Article 36 
1. Where a Member State considers that the variation of a marketing authorization which has been granted in accordance with the provisions of this Chapter or its suspension or withdrawal is necessary for the protection of public health, the Member State concerned shall forthwith refer the matter to the Agency for the application of the procedures laid down in Articles 32, 33 and 34. 2. Without prejudice to the provisions of Article 31, in exceptional cases, where urgent action is essential to protect public health, until a definitive decision is adopted a Member State may suspend the marketing and the use of the medicinal product concerned on its territory. It shall inform the Commission and the other Member States no later than the following working day of the reasons for its action.
Amendment rationale: Context of the proposal 1.1. Grounds for and objectives of the proposal Medicinal products contribute considerably to the health of EU citizens. The discovery, development and effective use of medicinal products improve quality of life, reduce the length of time spent in hospital and save lives. Medicinal products can, however, also have adverse effects and adverse drug reactions present an important public health burden in the Community. It is estimated that 5% of all hospital admissions are due to an adverse drug reaction, 5% of all hospital patients suffer an adverse drug reaction and adverse drug reactions are the fifth most common cause of hospital death. Some adverse reactions will only be detected after a medicine has been authorised and the full safety profile of medicinal products can only be known once they have entered the market. Pharmacovigilance rules are therefore necessary for the protection of public health in order to prevent, detect and assess adverse effects of medicinal products. Community rules so far adopted have made a major contribution to the achievement of the objective that medicinal products authorised to be placed on the Community market are continuously monitored as regards their safety. However, in the light of the experience acquired and following an assessment by the Commission of the Community system of pharmacovigilance, it has become clear that new measures are necessary to improve the operation of the Community rules on the pharmacovigilance of medicinal products for human use. Therefore, the proposals aim at the strengthening and rationalizing the Community pharmacovigilance system of medicinal products for human use through the amendment of the two legal acts governing this field, with the overall objectives of better protecting public health, ensuring proper functioning of the internal market. and simplifying the current rules and procedures. The specific objectives are: - Providing for clear roles and responsibilities for the key responsible parties and clear obligations against which they perform their roles; - Rationalising EU decision-making on drug safety issues in order to deliver measures that are equally and fully implemented for all relevant products and across the Community with a view to preventing unnecessary patient exposure to risks; - Strengthening medicines safety transparency and communication to increase the understanding and trust of patients and health professionals in the safety of medicines and improve the penetration of key warnings; - Strengthening companies' pharmacovigilance systems, allowing companies to improve their systems constantly while reducing administrative burden; - Ensuring the proactive and proportionate collection of high quality data relevant to the safety of medicines through risk management and structured data collection in the form of post authorisation safety studies, together with rationalised single case and periodic reporting of suspected adverse reactions; - Involving stakeholders in pharmacovigilance including through direct patient reporting of suspected adverse reactions and inclusion of patients and heath-care professionals in decision-making. - Simplification of the current Community pharmacovigilance procedures with consequent efficiency gains for both the pharmaceutical industry and medicines regulators. 1.2. General context Pharmacovigilance is defined as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects of medicinal products. The Community has had legislation on medicinal products on pharmacovigilance since 1965. Until now there has been no systematic review of the Community pharmacovigilance legislation, its operation and its effect on protecting public health. Therefore, in 2004 the Commission services launched an independent study into the functioning of the Community pharmacovigilance system. The independent report together with a subsequent broad public consultation revealed several shortcomings. 1.3. Existing provisions in the area of the proposal Harmonised Community rules on the pharmacovigilance of medicinal products for human use are laid down in: - 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[1], as regards medicinal products authorized by the Commission in accordance with the procedure of that Regulation (the so-called "centralised procedure"); and - Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use[2], as regards general rules on medicinal products for human use and specific rules for medicinal products authorised by the Member States. While the rules are broadly the same in substance, there are certain divergences and various provisions are duplicated in the two legal texts. It is appropriate to rationalise and simplify this by laying down all general rules in the Community code on medicinal products for human use (Directive 2001/83/EC), and cross-referring to them in the regulation governing the centralised procedure (Regulation (EC) No 726/2004), with specific provisions for centrally authorised products only when justified. 1.4. Consistency with the other policies and objectives of the Union The proposals are consistent with the overall objective of the Community legislation on medicinal products for human use, which is to remove disparities between national provisions in order to ensure the proper functioning of the internal market for such products, while at the same time safeguarding a high level of protection of public and human health. They are also consistent with Article 152(1) of the Treaty establishing the European Community, which provides that a high level of human health protection shall be ensured in the definition and implementation of all Community policies and activities. The proposal is equally consistent with the Commission patient safety initiative[3] and the Commission work to stimulate innovation in the pharmaceutical sector, through the 7th Framework programme in general and the Innovative Medicines Initiative[4] in particular. The proposal is also consistent with Community projects which aim to develop and validate the use of innovative information technology tools to identify medicines adverse events.
Article 37 
Articles 35 and 36 shall apply by analogy to medicinal products authorized by Member States following an opinion of the Committee given in accordance with Article 4 of Directive 87/22/EEC before 1 January 1995.
Article 38 
1. The Agency shall publish an annual report on the operation of the procedures laid down in this Chapter and shall forward that report to the European Parliament and the Council for information. 2. At least every ten years the Commission shall publish a report on the experience acquired on the basis of the procedures described in this Chapter and shall propose any amendments which may be necessary to improve those procedures. The Commission shall submit this report to the European Parliament and to the Council.
Article 39 
Article 29(4), (5) and (6) and Articles 30 to 34 shall not apply to the homeopathic medicinal products referred to in Article 14. Articles 28 to 34 shall not apply to the homeopathic medicinal products referred to in Article 16(2).
Article 40 
1. Member States shall take all appropriate measures to ensure that the manufacture of the medicinal products within their territory is subject to the holding of an authorization. This manufacturing authorization shall be required nothwithstanding that the medicinal products manufactured are intended for export. 2. The authorization referred to in paragraph 1 shall be required for both total and partial manufacture, and for the various processes of dividing up, packaging or presentation. However, such authorization shall not be required for preparation, dividing up, changes in packaging or presentation where these processes are carried out, solely for retail supply, by pharmacists in dispensing pharmacies or by persons legally authorized in the Member States to carry out such processes. 3. Authorization referred to in paragraph 1 shall also be required for imports coming from third countries into a Member State; this Title and Article 118 shall have corresponding application to such imports as they have to manufacture. 4. The Member States shall forward to the Agency a copy of the authorisation referred to in paragraph 1. The Agency shall enter that information on the Community database referred to in Article 111(6).
Amendment rationale: CONTEXT OF THE PROPOSAL On 15 December 2010, the European Parliament and the Council adopted Directive 2010/84/EU and Regulation (EU) No 1235/2010 ("2010 pharmacovigilance legislation") amending respectively, as regards pharmacovigilance, Directive 2001/83/EC and Regulation (EC) No 726/2004. The new legislation shall apply in July 2012. The adopted measures have substantially strengthened the legal framework for the surveillance of medicinal products, with provisions that reinforce the coordinating role of the European Medicines Agency, the possibilities for signal detection, and the operation of coordinated procedures at European level to respond to safety concerns. However, recent pharmacovigilance events in the European Union, in particular the so-called “Mediator case”, have shown the need for a further improvement of the pharmacovigilance system. Following an analysis of the Mediator case in the light of the 2010 pharmacovigilance legislation ("Stress test"), the Commission has detected certain weaknesses in the pharmacovigilance system which should be addressed. In particular, Directive 2001/83/EC provides for an automatic assessment at Union level when specific serious safety issues have been identified with regard to nationally authorised products. In the 2010 pharmacovigilance legislation, changes to the Commission's proposal during co-decision have led to the automatism being lost, as the initiation of the procedure is linked to an appreciation by the Member State or the Commission as to whether an urgent action is considered necessary. Thus, when a Member State considers suspending, revoking or refusing renewal of a marketing authorisation, but does not consider that urgent action is needed, no evaluation of the safety concern will be conducted at Union level. Moreover, marketing authorisation holders are not required to declare the reasons for the withdrawal of a marketing authorisation or product. Therefore, it cannot be ruled out that voluntary withdrawal of a marketing authorisation or product by the marketing authorisation holder could lead to safety issues being missed, in particular if the company is not transparent about possible safety concerns. Finally, the public list of medicinal product subject to additional monitoring provided for in Article 23 of Regulation (EC) No 726/2004 will include certain medicinal products subject to post-authorisation safety conditions. Those products will be included in the list, following consultation with the Pharmacovigilance Risk Assessment Committee, only if the Commission or a Member States' competent authorities make a request. Therefore, competent authorities will have to decide on a case-by-case basis whether to make public the fact that products are subject to strengthened surveillance.
Revised version (Article 40 ):
1. Member States shall take all appropriate measures to ensure that the manufacture of the medicinal products within their territory is subject to the holding of an authorization. This manufacturing authorization shall be required nothwithstanding that the medicinal products manufactured are intended for export. 2. The authorization referred to in paragraph 1 shall be required for both total and partial manufacture, and for the various processes of dividing up, packaging or presentation. However, such authorization shall not be required for preparation, dividing up, changes in packaging or presentation where these processes are carried out, solely for retail supply, by pharmacists in dispensing pharmacies or by persons legally authorized in the Member States to carry out such processes. 3. Authorization referred to in paragraph 1 shall also be required for imports coming from third countries into a Member State; this Title and Article 118 shall have corresponding application to such imports as they have to manufacture. 4. Member States shall enter the information relating to the authorisation referred to in paragraph 1 of this Article in the Union database referred to in Article 111(6).
Article 41 
In order to obtain the manufacturing authorization, the applicant shall meet at least the following requirements: (a) specify the medicinal products and pharmaceutical forms which are to be manufactured or imported and also the place where they are to be manufactured and/or controlled; (b) have at his disposal, for the manufacture or import of the above, suitable and sufficient premises, technical equipment and control facilities complying with the legal requirements which the Member State concerned lays down as regards both manufacture and control and the storage of medicinal products, in accordance with Article 20; (c) have at his disposal the services of at least one qualified person within the meaning of Article 48. The applicant shall provide particulars in support of the above in his application.
Article 42 
1. The competent authority of the Member State shall issue the manufacturing authorization only after having made sure of the accuracy of the particulars supplied pursuant to Article 41, by means of an inquiry carried out by its agents. 2. In order to ensure that the requirements referred to in Article 41 are complied with, authorization may be made conditional on the carrying out of certain obligations imposed either when authorization is granted or at a later date. 3. The authorization shall apply only to the premises specified in the application and to the medicinal products and pharmaceutical forms specified in that same application.
Article 43 
The Member States shall take all appropriate measures to ensure that the time taken for the procedure for granting the manufacturing authorization does not exceed 90 days from the day on which the competent authority receives the application.
Article 44 
If the holder of the manufacturing authorization requests a change in any of the particulars referred to in points (a) and (b) of the first paragraph of Article 41, the time taken for the procedure relating to this request shall not exceed 30 days. In exceptional cases this period of time may be extended to 90 days.
Article 45 
The competent authority of the Member State may require from the applicant further information concerning the particulars supplied pursuant to Article 41 and concerning the qualified person referred to in Article 48; where the competent authority concerned exercises this right, application of the time-limits referred to in Article 43 and 44 shall be suspended until the additional data required have been supplied.
