

Amendment  66

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 108 – paragraph 2a (new)

 

Text proposed by the Commission

Amendment

 

 

 

For the purposes of this Article and Article 102(3), the Commission, in cooperation with the Agency, Member States and stakeholders, shall prepare detailed guidelines on good record-keeping practices for pharmacies and others that dispense or administer medicinal products, to ensure retention of records necessary for filing a pharmacovigilance report or to provide information needed by a marketing authorisation holder conducting an evaluation of an adverse event and to facilitate follow-up investigations by the marketing authorisation holder and national competent authorities.

Justification

A pharmacovigilance system is only as good as the details in individual reports. The proposed addition to Article 108 would ensure uniformity between the content for reporting forms used for reporting adverse events directly to the Community Eudravigilance system from healthcare professionals and patients.

Amendment  67

Proposal for a directive – amending act

Article 1 - point 21

Directive 2001/83/EC

Article 108a

 

Text proposed by the Commission

Amendment

The Commission shall adopt any amendments which may be necessary to update the provisions of this Title to take account of scientific and technical progress.

deleted

Those measures, designed to amend non-essential elements of this Directive, shall be adopted in accordance with the regulatory procedure with scrutiny referred to in Article 121(2a).

 

Amendment  68

Proposal for a directive – amending act

Article 1 – point 24 a (new)

Directive 2001/83/EC

Article 119 a (new)

 

Text proposed by the Commission

Amendment

 

24a. The following Article is inserted:

 

“Article 119a

 

Environmental supervision and protection

 

Member States shall appoint one or several national authorities to monitor adverse environmental effects of medicinal products on public health or the environment. If one of these authorities identifies an environmental risk that is higher than that indicated in the evaluation pursuant to Article 8(3)(ca), or if it finds new adverse environmental effects, it shall forthwith transmit all findings to the European Medicines Evaluation Agency and to the competent authority. The Agency shall, upon receiving such information, assess whether the risk-benefit balance remains favourable when taking into account the new findings. This must not lead to the withdrawal of the authorisation for drugs necessary for treating life-threatening or serious diseases.”

Justification

Pharmaceutical residues are present in drinking water and surface water in most member countries. Since global water resources are limited, wells for tap water need to be protected from pollution. If not, the involuntary and unavoidable exposure of pregnant women to pharmaceuticals will increase, thereby increasing the risk for foetal malformation.

Amendment  69

Proposal for a directive – amending act

Article 1 - point 24 b (new)

Directive 2001/83/EC

Article 121 a (new)

 

Text proposed by the Commission

Amendment

 

(24b) The following Article is inserted:

 

Article 121a

 

Exercise of the delegation

 

1.The powers to adopt the delegated acts referred to in Article 11(3a),and 59(1)(aa) and 108 shall be conferred on the Commission for an indeterminate period of time.

 

2. As soon as it adopts a delegated act, the Commission shall notify it simultaneously to the European Parliament and to the Council.

 

3. The powers to adopt delegated acts are conferred on the Commission subject to the conditions laid down in Articles 121b and 121c

Amendment  70

Proposal for a directive – amending act

Article 1 - point 24 c (new)

Directive 2001/83/EC

Article 121 b (new)

 

Text proposed by the Commission

Amendment

 

(24c) The following Article is inserted:

 

Article 121b

 

Revocation of the delegation

 

1. The delegation of power referred to in Article 11(3a), 59(1)(aa )and 108 may be revoked at any time by the European Parliament or by the Council.

 

2. The institution which has commenced an internal procedure for deciding whether to revoke the delegation of power shall endeavour to inform the other institution and the Commission within a reasonable time before the final decision is taken, indicating the delegated powers which could be subject to revocation and possible reasons for a revocation.

 

3. The decision of revocation shall put an end to the delegation of the powers specified in that decision. It shall take effect immediately or at a later date specified therein. It shall not affect the validity of the delegated acts already in force. It shall be published in the Official Journal of the European Union.

Amendment  71

Proposal for a directive – amending act

Article 1 - point 24 d (new)

Directive 2001/83/EC

Article 121 c (new)

 

Text proposed by the Commission

Amendment

 

(24d) The following Article 121c is inserted:

 

Article 121c

 

Objections to delegated acts

 

1. The European Parliament or the Council may object to a delegated act within a period of two months from the date of notification.

 

At the initiative of the European Parliament or the Council this period shall be extended by two months.

 

 

2. If neither the European Parliament nor the Council has objected to the delegated act, it shall be published in the Official Journal of the European Union and enter into force at the date stated therein.

 

 

3. If the European Parliament or the Council objects to the adopted delegated act, it shall not enter into force. The institution which objects shall state the reasons for objecting to the delegated act.

Amendment  72

Proposal for a directive – amending act

Article 1 – point 28

Directive 2001/83/EC

Article 2 – paragraph 1

 

Text proposed by the Commission

Amendment

1. With regard to the requirement for the inclusion of a summary of the essential information necessary to use the medicine safely and effectively in the summary of the product characteristics and the package leaflet provided for in point 3a of Article 11 and in point (aa) of Article 59(1) of Directive 2001/83/EC as amended by this Directive, the Member States shall ensure that the requirement applies to a marketing authorisation granted before the date set out in the second subparagraph of Article 3(1) of this Directive from renewal of that authorisation or from the expiry of a period of three years starting from that date, whichever is the earliest.

deleted

Justification

The inclusion of a summary of essential information is superfluous (the summary of product characteristics already gives the main information), may be a source of confusion for patients (who may overlook important information given in the summary of product characteristics but not in the summary of essential information) and could create problems of legibility (if package leaflets are published in several languages, for example).

Amendment  73

Proposal for a directive – amending act

Article 2 – paragraph 2 a (new)

Text proposed by the Commission

Amendment

2a. Until the Agency can ensure the functionalities of the Eudravigilance database, all the periodic safety update reports shall also be submitted to the National Competent Authorities where the product is authorised.

 

2b. Member States shall ensure that the requirement for the marketing authorisation holder to submit information on adverse reactions electronically to the Eudravigilance database, as laid down in Article 107(3) of this Directive, is applied once the functionalities of the database make it possible to provide information on adverse reactions that is complete and of proper quality and that includes essential health data, codified data on the medicinal products, proper differentiation of follow-up reports and the elimination of duplicate cases.

 

2c. The Agency’s Management Board shall confirm, on the basis of an independent inquiry, that the functionalities referred to in paragraph 1 are operational.

Justification

The Commission’s proposal concerning the processing of information on cases of suspected adverse reactions received by market authorisation holders involves a substantial change to existing procedures.

It therefore seems inadvisable that the new procedure come into force without guarantees of the proper functioning of Eudravigilance. It must be borne in mind that, under the system proposed, Eudravigilance will receive data from different sources, which will create greater opportunities for the introduction of inaccurate information.

For that reason, it is essential to ensure that the Eudravigilance database does not contain reports:

- lacking minimum valid health data concerning the suspected adverse reaction,

- in which data on medicinal products has been introduced that does not permit their active agents to be identified according to a common codification system,

- that count, and evaluate as separate cases, one and the same case received at different times or from different sources (companies, national authorities or the European Medicines Agency itself).

(1)

OJ C 305, 16.12.2009, p. 28.

(2)

OJ C 79, 27.3.2010, p. 50.

(3)

 


EXPLANATORY STATEMENT

Pharmacovigilance is the system used to monitor the safety of medicines after they have been authorised for public use. Pharmacovigilance plays an important role in public health. An estimated 197,000 deaths per year are caused by Adverse Drug Reactions (ADRs) in the EU). Clinical trials can miss side effects from drugs if they are rare, only appear after long-term use or involve interaction with other drugs. Most of us will be aware of the tragedy of the drugs Thalidomide in the 1960s and Viox more recently. There can therefore be no doubt that systems for tracking drug use, reporting on ADRs and looking for patterns (“signal detection”) are a priority for European public health policy.

Under current EU legislation, medicines can be authorised in two ways: a) through a central procedure where one application is made by a pharmaceutical company to the EMEA (European Medicines Agency) or b) through a system of mutual recognition where one country leads on the assessment of the new drug and coordinates with other Member States through mutual recognition. There is an obligation for certain kinds of new products to go through the centralised system e.g. Biotech, cancer, HIV, neurodegenerative drugs. Rules governing the centralised procedure are set out in EU Regulation 726/2004 and for the decentralised system in Directive 2001/83/EC. The Commission proposal to update the rules on pharmacovigilance therefore requires amendment of both pieces of legislation. Your rapporteur has similarly drafted amendments to both the Regulation and the Directive, but given the overlapping nature of the two pieces of legislation, the narrative below refers to both.

The essence of a good pharmacovigilance system is proper reporting of ADRs by healthcare professionals, companies and patients themselves and proper recording of these ADRs by the public authorities so that “signals” pointing to potential problems can be detected. These signals must then be followed up with action which can include changes to the way a medicine is prescribed, better information on how it is used or, where the nature of the ADR is severe, the withdrawal of the medicine altogether. The advantage of strengthening cooperation on pharmacovigilance at EU level is that the “pool” of reported ADRs is larger, meaning rarer patterns can be picked up more quickly, duplicate work on following up the same ADRs in different Member States can be avoided and unsafe medicines can be withdrawn quickly when required. “Signals” are picked up from spontaneous reports of ADRs to national competent authorities, from the periodic safety update reports (PSURs) that companies are required to present once a product is on the market and from expert review of medical research papers. The current system of pharmacovigilance in the EU has evolved in recent years to better coordinate work between Member States. A single Eudravigilance database which collects data is up and running and a working party meets to discuss issues. However, gaps in the current legislation mean that the approach is somewhat ad hoc and inconsistent.

The Commission therefore proposes changes to strengthen EU pharmacovigilance and rationalise procedures. Your rapporteur generally welcomes the Commission’s approach but has strengthened its proposals in some areas. The following are, your rapporteur believes, the main points.

1.  Strengthened EU Committee on Pharmacovigilance:

The rapporteur believes the Commission is right to replace the existing Pharmacovigilance working party with the Pharmacovigilance Risk Assessment Advisory Committee (PRAAC). Most experts agree that the existing working party system works in a rather ad hoc manner, focusing only on drugs authorised through the central procedure and lacking the status to ensure its findings are acted on by the Committee for Medicinal Products for Human Use (CHMP) which oversees the whole system. However, the rapporteur believes that the PRAAC ‘s role can be strengthened still by giving it the power to recommend action to the CHMP rather than simply providing advice to it and be extending its membership to one representative per Member State. To reinforce the transparency of the work of the PRAAC, your rapporteur also proposes that two additional representatives be appointed to represent patients and healthcare professionals, as is the case with other EMEA Committees.

2. The role of Member States in the system:

Your rapporteur believes that Member States must remain key players in the EU pharmacovigilance system. As proposed by the Commission, the competent authority(CA) in each Member State should continue to act as the clearing house for all spontaneous reporting of ADRs and healthcare professionals and patients should continue to report ADRs to their CA and not directly to Eudravigilance (the EU database of ADRs). The rapporteur understands the concerns of Member States at the Commission proposal to allow a company to make a single report to Eudravigilance on an ADR rather than to every Member State (see point 2). She believes that Member States must be immediately informed if a company reports an ADR which happened on its territory to the Eudravigilance database and suggests that a system to alert relevant Member States simultaneously be established.

3. The role of companies in the system:

Several useful changes are proposed which affect companies. The rapporteur particularly welcomes proposals which ensure better follow up and coordination of the assessments of ADRs by preventing duplicate work in different Member States. She therefore supports direct reporting to Eudravigilance by companies (with the safeguards in point 3) and the work-sharing mechanisms for follow-up to Periodic Safety Reports coordinated through the PRAAC.

4. The role of Healthcare professionals:

Your rapporteur supports measures to encourage healthcare professionals to voluntarily report ADRs to their competent authority and wants to strengthen their role in informing and encouraging patients to report.

5. The role of patients:

Patients are key to “signal detection” of ADRs. Your rapporteur supports proposals to encourage the “informed patient” and strongly supports the new provisions to allow direct patient reporting of ADRs, though she believes this should be to competent authorities and not companies. At present, only a few Member States accept direct reporting but where it exists, the system has not overburdened the competent authority. The informed patient also needs to know when they are taking new drugs .The rapporteur therefore also supports the proposal for Intensively Monitored Products and believes the system should not only inform patients who are prescribed a new product but encourage them to report ADRs. She has tabled a number of amendments to improve information on the Patient Information Leaflet (PIL) to that effect.

6. The Patient Information Leaflet (PIL):

A number of stakeholders are unhappy with the proposal by the European Commission to include the “black box” with essential information on the PIL. Your rapporteur understands those concerns, in particular that what is essential to one patient may not be essential to all patients. However, she also feels that the current PIL is not satisfactory from a patient point of view and that there needs to be a clearer indication of the main features of the drug for patients . It is possible that the best solution would be to remit this problem to a general review of the PIL For this reason, she has not tabled any amendments herself to the Commission proposals .