Article 46 
The holder of a manufacturing authorization shall at least be obliged: (a) to have at his disposal the services of staff who comply with the legal requirements existing in the Member State concerned both as regards manufacture and controls; (b) to dispose of the authorized medicinal products only in accordance with the legislation of the Member States concerned; (c) to give prior notice to the competent authority of any changes he may wish to make to any of the particulars supplied pursuant to Article 41; the competent authority shall, in any event, be immediately informed if the qualified person referred to in Article 48 is replaced unexpectedly; (d) to allow the agents of the competent authority of the Member State concerned access to his premises at any time; (e) to enable the qualified person referred to in Article 48 to carry out his duties, for example by placing at his disposal all the necessary facilities; (f) to comply with the principles and guidelines of good manufacturing practice for medicinal products and to use as starting materials only active substances, which have been manufactured in accordance with the detailed guidelines on good manufacturing practice for starting materials. This point shall also be applicable to certain excipients, the list of which as well as the specific conditions of application of which shall be established by a Directive adopted by the Commission. That measure, designed to amend non-essential elements of this Directive by supplementing it, shall be adopted in accordance with the regulatory procedure with scrutiny referred to in Article 121(2a). (f) to comply with the principles and guidelines of good manufacturing practice for medicinal products and to use as starting materials only active substances, which have been manufactured in accordance with the detailed guidelines on good manufacturing practice for starting materials. This point shall also be applicable to certain excipients, the list of which as well as the specific conditions of application of which shall be established by a Directive adopted by the Commission. That measure, designed to amend non-essential elements of this Directive by supplementing it, shall be adopted in accordance with the regulatory procedure with scrutiny referred to in Article 121(2a).
Amendment rationale: CONTEXT OF THE PROPOSAL On 15 December 2010, the European Parliament and the Council adopted Directive 2010/84/EU and Regulation (EU) No 1235/2010 ("2010 pharmacovigilance legislation") amending respectively, as regards pharmacovigilance, Directive 2001/83/EC and Regulation (EC) No 726/2004. The new legislation shall apply in July 2012. The adopted measures have substantially strengthened the legal framework for the surveillance of medicinal products, with provisions that reinforce the coordinating role of the European Medicines Agency, the possibilities for signal detection, and the operation of coordinated procedures at European level to respond to safety concerns. However, recent pharmacovigilance events in the European Union, in particular the so-called “Mediator case”, have shown the need for a further improvement of the pharmacovigilance system. Following an analysis of the Mediator case in the light of the 2010 pharmacovigilance legislation ("Stress test"), the Commission has detected certain weaknesses in the pharmacovigilance system which should be addressed. In particular, Directive 2001/83/EC provides for an automatic assessment at Union level when specific serious safety issues have been identified with regard to nationally authorised products. In the 2010 pharmacovigilance legislation, changes to the Commission's proposal during co-decision have led to the automatism being lost, as the initiation of the procedure is linked to an appreciation by the Member State or the Commission as to whether an urgent action is considered necessary. Thus, when a Member State considers suspending, revoking or refusing renewal of a marketing authorisation, but does not consider that urgent action is needed, no evaluation of the safety concern will be conducted at Union level. Moreover, marketing authorisation holders are not required to declare the reasons for the withdrawal of a marketing authorisation or product. Therefore, it cannot be ruled out that voluntary withdrawal of a marketing authorisation or product by the marketing authorisation holder could lead to safety issues being missed, in particular if the company is not transparent about possible safety concerns. Finally, the public list of medicinal product subject to additional monitoring provided for in Article 23 of Regulation (EC) No 726/2004 will include certain medicinal products subject to post-authorisation safety conditions. Those products will be included in the list, following consultation with the Pharmacovigilance Risk Assessment Committee, only if the Commission or a Member States' competent authorities make a request. Therefore, competent authorities will have to decide on a case-by-case basis whether to make public the fact that products are subject to strengthened surveillance.
Revised version (Article 46 ):
The holder of a manufacturing authorization shall at least be obliged: (a) to have at his disposal the services of staff who comply with the legal requirements existing in the Member State concerned both as regards manufacture and controls; (b) to dispose of the authorized medicinal products only in accordance with the legislation of the Member States concerned; (c) to give prior notice to the competent authority of any changes he may wish to make to any of the particulars supplied pursuant to Article 41; the competent authority shall, in any event, be immediately informed if the qualified person referred to in Article 48 is replaced unexpectedly; (d) to allow the agents of the competent authority of the Member State concerned access to his premises at any time; (e) to enable the qualified person referred to in Article 48 to carry out his duties, for example by placing at his disposal all the necessary facilities; (f) to comply with the principles and guidelines of good manufacturing practice for medicinal products and to use only active substances, which have been manufactured in accordance with good manufacturing practice for active substances and distributed in accordance with good distribution practices for active substances. To this end, the holder of the manufacturing authorisation shall verify compliance by the manufacturer and distributors of active substances with good manufacturing practice and good distribution practices by conducting audits at the manufacturing and distribution sites of the manufacturer and distributors of active substances. The holder of the manufacturing authorisation shall verify such compliance either by himself or, without prejudice to his responsibility as provided for in this Directive, through an entity acting on his behalf under a contract. The holder of the manufacturing authorisation shall ensure that the excipients are suitable for use in medicinal products by ascertaining what the appropriate good manufacturing practice is. This shall be ascertained on the basis of a formalised risk assessment in accordance with the applicable guidelines referred to in the fifth paragraph of Article 47. Such risk assessment shall take into account requirements under other appropriate quality systems as well as the source and intended use of the excipients and previous instances of quality defects. The holder of the manufacturing authorisation shall ensure that the appropriate good manufacturing practice so ascertained, is applied. The holder of the manufacturing authorisation shall document the measures taken under this paragraph; (f) to comply with the principles and guidelines of good manufacturing practice for medicinal products and to use only active substances, which have been manufactured in accordance with good manufacturing practice for active substances and distributed in accordance with good distribution practices for active substances. To this end, the holder of the manufacturing authorisation shall verify compliance by the manufacturer and distributors of active substances with good manufacturing practice and good distribution practices by conducting audits at the manufacturing and distribution sites of the manufacturer and distributors of active substances. The holder of the manufacturing authorisation shall verify such compliance either by himself or, without prejudice to his responsibility as provided for in this Directive, through an entity acting on his behalf under a contract. The holder of the manufacturing authorisation shall ensure that the excipients are suitable for use in medicinal products by ascertaining what the appropriate good manufacturing practice is. This shall be ascertained on the basis of a formalised risk assessment in accordance with the applicable guidelines referred to in the fifth paragraph of Article 47. Such risk assessment shall take into account requirements under other appropriate quality systems as well as the source and intended use of the excipients and previous instances of quality defects. The holder of the manufacturing authorisation shall ensure that the appropriate good manufacturing practice so ascertained, is applied. The holder of the manufacturing authorisation shall document the measures taken under this paragraph; (g) to inform the competent authority and the marketing authorisation holder immediately if he obtains information that medicinal products which come under the scope of his manufacturing authorisation are, or are suspected of being, falsified irrespective of whether those medicinal products were distributed within the legal supply chain or by illegal means, including illegal sale by means of information society services; (h) to verify that the manufacturers, importers or distributors from whom he obtains active substances are registered with the competent authority of the Member State in which they are established; (i) to verify the authenticity and quality of the active substances and the excipients.
Article 46a 
1. For the purposes of this Directive, manufacture of active substances used as starting materials shall include both total and partial manufacture or import of an active substance used as a starting material as defined in Part I, point 3.2.1.1 (b) Annex I, and the various processes of dividing up, packaging or presentation prior to its incorporation into a medicinal product, including repackaging or re-labelling, such as are carried out by a distributor of starting materials. 2. The Commission shall be empowered to adapt paragraph 1 to take account of scientific and technical progress. That measure, 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).
Article 47 
The principles and guidelines of good manufacturing practices for medicinal products referred to in Article 46(f) shall be adopted in the form of a directive. That measure, designed to amend non-essential elements of this Directive by supplementing it, shall be adopted in accordance with the regulatory procedure with scrutiny referred to in Article 121(2a). Detailed guidelines in line with those principles will be published by the Commission and revised necessary to take account of technical and scientific progress. The principles of good manufacturing practice for active substances used as starting materials referred to in point (f) of Article 46 shall be adopted in the form of detailed guidelines. The Commission shall also publish guidelines on the form and content of the authorisation referred to in Article 40(1), on the reports referred to in Article 111(3) and on the form and content of the certificate of good manufacturing practice referred to in Article 111(5).
Amendment rationale: CONTEXT OF THE PROPOSAL On 15 December 2010, the European Parliament and the Council adopted Directive 2010/84/EU and Regulation (EU) No 1235/2010 ("2010 pharmacovigilance legislation") amending respectively, as regards pharmacovigilance, Directive 2001/83/EC and Regulation (EC) No 726/2004. The new legislation shall apply in July 2012. The adopted measures have substantially strengthened the legal framework for the surveillance of medicinal products, with provisions that reinforce the coordinating role of the European Medicines Agency, the possibilities for signal detection, and the operation of coordinated procedures at European level to respond to safety concerns. However, recent pharmacovigilance events in the European Union, in particular the so-called “Mediator case”, have shown the need for a further improvement of the pharmacovigilance system. Following an analysis of the Mediator case in the light of the 2010 pharmacovigilance legislation ("Stress test"), the Commission has detected certain weaknesses in the pharmacovigilance system which should be addressed. In particular, Directive 2001/83/EC provides for an automatic assessment at Union level when specific serious safety issues have been identified with regard to nationally authorised products. In the 2010 pharmacovigilance legislation, changes to the Commission's proposal during co-decision have led to the automatism being lost, as the initiation of the procedure is linked to an appreciation by the Member State or the Commission as to whether an urgent action is considered necessary. Thus, when a Member State considers suspending, revoking or refusing renewal of a marketing authorisation, but does not consider that urgent action is needed, no evaluation of the safety concern will be conducted at Union level. Moreover, marketing authorisation holders are not required to declare the reasons for the withdrawal of a marketing authorisation or product. Therefore, it cannot be ruled out that voluntary withdrawal of a marketing authorisation or product by the marketing authorisation holder could lead to safety issues being missed, in particular if the company is not transparent about possible safety concerns. Finally, the public list of medicinal product subject to additional monitoring provided for in Article 23 of Regulation (EC) No 726/2004 will include certain medicinal products subject to post-authorisation safety conditions. Those products will be included in the list, following consultation with the Pharmacovigilance Risk Assessment Committee, only if the Commission or a Member States' competent authorities make a request. Therefore, competent authorities will have to decide on a case-by-case basis whether to make public the fact that products are subject to strengthened surveillance.
Revised version (Article 47 ):
The principles and guidelines of good manufacturing practices for medicinal products referred to in Article 46(f) shall be adopted in the form of a directive. That measure, designed to amend non-essential elements of this Directive by supplementing it, shall be adopted in accordance with the regulatory procedure with scrutiny referred to in Article 121(2a). Detailed guidelines in line with those principles will be published by the Commission and revised necessary to take account of technical and scientific progress. The Commission shall adopt, by means of delegated acts in accordance with Article 121a and subject to the conditions laid down in Articles 121b and 121c, the principles and guidelines of good manufacturing practice for active substances referred to in the first paragraph of point (f) of Article 46 and in Article 46b. The principles of good distribution practices for active substances referred to in the first paragraph of point (f) of Article 46 shall be adopted by the Commission in the form of guidelines. The Commission shall adopt guidelines on the formalised risk assessment for ascertaining the appropriate good manufacturing practice for excipients referred to in the second paragraph of point (f) of Article 46.
Article 48 
1. Member States shall take all appropriate measures to ensure that the holder of the manufacturing authorization has permanently and continuously at his disposal the services of at least one qualified person, in accordance with the conditions laid down in Article 49, responsible in particular for carrying out the duties specified in Article 51. 2. If he personally fulfils the conditions laid down in Article 49, the holder of the authorization may himself assume the responsibility referred to in paragraph 1.
Article 49 
1. Member States shall ensure that the qualified person referred to in Article 48 fulfils the conditions of qualification set out in paragraphs 2 and 3. 2. A qualified person shall be in possession of a diploma, certificate or other evidence of formal qualifications awarded on completion of a university course of study, or a course recognized as equivalent by the Member State concerned, extending over a period of at least four years of theoretical and practical study in one of the following scientific disciplines: pharmacy, medicine, veterinary medicine, chemistry, pharmaceutical chemistry and technology, biology. However, the minimum duration of the university course may be three and a half years where the course is followed by a period of theoretical and practical training of a minimum duration of one year and including a training period of at least six months in a pharmacy open to the public, corroborated by an examination at university level. Where two university courses or two courses recognized by the State as equivalent co-exist in a Member State and where one of these extends over four years and the other over three years, the three-year course leading to a diploma, certificate or other evidence of formal qualifications awarded on completion of a university course or its recognized equivalent shall be considered to fulfil the condition of duration referred to in the second subparagraph in so far as the diplomas, certificates or other evidence of formal qualifications awarded on completion of both courses are recognized as equivalent by the State in question. The course shall include theoretical and practical study bearing upon at least the following basic subjects: — Experimental physics — General and inorganic chemistry — Organic chemistry — Analytical chemistry — Pharmaceutical chemistry, including analysis of medicinal products — General and applied biochemistry (medical) — Physiology — Microbiology — Pharmacology — Pharmaceutical technology — Toxicology — Pharmacognosy (study of the composition and effects of the natural active substances of plant and animal origin). Studies in these subjects should be so balanced as to enable the person concerned to fulfil the obligations specified in Article 51. In so far as certain diplomas, certificates or other evidence of formal qualifications mentioned in the first subparagraph do not fulfil the criteria laid down in this paragraph, the competent authority of the Member State shall ensure that the person concerned provides evidence of adequate knowledge of the subjects involved. 3. The qualified person shall have acquired practical experience over at least two years, in one or more undertakings which are authorized to manufacture medicinal products, in the activities of qualitative analysis of medicinal products, of quantitative analysis of active substances and of the testing and checking necessary to ensure the quality of medicinal products. The duration of practical experience may be reduced by one year where a university course lasts for at least five years and by a year and a half where the course lasts for at least six years.
Article 50 
1. A person engaging in the activities of the person referred to in Article 48 from the time of the application of Directive 75/319/EEC, in a Member State without complying with the provisions of Article 49 shall be eligible to continue to engage in those activities within the Community . 2. The holder of a diploma, certificate or other evidence of formal qualifications awarded on completion of a university course — or a course recognized as equivalent by the Member State concerned — in a scientific discipline allowing him to engage in the activities of the person referred to in Article 48 in accordance with the laws of that State may — if he began his course prior to 21 May 1975 — be considered as qualified to carry out in that State the duties of the person referred to in Article 48 provided that he has previously engaged in the following activities for at least two years before 21 May 1985 following notification of this directive in one or more undertakings authorized to manufacture: production supervision and/or qualitative and quantitative analysis of active substances, and the necessary testing and checking under the direct authority of the person referred to in Article 48 to ensure the quality of the medicinal products. If the person concerned has acquired the practical experience referred to in the first subparagraph before 21 May 1965, a further one year's practical experience in accordance with the conditions referred to in the first subparagraph will be required to be completed immediately before he engages in such activities.
Article 51 
1. Member States shall take all appropriate measures to ensure that the qualified person referred to in Article 48, without prejudice to his relationship with the holder of the manufacturing authorization, is responsible, in the context of the procedures referred to in Article 52, for securing: (a) in the case of medicinal products manufactured within the Member States concerned, that each batch of medicinal products has been manufactured and checked in compliance with the laws in force in that Member State and in accordance with the requirements of the marketing authorization; (b) in the case of medicinal products coming from third countries, irrespective of whether the product has been manufactured in the Community, that each production batch has undergone in a Member State a full qualitative analysis, a quantitative analysis of at least all the active substances and all the other tests or checks necessary to ensure the quality of medicinal products in accordance with the requirements of the marketing authorisation. The batches of medicinal products which have undergone such controls in a Member State shall be exempt from the controls if they are marketed in another Member State, accompanied by the control reports signed by the qualified person. 2. In the case of medicinal products imported from a third country, where appropriate arrangements have been made by the Community with the exporting country to ensure that the manufacturer of the medicinal product applies standards of good manufacturing practice at least equivalent to those laid down by the Community, and to ensure that the controls referred to under point (b) of the first subparagraph of paragraph 1 have been carried out in the exporting country, the qualified person may be relieved of responsibility for carrying out those controls. 3. In all cases and particularly where the medicinal products are released for sale, the qualified person must certify in a register or equivalent document provided for that purpose, that each production batch satisfies the provisions of this Article; the said register or equivalent document must be kept up to date as operations are carried out and must remain at the disposal of the agents of the competent authority for the period specified in the provisions of the Member State concerned and in any event for at least five years.
Amendment rationale: CONTEXT OF THE PROPOSAL On 15 December 2010, the European Parliament and the Council adopted Directive 2010/84/EU and Regulation (EU) No 1235/2010 ("2010 pharmacovigilance legislation") amending respectively, as regards pharmacovigilance, Directive 2001/83/EC and Regulation (EC) No 726/2004. The new legislation shall apply in July 2012. The adopted measures have substantially strengthened the legal framework for the surveillance of medicinal products, with provisions that reinforce the coordinating role of the European Medicines Agency, the possibilities for signal detection, and the operation of coordinated procedures at European level to respond to safety concerns. However, recent pharmacovigilance events in the European Union, in particular the so-called “Mediator case”, have shown the need for a further improvement of the pharmacovigilance system. Following an analysis of the Mediator case in the light of the 2010 pharmacovigilance legislation ("Stress test"), the Commission has detected certain weaknesses in the pharmacovigilance system which should be addressed. In particular, Directive 2001/83/EC provides for an automatic assessment at Union level when specific serious safety issues have been identified with regard to nationally authorised products. In the 2010 pharmacovigilance legislation, changes to the Commission's proposal during co-decision have led to the automatism being lost, as the initiation of the procedure is linked to an appreciation by the Member State or the Commission as to whether an urgent action is considered necessary. Thus, when a Member State considers suspending, revoking or refusing renewal of a marketing authorisation, but does not consider that urgent action is needed, no evaluation of the safety concern will be conducted at Union level. Moreover, marketing authorisation holders are not required to declare the reasons for the withdrawal of a marketing authorisation or product. Therefore, it cannot be ruled out that voluntary withdrawal of a marketing authorisation or product by the marketing authorisation holder could lead to safety issues being missed, in particular if the company is not transparent about possible safety concerns. Finally, the public list of medicinal product subject to additional monitoring provided for in Article 23 of Regulation (EC) No 726/2004 will include certain medicinal products subject to post-authorisation safety conditions. Those products will be included in the list, following consultation with the Pharmacovigilance Risk Assessment Committee, only if the Commission or a Member States' competent authorities make a request. Therefore, competent authorities will have to decide on a case-by-case basis whether to make public the fact that products are subject to strengthened surveillance.
Revised version (Article 51 ):
1. Member States shall take all appropriate measures to ensure that the qualified person referred to in Article 48, without prejudice to his relationship with the holder of the manufacturing authorization, is responsible, in the context of the procedures referred to in Article 52, for securing: (a) in the case of medicinal products manufactured within the Member States concerned, that each batch of medicinal products has been manufactured and checked in compliance with the laws in force in that Member State and in accordance with the requirements of the marketing authorization; (b) in the case of medicinal products coming from third countries, irrespective of whether the product has been manufactured in the Community, that each production batch has undergone in a Member State a full qualitative analysis, a quantitative analysis of at least all the active substances and all the other tests or checks necessary to ensure the quality of medicinal products in accordance with the requirements of the marketing authorisation. The qualified person referred to in Article 48 shall in the case of medicinal products intended to be placed on the market in the Union, ensure that the safety features referred to in point (o) of Article 54 have been affixed on the packaging. The batches of medicinal products which have undergone such controls in a Member State shall be exempt from the controls if they are marketed in another Member State, accompanied by the control reports signed by the qualified person. 2. In the case of medicinal products imported from a third country, where appropriate arrangements have been made by the Community with the exporting country to ensure that the manufacturer of the medicinal product applies standards of good manufacturing practice at least equivalent to those laid down by the Community, and to ensure that the controls referred to under point (b) of the first subparagraph of paragraph 1 have been carried out in the exporting country, the qualified person may be relieved of responsibility for carrying out those controls. 3. In all cases and particularly where the medicinal products are released for sale, the qualified person must certify in a register or equivalent document provided for that purpose, that each production batch satisfies the provisions of this Article; the said register or equivalent document must be kept up to date as operations are carried out and must remain at the disposal of the agents of the competent authority for the period specified in the provisions of the Member State concerned and in any event for at least five years.
Article 52 
Member States shall ensure that the duties of qualified persons referred to in Article 48 are fulfilled, either by means of appropriate administrative measures or by making such persons subject to a professional code of conduct. Member States may provide for the temporary suspension of such a person upon the commencement of administrative or disciplinary procedures against him for failure to fulfil his obligations.
Article 53 
The provisions of this Title shall also apply to homeopathic medicinal products.
Article 54 
The following particulars shall appear on the outer packaging of medicinal products or, where there is no outer packaging, on the immediate packaging: (a) the name of the medicinal product followed by its strength and pharmaceutical form, and, if appropriate, whether it is intended for babies, children or adults; where the product contains up to three active substances, the international non-proprietary name (INN) shall be included, or, if one does not exist, the common name; (b) a statement of the active substances expressed qualitatively and quantitatively per dosage unit or according to the form of administration for a given volume or weight, using their common names; (c) the pharmaceutical form and the contents by weight, by volume or by number of doses of the product; (d) a list of those excipients known to have a recognized action or effect and included in the detailed guidance published pursuant to Article 65. However, if the product is injectable, or a topical or eye preparation, all excipients must be stated; (e) the method of administration and, if necessary, the route of administration. Space shall be provided for the prescribed dose to be indicated; (f) a special warning that the medicinal product must be stored out of the reach and sight of children; (g) a special warning, if this is necessary for the medicinal product; (h) the expiry date in clear terms (month/year); (i) special storage precautions, if any; (j) specific precautions relating to the disposal of unused medicinal products or waste derived from medicinal products, where appropriate, as well as reference to any appropriate collection system in place; (k) the name and address of the marketing authorisation holder and, where applicable, the name of the representative appointed by the holder to represent him; (l) the number of the authorization for placing the medicinal product on the market; (m) the manufacturer's batch number; (n) in the case of non-prescription medicinal products, instructions for use.