7. The reporting of ADRs:

The new system proposes that all ADRs (and not just serious ones) are reported to the Eudravigilance database by Competent Authorities and Companies. This means that information on all ADRs will, for the first time, be centralised in one place in the EU. This can be a valuable research tool for all. The Commission needs to ensure, however, that Eudravigilance is able to cope with the surge of information and by putting systems in place so that the most serious ADRs are clearly flagged up. If all ADRs are recorded on Eudravigilance, the rapporteur sees the logic of cutting back on the requirement by companies to provide line by line reporting of ADRs in PSURs . Instead of just presenting raw data, companies will be required instead to analyse the ADRs and present summaries of their findings. This makes sense, particularly since the rapporteur has learned that competent authorities have often been overwhelmed by the sheer volume of PSURS they have received in the past, with the result that many have gone unread. The speed with which ADRs are reported to Eudravigilance is of paramount importance for patient safety. The rapporteur is therefore concerned to hear that both companies and Member States have failed to meet the current requirement to report ADRs within 15 days. However, Member States are by far the worst “offenders”: 5% of company reports were late compared with 50% of Member State reports. The Rapporteur has therefore sought to include provisions to ensure better compliance mechanisms.

8. Urgent action or “Community procedure” :

Your rapporteur welcomes the inclusion of clearer provisions for when an urgent procedure is triggered. Member States need to work quickly together to act when a serious ADR occurs.

9.        Transparency:

Your rapporteur welcomes the proposals to bring more transparency to the EU pharmacovigilance system. She welcomes the expansion of the web portal and the use of public hearings to gather evidence about ADRs. She believes public hearings should not only be used in the case of urgent action, but could also be useful tools for normal pharmacovigilance and has therefore proposed an amendment along these lines.


OPINION of the Committee on Industry, Research and Energy (15.4.2010)

for the Committee on the Environment, Public Health and Food Safety

on the proposal for a directive of the European Parliament and of the Council amending, as regards pharmacovigilance, Directive 2001/83/EC on the Community code relating to medicinal products for human use

(COM(2008)0665 – C6-0514/2008 – 2008/0260(COD))

Rapporteur: Michèle Rivasi

SHORT JUSTIFICATION

These two proposals (a regulation and a directive) on pharmacovigilance place us right at the heart of current issues. The arguments surrounding the vaccine against AH1N1 influenza, which was put on the market following a very quick procedure, illustrate the public's loss of confidence in the ability of the authorities to guarantee their protection. A recent study shows that 61% of French doctors do not intend to have themselves vaccinated. This context further highlights (if it were necessary to do so) the need for the European Union to have an effective pharmacovigilance policy, to reassure and protect its citizens.

We are unfortunately able to point to several cases of medicinal products in recent years which, despite having been placed on the market upon completion of a traditional procedure, have produced substantial side-effects:

- rofecoxib (Vioxx®, Ceox®, Ceeoxx®): an anti-inflammatory which is no more effective than ibuprofene and which triggered thousands of fatal heart attacks; authorised in 1999 and withdrawn from the market in 2004;

- paroxetine: an anti-depressant (Deroxat®, Seroxat®) which increased the risk of suicide;

- rimonabant (Acomplia®): an anti-obesity medicine, which was put on the market without adequate assessment and withdrawn from the European market a year and a half later.

Several court cases have shown that pharmaceutical companies have a tendency to conceal information about adverse reactions to their medicinal products, which might damage sales, for as long as possible.

In each of these cases we were able to see that the length of the decision-making process and the withholding of information about adverse reactions were harmful to patients.

The human cost of such side-effects is unacceptable; as for the financial costs, these are massive, and it is society as a whole which bears them, because they account for 5% of hospital admissions and 5% of the causes of hospital deaths.

From assessment, via supervision and information relating to medicinal products, to placing them on the market

Before medicinal products are granted marketing authorisation they have to be assessed. This is done over a limited period using a sample of selected patients. Pharmacovigilance's role is subsequently to extend our knowledge of adverse reactions, so as to limit the harm caused to the public.

Your rapporteur fears that the Directive will weaken the pharmacovigilance system, instead of strengthening it, for the reasons given below.

1. The risk management plans and other post-authorisation studies may be used as a backstop in order to reduce assessment before marketing authorisations are granted. This must remain an exception.

2. The ending of the requirement for funding to be public threatens to reduce the pharmacovigilance system to the status of service provider to pharmaceutical firms. The rapporteur proposes, instead, to strengthen the independent national and regional pharmacovigilance systems.

3. Companies' increased control over the collection, analysis and interpretation of the data places them in an untenable situation regarding conflicts of interest. Firms should be able to take part in the study of adverse reactions, but under the control of the authorities, and in no circumstances in a monopoly position.

4. The organisation of dilution of the data, which are stored directly in Eudravigilance, a mega-database, without any procedure to ensure that the quality of the content of Eudravigilance is safeguarded. Your rapporteur proposes that input to Eudravigilance be restricted to the Member States' relevant pharmacovigilance authorities (no direct input by patients, nor by pharmaceutical firms, with the risk of creating too much background noise and thus making the relevant data unusable).

5. The very limited access to the Eudravigilance database for the public and independent experts. Transparency with regard to pharmacovigilance data is essential in order to restore public confidence in the health authorities.

Several proposals are still too cautious and should be strengthened.

1. The formal establishment of a European risk management advisory committee (PRAAC), without any more genuine authority or autonomy than the current Pharmacovigilance Working Party, does not contribute any significant added value.

2. Lack of transparency where pharmacovigilance data is concerned remains the rule: for instance, there is no access to PSURs, on the pretext of commercial confidentiality. PSURs and all assessment reports should be published immediately.

To conclude:

· Strengthen the criteria to enable marketing authorisation to be granted on surer grounds, entailing the requirement for new medicinal products to bring genuine therapeutic advances; no widespread use of the fast-track procedure

· Ensure the quality of pharmacovigilance data

· Provide the resources to ensure effective public pharmacovigilance

Increase transparency

AMENDMENTS

The Committee on Industry, Research and Energy calls on the Committee on the Environment, Public Health and Food Safety, as the committee responsible, to incorporate the following amendments in its report:

Amendment   1

Proposal for a directive – amending act

Recital 5

Text proposed by the Commission

Amendment

(5) For the sake of clarity, the definition of adverse reaction should be amended to ensure that it not only covers noxious and unintended effects derived from the authorised use of a medicinal product at the normal doses, but also medication errors and uses outside the authorised summary of the product characteristics, including the misuse and abuse of the product.

(5) For the sake of clarity, the definition of adverse reaction should be amended to ensure that it not only covers noxious and unintended effects derived from the authorised use of a medicinal product at the normal doses, but also noxious and unintended effects derived from medication errors and uses outside the authorised summary of the product characteristics, including the misuse and abuse of the product.

Justification

The definition of adverse reaction covers all unintended effects derived from misuse, including medication errors. The directive does not, however, aim to give information on medication errors in general, but only on medication errors leading to unintended effects.

Amendment  2

Proposal for a directive – amending act

Recital 7

Text proposed by the Commission

Amendment

(7) The planning of pharmacovigilance for each individual medicinal product by the marketing authorisation holder should take place in the context of a risk management system and should be proportionate to the identified risks, potential risks, and the need for additional information on the medicinal product. It should also be foreseen that any key measures contained in a risk management system are included in the marketing authorisation as conditions.

(7) The planning of pharmacovigilance for each individual medicinal product by the marketing authorisation holder should take place in the context of a risk management system and should be proportionate to the identified risks, potential risks, and the need for additional information on the medicinal product. It should also be foreseen that any key measures contained in a risk management system are included in the marketing authorisation as conditions. If the conditions included in the marketing authorisation are not fulfilled within the corresponding deadline, the competent authorities should have the power and appropriate resources to immediately suspend or revoke the marketing authorisation.

Justification

Experience shows that in many cases where companies were required to conduct post-authorisation safety studies they failed to do so. The result is that doctors and patients remain unsure whether some critical medicines used to treat illnesses like cancer and heart disease are actually beneficial. That is why it is essential to introduce stricter requirements in the legislation in order to ensure that pharmaceutical companies complete their promised studies.

Amendment  3

Proposal for a directive – amending act

Recital 8

Text proposed by the Commission

Amendment

(8) In order to ensure the collection of any necessary additional data about the safety of authorised medicinal products, competent authorities should be empowered to require post-authorisation safety studies at the time of the granting of the marketing authorisation or later, and this requirement should be included as a condition of the marketing authorisation.

(8) In order to ensure the collection of any necessary additional data about the safety of authorised medicinal products, competent authorities should be empowered to require post-authorisation safety studies at the time of the granting of the marketing authorisation or later, and this requirement should be included as a condition of the marketing authorisation. If the conditions included in the marketing authorisation are not fulfilled within the deadline set, the competent authorities should have the power and appropriate resources to immediately suspend or revoke the marketing authorisation.

Justification

Experience shows that in many cases where companies were required to conduct post-authorisation safety studies they failed to do so. The result is that doctors and patients remain unsure whether some critical medicines used to treat illnesses like cancer and heart disease are actually beneficial. That is why it is essential to introduce stricter requirements in the legislation in order to ensure that pharmaceutical companies complete their promised studies.

Amendment   4

Proposal for a directive – amending act

Recital 9

Text proposed by the Commission

Amendment

(9) Where a medicinal product is authorized subject to the requirement to conduct a post-authorisation safety study or where there are conditions or restrictions with regard to the safe and effective use of the medicinal product, the medicinal product should be intensively monitored on the market. Patients and healthcare professionals should be encouraged to report all suspect adverse reactions to such medicinal products, and a publicly available list of such medicinal products should be maintained up to date by the European Medicines Agency established by Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (hereinafter referred to as the ‘Agency’).

(9) Where, in the case of an unmet medical need, a medicinal product is authorized subject to the requirement to conduct a post-authorisation safety study or where there are conditions or restrictions with regard to the safe and effective use of the medicinal product, the medicinal product should be intensively monitored on the market. Steps must be taken to ensure that tightening up the pharmacovigilance system does not result in marketing authorisations being issued prematurely. Patients and healthcare professionals should be encouraged to report all suspect adverse reactions to such medicinal products, which should be identified by a specific symbol on the outer packaging and by a corresponding explanatory sentence in the leaflet, and a publicly available list of such medicinal products should be maintained up to date by the European Medicines Agency established by Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (hereinafter referred to as the ‘Agency’).

Justification

Special warnings for intensively monitored medicines will help both the health professionals and the patients to identify new medicines under intensive surveillance and would increase their awareness to report any adverse reaction that might appear as already recommended by the US Institute of Medicine in its 2006 report . This measure could be further improved by adding on the box a pictogram like for example the black triangle ( ) already well known and used in some Member States.

Amendment  5

Proposal for a directive – amending act

Recital 10

Text proposed by the Commission

Amendment

(10) In order to make it possible for the healthcare professionals and patients to identify easily the most relevant information about the medicines they use, the summary of the product characteristics and the package leaflet should include a concise section on the key information about the medicinal product and information how to minimize its risks and maximize its benefits.

(10) Within five years of the entry into force of this Directive, the Commission should, following consultations with patient and consumer organisations, healthcare professional organisations, Member States and other interested parties, present to the European Parliament and the Council an assessment report regarding the readability of the summaries of product characteristics and the packaging leaflets. Following an analysis of such data, the Commission should, if appropriate, put forward proposals to improve the layout and the content of the summaries of product characteristics and of the packaging leaflet to ensure they are a valuable source of information for the general public and healthcare professionals.

Justification

The notion of a summary poses a problem. It is more important for the report to be drawn up legibly to ensure that the patient reads all the necessary information.

Amendment  6

Proposal for a directive – amending act

Recital 17

Text proposed by the Commission

Amendment

(17) To further increase the coordination of resources between the Member States, Member State should be authorised to delegate certain pharmacovigilance tasks to another Member State.

(17) Each Member State should be responsible for the oversight of the adverse reactions occurring in its territory. To further increase the level of expertise in pharmacovigilance, Member States should be encouraged to organise training and to regularly exchange information and expertise.

Justification

Each member state should be fully responsible for the detection and the follow up of any adverse event related to a medicine marketed within its territory.

Amendment  7

Proposal for a directive – amending act

Recital 19

Text proposed by the Commission

Amendment

(19) In order to increase the level of transparency on the processes of pharmacovigilance, the Member States should create and maintain medicines safety web-portals. To the same end, the marketing authorisation holders should provide the authorities with prior warning about safety announcements and the authorities should provide each other with such a warning.

(19) In order to increase the level of transparency on the processes of pharmacovigilance, the Member States should create and maintain medicines safety web-portals. The marketing authorisation holders should be required to submit to the authorities the safety announcements which they plan to disseminate for prior authorisation. Without delay following such a request, the authorities should provide each other with a prior warning about these safety announcements.