Amendment rationale: CONTEXT OF THE PROPOSAL On 15 December 2010, the European Parliament and the Council adopted Directive 2010/84/EU and Regulation (EU) No 1235/2010 ("2010 pharmacovigilance legislation") amending respectively, as regards pharmacovigilance, Directive 2001/83/EC and Regulation (EC) No 726/2004. The new legislation shall apply in July 2012. The adopted measures have substantially strengthened the legal framework for the surveillance of medicinal products, with provisions that reinforce the coordinating role of the European Medicines Agency, the possibilities for signal detection, and the operation of coordinated procedures at European level to respond to safety concerns. However, recent pharmacovigilance events in the European Union, in particular the so-called “Mediator case”, have shown the need for a further improvement of the pharmacovigilance system. Following an analysis of the Mediator case in the light of the 2010 pharmacovigilance legislation ("Stress test"), the Commission has detected certain weaknesses in the pharmacovigilance system which should be addressed. In particular, Directive 2001/83/EC provides for an automatic assessment at Union level when specific serious safety issues have been identified with regard to nationally authorised products. In the 2010 pharmacovigilance legislation, changes to the Commission's proposal during co-decision have led to the automatism being lost, as the initiation of the procedure is linked to an appreciation by the Member State or the Commission as to whether an urgent action is considered necessary. Thus, when a Member State considers suspending, revoking or refusing renewal of a marketing authorisation, but does not consider that urgent action is needed, no evaluation of the safety concern will be conducted at Union level. Moreover, marketing authorisation holders are not required to declare the reasons for the withdrawal of a marketing authorisation or product. Therefore, it cannot be ruled out that voluntary withdrawal of a marketing authorisation or product by the marketing authorisation holder could lead to safety issues being missed, in particular if the company is not transparent about possible safety concerns. Finally, the public list of medicinal product subject to additional monitoring provided for in Article 23 of Regulation (EC) No 726/2004 will include certain medicinal products subject to post-authorisation safety conditions. Those products will be included in the list, following consultation with the Pharmacovigilance Risk Assessment Committee, only if the Commission or a Member States' competent authorities make a request. Therefore, competent authorities will have to decide on a case-by-case basis whether to make public the fact that products are subject to strengthened surveillance.
Revised version (Article 54 ):
The following particulars shall appear on the outer packaging of medicinal products or, where there is no outer packaging, on the immediate packaging: (a) the name of the medicinal product followed by its strength and pharmaceutical form, and, if appropriate, whether it is intended for babies, children or adults; where the product contains up to three active substances, the international non-proprietary name (INN) shall be included, or, if one does not exist, the common name; (b) a statement of the active substances expressed qualitatively and quantitatively per dosage unit or according to the form of administration for a given volume or weight, using their common names; (c) the pharmaceutical form and the contents by weight, by volume or by number of doses of the product; (d) a list of those excipients known to have a recognized action or effect and included in the detailed guidance published pursuant to Article 65. However, if the product is injectable, or a topical or eye preparation, all excipients must be stated; (e) the method of administration and, if necessary, the route of administration. Space shall be provided for the prescribed dose to be indicated; (f) a special warning that the medicinal product must be stored out of the reach and sight of children; (g) a special warning, if this is necessary for the medicinal product; (h) the expiry date in clear terms (month/year); (i) special storage precautions, if any; (j) specific precautions relating to the disposal of unused medicinal products or waste derived from medicinal products, where appropriate, as well as reference to any appropriate collection system in place; (k) the name and address of the marketing authorisation holder and, where applicable, the name of the representative appointed by the holder to represent him; (l) the number of the authorization for placing the medicinal product on the market; (m) the manufacturer's batch number; (n) in the case of non-prescription medicinal products, instructions for use; (o) for medicinal products other than radiopharmaceuticals referred to in Article 54a(1), safety features enabling wholesale distributors and persons authorised or entitled to supply medicinal products to the public to: — verify the authenticity of the medicinal product, and — identify individual packs, as well as a device allowing verification of whether the outer packaging has been tampered with. (o) for medicinal products other than radiopharmaceuticals referred to in Article 54a(1), safety features enabling wholesale distributors and persons authorised or entitled to supply medicinal products to the public to: — verify the authenticity of the medicinal product, and — identify individual packs, as well as a device allowing verification of whether the outer packaging has been tampered with.
Article 55 
1. The particulars laid down in Article 54 shall appear on immediate packagings other than those referred to in paragraphs 2 and 3. 2. The following particulars at least shall appear on immediate packagings which take the form of blister packs and are placed in an outer packaging that complies with the requirements laid down in Articles 54 and 62. — the name of the medicinal product as laid down in point (a) of Article 54, — the name of the holder of the authorization for placing the product on the market, — the expiry date, — the batch number. 3. The following particulars at least shall appear on small immediate packaging units on which the particulars laid down in Articles 54 and 62 cannot be displayed: — the name of the medicinal product as laid down in point (a) of Article 54 and, if necessary, the route of administration, — the method of administration, — the contents by weight, by volume or by unit.
Article 56 
The particulars referred to in Articles 54, 55 and 62 shall be easily legible, clearly comprehensible and indelible.
Article 56a 
The name of the medicinal product, as referred to in Article 54, point (a) must also be expressed in Braille format on the packaging. The marketing authorisation holder shall ensure that the package information leaflet is made available on request from patients' organisations in formats appropriate for the blind and partially-sighted.
Article 57 
Notwithstanding Article 60, Member States may require the use of certain forms of labelling of the medicinal product making it possible to ascertain: — the price of the medicinal product, — the reimbursement conditions of social security organizations, — the legal status for supply to the patient, in accordance with Title VI, — identification and authenticity. For medicinal products authorised under Regulation (EC) No 726/2004, Member States shall, when applying this Article, observe the detailed guidance referred to in Article 65 of this Directive.
Amendment rationale: CONTEXT OF THE PROPOSAL On 15 December 2010, the European Parliament and the Council adopted Directive 2010/84/EU and Regulation (EU) No 1235/2010 ("2010 pharmacovigilance legislation") amending respectively, as regards pharmacovigilance, Directive 2001/83/EC and Regulation (EC) No 726/2004. The new legislation shall apply in July 2012. The adopted measures have substantially strengthened the legal framework for the surveillance of medicinal products, with provisions that reinforce the coordinating role of the European Medicines Agency, the possibilities for signal detection, and the operation of coordinated procedures at European level to respond to safety concerns. However, recent pharmacovigilance events in the European Union, in particular the so-called “Mediator case”, have shown the need for a further improvement of the pharmacovigilance system. Following an analysis of the Mediator case in the light of the 2010 pharmacovigilance legislation ("Stress test"), the Commission has detected certain weaknesses in the pharmacovigilance system which should be addressed. In particular, Directive 2001/83/EC provides for an automatic assessment at Union level when specific serious safety issues have been identified with regard to nationally authorised products. In the 2010 pharmacovigilance legislation, changes to the Commission's proposal during co-decision have led to the automatism being lost, as the initiation of the procedure is linked to an appreciation by the Member State or the Commission as to whether an urgent action is considered necessary. Thus, when a Member State considers suspending, revoking or refusing renewal of a marketing authorisation, but does not consider that urgent action is needed, no evaluation of the safety concern will be conducted at Union level. Moreover, marketing authorisation holders are not required to declare the reasons for the withdrawal of a marketing authorisation or product. Therefore, it cannot be ruled out that voluntary withdrawal of a marketing authorisation or product by the marketing authorisation holder could lead to safety issues being missed, in particular if the company is not transparent about possible safety concerns. Finally, the public list of medicinal product subject to additional monitoring provided for in Article 23 of Regulation (EC) No 726/2004 will include certain medicinal products subject to post-authorisation safety conditions. Those products will be included in the list, following consultation with the Pharmacovigilance Risk Assessment Committee, only if the Commission or a Member States' competent authorities make a request. Therefore, competent authorities will have to decide on a case-by-case basis whether to make public the fact that products are subject to strengthened surveillance.
Revised version (Article 57 ):
Notwithstanding Article 60, Member States may require the use of certain forms of labelling of the medicinal product making it possible to ascertain: — the price of the medicinal product, — the reimbursement conditions of social security organizations, — the legal status for supply to the patient, in accordance with Title VI, — authenticity and identification in accordance with Article 54a(5). For medicinal products authorised under Regulation (EC) No 726/2004, Member States shall, when applying this Article, observe the detailed guidance referred to in Article 65 of this Directive.
Article 58 
The inclusion in the packaging of all medicinal products of a package leaflet shall be obligatory unless all the information required by Articles 59 and 62 is directly conveyed on the outer packaging or on the immediate packaging.
Article 59 
1. The package leaflet shall be drawn up in accordance with the summary of the product characteristics; it shall include, in the following order: (a) for the identification of the medicinal product: (i) the name of the medicinal product followed by its strength and pharmaceutical form, and, if appropriate, whether it is intended for babies, children or adults. The common name shall be included where the product contains only one active substance and if its name is an invented name; (ii) the pharmaco-therapeutic group or type of activity in terms easily comprehensible for the patient; (a) for the identification of the medicinal product: (i) the name of the medicinal product followed by its strength and pharmaceutical form, and, if appropriate, whether it is intended for babies, children or adults. The common name shall be included where the product contains only one active substance and if its name is an invented name; (ii) the pharmaco-therapeutic group or type of activity in terms easily comprehensible for the patient; (b) the therapeutic indications; (c) a list of information which is necessary before the medicinal product is taken: (i) contra-indications; (ii) appropriate precautions for use; (iii) forms of interaction with other medicinal products and other forms of interaction (e.g. alcohol, tobacco, foodstuffs) which may affect the action of the medicinal product; (iv) special warnings; (c) a list of information which is necessary before the medicinal product is taken: (i) contra-indications; (ii) appropriate precautions for use; (iii) forms of interaction with other medicinal products and other forms of interaction (e.g. alcohol, tobacco, foodstuffs) which may affect the action of the medicinal product; (iv) special warnings; (d) the necessary and usual instructions for proper use, and in particular: (i) the dosage, (ii) the method and, if necessary, route of administration; (iii) the frequency of administration, specifying if necessary the appropriate time at which the medicinal product may or must be administered; and, as appropriate, depending on the nature of the product: (iv) the duration of treatment, where it should be limited; (v) the action to be taken in case of an overdose (such as symptoms, emergency procedures); (vi) what to do when one or more doses have not been taken; (vii) indication, if necessary, of the risk of withdrawal effects; (viii) a specific recommendation to consult the doctor or the pharmacist, as appropriate, for any clarification on the use of the product; (d) the necessary and usual instructions for proper use, and in particular: (i) the dosage, (ii) the method and, if necessary, route of administration; (iii) the frequency of administration, specifying if necessary the appropriate time at which the medicinal product may or must be administered; and, as appropriate, depending on the nature of the product: (iv) the duration of treatment, where it should be limited; (v) the action to be taken in case of an overdose (such as symptoms, emergency procedures); (vi) what to do when one or more doses have not been taken; (vii) indication, if necessary, of the risk of withdrawal effects; (viii) a specific recommendation to consult the doctor or the pharmacist, as appropriate, for any clarification on the use of the product; (e) a description of the adverse reactions which may occur under normal use of the medicinal product and, if necessary, the action to be taken in such a case; the patient should be expressly asked to communicate any adverse reaction which is not mentioned in the package leaflet to his doctor or pharmacist; (f) a reference to the expiry date indicated on the label, with: (i) a warning against using the product after that date; (ii) where appropriate, special storage precautions; (iii) if necessary, a warning concerning certain visible signs of deterioration; (iv) the full qualitative composition (in active substances and excipients) and the quantitative composition in active substances, using common names, for each presentation of the medicinal product; (v) for each presentation of the product, the pharmaceutical form and content in weight, volume or units of dosage; (vi) the name and address of the marketing authorisation holder and, where applicable, the name of his appointed representatives in the Member States; (vii) the name and address of the manufacturer; (f) a reference to the expiry date indicated on the label, with: (i) a warning against using the product after that date; (ii) where appropriate, special storage precautions; (iii) if necessary, a warning concerning certain visible signs of deterioration; (iv) the full qualitative composition (in active substances and excipients) and the quantitative composition in active substances, using common names, for each presentation of the medicinal product; (v) for each presentation of the product, the pharmaceutical form and content in weight, volume or units of dosage; (vi) the name and address of the marketing authorisation holder and, where applicable, the name of his appointed representatives in the Member States; (vii) the name and address of the manufacturer; (g) where the medicinal product is authorised in accordance with Articles 28 to 39 under different names in the Member States concerned, a list of the names authorised in each Member State; (h) the date on which the package leaflet was last revised. 2. The list set out in point (c) of paragraph 1 shall: (a) take into account the particular condition of certain categories of users (children, pregnant or breastfeeding women, the elderly, persons with specific pathological conditions); (b) mention, if appropriate, possible effects on the ability to drive vehicles or to operate machinery; (c) list those excipients knowledge of which is important for the safe and effective use of the medicinal product and which are included in the detailed guidance published pursuant to Article 65. 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.
Amendment rationale: Context of the proposal 1.1. Grounds for and objectives of the proposal Medicinal products contribute considerably to the health of EU citizens. The discovery, development and effective use of medicinal products improve quality of life, reduce the length of time spent in hospital and save lives. Medicinal products can, however, also have adverse effects and adverse drug reactions present an important public health burden in the Community. It is estimated that 5% of all hospital admissions are due to an adverse drug reaction, 5% of all hospital patients suffer an adverse drug reaction and adverse drug reactions are the fifth most common cause of hospital death. Some adverse reactions will only be detected after a medicine has been authorised and the full safety profile of medicinal products can only be known once they have entered the market. Pharmacovigilance rules are therefore necessary for the protection of public health in order to prevent, detect and assess adverse effects of medicinal products. Community rules so far adopted have made a major contribution to the achievement of the objective that medicinal products authorised to be placed on the Community market are continuously monitored as regards their safety. However, in the light of the experience acquired and following an assessment by the Commission of the Community system of pharmacovigilance, it has become clear that new measures are necessary to improve the operation of the Community rules on the pharmacovigilance of medicinal products for human use. Therefore, the proposals aim at the strengthening and rationalizing the Community pharmacovigilance system of medicinal products for human use through the amendment of the two legal acts governing this field, with the overall objectives of better protecting public health, ensuring proper functioning of the internal market. and simplifying the current rules and procedures. The specific objectives are: - Providing for clear roles and responsibilities for the key responsible parties and clear obligations against which they perform their roles; - Rationalising EU decision-making on drug safety issues in order to deliver measures that are equally and fully implemented for all relevant products and across the Community with a view to preventing unnecessary patient exposure to risks; - Strengthening medicines safety transparency and communication to increase the understanding and trust of patients and health professionals in the safety of medicines and improve the penetration of key warnings; - Strengthening companies' pharmacovigilance systems, allowing companies to improve their systems constantly while reducing administrative burden; - Ensuring the proactive and proportionate collection of high quality data relevant to the safety of medicines through risk management and structured data collection in the form of post authorisation safety studies, together with rationalised single case and periodic reporting of suspected adverse reactions; - Involving stakeholders in pharmacovigilance including through direct patient reporting of suspected adverse reactions and inclusion of patients and heath-care professionals in decision-making. - Simplification of the current Community pharmacovigilance procedures with consequent efficiency gains for both the pharmaceutical industry and medicines regulators. 1.2. General context Pharmacovigilance is defined as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects of medicinal products. The Community has had legislation on medicinal products on pharmacovigilance since 1965. Until now there has been no systematic review of the Community pharmacovigilance legislation, its operation and its effect on protecting public health. Therefore, in 2004 the Commission services launched an independent study into the functioning of the Community pharmacovigilance system. The independent report together with a subsequent broad public consultation revealed several shortcomings. 1.3. Existing provisions in the area of the proposal Harmonised Community rules on the pharmacovigilance of medicinal products for human use are laid down in: - 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[1], as regards medicinal products authorized by the Commission in accordance with the procedure of that Regulation (the so-called "centralised procedure"); and - Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use[2], as regards general rules on medicinal products for human use and specific rules for medicinal products authorised by the Member States. While the rules are broadly the same in substance, there are certain divergences and various provisions are duplicated in the two legal texts. It is appropriate to rationalise and simplify this by laying down all general rules in the Community code on medicinal products for human use (Directive 2001/83/EC), and cross-referring to them in the regulation governing the centralised procedure (Regulation (EC) No 726/2004), with specific provisions for centrally authorised products only when justified. 1.4. Consistency with the other policies and objectives of the Union The proposals are consistent with the overall objective of the Community legislation on medicinal products for human use, which is to remove disparities between national provisions in order to ensure the proper functioning of the internal market for such products, while at the same time safeguarding a high level of protection of public and human health. They are also consistent with Article 152(1) of the Treaty establishing the European Community, which provides that a high level of human health protection shall be ensured in the definition and implementation of all Community policies and activities. The proposal is equally consistent with the Commission patient safety initiative[3] and the Commission work to stimulate innovation in the pharmaceutical sector, through the 7th Framework programme in general and the Innovative Medicines Initiative[4] in particular. The proposal is also consistent with Community projects which aim to develop and validate the use of innovative information technology tools to identify medicines adverse events.
Revised version (Article 59 ):
1. The package leaflet shall be drawn up in accordance with the summary of the product characteristics; it shall include, in the following order: (a) for the identification of the medicinal product: (i) the name of the medicinal product followed by its strength and pharmaceutical form, and, if appropriate, whether it is intended for babies, children or adults. The common name shall be included where the product contains only one active substance and if its name is an invented name; (ii) the pharmaco-therapeutic group or type of activity in terms easily comprehensible for the patient; (a) for the identification of the medicinal product: (i) the name of the medicinal product followed by its strength and pharmaceutical form, and, if appropriate, whether it is intended for babies, children or adults. The common name shall be included where the product contains only one active substance and if its name is an invented name; (ii) the pharmaco-therapeutic group or type of activity in terms easily comprehensible for the patient; (b) the therapeutic indications; (c) a list of information which is necessary before the medicinal product is taken: (i) contra-indications; (ii) appropriate precautions for use; (iii) forms of interaction with other medicinal products and other forms of interaction (e.g. alcohol, tobacco, foodstuffs) which may affect the action of the medicinal product; (iv) special warnings; (c) a list of information which is necessary before the medicinal product is taken: (i) contra-indications; (ii) appropriate precautions for use; (iii) forms of interaction with other medicinal products and other forms of interaction (e.g. alcohol, tobacco, foodstuffs) which may affect the action of the medicinal product; (iv) special warnings; (d) the necessary and usual instructions for proper use, and in particular: (i) the dosage, (ii) the method and, if necessary, route of administration; (iii) the frequency of administration, specifying if necessary the appropriate time at which the medicinal product may or must be administered; and, as appropriate, depending on the nature of the product: (iv) the duration of treatment, where it should be limited; (v) the action to be taken in case of an overdose (such as symptoms, emergency procedures); (vi) what to do when one or more doses have not been taken; (vii) indication, if necessary, of the risk of withdrawal effects; (viii) a specific recommendation to consult the doctor or the pharmacist, as appropriate, for any clarification on the use of the product; (d) the necessary and usual instructions for proper use, and in particular: (i) the dosage, (ii) the method and, if necessary, route of administration; (iii) the frequency of administration, specifying if necessary the appropriate time at which the medicinal product may or must be administered; and, as appropriate, depending on the nature of the product: (iv) the duration of treatment, where it should be limited; (v) the action to be taken in case of an overdose (such as symptoms, emergency procedures); (vi) what to do when one or more doses have not been taken; (vii) indication, if necessary, of the risk of withdrawal effects; (viii) a specific recommendation to consult the doctor or the pharmacist, as appropriate, for any clarification on the use of the product; (e) a description of the adverse reactions which may occur under normal use of the medicinal product and, if necessary, the action to be taken in such a case; (f) a reference to the expiry date indicated on the label, with: (i) a warning against using the product after that date; (ii) where appropriate, special storage precautions; (iii) if necessary, a warning concerning certain visible signs of deterioration; (iv) the full qualitative composition (in active substances and excipients) and the quantitative composition in active substances, using common names, for each presentation of the medicinal product; (v) for each presentation of the product, the pharmaceutical form and content in weight, volume or units of dosage; (vi) the name and address of the marketing authorisation holder and, where applicable, the name of his appointed representatives in the Member States; (vii) the name and address of the manufacturer; (f) a reference to the expiry date indicated on the label, with: (i) a warning against using the product after that date; (ii) where appropriate, special storage precautions; (iii) if necessary, a warning concerning certain visible signs of deterioration; (iv) the full qualitative composition (in active substances and excipients) and the quantitative composition in active substances, using common names, for each presentation of the medicinal product; (v) for each presentation of the product, the pharmaceutical form and content in weight, volume or units of dosage; (vi) the name and address of the marketing authorisation holder and, where applicable, the name of his appointed representatives in the Member States; (vii) the name and address of the manufacturer; (g) where the medicinal product is authorised in accordance with Articles 28 to 39 under different names in the Member States concerned, a list of the names authorised in each Member State; (h) the date on which the package leaflet was last revised. For medicinal products included in 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 additional monitoring’. This statement shall be preceded by the black symbol referred to in Article 23 of Regulation (EC) No 726/2004 and followed by an appropriate standardised explanatory sentence. For all medicinal products, a standardised text shall be included, expressly asking patients to communicate any suspected adverse reaction to his/her doctor, pharmacist, healthcare professional or directly to the national spontaneous reporting system referred to in Article 107a(1), and specifying the different ways of reporting available (electronic reporting, postal address and/or others) in compliance with the second subparagraph of Article 107a(1). 2. The list set out in point (c) of paragraph 1 shall: (a) take into account the particular condition of certain categories of users (children, pregnant or breastfeeding women, the elderly, persons with specific pathological conditions); (b) mention, if appropriate, possible effects on the ability to drive vehicles or to operate machinery; (c) list those excipients knowledge of which is important for the safe and effective use of the medicinal product and which are included in the detailed guidance published pursuant to Article 65. 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. 4. By 1 January 2013, the Commission shall present to the European Parliament and the Council an assessment report on current shortcomings in the summary of product characteristics and the package leaflet and how they could be improved in order to better meet the needs of patients and healthcare professionals. The Commission shall, if appropriate, and on the basis of the report, and consultation with appropriate stakeholders, present proposals in order to improve the readability, layout and content of these documents.