Justification

It is important to ensure that any information on medicines provided by companies to the general public is non promotional. The principle of prior validation of the information is already applied for package leaflets, public campaigns and also in the proposal on information to the general public on prescription medicines currently under discussion and for consistency it should be applied to pharmacovigilance information.

Amendment  8

Proposal for a directive – amending act

Recital 28

Text proposed by the Commission

Amendment

(28) In order to protect public health, there should be adequate funding of activities related to pharmacovigilance by the national competent authorities. It should be possible to ensure adequate funding for pharmacovigilance activities through the collection of fees. However, the management of those collected funds should be under the permanent control of the national competent authorities in order to guarantee their independence.

(28) In order to protect public health, there should be adequate funding of activities related to pharmacovigilance by the national competent authorities.

Justification

Pharmacovigilance activities should be publicly financed not only to ensure their independence but also because the Member States should be fully responsible for pharmacovigilance (also in terms of funding) as they are those who bear the costs associated with side effects both in terms of morbidity and in terms of mortality. According to the European Commission “it is estimated that 5% of all hospital admissions are due to an adverse drug reaction, 5% of all hospital patients suffer an adverse reaction and adverse reactions are the fifth most common cause of hospital death.

Amendment  9

Proposal for a directive – amending act

Recital 29 a (new)

Text proposed by the Commission

Amendment

 

(29a) This Directive should apply without prejudice to Directive 95/46/EC of the European Parliament and of the Council of 24 October 1995 on the protection of individuals with regard to the processing of personal data and on the free movement of such data1 and Regulation (EC) No 45/2001 of the European Parliament and of the Council of 18 December 2000 on the protection of individuals with regard to the processing of personal data by the Community institutions and bodies and on the free movement of such data2. In order to detect, assess, understand and prevent adverse reactions, identify and take action to reduce the risks and increase the benefits of medicinal products for the purpose of safeguarding public health, it should be possible to process personal data within the Eudravigilance system while complying with EU data protection legislation. That purpose constitutes a substantial public interest which can be justified if identifiable health data are processed only when necessary and the parties involved assess such necessity at every stage of the pharmacovigilance process.

 

1 OJ L 281, 23.11.1995, p. 31.

 

2 OJ L 8, 12.1.2001, p. 1.

Justification

The proposal covers highly sensitive personal information which should be fully protected. See also opinion of the European data protection supervisor of April 2009.

Amendment  10

Proposal for a directive – amending act

Article 1 – point 1 – point a

Directive 2001/83/EC

Article 1 – point 11

 

Text proposed by the Commission

Amendment

(a) point 11 is replaced by the following:

deleted

´(11) Adverse reaction: A response to a medicinal product which is noxious and unintended´

 

Justification

The initial wording (Article 1, point 11, of consolidated Directive 2001/83/EC), which clearly states that it refers to normal conditions of use and avoids confusion with cases involving misuse or abuse, should be reinstated.

Amendment  11

Proposal for a directive – amending act

Article 1 – point 1 – point b

Directive 2001/83/EC

Article 1 – point 14

 

Text proposed by the Commission

Amendment

(14) Suspected adverse reaction: An adverse reaction in respect of which a causal relationship between the event and the medicinal product cannot be excluded.

(14) Suspected adverse drug reaction: An unintended event in respect of which a causal relationship between the event and the medicinal product cannot be excluded.

Justification

The term ‘adverse reaction’ should be replaced by the more precise term ‘adverse drug reaction’, which is used by experts and is internationally accepted. Drafting note: The remaining text of the directive and of Regulation (EC) No 726/2004 will have to be changed accordingly if this amendment is adopted.

Amendment  12

Proposal for a directive – amending act

Article 1 – point 1 – point c

Directive 2001/83/EC

Article 1 – point 15

 

Text proposed by the Commission

Amendment

(15) Post-authorisation safety study: Any study with an authorised medicinal product conducted with the aim of identifying, characterising or quantifying a safety hazard, confirming the safety profile of the medicinal product, or of measuring the effectiveness of risk management measures.

(15) Post-authorisation pharmacovigilance study: Any study with a medicinal product authorised early for reasons of public health in the absence of a therapeutic alternative, or carried out at the request of the health authorities once a medicinal product has been placed on the market, with the aim of identifying, characterising or quantifying an adverse reaction risk or of assessing the adverse reaction profile of the medicinal product and its risk/benefit balance, or of measuring the effectiveness of risk management measures.

Justification

The aim of a post-authorisation study is to monitor the adverse reactions of medicinal products in human beings. It is not intended to monitor ‘post-authorisation safety’. Post-authorisation safety studies must not be used to obtain marketing authorisations on the cheap, without sufficient evaluation.

Amendment   13

Proposal for a directive – amending act

Article 1 – point 1 – point d

Directive 2001/83/EC

Article 1 – point 28b

 

Text proposed by the Commission

Amendment

(28b) Risk management system: a set of pharmacovigilance activities and interventions designed to identify, characterise, prevent or minimise risks relating to a medicinal product, including the assessment of the effectiveness of those interventions.

(28b) Risk management system: a set of specific pharmacovigilance activities and interventions designed to quantify or prevent risks already detected, and risks identified subsequently, relating to a medicinal product, including the assessment of the effectiveness of those interventions, or to ensure early identification of new risks.

Justification

All medicinal products available on the European market must be seriously monitored by the general pharmacovigilance system, which needs to be made more effective both at European and national levels. The aim of a risk management system should not be to ‘identify the risks of a medicinal product’: that is the role of the pre-marketing authorisation assessment. A risk management system should make it possible to prevent risks already identified thanks to the pre-marketing authorisation assessment.

Amendment  14

Proposal for a directive – amending act

Article 1 – point 1 – point d

Directive 2001/83/EC

Article 1 – point 28c

 

Text proposed by the Commission

Amendment

(28c) Pharmacovigilance system: a system utilized by marketing authorisation holders and by Member States to fulfil the tasks and responsibilities listed in Title IX and designed to monitor the safety of authorised medicinal products and detect any change to their risk-benefit balance.

(28c) Pharmacovigilance system: a system allowing marketing authorisation holders and Member States, with a view to fulfilling the tasks and responsibilities listed in Title IX:

 

(a) to collect information useful in the surveillance of medicinal products, with particular reference to adverse reactions in human beings, including misuse and abuse of medicinal products and medication errors; and

 

(b) to evaluate such information scientifically in order to detect any change to the risk-benefit balance of authorised medicinal products.

Justification

Pharmacovigilance is an observational scientific discipline first and foremost for the benefit of patients. It is not designed to monitor the ‘safety of medicinal products’ (an ambiguous expression whose vocabulary is misleading because of its positive connotation): pharmacovigilance data are not commercial data collected by companies as part of their after-sales service. The aim of pharmacovigilance is to monitor the adverse reactions of medicinal products in human beings.

Amendment  15

Proposal for a directive – amending act

Article 1 – point 1 – point d a (new)

Directive 2001/83/EC

Article 1 – points 32 a, 32 b and 32 c (new)

 

Text proposed by the Commission

Amendment

 

(da) The following points are inserted:

 

‘(32a) Medication error: a non-intentional omission or action relating to a medicinal product which can be the cause of a risk or of an adverse event for the patient. A medication error is by definition preventable because it evidences what should have been done and what was not done during the patient’s medicinal therapy. A medication error can concern one or more stages in the medicinal product’s cycle, such as formulary selection, prescription, dispensing, validation, preparation, storage, delivery, administration and therapeutic monitoring and information, but also its interfaces, such as communications and transcriptions.

 

(32b) Misuse: use, of a medicinal product, that is not in compliance with the recommendations in the summary of the product characteristics.

 

(32c) Medically justified use not in accordance with indications: specific case of use deliberately not in compliance with the recommendations under the ‘indications’ section of the summary of the product characteristics but based on the assessment data.’

Amendment  16

Proposal for a directive – amending act

Article 1 - point 3 - point a

Directive 2001/83/EC

Article 11 – point 3a

 

Text proposed by the Commission

Amendment

(a) the following point 3a is inserted:

deleted

“(3a) a summary of the essential information necessary to use the medicine safely and effectively;”

 

Amendment  17

Proposal for a directive – amending act

Article 1 – point 3 – point b

Directive 2001/83/EC

Article 11 - subparagraph 3

 

Text proposed by the Commission

Amendment

For the purposes of point (3a) of the first subparagraph, for medicinal products included on the list referred to in Article 23 of Regulation (EC) No 726/2004, the summary shall include the statement: “This medicinal product is under intensive monitoring. All suspected adverse reactions should be reported to name and web-address of the national competent authority.

For medicinal products included on the list referred to in Article 23 of Regulation (EC) No 726/2004, the summary shall include the following:

 

(a) a statement reading "This newly authorised medicinal product is under intensive monitoring in order to increase knowledge of its adverse reactions. All suspected adverse reactions should be reported to name, web-address, postal address and telephone number of the national competent authority, or reported directly to the pharmacy";

 

(b) an exclamation mark surrounded by a red triangle. This symbol shall also appear on the outer packaging, accompanied by an indication that it is advisable to read the package leaflet before taking the medicinal product.

Justification

Informar que o medicamento está sob fiscalização intensiva, dada a sua introdução recente no mercado, serve para prevenir alarmismos injustificados que induzam o doente a não cumprir a medicação prescrita. A sinalética escolhida para alertar os doentes deve ter um significado comummente reconhecido pelo público, pelo que alguns sistemas usados nalguns países entre a comunidade médica podem ser desprovidos de sentido para o doente. Para aumentar a frequência de notificação de reacções adversas pelos doentes, convém torná-la fácil de concretizar, por meios informáticos e não informáticos.

Amendment  18

Proposal for a directive – amending act

Article 1 — point 7

Directive 2001/83/EC

Article 21 – paragraph 4 – subparagraph 1

 

Text proposed by the Commission

Amendment

4. The national competent authorities shall draw up an assessment report and comments on the file as regards the results of the pharmaceutical and pre-clinical tests, the clinical trials and the risk management system and the pharmacovigilance system of the medicinal product concerned. The assessment report shall be updated whenever new information becomes available which is of importance for the evaluation of the quality, safety or efficacy of the medicinal product concerned.

4. The national competent authorities shall draw up an assessment report and comments on the file as regards the results of the pharmaceutical and pre-clinical tests, the clinical trials and the risk management system and the pharmacovigilance system of the medicinal product concerned. The assessment report shall detail the natural development of the disease and, where appropriate, the existing treatments for that disease. The assessment report shall be updated whenever new information becomes available which is of importance for the evaluation of the quality, safety or efficacy of the medicinal product concerned.

Amendment  19

Proposal for a directive – amending act

Article 1 — point 8

Directive 2001/83/EC

Article 21a

 

Text proposed by the Commission

Amendment

A marketing authorisation may be granted subject to one or more of the following conditions:

If the medicinal product responds to unmet medical needs and if its risk-benefit balance may be considered positive, a marketing authorisation may be granted subject to one or more of the following conditions:

(1) to take certain measures for the safe use of the medicinal product contained in the risk management system;

(1) to take certain measures for the safe use of the medicinal product contained in the risk management system;

(2) to conduct post-authorisation safety studies;

(2) to conduct post-authorisation safety studies;

(3) to comply with requirements on adverse reaction recording or reporting which are stricter than those referred to in Title IX;

(3) to comply with requirements on adverse reaction recording or reporting which are stricter than those referred to in Title IX;

(4) any other conditions or restrictions with regard to the safe and effective use of the medicinal product.

(4) any other conditions or restrictions with regard to the safe and effective use of the medicinal product.

The marketing authorisation shall lay down deadlines for the fulfilment of the conditions where necessary.

The marketing authorisation shall lay down deadlines for the fulfilment of the conditions where necessary. The competent authorities shall have the power and appropriate resources to immediately suspend or revoke the marketing authorisation, where the conditions included in that marketing authorisation are not fulfilled by the relevant deadline.

Justification

This amendment is to align the text with the provisions currently in force (Regulation 507/2006) whereby a centralised conditional marketing authorisation may be granted only if the risk benefit balance is positive, the benefit to public health outweighs the risks inherent in the fact that additional data are required and that unmet medical needs will be fulfilled. At the moment, the conditional marketing authorisations must be reassessed annually and in the package leaflet there is a reference specifying that the renewal of the marketing authorisation is linked to the fulfilment of the established conditions.

Amendment  20

Proposal for a directive – amending act

Article 1 — point 11

Directive 2001/83/EC

Article 23 – paragraph 4 – subparagraph 1

 

Text proposed by the Commission

Amendment

4. In order that the risk-benefit balance may be continuously assessed, the national competent authority may at any time ask the holder of the marketing authorisation to forward data demonstrating that the risk-benefit balance remains favourable.

4. In order that the risk-benefit balance may be continuously assessed, the national competent authority may at any time ask the holder of the marketing authorisation and its pharmacovigilance system to forward the data necessary for a reassessment of the risk-benefit balance.

Amendment  21

Proposal for a directive – amending act

Article 1 – point 14 – point a

Directive 2001/83/EC

Article 27 – paragraph 1

 

Text proposed by the Commission

Amendment

1. A coordination group shall be set up for the following purposes:

1. Two coordination groups shall be set up:

 

(a) A coordination group for mutual recognition and decentralised procedures shall be responsible for the following tasks:

(a) the examination of any question relating to a marketing authorisation of a medicinal product in two or more Member States in accordance with the procedures laid down in Chapter 4;

(i) the examination of any question relating to a marketing authorisation of a medicinal product in two or more Member States in accordance with the procedures laid down in Chapter 4;

(b) the examination of questions related to the pharmacovigilance of medicinal products authorised by the Member States, in accordance with Articles 107c, 107e, 107g, 107l and 107r;

 

(c) the examination of questions related to the variations to the terms of marketing authorisations granted by the Member States, in accordance with Article 35(1).

(ii) the examination of questions related to the variations to the terms of marketing authorisations granted by the Member States, in accordance with Article 35(1), with the exception of all questions relating to pharmacovigilance.

 

For the fulfilment of its tasks, the coordination group for mutual recognition and decentralised procedures shall be assisted by the Committee for Medicinal Products for Human Use referred to in Article 5(1) of Regulation (EC) No 726/2004.

 

(b) A coordination group for pharmacovigilance risk assessment shall be responsible for the following tasks:

 

i) the examination of questions related to the pharmacovigilance of medicinal products authorised by the Member States, in accordance with Articles 107c, 107e, 107g, 107l and 107r;

 

ii) the examination of questions related to the variations to the terms of marketing authorisations granted by the Member States, in accordance with Article 35(1), for all questions relating to pharmacovigilance.

The Agency shall provide the secretariat of this coordination group.

 

For the fulfilment of its pharmacovigilance tasks, the coordination group shall be assisted by the Pharmacovigilance Risk Assessment Advisory Committee referred to in Article 56(1)(aa) of Regulation (EC) No 726/2004.

For the fulfilment of its pharmacovigilance tasks, the coordination group for pharmacovigilance risk assessment shall be assisted by the European Pharmacovigilance Committee referred to in Article 56(1)(aa) of Regulation (EC) No 726/2004.

 

The Agency shall provide the secretariat for these coordination groups.

Amendment  22

Proposal for a directive – amending act

Article 1 – point 14 – point a

Directive 2001/83/EC

Article 27 – paragraph 1 – subparagraph 3

 

Text proposed by the Commission

Amendment

For the fulfilment of its pharmacovigilance tasks, the coordination group shall be assisted by the Pharmacovigilance Risk Assessment Advisory Committee referred to in Article 56(1)(aa) of Regulation (EC) No 726/2004.

For the fulfilment of its pharmacovigilance tasks, the coordination group shall be assisted by the Pharmacovigilance Committee referred to in Article 56(1)(aa) of Regulation (EC) No 726/2004.

Justification

Horizontal Change Required throughout Proposal - The proposal establishes a European Pharmacovigilance Risk assessment advisory committee and entrusts it with important pharmacovigilance tasks but with a mere advisory role and no authority - the committee's role should be strengthened and that is to be reflected in its title.

Amendment   23

Proposal for a directive – amending act

Article 1 – point 14 – point b

Directive 2001/83/EC

Article 27 – paragraph 2 - subparagraphs 2 and 3

 

Text proposed by the Commission

Amendment

Members of the coordination group and experts shall, for the fulfilment of their tasks, rely on the scientific and regulatory resources available to national marketing authorisation bodies. Each national competent authority shall monitor the level of expertise of the evaluations carried out and facilitate the activities of nominated coordination group members and experts.

Members of the coordination groups and experts shall, for the fulfilment of their tasks, rely on the scientific and regulatory resources available to the national bodies responsible for, respectively, issuing marketing authorisations and pharmacovigilance. Each national competent authority shall monitor the level of expertise of the evaluations carried out and facilitate the activities of nominated coordination group members and experts.

Article 63 of Regulation (EC) No 726/2004 shall apply to the coordination group as regards the transparency and independence of its members.

Article 63 of Regulation (EC) No 726/2004 shall apply to the coordination groups as regards the transparency and independence of their members from both the Agency and marketing authorisation holders.

 

A member of one coordination group may not simultaneously be a member of the other coordination group.

 

The members of the coordination group for pharmacovigilance risk assessment shall be hierarchically independent of the national marketing authorisation bodies.

Amendment  24

Proposal for a directive – amending act

Article 1 – point 18 – point a

Directive 2001/83/EC

Article 59 – paragraph 1 – point aa

 

Text proposed by the Commission

Amendment

(a) the following point (aa) is inserted:

deleted

“(aa) a summary of the essential information necessary to use the medicine safely and effectively;”

 

Amendment  25

Proposal for a directive – amending act

Article 1 – point 18 – point a a (new)

Directive 2001/83/EC

Article 59 – paragraph 1 – point h a (new)

 

Text proposed by the Commission

Amendment

 

(aa) the following point (ha) is inserted:

 

“(ha) a detachable portion of the leaflet that the patient can tear off, including the following statement: “Suspected adverse reactions should be reported to your doctor, pharmacist, or to name, web-address, postal address and/or telephone and fax number of the national competent authority;”

Amendment  26

Proposal for a directive – amending act

Article 1 – point 18 – point b

Directive 2001/83/EC

Article 59 – paragraph 1 – subparagraphs 2 and 3

 

Text proposed by the Commission

Amendment

The information referred to in point (aa) of the first subparagraph shall be presented in a box surrounded by a black border. Any new or amended text shall for a period of 1-year be presented in bold text and preceded by the following symbol and text "New information".

 

For medicinal products included on the list referred to in Article 23 of Regulation (EC) No 726/2004, the following additional statement shall be included “This medicinal product is under intensive monitoring. All suspected adverse reactions should be reported to name and web-address of the national competent authority".

For medicinal products included on the list referred to in Article 23 of Regulation (EC) No 726/2004, the following additional statement shall be included “This medicinal product is subject to post-authorisation safety monitoring. All suspected adverse reactions should be reported to name and web-address of the national competent authority".

Justification

As the information in package leaflets are often updated several times per year (2/3 times on average) highlighting the new information in bold and with a special symbol runs the risk of giving patients a wrong impression that this information is the more important information as well as provide a confusing leaflet.

Amendment  27

Proposal for a directive – amending act

Article 1 – point 18 – point b

Directive 2001/83/EC

Article 59 – paragraph 1 – subparagraph 3

 

Text proposed by the Commission

Amendment

For medicinal products included on the list referred to in Article 23 of Regulation (EC) No 726/2004, the following additional statement shall be included “This medicinal product is under intensive monitoring. All suspected adverse reactions should be reported to name and web-address of the national competent authority.

For medicinal products included on the list referred to in Article 23 of Regulation (EC) No 726/2004, the following additional elements shall be included:

 

(a) a statement reading “This newly authorised medicinal product is under intensive monitoring in order to increase knowledge of its adverse reactions. All suspected adverse reactions should be reported to name, web-address, postal address and telephone number of the national competent authority, or reported directly to the pharmacy.";

 

(b) an exclamation mark surrounded by a red triangle. This symbol shall also appear on the outer packaging, accompanied by an indication that it is advisable to read the package leaflet before taking the medicinal product.

Justification

Informar que o medicamento está sob fiscalização intensiva dada a sua introdução recente no mercado serve para prevenir alarmismos injustificados que induzam o doente a não cumprir a medicação prescrita. A sinalética escolhida para alertar os doentes deve ter um significado comummente reconhecido pelo público, pelo que alguns sistemas usados nalguns países entre a comunidade médica podem ser desprovidos de sentido para o doente. Para aumentar a frequência de notificação de reacções adversas pelos doentes, convém torná-la fácil de concretizar, por meios informáticos e não informáticos.

Amendment  28

Proposal for a directive – amending act

Article 1 — point 20

Directive 2001/83/EC

Article 65 - point g

 

Text proposed by the Commission

Amendment

20. In Article 65, the following point (g) is added:

deleted

“(g) the summary of the essential information necessary to use the medicine safely and effectively provided for in Article 11(3a) and Article 59(1)(aa).”

 

Amendment   29

Proposal for a directive – amending act

Article 1 — point 21

Directive 2001/83/EC

Article 102

 

Text proposed by the Commission

Amendment

The Member States shall:

The Member States shall:

(1) take all appropriate measures to encourage doctors, pharmacists and other health-care professionals to report suspected adverse reactions to the national competent authority or the marketing authorisation holder;

(1) take all appropriate measures to encourage patients, doctors, pharmacists and other health-care professionals to report suspected adverse reactions to the national competent authority. Those measures shall include training for healthcare professionals and for patients, and a public information campaign for patients. Patient organisations should be involved in providing information and training to patients;

 

(1a) conduct public awareness campaigns on the importance of reporting adverse reactions and possible ways of doing so;

 

(1b) facilitate direct patient reporting, in addition to web-based formats, through the provision on the patient information leaflet of a detachable portion that can be reported to the doctors, pharmacists or the national competent authority;

(2) ensure that adverse reaction reports contain the highest quality information possible;

(2) ensure that adverse reaction reports and the databases contain the highest quality information possible;

(3) through the methods of collecting information and where necessary through the follow up of adverse reaction reports, ensure that any biological medicinal product prescribed, dispensed, or sold in their territory which is the subject of an adverse reaction report is identifiable;

(3) ensure that any biological medicinal product prescribed, dispensed, or sold in their territory which is the subject of a suspected adverse reaction report is identifiable by, as far as available, the name of the marketing authorisation holder, the International Non-proprietary Name (INN), the name of the medicinal product and the batch number, using the standard forms and procedures developed in accordance with Article 25 of Regulation (EC) No 726/2004, taking due account of the developments within the EudraVigilance system; and implement the necessary measures to ensure the traceability of biological medicinal products dispensed to patients;

 

(3a) ensure that the public is given important information in good time on pharmacovigilance concerns relating to the use of a medicinal product and that data is permanently accessible to the public;

 

(3b) take the necessary steps to enable the public to report adverse reactions, in particular by ensuring that appropriate forms are available at pharmacies, drawn up in line with technical criteria and complying with the principles of simplified language and structure, accessible to the general public; these forms shall be sent by the pharmacists to the competent authorities;

(4) take the necessary measures to ensure that a marketing authorisation holder who fails to discharge the obligations laid down in this Title is subject to effective, proportionate and dissuasive penalties.

(4) take the necessary measures to ensure that a marketing authorisation holder who fails to discharge the obligations laid down in this Title is subject to effective, proportionate and dissuasive penalties.

For the purposes of point (1) of the first paragraph the Member States may impose specific requirements on doctors, pharmacists and other health-care professionals in respect of the reporting of suspected serious or unexpected adverse reactions.

For the purposes of point (1) of the first paragraph the Member States may impose specific requirements on doctors, pharmacists and other health-care professionals in respect of the reporting of suspected serious or unexpected adverse reactions.

Justification

It is more appropriate to encourage patients & health professionals to submit their reports to the competent authorities rather than to pharmaceutical companies. Direct reporting to companies raises concerns both in terms of privacy of users and in terms of medical feedback. In addition they will be in the position to decide if the report is an “adverse reaction”, a medication error, or else. Patient reporting should be accompanied by information campaigns about the importance of reporting.

Amendment  30

Proposal for a directive – amending act

Article 1 — point 21

Directive 2001/83/EC

Article 103

 

Text proposed by the Commission

Amendment

Article 103

deleted

A Member State may delegate any of the tasks entrusted to it under this Title to another Member State subject to a written agreement of the latter.

 

The delegating Member State shall inform the Commission, the Agency and all other Member States of the delegation in writing. The delegating Member State and the Agency shall make that information public.

 

Justification

Each member state should be fully responsible for the detection and the follow up of any adverse event related to a medicine marketed within its territory.

Amendment  31

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 105 – paragraph 2

 

Text proposed by the Commission

Amendment

The first paragraph shall not preclude the collection of fees to be paid by marketing authorisation holders for the carrying out of those activities by the national competent authorities.

The first paragraph shall not preclude the collection of fees to be paid by marketing authorisation holders as a complementary contribution to the carrying out of those activities by the national competent authorities.