Article 60 
Member States may not prohibit or impede the placing on the market of medicinal products within their territory on grounds connected with labelling or the package leaflet where these comply with the requirements of this Title.
Article 61 
1. One or more mock-ups of the outer packaging and the immediate packaging of a medicinal product, together with the draft package leaflet, shall be submitted to the authorities competent for authorising marketing when the marketing authorisation is requested. The results of assessments carried out in cooperation with target patient groups shall also be provided to the competent authority. 2. The competent authority shall refuse the marketing authorization if the labelling or the package leaflet do not comply with the provisions of this Title or if they are not in accordance with the particulars listed in the summary of product characteristics. 3. All proposed changes to an aspect of the labelling or the package leaflet covered by this Title and not connected with the summary of product characteristics shall be submitted to the authorities competent for authorizing marketing. If the competent authorities have not opposed a proposed change within 90 days following the introduction of the request, the applicant may put the change into effect. 4. The fact that the competent authority do not refuse a marketing authorization pursuant to paragraph 2 or a change to the labelling or the package leaflet pursuant to paragraph 3 does not alter the general legal liability of the manufacturer and the marketing authorization holder.
Article 62 
The outer packaging and the package leaflet may include symbols or pictograms designed to clarify certain information mentioned in Articles 54 and 59(1) and other information compatible with the summary of the product characteristics which is useful to the patient , to the exclusion of any element of a promotional nature.
Article 63 
1. The particulars for labelling listed in Articles 54, 59 and 62 shall appear in the official language or languages of the Member State where the product is placed on the market. The first subparagraph shall not prevent these particulars from being indicated in several languages, provided that the same particulars appear in all the languages used. In the case of certain orphan medicinal products, the particulars listed in Article 54 may, on reasoned request, appear in only one of the official languages of the Community. 2. The package leaflet must be written and designed to be clear and understandable, enabling the users to act appropriately, when necessary with the help of health professionals. The package leaflet must be clearly legible in the official language or languages of the Member State in which the medicinal product is placed on the market. The first subparagraph shall not prevent the package leaflet from being printed in several languages, provided that the same information is given in all the languages used. 3. When the product is not intended to be delivered directly to the patient, the competent authorities may grant an exemption to the obligation that certain particulars should appear on the labelling and in the package leaflet and that the leaflet must be in the official language or languages of the Member State in which the product is placed on the market.
Amendment rationale: Context of the proposal 1.1. Grounds for and objectives of the proposal Medicinal products contribute considerably to the health of EU citizens. The discovery, development and effective use of medicinal products improve quality of life, reduce the length of time spent in hospital and save lives. Medicinal products can, however, also have adverse effects and adverse drug reactions present an important public health burden in the Community. It is estimated that 5% of all hospital admissions are due to an adverse drug reaction, 5% of all hospital patients suffer an adverse drug reaction and adverse drug reactions are the fifth most common cause of hospital death. Some adverse reactions will only be detected after a medicine has been authorised and the full safety profile of medicinal products can only be known once they have entered the market. Pharmacovigilance rules are therefore necessary for the protection of public health in order to prevent, detect and assess adverse effects of medicinal products. Community rules so far adopted have made a major contribution to the achievement of the objective that medicinal products authorised to be placed on the Community market are continuously monitored as regards their safety. However, in the light of the experience acquired and following an assessment by the Commission of the Community system of pharmacovigilance, it has become clear that new measures are necessary to improve the operation of the Community rules on the pharmacovigilance of medicinal products for human use. Therefore, the proposals aim at the strengthening and rationalizing the Community pharmacovigilance system of medicinal products for human use through the amendment of the two legal acts governing this field, with the overall objectives of better protecting public health, ensuring proper functioning of the internal market. and simplifying the current rules and procedures. The specific objectives are: - Providing for clear roles and responsibilities for the key responsible parties and clear obligations against which they perform their roles; - Rationalising EU decision-making on drug safety issues in order to deliver measures that are equally and fully implemented for all relevant products and across the Community with a view to preventing unnecessary patient exposure to risks; - Strengthening medicines safety transparency and communication to increase the understanding and trust of patients and health professionals in the safety of medicines and improve the penetration of key warnings; - Strengthening companies' pharmacovigilance systems, allowing companies to improve their systems constantly while reducing administrative burden; - Ensuring the proactive and proportionate collection of high quality data relevant to the safety of medicines through risk management and structured data collection in the form of post authorisation safety studies, together with rationalised single case and periodic reporting of suspected adverse reactions; - Involving stakeholders in pharmacovigilance including through direct patient reporting of suspected adverse reactions and inclusion of patients and heath-care professionals in decision-making. - Simplification of the current Community pharmacovigilance procedures with consequent efficiency gains for both the pharmaceutical industry and medicines regulators. 1.2. General context Pharmacovigilance is defined as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects of medicinal products. The Community has had legislation on medicinal products on pharmacovigilance since 1965. Until now there has been no systematic review of the Community pharmacovigilance legislation, its operation and its effect on protecting public health. Therefore, in 2004 the Commission services launched an independent study into the functioning of the Community pharmacovigilance system. The independent report together with a subsequent broad public consultation revealed several shortcomings. 1.3. Existing provisions in the area of the proposal Harmonised Community rules on the pharmacovigilance of medicinal products for human use are laid down in: - 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[1], as regards medicinal products authorized by the Commission in accordance with the procedure of that Regulation (the so-called "centralised procedure"); and - Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use[2], as regards general rules on medicinal products for human use and specific rules for medicinal products authorised by the Member States. While the rules are broadly the same in substance, there are certain divergences and various provisions are duplicated in the two legal texts. It is appropriate to rationalise and simplify this by laying down all general rules in the Community code on medicinal products for human use (Directive 2001/83/EC), and cross-referring to them in the regulation governing the centralised procedure (Regulation (EC) No 726/2004), with specific provisions for centrally authorised products only when justified. 1.4. Consistency with the other policies and objectives of the Union The proposals are consistent with the overall objective of the Community legislation on medicinal products for human use, which is to remove disparities between national provisions in order to ensure the proper functioning of the internal market for such products, while at the same time safeguarding a high level of protection of public and human health. They are also consistent with Article 152(1) of the Treaty establishing the European Community, which provides that a high level of human health protection shall be ensured in the definition and implementation of all Community policies and activities. The proposal is equally consistent with the Commission patient safety initiative[3] and the Commission work to stimulate innovation in the pharmaceutical sector, through the 7th Framework programme in general and the Innovative Medicines Initiative[4] in particular. The proposal is also consistent with Community projects which aim to develop and validate the use of innovative information technology tools to identify medicines adverse events.
Revised version (Article 63 ):
1. The particulars for labelling listed in Articles 54, 59 and 62 shall appear in the official language or languages of the Member State where the product is placed on the market. The first subparagraph shall not prevent these particulars from being indicated in several languages, provided that the same particulars appear in all the languages used. In the case of certain orphan medicinal products, the particulars listed in Article 54 may, on reasoned request, appear in only one of the official languages of the Community. 2. The package leaflet must be written and designed to be clear and understandable, enabling the users to act appropriately, when necessary with the help of health professionals. The package leaflet must be clearly legible in the official language or languages of the Member State in which the medicinal product is placed on the market. The first subparagraph shall not prevent the package leaflet from being printed in several languages, provided that the same information is given in all the languages used. 3. When the medicinal product is not intended to be delivered directly to the patient, or where there are severe problems in respect of the availability of the medicinal product, the competent authorities may, subject to measures they consider necessary to safeguard human health, grant an exemption to the obligation that certain particulars should appear on the labelling and in the package leaflet. They may also grant a full or partial exemption to the obligation that the labelling and the package leaflet must be in the official language or languages of the Member State in which the medicinal product is placed on the market.
Article 64 
Where the provisions of this Title are not complied with, and a notice served on the person concerned has remained without effect, the competent authorities of the Member States may suspend the marketing authorization, until the labelling and the package leaflet of the medicinal product in question have been made to comply with the requirements of this Title.
Article 65 
In consultation with the Member States and the parties concerned, the Commission shall draw up and publish detailed guidance concerning in particular: (a) the wording of certain special warnings for certain categories of medicinal products; (b) the particular information needs relating to non-prescription medicinal products; (c) the legibility of particulars on the labelling and package leaflet; (d) the methods for the identification and authentication of medicinal products; (e) the list of excipients which must feature on the labelling of medicinal products and the way in which these excipients must be indicated; (f) harmonised provisions for the implementation of Article 57.
Article 66 
1. The outer carton and the container of medicinal products containing radionuclides shall be labelled in accordance with the regulations for the safe transport of radioactive materials laid down by the International Atomic Energy Agency. Moreover, the labelling shall comply with the provisions set out in paragraphs 2 and 3. 2. The label on the shielding shall include the particulars mentioned in Article 54. In addition, the labelling on the shielding shall explain in full, the codings used on the vial and shall indicate, where necessary, for a given time and date, the amount of radioactivity per dose or per vial and the number of capsules, or, for liquids, the number of millilitres in the container. 3. The vial shall be labelled with the following information: — the name or code of the medicinal product, including the name or chemical symbol of the radionuclide, — the batch identification and expiry date, — the international symbol for radioactivity, — the name and address of the manufacturer, — the amount of radioactivity as specified in paragraph 2.
Article 67 
The competent authority shall ensure that a detailed instruction leaflet is enclosed with the packaging of radiopharmaceuticals, radionuclide generators, radionuclide kits or radionuclide precursors. The text of this leaflet shall be established in accordance with the provisions of Article 59. In addition, the leaflet shall include any precautions to be taken by the user and the patient during the preparation and administration of the medicinal product and special precautions for the disposal of the packaging and its unused contents.
Article 68 
Without prejudice to the provisions of Article 69, homeopathic medicinal products shall be labelled in accordance with the provisions of this title and shall be identified by a reference on their labels, in clear and legible form, to their homeopathic nature.
Article 69 
1. In addition to the clear mention of the words ‘homeopathic medicinal product’, the labelling and, where appropriate, the package insert for the medicinal products referred to in Article 14(1) shall bear the following, and no other, information: — the scientific name of the stock or stocks followed by the degree of dilution, making use of the symbols of the pharmacopoeia used in accordance with Article 1(5); if the homeopathic medicinal product is composed of two or more stocks, the scientific names of the stocks on the labelling may be supplemented by an invented name, — name and address of the registration holder and, where appropriate, of the manufacturer, — method of administration and, if necessary, route, — expiry date, in clear terms (month, year), — pharmaceutical form, — contents of the sales presentation, — special storage precautions, if any, — a special warning if necessary for the medicinal product, — manufacturer's batch number, — registration number, — ‘homeopathic medicinal product without approved therapeutic indications’, — a warning advising the user to consult a doctor if the symptoms persist. 2. Notwithstanding paragraph 1, Member States may require the use of certain types of labelling in order to show: — the price of the medicinal product, — the conditions for refunds by social security bodies.
Article 70 
1. When a marketing authorization is granted, the competent authorities shall specify the classification of the medicinal product into: — a medicinal product subject to medical prescription, — a medicinal product not subject to medical prescription. To this end, the criteria laid down in Article 71(1) shall apply. 2. The competent authorities may fix sub-categories for medicinal products which are available on medical prescription only. In that case, they shall refer to the following classification: (a) medicinal products on medical prescription for renewable or non-renewable delivery; (b) medicinal products subject to special medical prescription; (c) medicinal products on ‘restricted’ medical prescription, reserved for use in certain specialised areas.
Article 71 
1. Medicinal products shall be subject to medical prescription where they: — are likely to present a danger either directly or indirectly, even when used correctly, if utilized without medical supervision, or — are frequently and to a very wide extent used incorrectly, and as a result are likely to present a direct or indirect danger to human health, or — contain substances or preparations thereof, the activity and/or adverse reactions of which require further investigation, or — are normally prescribed by a doctor to be administered parenterally. 2. Where Member States provide for the sub-category of medicinal products subject to special medical prescription, they shall take account of the following factors: — the medicinal product contains, in a non-exempt quantity, a substance classified as a narcotic or a psychotropic substance within the meaning of the international conventions in force, such as the United Nations Conventions of 1961 and 1971, or — the medicinal product is likely, if incorrectly used, to present a substantial risk of medicinal abuse, to lead to addiction or be misused for illegal purposes, or — the medicinal product contains a substance which, by reason of its novelty or properties, could be considered as belonging to the group envisaged in the second indent as a precautionary measure. 3. Where Member States provide for the sub-category of medicinal products subject to restricted prescription, they shall take account of the following factors: — the medicinal product, because of its pharmaceutical characteristics or novelty or in the interests of public health, is reserved for treatments which can only be followed in a hospital environment, — the medicinal product is used in the treatment of conditions which must be diagnosed in a hospital environment or in institutions with adequate diagnostic facilities, although administration and follow-up may be carried out elsewhere, or — the medicinal product is intended for outpatients but its use may produce very serious adverse reactions requiring a prescription drawn up as required by a specialist and special supervision throughout the treatment. 4. A competent authority may waive application of paragraphs 1, 2 and 3 having regard to: (a) the maximum single dose, the maximum daily dose, the strength, the pharmaceutical form, certain types of packaging; and/or (b) other circumstances of use which it has specified. 5. If a competent authority does not designate medicinal products into sub-categories referred to in Article 70(2), it shall nevertheless take into account the criteria referred to in paragraphs 2 and 3 of this Article in determining whether any medicinal product shall be classified as a prescription-only medicine.
Article 72 
Medicinal products not subject to prescription shall be those which do not meet the criteria listed in Article 71.
Article 73 
The competent authorities shall draw up a list of the medicinal products subject, on their territory, to medical prescription, specifying, if necessary, the category of classification. They shall update this list annually.
Article 74 
When new facts are brought to their attention, the competent authorities shall examine and, as appropriate, amend the classification of a medicinal product by applying the criteria listed in Article 71.
Article 74a 
Where a change of classification of a medicinal product has been authorised on the basis of significant pre-clinical tests or clinical trials, the competent authority shall not refer to the results of those tests or trials when examining an application by another applicant for or holder of marketing authorisation for a change of classification of the same substance for one year after the initial change was authorised.
Article 75 
Each year, Member States shall communicate to the Commission and to the other Member States, the changes that have been made to the list referred to in Article 73.
Article 76 
1. thout prejudice to Article 6, Member States shall take all appropriate action to ensure that only medicinal products in respect of which a marketing authorization has been granted in accordance with Community law are distributed on their territory. 2. In the case of wholesale distribution and storage, medicinal products shall be covered by a marketing authorisation granted pursuant to Regulation (EC) No 726/2004 or by the competent authorities of a Member State in accordance with this Directive. 3. Any distributor, not being the marketing authorisation holder, who imports a product from another Member State shall notify the marketing authorisation holder and the competent authority in the Member State to which the product will be imported of his intention to import it. In the case of products which have not been granted an authorisation pursuant to Regulation (EC) No 726/2004, the notification to the competent authority shall be without prejudice to additional procedures provided for in the legislation of that Member State.
Amendment rationale: CONTEXT OF THE PROPOSAL On 15 December 2010, the European Parliament and the Council adopted Directive 2010/84/EU and Regulation (EU) No 1235/2010 ("2010 pharmacovigilance legislation") amending respectively, as regards pharmacovigilance, Directive 2001/83/EC and Regulation (EC) No 726/2004. The new legislation shall apply in July 2012. The adopted measures have substantially strengthened the legal framework for the surveillance of medicinal products, with provisions that reinforce the coordinating role of the European Medicines Agency, the possibilities for signal detection, and the operation of coordinated procedures at European level to respond to safety concerns. However, recent pharmacovigilance events in the European Union, in particular the so-called “Mediator case”, have shown the need for a further improvement of the pharmacovigilance system. Following an analysis of the Mediator case in the light of the 2010 pharmacovigilance legislation ("Stress test"), the Commission has detected certain weaknesses in the pharmacovigilance system which should be addressed. In particular, Directive 2001/83/EC provides for an automatic assessment at Union level when specific serious safety issues have been identified with regard to nationally authorised products. In the 2010 pharmacovigilance legislation, changes to the Commission's proposal during co-decision have led to the automatism being lost, as the initiation of the procedure is linked to an appreciation by the Member State or the Commission as to whether an urgent action is considered necessary. Thus, when a Member State considers suspending, revoking or refusing renewal of a marketing authorisation, but does not consider that urgent action is needed, no evaluation of the safety concern will be conducted at Union level. Moreover, marketing authorisation holders are not required to declare the reasons for the withdrawal of a marketing authorisation or product. Therefore, it cannot be ruled out that voluntary withdrawal of a marketing authorisation or product by the marketing authorisation holder could lead to safety issues being missed, in particular if the company is not transparent about possible safety concerns. Finally, the public list of medicinal product subject to additional monitoring provided for in Article 23 of Regulation (EC) No 726/2004 will include certain medicinal products subject to post-authorisation safety conditions. Those products will be included in the list, following consultation with the Pharmacovigilance Risk Assessment Committee, only if the Commission or a Member States' competent authorities make a request. Therefore, competent authorities will have to decide on a case-by-case basis whether to make public the fact that products are subject to strengthened surveillance.
Revised version (Article 76 ):
1. thout prejudice to Article 6, Member States shall take all appropriate action to ensure that only medicinal products in respect of which a marketing authorization has been granted in accordance with Community law are distributed on their territory. 2. In the case of wholesale distribution and storage, medicinal products shall be covered by a marketing authorisation granted pursuant to Regulation (EC) No 726/2004 or by the competent authorities of a Member State in accordance with this Directive. 3. Any distributor, not being the marketing authorisation holder, who imports a medicinal product from another Member State shall notify the marketing authorisation holder and the competent authority in the Member State to which the medicinal product will be imported of his intention to import that product. In the case of medicinal products which have not been granted an authorisation pursuant to Regulation (EC) No 726/2004, the notification to the competent authority shall be without prejudice to additional procedures provided for in the legislation of that Member State and to fees payable to the competent authority for examining the notification. 4. In the case of medicinal products which have been granted an authorisation pursuant to Regulation (EC) No 726/2004, the distributor shall submit the notification in accordance with paragraph 3 of this Article to the marketing authorisation holder and the Agency. A fee shall be payable to the Agency for checking that the conditions laid down in Union legislation on medicinal products and in the marketing authorisations are observed.
Article 77 
1. Member States shall take all appropriate measures to ensure that the wholesale distribution of medicinal products is subject to the possession of an authorization to engage in activity as a wholesaler in medicinal products, stating the place for which it is valid. 2. Where persons authorized or entitled to supply medicinal products to the public may also, under national law, engage in wholesale business, such persons shall be subject to the authorization provided for in paragraph 1. 3. Possession of a manufacturing authorization shall include authorization to distribute by wholesale the medicinal products covered by that authorization. Possession of an authorization to engage in activity as a wholesaler in medicinal products shall not give dispensation from the obligation to possess a manufacturing authorization and to comply with the conditions set out in that respect, even where the manufacturing or import business is secondary. 4. At the request of the Commission or any Member State, Member States shall supply all appropriate information concerning the individual authorizations which they have granted under paragraph 1. 5. Checks on the persons authorized to engage in the activity of wholesaler in medicinal products and the inspection of their premises, shall be carried out under the responsibility of the Member State which granted the authorization. 6. The Member State which granted the authorization referred to in paragraph 1 shall suspend or revoke that authorization if the conditions of authorization cease to be met. It shall forthwith inform the other Member States and the Commission thereof. 7. Should a Member State consider that, in respect of a person holding an authorization granted by another Member State under the terms of paragraph 1, the conditions of authorization are not, or are no longer met, it shall forthwith inform the Commission and the other Member State involved. The latter shall take the measures necessary and shall inform the Commission and the first Member State of the decisions taken and the reasons for those decisions.
Amendment rationale: CONTEXT OF THE PROPOSAL On 15 December 2010, the European Parliament and the Council adopted Directive 2010/84/EU and Regulation (EU) No 1235/2010 ("2010 pharmacovigilance legislation") amending respectively, as regards pharmacovigilance, Directive 2001/83/EC and Regulation (EC) No 726/2004. The new legislation shall apply in July 2012. The adopted measures have substantially strengthened the legal framework for the surveillance of medicinal products, with provisions that reinforce the coordinating role of the European Medicines Agency, the possibilities for signal detection, and the operation of coordinated procedures at European level to respond to safety concerns. However, recent pharmacovigilance events in the European Union, in particular the so-called “Mediator case”, have shown the need for a further improvement of the pharmacovigilance system. Following an analysis of the Mediator case in the light of the 2010 pharmacovigilance legislation ("Stress test"), the Commission has detected certain weaknesses in the pharmacovigilance system which should be addressed. In particular, Directive 2001/83/EC provides for an automatic assessment at Union level when specific serious safety issues have been identified with regard to nationally authorised products. In the 2010 pharmacovigilance legislation, changes to the Commission's proposal during co-decision have led to the automatism being lost, as the initiation of the procedure is linked to an appreciation by the Member State or the Commission as to whether an urgent action is considered necessary. Thus, when a Member State considers suspending, revoking or refusing renewal of a marketing authorisation, but does not consider that urgent action is needed, no evaluation of the safety concern will be conducted at Union level. Moreover, marketing authorisation holders are not required to declare the reasons for the withdrawal of a marketing authorisation or product. Therefore, it cannot be ruled out that voluntary withdrawal of a marketing authorisation or product by the marketing authorisation holder could lead to safety issues being missed, in particular if the company is not transparent about possible safety concerns. Finally, the public list of medicinal product subject to additional monitoring provided for in Article 23 of Regulation (EC) No 726/2004 will include certain medicinal products subject to post-authorisation safety conditions. Those products will be included in the list, following consultation with the Pharmacovigilance Risk Assessment Committee, only if the Commission or a Member States' competent authorities make a request. Therefore, competent authorities will have to decide on a case-by-case basis whether to make public the fact that products are subject to strengthened surveillance.