Amendment  32

Proposal for a directive – amending act

Article 1 — point 21

Directive 2001/83/EC

Article 106

 

Text proposed by the Commission

Amendment

Each Member State shall set up and maintain a national medicines safety web-portal which shall be linked to the European medicines safety web-portal established in accordance with Article 26 of Regulation (EC) No 726/2004. By means of the national medicines safety web-portals, the Member States shall make public at least the following:

Each Member State shall set up and maintain a national medicines safety web-portal which shall be linked to the European medicines safety web-portal established in accordance with Article 26 of Regulation (EC) No 726/2004. By means of the national medicines safety web-portals, the Member States shall make public at least the following:

 

- (1) the leaflets for the medicines available on the national market in the national language (and where applicable the link to the EMEA EudraPharm database);

(1) risk management systems for medicinal products authorised in accordance with this Directive;

(1) risk management systems for medicinal products authorised in accordance with this Directive;

(2) the list of medicinal products under intensive monitoring referred to in Article 23 of Regulation (EC) No 726/2004;

(2) the list of medicinal products under intensive monitoring referred to in Article 23 of Regulation (EC) No 726/2004;

(3) web-based structured forms for the reporting of suspected adverse reactions by healthcare professionals and patients based on the forms referred to in Article 25 of Regulation (EC) No 726/2004.

(3) web-based structured forms for the reporting of suspected adverse reactions by healthcare professionals and patients based on the forms referred to in Article 25 of Regulation (EC) No 726/2004;

 

(4) agendas for meetings of the Pharmacovigilance Committee and of the coordination group and records of their meetings, accompanied by the decisions taken and by details and explanations of the votes, including minority opinions;

 

(5) requests from the national competent authority to the marketing authorisation holder to operate a risk management system or to conduct a post-authorisation study, together with the explanations provided by the marketing authorisation holder to the national competent authority where necessary, and the final decision of the competent authority.

Justification

Each member states should have a national medicine agency portal to provide high quality information on medicines to the general public. Most countries already have such a portal as a source of validated and reliable information on medicines and this amendments aims at establishing the legal basis for such portals in response to the European Commission report on current practice with regard to the provision of information to patients on medicinal products. The web portal should include a dedicated area for all information related to safety issues and pharmacovigilance.

Amendment  33

Proposal for a directive – amending act

Article 1 — point 21

Directive 2001/83/EC

Article 107

 

Text proposed by the Commission

Amendment

1. Marketing authorisation holders shall be required to record all suspected adverse reactions in the Community or in third countries which are brought to their attention, whether reported spontaneously by patients or healthcare professionals or occurring in the context of a post-authorisation safety study.

1. Marketing authorisation holders shall be required to record all suspected adverse reactions in the Community or in third countries which are brought to their attention, whether reported spontaneously by patients or healthcare professionals or occurring in the context of a clinical trial or a post-authorisation safety study.

Marketing authorisation holders shall be required to ensure that those reports are accessible at a single point within the Community.

 

By way of derogation to the first subparagraph, suspected adverse reactions occurring in the context of a clinical trial shall be recorded and reported in accordance with Directive 2001/20/EC.

Suspected adverse reactions occurring in the context of a clinical trial shall also be recorded and reported in accordance with Directive 2001/20/EC.

2. The marketing authorisation holder may not refuse reports of suspected adverse reactions received electronically from patients and health-care professionals.

2. The marketing authorisation holder shall forward to the national competent authorities any reports of suspected adverse reactions received from patients and health-care professionals within 7 days of receiving the reports. The marketing authorization holder shall inform the patient and healthcare professional that their report has been forwarded to the competent authorities who will be in charge of following it up.

 

The national competent authorities may not refuse any reports of suspected adverse reactions received by post, telephone, facsimile transmission or in electronic format from patients and healthcare professionals.

3. Marketing authorisation holders shall be required to submit electronically to the database and data-processing network referred to in Article 24 of Regulation (EC) No 726/2004 (hereinafter referred to as ‘the Eudravigilance database’) information on all serious suspected adverse reactions that occur in the Community and in third countries within 15 days following the receipt of the report or, in the absence of a report, following the day on which the holder concerned gained knowledge of the event.

3. Marketing authorisation holders shall be required to submit electronically to the national competent authorities information on all serious suspected adverse reactions that occur in the Community and in third countries within 15 days following the receipt of the report or, in the absence of a report, following the day on which the holder concerned gained knowledge of the event.

Marketing authorisation holders shall be required to submit electronically to the Eudravigilance database information on all non-serious suspected adverse reactions that occur in the Community, within 90 days following the receipt of the report or, in the absence of a report, following the day on which the holder concerned gained knowledge of the event.

Marketing authorisation holders shall be required to submit electronically to the national competent authorities information on all non-serious suspected adverse reactions that occur on the markets in which they operate, within 90 days following the receipt of the report or, in the absence of a report, following the day on which the holder concerned gained knowledge of the event.

For medicinal products containing the active substances referred to in the list of publications monitored by the Agency pursuant to Article 27 of Regulation (EC) No 726/2004, marketing authorisation holders shall not be required to report to the Eudravigilance database the suspected adverse reactions recorded in the listed medical literature, but they shall monitor all other medical literature and report any suspected adverse reactions.

For medicinal products containing the active substances referred to in the list of publications monitored by the Agency pursuant to Article 27 of Regulation (EC) No 726/2004, marketing authorisation holders shall not be required to report to the Eudravigilance database the suspected adverse reactions recorded in the listed medical literature, but they shall monitor all other medical literature and report any suspected adverse reactions.

4. Member States shall access reports on adverse reactions through the Eudravigilance database and shall assess the quality of the data received from marketing authorisation holders. They shall, as appropriate, involve patients and health-care professionals in the follow up of any reports they receive and request follow up of such reports to be conducted by the marketing authorisation holders. The marketing authorisation holders shall be required to report any follow up information received to the Eudravigilance database.

4. Member States shall assess the quality of the data received from marketing authorisation holders. They shall, as appropriate, involve patients and health-care professionals in the follow up of any reports they receive.

Amendment   34

Proposal for a directive – amending act

Article 1 — point 21

Directive 2001/83/EC

Article 107a

 

Text proposed by the Commission

Amendment

1. The Member States shall record all suspected adverse reactions that occur in their territory which are brought to their attention from healthcare professionals and patients.

1. The Member States shall record all suspected adverse reactions that occur in their territory which are brought to their attention by healthcare professionals, patients, marketing authorisation holders and programmes for the reporting and prevention of medication errors.

Member States shall ensure that reports of such reactions are submitted by means of the national medicines safety web-portals.

Member States shall ensure that reports of such reactions can be submitted by means of the national medicines safety web-portals, as well as by post, telephone and fax.

2. Member States shall, within 15 days following the receipt of the reports referred to in paragraph 1, submit the reports electronically to the Eudravigilance database.

2. Member States shall, within 15 days following the receipt of the reports referred to in paragraph 1, submit electronically to the database and data-processing network referred to in Article 24 of Regulation (EC) No 726/2004 (hereinafter referred to as ‘the Eudravigilance database’) information on all adverse reactions that occur within their territory within 15 days following receipt of the report or, in the absence of a report, following the day on which the competent authority acquired knowledge of the event.

Marketing authorisation holders shall access those reports through the Eudravigilance database.

Marketing authorisation holders, healthcare professionals and the public shall access those reports through the Eudravigilance database, which must be made permanently accessible without delay.

3. The Member States shall ensure that reports of medication errors brought to their attention in the framework of suspected adverse reaction reporting for medicinal products are made available to the Eudravigilance database and to any authorities responsible for patient safety within that Member State. They shall also ensure that the authorities responsible for medicinal products within that Member State are informed of any suspected adverse reactions brought to the attention of the authorities responsible for patient safety within that Member State.

3. The Member States shall ensure that reports of medication errors, or of the unintended effects of medicinal products used contrary to the indications covered by the authorisation, brought to their attention in the framework of suspected adverse reaction reporting for medicinal products are made available to the Eudravigilance database, to any authorities responsible for patient safety within that Member State and to independent programmes for the reporting and prevention of medication errors. They shall also ensure that the authorities responsible for medicinal products within that Member State are informed of any suspected adverse reactions brought to the attention of the authorities responsible for patient safety within that Member State.

Amendment  35

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 107a – paragraph 3 a (new)

 

Text proposed by the Commission

Amendment

 

3a. The Member States shall ensure that marketing authorisation holders may electronically transmit information on unintended effects of medicinal products to national databases so that country-specific safety problems can be identified more effectively and more promptly.

Amendment  36

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 107i – paragraph 1 – points a, b, c

 

Text proposed by the Commission

Amendment

(a) it considers suspending or revoking of a marketing authorisation;

(a) it considers, as a result of the evaluation of pharmacovigilance data:

 

- suspending or revoking of a marketing authorisation;

(b) it considers prohibiting the supply of a medicinal product;

- prohibiting the supply of a medicinal product;

(c) it considers refusing the renewal of a marketing authorisation;

- refusing the renewal of a marketing authorisation;

Justification

Clarification of the Community procedure

Amendment  37

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 107k – paragraph 1 – subparagraph 1

 

Text proposed by the Commission

Amendment

1. Following the information referred to in Article 107i(1), the Agency shall publicly announce the initiation of the procedure by means of the European medicines safety web-portal.

1. Following the information referred to in Article 107i(1), the Agency shall notify the concerned marketing authorisation holders and publicly announce the initiation of the procedure by means of the European medicines safety web-portal.

Amendment   38

Proposal for a directive – amending act

Article 1 — point 21

Directive 2001/83/EC

Article 108

 

Text proposed by the Commission

Amendment

Following consultation with the Agency, Member States and interested parties, the Commission shall adopt and make public guidelines on good pharmacovigilance practice for medicinal products authorised in accordance with Article 6(1) in the following areas:

Following consultation with the Agency, Member States and interested parties, the Commission shall adopt and make public guidelines on good pharmacovigilance practice for medicinal products authorised in accordance with Article 6(1) in the following areas:

(1) the establishment and operation of the pharmacovigilance system by the marketing authorisation holder and the content and maintenance of the pharmacovigilance system master file;

(1) the establishment and operation of the pharmacovigilance system by the marketing authorisation holder and the content and maintenance of the pharmacovigilance system master file;

(2) quality assurance and quality control by the marketing authorisation holder, the national competent authorities and the Agency of their performance of pharmacovigilance activities.

(2) quality assurance and quality control by the marketing authorisation holder, the national competent authorities and the Agency of their performance of pharmacovigilance activities;

(3) the use of internationally agreed terminologies, formats and standards for the conduct of pharmacovigilance;

(3) the use of internationally agreed terminologies, formats and standards for the conduct of pharmacovigilance allowing the clinical significance of reported cases to be preserved;

(4) the methodology for the monitoring of data in the Eudravigilance database to determine whether there are new or changed risks;

(4) the methodology for the monitoring of data in the Eudravigilance database to determine whether there are new or changed risks;

(5) the format of electronic reporting of adverse reactions by Member States and marketing authorisation holders;

(5) the format of electronic reporting of adverse reactions by Member States and marketing authorisation holders;

(6) the format of electronic periodic safety update reports;

(6) the format of electronic periodic safety update reports;

(7) the format of protocols, abstracts and final study reports for the post-authorisation safety studies;

(7) the format of protocols, abstracts and final study reports for the post-authorisation safety studies;

(8) the procedures and formats for pharmacovigilance communications.

(8) the procedures and formats for pharmacovigilance communications.

Those guidelines shall take account of international harmonisation work carried out in the field of pharmacovigilance and shall where necessary be revised to take account of technical and scientific progress.

Those guidelines shall be based on patient needs from a scientific perspective, shall take account of international harmonisation work carried out in the field of pharmacovigilance and shall where necessary be revised to take account of technical and scientific progress.

 

For the purposes of Article 102(3) and this Article, the Commission, in cooperation with the Agency, Member States, and stakeholders, shall prepare detailed guidelines on good record-keeping practices for pharmacies and others that dispense or administer medicinal products, to ensure retention of records required in the event of needing to file a pharmacovigilance report or to provide information required by a marketing authorisation holder conducting an evaluation of an adverse event, and to facilitate follow-up investigations by the marketing authorisation holder and national competent authorities.

Justification

The need to comply with the standards of the international conference on harmonisation strengthens the conceptual and technical dependence of the healthcare authorities on pharmaceutical laboratories. Good European pharmacovigilance practice would influence the organisation of the European pharmacovigilance system. That good practice must be drawn up openly, by means of a transparent consultation process based on the needs of European patients and from a scientific perspective.

Amendment  39

Proposal for a directive – amending act

Article 2 – paragraph 1

Text proposed by the Commission

Amendment

1. With regard to the requirement for the inclusion of a summary of the essential information necessary to use the medicine safely and effectively in the summary of the product characteristics and the package leaflet provided for in point 3a of Article 11 and in point (aa) of Article 59(1) of Directive 2001/83/EC as amended by this Directive, the Member States shall ensure that the requirement applies to a marketing authorisation granted before the date set out in the second subparagraph of Article 3(1) of this Directive from renewal of that authorisation or from the expiry of a period of three years starting from that date, whichever is the earliest.

1. With regard to the requirement for the inclusion of the medicinal product’s adverse reaction profile in the summary of the product characteristics and the package leaflet provided for in point 3a of Article 11 and in point (aa) of Article 59(1) of Directive 2001/83/EC as amended by this Directive, the Member States shall ensure that the requirement applies to a marketing authorisation granted before the date set out in the second subparagraph of Article 3(1) of this Directive from renewal of that authorisation or from the expiry of a period of three years starting from that date, whichever is the earliest.

PROCEDURE

Title

Pharmacovigilance (amendment of Directive 2001/83/EC)

References

COM(2008)0665 – C6-0514/2008 – 2008/0260(COD)

Committee responsible

ENVI

Opinion by

       Date announced in plenary

ITRE

19.10.2009

 

 

 

Rapporteur

       Date appointed

Michèle Rivasi

16.9.2009

 

 

Discussed in committee

15.10.2009

27.1.2010

 

 

Date adopted

7.4.2010

 

 

 

Result of final vote

+:

–:

0:

47

5

0

Members present for the final vote

Jean-Pierre Audy, Zigmantas Balčytis, Bendt Bendtsen, Jan Březina, Maria Da Graça Carvalho, Giles Chichester, Pilar del Castillo Vera, Lena Ek, Ioan Enciu, Adam Gierek, Norbert Glante, Robert Goebbels, Fiona Hall, Jacky Hénin, Edit Herczog, Oriol Junqueras Vies, Sajjad Karim, Arturs Krišjānis Kariņš, Bogdan Kazimierz Marcinkiewicz, Marisa Matias, Judith A. Merkies, Jaroslav Paška, Aldo Patriciello, Miloslav Ransdorf, Herbert Reul, Michèle Rivasi, Jens Rohde, Paul Rübig, Amalia Sartori, Francisco Sosa Wagner, Konrad Szymański, Silvia-Adriana Ţicău, Patrizia Toia, Evžen Tošenovský, Ioannis A. Tsoukalas, Claude Turmes, Niki Tzavela, Vladimir Urutchev, Adina-Ioana Vălean, Kathleen Van Brempt, Alejo Vidal-Quadras

Substitute(s) present for the final vote

Lara Comi, António Fernando Correia De Campos, Rachida Dati, Françoise Grossetête, Jolanta Emilia Hibner, Bernd Lange, Marian-Jean Marinescu, Ivari Padar, Vladko Todorov Panayotov, Mario Pirillo

Substitute(s) under Rule 187(2) present for the final vote

Isabelle Durant


OPINION of the Committee on the Internal Market and Consumer Protection (5.3.2010)

for the Committee on the Environment, Public Health and Food Safety

on the proposal for a directive of the European Parliament and of the Council amending, as regards pharmacovigilance, Directive 2001/83/EC on the Community code relating to medicinal products for human use

(COM(2008)0665 – C6-0514/2008 – 2008/0260(COD))

Rapporteur: Claude Turmes

SHORT JUSTIFICATION

Medicinal products contribute considerably to the health of EU citizens. They can however also have adverse effects, leading to about 5% of all hospital admissions according to the European Commission (underreporting does however not allow for accurate estimates). The rofecoxib (Vioxx) case, an anti-inflammatory that was withdrawn of the market in 2004 because of increased cardiovascular risks (more than 30.000 estimated strokes in the US, some of which were fatal) permitted to raise awareness about the need to strengthen pharmacovigilance.

Pharmacovigilance is the process and science of monitoring the safety of medicines, including the collection and management of data on the safety of medicines, the assessment of that data to detect whether there is a safety issue, action to address the possible safety issue including informing on this issue, and the evaluation of the procedure followed and results obtained.

As regards centrally authorised medicines the pharmacovigilance procedure is laid down in Regulation 726/2004. As regards nationally authorised medicinal products the procedure is laid down by Directive 2001/83. This opinion concerns the Commission's proposed amendments to Directive 2001/83.

The Commission wishes to improve the current system of pharmacovigilance by clarifying the roles of the various actors involved, simplifying procedures, enhanced transparency and communication, better data collection and evaluation procedures, more involvement of stakeholders and the establishment of best practices.

Though the rapporteur for opinion welcomes the proposal, he is of the view that there is a room for further improvements, mainly with regard to consumer protection issues, transparency and data protection. He therefore proposes amendments along the following lines:

· Patient reports can bring a new contribution to the understanding of adverse drug reactions (ADR) as it was the case for paroxetine (Deroxat/Seroxat), an antidepressant which was found, thanks to patient reports, to increase the risk of suicides and to cause a deprivation syndrome (“electric head”) if the patients wished to stop their treatment.

· Consumers should report directly to national authorities. Decentralised reporting systems whereby communication of all adverse drug reactions (reported whether by patients, hospitals, health professionals and pharmaceutical companies) to the European database is coordinated at a national level, increase the safety for data protection and guarantees the quality of the data which are registered at the European level. Proximity also allows national health authorities to:

- investigate the reports to add valuable information whereby they apply their particular expertise,

- to have a clear view of the adverse effects occurring on their territory,

- and to make this information accessible to their country’s population in its own language (as the UK and the Netherlands already do).

· Consumers and Healthcare professionals should also have full access to the central European EUDRAVigilance database in order to prevent the repetition of preventable adverse drug reactions by making validated information easily available. It is an effective way to tackle inequalities of information on adverse drug reactions among Member States. This public access to Eudravigilance is needed to restore citizens’ trust in health authorities’ capacity to protect public health.

· The use of a web format for reporting should be supplemented by other means, such as mail, fax and phone as it is the case in the US and in the UK, in order to not exclude those who do not have access to or cannot use the internet and to improve patient reporting.

· All assessment reports concerning a medication in the framework of the national and European pharmacovigilance systems should be available to the public. When an overriding public interest is at stake, as it is the case concerning pharmacovigilance data, full disclosure has always to be guaranteed.

· The funding of the pharmacovigilance systems should remain public as recognition of the public authorities’ responsibility to protect their populations, and in order to guarantee their independency.

AMENDMENTS

The Committee on the Internal Market and Consumer Protection calls on the Committee on the Environment, Public Health and Food Safety, as the committee responsible, to incorporate the following amendments in its report:

Amendment  1

Proposal for a directive – amending act

Recital 9

Text proposed by the Commission

Amendment

(9) Where a medicinal product is authorized subject to the requirement to conduct a post-authorisation safety study or where there are conditions or restrictions with regard to the safe and effective use of the medicinal product, the medicinal product should be intensively monitored on the market. Patients and healthcare professionals should be encouraged to report all suspect adverse reactions to such medicinal products, and a publicly available list of such medicinal products should be maintained up to date by the European Medicines Agency established by Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (hereinafter referred to as the ‘Agency’).

(9) Where a medicinal product is authorized subject to the requirement to conduct a post-authorisation safety study or where there are conditions or restrictions with regard to the safe and effective use of the medicinal product, the medicinal product should be subject to extended monitoring on the market. Patients and healthcare professionals should be encouraged to report all suspect adverse reactions to such medicinal products, and a publicly available list of such medicinal products should be maintained up to date by the European Medicines Agency established by Regulation (EC) No 726/2004 of the European Parliament and of the Council of 31 March 2004 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Medicines Agency (hereinafter referred to as the ‘Agency’).

Amendment  2

Proposal for a directive – amending act

Recital 10

Text proposed by the Commission

Amendment

(10) In order to make it possible for the healthcare professionals and patients to identify easily the most relevant information about the medicines they use, the summary of the product characteristics and the package leaflet should include a concise section on the key information about the medicinal product and information how to minimize its risks and maximize its benefits.

deleted

Amendment  3

Proposal for a directive – amending act

Recital 10 a (new)

Text proposed by the Commission

Amendment

 

(10a) Within three years of the entry into force of this Directive, the Commission should, following consultations with patient and consumer organisations, doctor and pharmacist organisations, Member States and other interested parties, present to the European Parliament and the Council an assessment report regarding the readability of the summaries of product characteristics and the packaging leaflets and their value to the general public and healthcare professionals. Following an analysis of the above data, the Commission should, if appropriate, put forward proposals to improve the layout and the content of the summaries of product characteristics and of the packaging leaflet to ensure they are a valuable source of information for the general public and healthcare professionals.

Justification

Medication leaflets are still often not clear and easy understandable for consumers. It is the duty of the European Commission to come up with reflected proposals discussed with all relevant stakeholders.

Amendment  4

Proposal for a directive – amending act

Recital 13

Text proposed by the Commission

Amendment

(13) With a view to ensuring that the same level of scientific expertise in the area of pharmacovigilance decision-making at both Community and national level, when fulfilling pharmacovigilance tasks the coordination group should be able to rely on the advice of the Pharmacovigilance Risk Assessment Advisory Committee of the Agency.

(13) With a view to ensuring the same level of scientific expertise in the area of pharmacovigilance decision-making at both Community and national level, when fulfilling pharmacovigilance tasks the coordination group should be able to rely on the advice of the Agency’s Pharmacovigilance Risk-Benefit Balance Assessment Advisory Committee.

Justification

The designation ‘Pharmacovigilance Risk Assessment Advisory Committee’ is too restrictive and ignores the need for analysis of a drug’s risk-benefit balance by insisting on risk assessment as a separate issue. But the Committee’s remit is for ‘questions related to … pharmacovigilance’ (proposal for a directive, Article 1, point 14).

Amendment  5

Proposal for a directive – amending act

Recital 18

Text proposed by the Commission

Amendment

(18) In order to simplify the reporting of suspected adverse reactions the marketing authorisation holders and the Member States should report those reactions only to the Community pharmacovigilance database and data-processing network referred to in Article 57(1)(d) of Regulation (EC) No 726/2004 (hereinafter ‘the Eudravigilance database’).

(18) In order to simplify the reporting of suspected adverse reactions the marketing authorisation holders should report those reactions to the Community pharmacovigilance database and data-processing network referred to in Article 57(1)(d) of Regulation (EC) No 726/2004 (hereinafter ‘the Eudravigilance database’) and simultaneously to competent national authorities. Any change in the national database should be immediately and automatically reflected in the Eudravigilance database. The Eudravigilance database and the national database should be fully interoperable.

Justification

Only indirect reporting of adverse reactions from patients, health professionals, and marketing authorization holders to national competent authorities guarantees quality data in the Eudravigilance system. It allows benefiting from their expertise and recognises their responsibility in terms of public health protection, at both national and European levels.

It is however essential that patients have a direct access to the data on the Eudravigilance database. This guarantees that good quality information of public interest is easily accessible and rapidly spread.

Amendment  6

Proposal for a directive – amending act

Recital 22

Text proposed by the Commission

Amendment

(22) Requirements for periodic safety update reports should be proportional to the risks posed by medicinal products. Periodic safety update reporting should therefore be linked to the risk management system for newly authorised medicinal products and routine reporting should not be necessary for generic, well-established use, informed consent, homeopathic, or traditional use registered herbal medicinal products. However, in the interest of public health the authorities should require periodic safety update reports for such products when there is a need to assess their risk or review the adequacy of product information.

(22) Requirements for periodic safety update reports should be proportional to the risks posed by medicinal products. Periodic safety update reporting should therefore be linked to the risk management system for newly authorised medicinal products and the intervals between reports should be extended for generic, well-established use, informed consent, homeopathic, or traditional use registered herbal medicinal products. However, in the interest of public health the authorities should require safety update reports for such products at specific intervals when there is a need to assess their risk or review the adequacy of product information.

Justification

L'exclusion de certains types de médicaments du régime des rapports périodiques actualisés de sécurité (génériques de médicaments, médicaments dont les substances actives sont d'un usage médical bien établi depuis au moins dix ans, certains médicaments homéopathiques, certains médicaments traditionnels à base de plantes, etc.) peut poser problème. Dans le cas de génériques, si le produit princeps n'est plus sur le marché, il n'y aura alors plus de rapport périodique disponible pour ces médicaments. De plus, des effets indésirables peuvent apparaître longtemps après la mise sur le marché (cas du DiAntalvic). Il ne peut donc pas y avoir d'exclusion de principe de certains médicaments, mais une périodicité plus longue est acceptable.

Amendment  7

Proposal for a directive – amending act

Recital 28 a (new)

Text proposed by the Commission

Amendment

 

(28a) This Directive should apply without prejudice to Directive 95/46/EC of the European Parliament and of the Council of 24 October 1995 on the protection of individuals with regard to the processing of personal data and on the free movement of such data1 and Regulation (EC) No 45/2001 of the European Parliament and of the Council of 18 December 2000 on the protection of individuals with regard to the processing of personal data by the Community institutions and bodies and on the free movement of such data2. In order to detect, assess, understand and prevent adverse reactions, identify and take action to reduce the risks and increase the benefits of medicinal products for the purpose of safeguarding public health, it should be possible to process personal data within the Eudravigilance system while complying with EU data protection legislation.

 

____________________

1 OJ L 281, 23.11.1995, p. 31.

2 OJ L 8, 12.1.2001, p. 1.

Justification

The processing of personal data of users of medication taking place at several stages of the pharmacovigilance process, should take place in accordance with the data protection principles laid down by Directive 95/46/EC.

Amendment  8

Proposal for a directive – amending act

Article 1 – point 3 – subpoint b

Directive 2001/83/EC

Article 11 – paragraph 2 a (new)

 

Text proposed by the Commission

Amendment

For the purposes of point 3(a) of the first subparagraph, for medicinal products included on the list referred to in Article 23 of the Regulation (EC) No 726/2004, the summary shall include the statement:

For the purposes of point 3(a) of the first subparagraph, for medicinal products included on the list referred to in Article 23 of the Regulation (EC) No 726/2004, the summary shall include the statement:

"This medicinal product is under intensive monitoring. All suspected adverse reactions should be reported to name and web-address of the national competent authority."

"This newly authorised medicinal product is subject to extended monitoring. All suspected adverse reactions should be reported to your doctor, pharmacist or name and web-address of the national competent authority."

Amendment  9

Proposal for a directive – amending act

Article 1 – point 7

Directive 2001/83/EC

Article 21 – paragraph 3

 

Text proposed by the Commission

Amendment

“3. The national competent authorities shall make publicly available without delay the marketing authorisation together with the summary of the product characteristics and any conditions established in accordance with Articles 21a, 22 and 22a, together with any deadlines for their fulfilment, for each medicinal product which they have authorised.

“3. The national competent authorities shall make publicly available without delay the marketing authorisation together with the package leaflet, the summary of the product characteristics and any conditions established in accordance with Articles 21a, 22 and 22a, together with any deadlines for their fulfilment, for each medicinal product which they have authorised.

Justification

In the interest of providing complete and accurate information to the general public, the package leaflet should also be made public when marketing authorisation is granted.

Amendment  10

Proposal for a directive – amending act

Article 1 – point 8

Directive 2001/83/EC

Article 21a – introductory part

 

Text proposed by the Commission

Amendment

A marketing authorisation may be granted subject to one or more of the following conditions:

Without prejudice to the provisions of Article 19, marketing authorisation may be granted subject to one or more of the following conditions:

Justification

This new article must not open the door to ‘easy’ marketing authorisations similar to the conditional – and strictly limited – authorisations laid down in Article 22.

Amendment  11

Proposal for a directive – amending act

Article 1 – point 9

Directive 2001/83/EC

Article 22 – subparagraph 3

 

Text proposed by the Commission

Amendment

Continuation of the authorisation shall be linked to the annual reassessment of these conditions.

Continuation of the authorisation shall be linked to the annual reassessment of these conditions. The list of these conditions shall be made accessible to the public without delay, together with deadlines and dates of fulfilment.

Justification

Restores the requirement to publish the conditions. Their deletion is not justified.

Amendment  12

Proposal for a directive – amending act

Article 1 – point 10

Directive 2001/83/EC

Article 22a

 

Text proposed by the Commission

Amendment

1. After the granting of a marketing authorisation, the national competent authority may require a marketing authorisation holder to conduct a post-authorisation safety study if there are concerns about the risks of an authorised medicinal product. The requirement shall be made in writing, provide a detailed justification and include the objectives and timeframe for submission and conduct of the study.

1. After the granting of a marketing authorisation, the national competent authority may require a marketing authorisation holder to conduct a post-authorisation safety study if there are concerns about the risks of an authorised medicinal product. The requirement shall be made in writing, provide a detailed justification and include the objectives and timeframe for submission and conduct of the study. It shall be made public without delay.

2. The national competent authority shall provide the marketing authorisation holder with an opportunity to present explanations on the requirement within a time limit which it shall specify, if the marketing authorisation holder requests this within 30-days of receipt of the written requirement.

2. The national competent authority shall provide the marketing authorisation holder with an opportunity to present explanations on the requirement within a time limit which it shall specify, if the marketing authorisation holder requests this in writing and with a detailed justification within 30 days of receipt of the written requirement. Such requests shall be made public without delay.

3. On the basis of explanations submitted by the marketing authorisation holder, the national competent authority shall withdraw or confirm the requirement. Where the national competent authority confirms the requirement, the marketing authorisation shall be varied to include the requirement as a condition of the marketing authorisation and the risk management system shall be updated accordingly.

3. On the basis of explanations submitted by the marketing authorisation holder, the national competent authority shall withdraw or confirm the requirement. That decision shall be made public without delay. Where the national competent authority confirms the requirement, the marketing authorisation shall be modified to include the requirement as a condition of the marketing authorisation and the risk management system shall be updated accordingly.

Justification

Authorisation in exceptional circumstances should be granted with in a fully transparent manner.

Amendment  13

Proposal for a directive – amending act

Article 1 – point 14 – subpoint a

Directive 2001/83/EC

Article 27 – paragraph 1 – subparagraph 3

 

Text proposed by the Commission

Amendment

For the fulfilment of its pharmacovigilance tasks, the coordination group shall be assisted by the Pharmacovigilance Risk Assessment Advisory Committee referred to in Article 56(1)(aa) of Regulation (EC) No 726/2004.”

For the fulfilment of its pharmacovigilance tasks, the coordination group shall be assisted by the Agency’s Pharmacovigilance Risk-Benefit Balance Assessment Advisory Committee

referred to in Article 56(1)(aa) of Regulation (EC) No 726/2004.”

Justification

The designation ‘Pharmacovigilance Risk Assessment Advisory Committee’ is too restrictive and ignores the need for analysis of a drug’s risk-benefit balance by insisting on risk assessment as a separate issue. But the Committee’s remit is for ‘questions related to … pharmacovigilance’ (proposed regulation, Article 1, point 14). This amendment applies throughout the text of the proposed directive.

Amendment  14

Proposal for a directive – amending act

Article 1 – point 14 – subpoint c

Directive 2001/83/EC

Article 27 – paragraph 7

 

Text proposed by the Commission

Amendment

7. Members of the coordination group shall be required, even after their duties have ceased, not to disclose information of the kind covered by the obligation of professional secrecy.”

7. Detailed agendas of coordination group meetings shall be made public not later than one day before the meeting concerned. Detailed minutes of coordination group meetings, containing the decisions taken, details of votes and explanations of votes, including minority opinions, shall be made public not later than one month following the meeting.”

Justification

Consistency with the Agency’s new structure, strictly separating pharmacovigilance from marketing authorisation.

Amendment  15

Proposal for a directive – amending act

Article 1 – point 18 – subpoint b

Directive 2001/83/EC

Article 59 – paragraph 1 – subparagraph 2 a (new)

 

Text proposed by the Commission

Amendment

For medicinal products included on the list referred to in Article 23 of Regulation (EC) No 726/2004, the following additional statement shall be included “This medicinal product is under intensive monitoring. All suspected adverse reactions should be reported to name and web-address of the national competent authority.”

For medicinal products included on the list referred to in Article 23 of Regulation (EC) No 726/2004, the following additional statement shall be included “This newly authorised medicinal product is subject to extended monitoring. All suspected adverse reactions should be reported to your doctor, pharmacist or name and web-address of the national competent authority".”

Amendment  16

Proposal for a directive – amending act

Article 1 – point 20

Directive 2001/83/EC

Article 65 – point g

 

Text proposed by the Commission

Amendment

20. In Article 65, the following point (g) is added:

deleted

“(g) the summary of the essential information necessary to use the medicine safely and effectively provided for in Article 11(3a) and Article 59(1)(aa).”

 

Justification

The proposed summary of essential information about the safe and effective use of medicines should be rejected since the concept of 'essential information' is misleading and might be misunderstood

Amendment  17

Proposal for a directive – amending act

Article 1 – point 20

Directive 2001/83/EC

Article 65 – point g a (new)

 

Text proposed by the Commission

Amendment

 

(ga) the Community procedure defining a procedural timeline, a clear structure and defined roles for all the stakeholders involved, including for the conduct of public hearings.

Justification

Guidance should be developed to clarify the procedures and timelines for the community procedure, including public hearings.

Amendment  18

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 102 – paragraph 1 – point 1

 

Text proposed by the Commission

Amendment

 

 

(1) take all appropriate measures to encourage doctors, pharmacists and other health-care professionals to report suspected adverse reactions to the national competent authority or the marketing authorisation holder;

(1) take all appropriate measures to encourage patients, doctors, hospitals, pharmacists and other health-care professionals to report suspected adverse reactions to the national competent authority;

Justification

It is the duty of national authorities to guarantee the quality and the critical follow up of all relevant data.

Amendment  19

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 102 – paragraph 1 – point 3 a (new)

 

Text proposed by the Commission

Amendment

 

(3a) ensure that the public are informed in good time about pharmacovigilance concerns relating to the use of a medicinal product;

Justification

Pharmacovigilance data should reach health care professionals and patients as quickly as possible in order to apply the precautionary principle.

Amendment  20

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 102 – paragraph 1 – point 4 a (new)

 

Text proposed by the Commission

Amendment

 

(4a) ensure that information about adverse reactions to medicines is rapidly made publicly accessible.

Justification

Pharmacovigilance data should reach health care professionals and patients as quickly as possible in order to apply the precautionary principle.

Amendment  21

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 105 – paragraph -1 (new)

 

Text proposed by the Commission

Amendment

 

The activities connected with pharmacovigilance, the operation of communication networks and market surveillance shall receive public funding.

 

 

 

 

Amendment  22

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 106 – point 2

 

Text proposed by the Commission

Amendment

(2) the list of medicinal products under intensive monitoring referred to in Article 23 of Regulation (EC) No 726/2004;

(2) the list of newly authorised of medicinal products subject to extended monitoring referred to in Article 23 of Regulation (EC) No 726/2004;

Amendment  23

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 106 – point 3 a (new)

 

Text proposed by the Commission

Amendment

 

(3a) agendas and detailed minutes of the meetings of the Pharmacovigilance Risk-Benefit Balance Assessment Advisory Committee

and coordination group.

Justification

The Pharmacovigilance system should be entirely transparent in order to guarantee full information of all stakeholders, notably in order to restore patients' and citizens' trust in health authorities' accountability.

Amendment  24

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 106 – point 3 b (new) and point 3 c (new)

 

Text proposed by the Commission

Amendment

 

(3b) the most up-to-date electronic version of the package leaflet and summary of product characteristics for all existing and new medicinal products;

 

(3c) a brief document history of changes made to the product information.

 

All information on the medicine safety web-portals, including all of the information set out in points 1 to 3b, shall be presented in a manner that is comprehensible to the general public.

Justification

Information on national safety web portals should be presented in an easy and understandable way. While the legislation provides for very detailed information to be published on the national safety portals, it does not include reference to the key information to ensure safe use of medicines : that is why the package leaflet should be made accessible to the public.

Amendment  25

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 107 – paragraph 1 – subparagraph 1

 

Text proposed by the Commission

Amendment

1. Marketing authorisation holders shall be required to record all suspected adverse reactions in the Community or in third countries which are brought to their attention, whether reported spontaneously by patients or healthcare professionals or occurring in the context of a post-authorisation safety study.

1. Marketing authorisation holders shall be required to record all suspected adverse reactions in the Community or in third countries which are brought to their attention, specifying whether they have occurred at doses normally used in humans for prophylaxis, diagnosis or treatment of a disease or for restoring, correcting or modifying a physiological function; following a medication error; or following use not consistent with the authorised summary of product characteristics, whether reported spontaneously by patients or healthcare professionals or occurring in the context of a post-authorisation safety study.

Justification

Extending the concept of ‘adverse reaction’ to include secondary effects resulting from a medication error or use that is not consistent with the authorised summary of the product’s characteristics (including misuse and abuse of the medicine) will make it possible to ascertain more comprehensively the secondary effects that may be harmful to patients. But it is still important to make a clear distinction between secondary effects that result from normal use and those that do not. This distinction should be clear in the reporting procedure.

Amendment  26

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 107 – paragraph 2

 

Text proposed by the Commission

Amendment

2. The marketing authorisation holder may not refuse reports of suspected adverse reactions received electronically from patients and health-care professionals.

2. The marketing authorisation holder may not refuse reports of suspected adverse reactions received electronically or by any other suitable means from patients and health-care professionals.

Justification

It is important not to prevent the reporting of adverse reactions by creating technological barriers. Some people do not necessarily have access to the internet or have difficulty using it.

Amendment  27

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 107 – paragraph 3 – subparagraph 1 and 2

 

Text proposed by the Commission

Amendment

3. Marketing authorisation holders shall be required to submit electronically to the database and data-processing network referred to in Article 24 of Regulation (EC) No 726/2004 (hereinafter referred to as ‘the Eudravigilance database’) information on all serious suspected adverse reactions that occur in the Community and in third countries within 15 days following the receipt of the report or, in the absence of a report, following the day on which the holder concerned gained knowledge of the event.

3. Marketing authorisation holders shall be required to submit electronically to the database and data-processing network referred to in Article 24 of Regulation (EC) No 726/2004 (hereinafter referred to as ‘the Eudravigilance database’), and simultaneously to national competent authorities, all information on all serious suspected adverse reactions that occur within 15 days following the receipt of the report or, in the absence of a report, following the day on which the holder concerned gained knowledge of the event.

Marketing authorisation holders shall be required to submit electronically to the Eudravigilance database information on all non-serious suspected adverse reactions that occur in the Community, within 90 days following the receipt of the report or, in the absence of a report, following the day on which the holder concerned gained knowledge of the event.

Marketing authorisation holders shall be required to submit electronically to the Eudravigilance database, and simultaneously to national competent authorities, all information on all non-serious suspected adverse reactions that occur in the Community, within 90 days following the receipt of the report or, in the absence of a report, following the day on which the holder concerned gained knowledge of the event.

Amendment  28

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 107 – paragraph 4 a (new)

 

Text proposed by the Commission

Amendment

 

(4a) Member States and the public shall be able to access reports on adverse reactions occurring in other Member States through the Eudravigilance database.

Justification

The European pharmacovigilance database should be entirely transparent in order to deliver information in due time to all stakeholders and also patients. It is also an effective way to tackle inequalities of information on adverse drug reactions among Member States.

Amendment  29

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 107a – paragraph 1

 

Text proposed by the Commission

Amendment

1. The Member States shall record all suspected adverse reactions that occur in their territory which are brought to their attention from healthcare professionals and patients.

1. The Member States shall record all suspected adverse reactions that occur in their territory which are brought to their attention from healthcare professionals, hospitals and patients, marketing authorisation holders and medication error reporting and prevention programmes, specifying whether they have occurred at doses normally used in humans for prophylaxis, diagnosis or treatment of a disease or for restoring, correcting or modifying a physiological function; following a medication error; or following use not consistent with the authorised summary of product characteristics.

Member States shall ensure that reports of such reactions are submitted by means of the national medicines safety web-portals.

 

Member States shall ensure that reports of such reactions are submitted by means of the national medicines safety web-portals, and by any other appropriate means.

Justification

Extending the concept of ‘adverse reaction’ to include secondary effects resulting from a medication error or use that inconsistent with the authorised summary of the product’s characteristics (including misuse and abuse of the medicine) will make it possible to ascertain more comprehensively the secondary effects that may be harmful to patients. But it is still important to make a clear distinction between secondary effects resulting from normal use and the others. This distinction should be clear in the reporting procedure. It is the duty of national authorities to guarantee the quality and the critical follow up of all relevant data.

Amendment  30

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 107a – paragraph 2 – subparagraph 1

 

Text proposed by the Commission

Amendment

2. Member States shall, within 15 days following the receipt of the reports referred to in paragraph 1, submit the reports electronically to the Eudravigilance database.

2. Member States shall, within 15 days following the receipt of the reports referred to in paragraph 1, submit the reports electronically to the Eudravigilance database, specifying whether they have occurred at doses normally used in humans for prophylaxis, diagnosis or treatment of a disease or for restoring, correcting or modifying a physiological function; following a medication error; or following use not consistent with the authorised summary of product characteristics.

Justification

Extending the concept of ‘adverse reaction’ to include secondary effects resulting from a medication error or use that is inconsistent with the authorised summary of the product’s characteristics (including misuse and abuse of the medicine) will make it possible to ascertain more comprehensively the secondary effects that may be harmful to patients. But it is still important to make a clear distinction between secondary effects resulting from normal use and those that do not. This distinction should be clear in the reporting procedure.

Amendment  31

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 107b – paragraph 3 – introductory part

 

Text proposed by the Commission

Amendment

3. By way of derogation from paragraph 1 of this Article, holders of marketing authorisations for medicinal products referred to in Articles 10, 10a or 10c, and holders of registrations for medicinal products referred to in Articles 14 or 16a, shall be required to submit periodic safety update reports for such products only in the following cases:

3. By way of derogation from paragraph 1 of this Article, holders of marketing authorisations for medicinal products referred to in Articles 10, 10a or 10c, and holders of registrations for medicinal products referred to in Articles 14 or 16a, shall be required to submit periodic safety update reports for such products only every three years, save in the following cases:

Justification

Excluding some types of medicine (generic medicines, medicines whose active substances have been in well-established use for at least 10 years, certain homeopathic medicines, certain traditional plant-based medicines, and so on) from the periodic safety update reporting scheme may pose problems. In the case of generic medicines, if the original product is no longer marketed a periodic report will no longer be available for such medicines. Moreover, adverse reactions can appear long after they are placed on the market (as with DiAntalvic). So certain medicines cannot be excluded on principle, but a longer reporting interval is acceptable.

Amendment  32

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 107e – paragraph 3

 

Text proposed by the Commission

Amendment

3. At its next meeting following the end of the period for comments by the marketing authorisation holder referred to in paragraph 2, the Pharmacovigilance Risk Assessment Advisory Committee shall adopt the assessment report with or without changes, taking into account any comments submitted in accordance with that paragraph.

3. At its next meeting following the end of the period for comments by the marketing authorisation holder referred to in paragraph 2, the Pharmacovigilance Risk Assessment Advisory Committee shall adopt the assessment report with or without changes.

 

That assessment report shall be made publicly accessible without delay by means of the European medicines safety web-portal.

Justification

The Pharmacovigilance system should be entirely transparent in order to guarantee full information of all stakeholders, notably in order to restore patients' and citizens' trust in health authorities' accountability.

Amendment  33

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 107 f

 

Text proposed by the Commission

Amendment

Following the assessment of periodic safety update reports, the national competent authorities shall consider whether any action concerning the terms of the marketing authorisation for the medicinal product concerned is necessary.

The national competent authorities shall consider whether any action concerning the terms of the marketing authorisation for the medicinal product concerned is necessary.

They shall maintain, vary, suspend or revoke the marketing authorisation as appropriate.

They shall maintain, modify, suspend or revoke the marketing authorisation as appropriate.

 

Their decisions shall be made publicly accessible without delay. Where a marketing authorisation is modified for reasons relating to pharmacovigilance, the national competent authorities or the reference Member State shall immediately publish an update of the assessment report of the medicinal product concerned or a detailed report about the modification.

Justification

The Pharmacovigilance system should be entirely transparent in order to guarantee full information of all stakeholders, notably in order to restore patients' and citizens' trust in health authorities' accountability.

Amendment  34

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 107k – paragraph 2 – subparagraph 1

 

Text proposed by the Commission

Amendment

2. The Pharmacovigilance Risk Assessment Advisory Committee shall assess the matter which has been submitted. For the purposes of that assessment, it may hold a public hearing.

2. The Pharmacovigilance Risk-Benefit Balance Assessment Advisory Committee shall assess the matter which has been submitted. For the purposes of that assessment, it may hold a public hearing, together with representatives from the Committee for Medicinal Products for Human Use (CHMP). The Agency, in consultation with stakeholders, shall develop guidelines for the organisation and conduct of public hearings.

 

The public hearing should also consider the effectiveness and benefits of the product as well as prior risk/benefit evaluations carried out by the CHMP or the coordination group under the procedure for granting marketing authorisation as described in Article 107l.

Justification

The organisation of public hearings by this committee is a useful tool, provided that the organization can be defined properly taking into account not only risks but also the benefits of the product (s) concerned in order to have a credible and objective discussion. This is primarily to safeguard the well being of the patient and assess the risks against the benefits of a medicinal product in view of all elements available

Amendment  35

Proposal for a directive – amending act

Article 1 – point 21

Directive 2001/83/EC

Article 107k – paragraph 2 – subparagraph 4 a (new)

 

Text proposed by the Commission

Amendment

 

In cases where a public hearing is held, a preliminary report shall be published following the hearing.

Justification

L'organisation d'auditions publiques est un des moyens d'améliorer la transparence du système de pharmacovigilance. Néanmoins, le délai au terme duquel le Comité consultatif de pharmacovigilance rend une recommandation motivée (60 jours) est relativement long. Afin d'éviter tout effet de panique et d'agitation médiatique, il est important de permettre la publication d'un rapport préliminaire à l'issue de l'audition publique, sans préjuger pour autant des conclusions finales du comité. Par ailleurs, il est important que l'audition soit organisée dans une perspective bénéfice-risque, et non purement dans une logique d'analyse du risque. L'important est que le rapport bénéfice-risque soit favorable.

Amendment  36

Proposal for a directive – amending act

Article 2 – paragraph 1

Text proposed by the Commission

Amendment

1. With regard to the requirement for the inclusion of a summary of the essential information necessary to use the medicine safely and effectively in the summary of the product characteristics and the package leaflet provided for in point 3a of Article 11 and in point (aa) of Article 59(1) of Directive 2001/83/EC as amended by this Directive, the Member States shall ensure that the requirement applies to a marketing authorisation granted before the date set out in the second subparagraph of Article 3(1) of this Directive from renewal of that authorisation or from the expiry of a period of three years starting from that date, whichever is the earliest.

deleted

Justification

Including a summary of key information is unnecessary, as the summary of product characteristics (SPC) is itself a summary of key information. It may confuse patients, who may overlook important information that is included in the SPC but not in the summary of key information. It may also create readability problems, for instance when leaflets are published in several languages.

Amendment  37

Proposal for a directive – amending act

Article 2 – paragraph 2 a (new)

Text proposed by the Commission

Amendment

2a. Until the Agency can ensure the functionalities of the Eudravigilance database, all the periodic safety update reports shall also be submitted to the National Competent Authorities where the product is authorised.

PROCEDURE

Title

Pharmacovigilance (amendment of Directive 2001/83/EC)

References

COM(2008)0665 – C6-0514/2008 – 2008/0260(COD)

Committee responsible

ENVI

Opinion by

       Date announced in plenary

IMCO

19.10.2009

 

 

 

Rapporteur

       Date appointed

Claude Turmes

28.9.2009

 

 

Discussed in committee

2.12.2009

27.1.2010

 

 

Date adopted

23.2.2010

 

 

 

Result of final vote

+:

–:

0:

38

0

0

Members present for the final vote

Pablo Arias Echeverría, Adam Bielan, Cristian Silviu Buşoi, Lara Comi, Anna Maria Corazza Bildt, António Fernando Correia De Campos, Jürgen Creutzmann, Christian Engström, Evelyne Gebhardt, Louis Grech, Iliana Ivanova, Philippe Juvin, Sandra Kalniete, Alan Kelly, Eija-Riitta Korhola, Edvard Kožušník, Toine Manders, Tiziano Motti, Zuzana Roithová, Heide Rühle, Matteo Salvini, Christel Schaldemose, Andreas Schwab, Laurence J.A.J. Stassen, Catherine Stihler, Róża, Gräfin von Thun Und Hohenstein, Kyriacos Triantaphyllides, Emilie Turunen, Bernadette Vergnaud, Barbara Weiler

Substitute(s) present for the final vote

Cornelis de Jong, Frank Engel, Ashley Fox, Anna Hedh, Othmar Karas, Morten Løkkegaard, Konstantinos Poupakis, Oreste Rossi, Kerstin Westphal


PROCEDURE

Title

Pharmacovigilance (amendment of Directive 2001/83/EC)

References

COM(2008)0665 – C6-0514/2008 – 2008/0260(COD)

Date submitted to Parliament

10.12.2008

Committee responsible

       Date announced in plenary

ENVI

19.10.2009

Committee(s) asked for opinion(s)

       Date announced in plenary

ITRE

19.10.2009

IMCO

19.10.2009

 

 

Rapporteur(s)

       Date appointed

Linda McAvan

10.9.2009

 

 

Discussed in committee

5.11.2009

25.1.2010

26.4.2010

 

Date adopted

27.4.2010

 

 

 

Result of final vote

+:

–:

0:

49

0

5

Members present for the final vote

János Áder, Elena Oana Antonescu, Kriton Arsenis, Pilar Ayuso, Paolo Bartolozzi, Sandrine Bélier, Sergio Berlato, Martin Callanan, Nessa Childers, Chris Davies, Esther de Lange, Bas Eickhout, Edite Estrela, Elisabetta Gardini, Julie Girling, Françoise Grossetête, Cristina Gutiérrez-Cortines, Satu Hassi, Dan Jørgensen, Karin Kadenbach, Christa Klaß, Jo Leinen, Corinne Lepage, Peter Liese, Linda McAvan, Radvilė Morkūnaitė-Mikulėnienė, Miroslav Ouzký, Vladko Todorov Panayotov, Gilles Pargneaux, Antonyia Parvanova, Andres Perello Rodriguez, Sirpa Pietikäinen, Mario Pirillo, Frédérique Ries, Anna Rosbach, Oreste Rossi, Dagmar Roth-Behrendt, Horst Schnellhardt, Richard Seeber, Theodoros Skylakakis, Bogusław Sonik, Catherine Soullie, Anja Weisgerber, Glenis Willmott, Sabine Wils, Marina Yannakoudakis

Substitute(s) present for the final vote

Matthias Groote, Marisa Matias, Mairead McGuinness, Judith A. Merkies, Alojz Peterle, Rovana Plumb, Thomas Ulmer

Substitute(s) under rule 187(2) present for the final vote

Mario Mauro

Last updated: 4 June 2010Legal notice