Revised version (Article 77 ):
1. Member States shall take all appropriate measures to ensure that the wholesale distribution of medicinal products is subject to the possession of an authorisation to engage in activity as a wholesaler in medicinal products, stating the premises located on their territory for which it is valid. 2. Where persons authorized or entitled to supply medicinal products to the public may also, under national law, engage in wholesale business, such persons shall be subject to the authorization provided for in paragraph 1. 3. Possession of a manufacturing authorization shall include authorization to distribute by wholesale the medicinal products covered by that authorization. Possession of an authorization to engage in activity as a wholesaler in medicinal products shall not give dispensation from the obligation to possess a manufacturing authorization and to comply with the conditions set out in that respect, even where the manufacturing or import business is secondary. 4. Member States shall enter the information relating to the authorisations referred to in paragraph 1 of this Article in the Union database referred to in Article 111(6). At the request of the Commission or any Member State, Member States shall provide all appropriate information concerning the individual authorisations which they have granted under paragraph 1 of this Article. 5. Checks on the persons authorised to engage in activity as a wholesaler in medicinal products, and the inspection of their premises, shall be carried out under the responsibility of the Member State which granted the authorisation for premises located on its territory. 6. The Member State which granted the authorization referred to in paragraph 1 shall suspend or revoke that authorization if the conditions of authorization cease to be met. It shall forthwith inform the other Member States and the Commission thereof. 7. Should a Member State consider that, in respect of a person holding an authorization granted by another Member State under the terms of paragraph 1, the conditions of authorization are not, or are no longer met, it shall forthwith inform the Commission and the other Member State involved. The latter shall take the measures necessary and shall inform the Commission and the first Member State of the decisions taken and the reasons for those decisions.
Article 78 
Member States shall ensure that the time taken for the procedure for examining the application for the distribution authorization does not exceed 90 days from the day on which the competent authority of the Member State concerned receives the application. The competent authority may, if need be, require the applicant to supply all necessary information concerning the conditions of authorization. Where the authority exercises this option, the period laid down in the first paragraph shall be suspended until the requisite additional data have been supplied.
Article 79 
In order to obtain the distribution authorization, applicants must fulfil the following minimum requirements: (a) they must have suitable and adequate premises, installations and equipment, so as to ensure proper conservation and distribution of the medicinal products; (b) they must have staff, and in particular, a qualified person designated as responsible, meeting the conditions provided for by the legislation of the Member State concerned; (c) they must undertake to fulfil the obligations incumbent on them under the terms of Article 80.
Article 80 
Holders of the distribution authorization must fulfil the following minimum requirements: (a) they must make the premises, installations and equipment referred to in Article 79(a) accessible at all times to the persons responsible for inspecting them; (b) they must obtain their supplies of medicinal products only from persons who are themselves in possession of the distribution authorization or who are exempt from obtaining such authorization under the terms of Article 77(3); (c) they must supply medicinal products only to persons who are themselves in possession of the distribution authorization or who are authorized or entitled to supply medicinal products to the public in the Member State concerned; (d) they must have an emergency plan which ensures effective implementation of any recall from the market ordered by the competent authorities or carried out in cooperation with the manufacturer or marketing authorization holder for the medicinal product concerned; (e) they must keep records either in the form of purchase/sales invoices, or on computer, or in any other form, giving for any transaction in medicinal products received or dispatched at least the following information: — date, — name of the medicinal product, — quantity received or supplied, — name and address of the supplier or consignee, as appropriate; (e) they must keep records either in the form of purchase/sales invoices, or on computer, or in any other form, giving for any transaction in medicinal products received or dispatched at least the following information: — date, — name of the medicinal product, — quantity received or supplied, — name and address of the supplier or consignee, as appropriate; (f) they must keep the records referred to under (e) available to the competent authorities, for inspection purposes, for a period of five years; (g) they must comply with the principles and guidelines of good distribution practice for medicinal products as laid down in Article 84.
Amendment rationale: CONTEXT OF THE PROPOSAL On 15 December 2010, the European Parliament and the Council adopted Directive 2010/84/EU and Regulation (EU) No 1235/2010 ("2010 pharmacovigilance legislation") amending respectively, as regards pharmacovigilance, Directive 2001/83/EC and Regulation (EC) No 726/2004. The new legislation shall apply in July 2012. The adopted measures have substantially strengthened the legal framework for the surveillance of medicinal products, with provisions that reinforce the coordinating role of the European Medicines Agency, the possibilities for signal detection, and the operation of coordinated procedures at European level to respond to safety concerns. However, recent pharmacovigilance events in the European Union, in particular the so-called “Mediator case”, have shown the need for a further improvement of the pharmacovigilance system. Following an analysis of the Mediator case in the light of the 2010 pharmacovigilance legislation ("Stress test"), the Commission has detected certain weaknesses in the pharmacovigilance system which should be addressed. In particular, Directive 2001/83/EC provides for an automatic assessment at Union level when specific serious safety issues have been identified with regard to nationally authorised products. In the 2010 pharmacovigilance legislation, changes to the Commission's proposal during co-decision have led to the automatism being lost, as the initiation of the procedure is linked to an appreciation by the Member State or the Commission as to whether an urgent action is considered necessary. Thus, when a Member State considers suspending, revoking or refusing renewal of a marketing authorisation, but does not consider that urgent action is needed, no evaluation of the safety concern will be conducted at Union level. Moreover, marketing authorisation holders are not required to declare the reasons for the withdrawal of a marketing authorisation or product. Therefore, it cannot be ruled out that voluntary withdrawal of a marketing authorisation or product by the marketing authorisation holder could lead to safety issues being missed, in particular if the company is not transparent about possible safety concerns. Finally, the public list of medicinal product subject to additional monitoring provided for in Article 23 of Regulation (EC) No 726/2004 will include certain medicinal products subject to post-authorisation safety conditions. Those products will be included in the list, following consultation with the Pharmacovigilance Risk Assessment Committee, only if the Commission or a Member States' competent authorities make a request. Therefore, competent authorities will have to decide on a case-by-case basis whether to make public the fact that products are subject to strengthened surveillance.
Revised version (Article 80 ):
Holders of the distribution authorization must fulfil the following minimum requirements: (a) they must make the premises, installations and equipment referred to in Article 79(a) accessible at all times to the persons responsible for inspecting them; (b) they must obtain their supplies of medicinal products only from persons who are themselves in possession of the distribution authorization or who are exempt from obtaining such authorization under the terms of Article 77(3); (c) they must supply medicinal products only to persons who are themselves in possession of the distribution authorization or who are authorized or entitled to supply medicinal products to the public in the Member State concerned; (ca) they must verify that the medicinal products received are not falsified by checking the safety features on the outer packaging, in accordance with the requirements laid down in the delegated acts referred to in Article 54a(2); (d) they must have an emergency plan which ensures effective implementation of any recall from the market ordered by the competent authorities or carried out in cooperation with the manufacturer or marketing authorization holder for the medicinal product concerned; (e) they must keep records either in the form of purchase/sales invoices or on computer, or in any other form, giving for any transaction in medicinal products received, dispatched or brokered at least the following information: — date, — name of the medicinal product, — quantity received, supplied or brokered, — name and address of the supplier or consignee, as appropriate, — batch number of the medicinal products at least for products bearing the safety features referred to in point (o) of Article 54; (e) they must keep records either in the form of purchase/sales invoices or on computer, or in any other form, giving for any transaction in medicinal products received, dispatched or brokered at least the following information: — date, — name of the medicinal product, — quantity received, supplied or brokered, — name and address of the supplier or consignee, as appropriate, — batch number of the medicinal products at least for products bearing the safety features referred to in point (o) of Article 54; (f) they must keep the records referred to under (e) available to the competent authorities, for inspection purposes, for a period of five years; (g) they must comply with the principles and guidelines of good distribution practice for medicinal products as laid down in Article 84; (h) they must maintain a quality system setting out responsibilities, processes and risk management measures in relation to their activities; (i) they must immediately inform the competent authority and, where applicable, the marketing authorisation holder, of medicinal products they receive or are offered which they identify as falsified or suspect to be falsified. For the purposes of point (b), where the medicinal product is obtained from another wholesale distributor, wholesale distribution authorisation holders must verify compliance with the principles and guidelines of good distribution practices by the supplying wholesale distributor. This includes verifying whether the supplying wholesale distributor holds a wholesale distribution authorisation. Where the medicinal product is obtained from the manufacturer or importer, wholesale distribution authorisation holders must verify that the manufacturer or importer holds a manufacturing authorisation. Where the medicinal product is obtained through brokering, the wholesale distribution authorisation holders must verify that the broker involved fulfils the requirements set out in this Directive.
Article 81 
With regard to the supply of medicinal products to pharmacists and persons authorised or entitled to supply medicinal products to the public, Member States shall not impose upon the holder of a distribution authorisation which has been granted by another Member State any obligation, in particular public service obligations, more stringent than those they impose on persons whom they have themselves authorised to engage in equivalent activities. The holder of a marketing authorisation for a medicinal product and the distributors of the said medicinal product actually placed on the market in a Member State shall, within the limits of their responsibilities, ensure appropriate and continued supplies of that medicinal product to pharmacies and persons authorised to supply medicinal products so that the needs of patients in the Member State in question are covered. The arrangements for implementing this Article should, moreover, be justified on grounds of public health protection and be proportionate in relation to the objective of such protection, in compliance with the Treaty rules, particularly those concerning the free movement of goods and competition.
Article 82 
For all supplies of medicinal products to a person authorized or entitled to supply medicinal products to the public in the Member State concerned, the authorized wholesaler must enclose a document that makes it possible to ascertain: — the date, — the name and pharmaceutical form of the medicinal product, — the quantity supplied, — the name and address of the supplier and consignor. Member States shall take all appropriate measures to ensure that persons authorized or entitled to supply medicinal products to the public are able to provide information that makes it possible to trace the distribution path of every medicinal product.
Amendment rationale: CONTEXT OF THE PROPOSAL On 15 December 2010, the European Parliament and the Council adopted Directive 2010/84/EU and Regulation (EU) No 1235/2010 ("2010 pharmacovigilance legislation") amending respectively, as regards pharmacovigilance, Directive 2001/83/EC and Regulation (EC) No 726/2004. The new legislation shall apply in July 2012. The adopted measures have substantially strengthened the legal framework for the surveillance of medicinal products, with provisions that reinforce the coordinating role of the European Medicines Agency, the possibilities for signal detection, and the operation of coordinated procedures at European level to respond to safety concerns. However, recent pharmacovigilance events in the European Union, in particular the so-called “Mediator case”, have shown the need for a further improvement of the pharmacovigilance system. Following an analysis of the Mediator case in the light of the 2010 pharmacovigilance legislation ("Stress test"), the Commission has detected certain weaknesses in the pharmacovigilance system which should be addressed. In particular, Directive 2001/83/EC provides for an automatic assessment at Union level when specific serious safety issues have been identified with regard to nationally authorised products. In the 2010 pharmacovigilance legislation, changes to the Commission's proposal during co-decision have led to the automatism being lost, as the initiation of the procedure is linked to an appreciation by the Member State or the Commission as to whether an urgent action is considered necessary. Thus, when a Member State considers suspending, revoking or refusing renewal of a marketing authorisation, but does not consider that urgent action is needed, no evaluation of the safety concern will be conducted at Union level. Moreover, marketing authorisation holders are not required to declare the reasons for the withdrawal of a marketing authorisation or product. Therefore, it cannot be ruled out that voluntary withdrawal of a marketing authorisation or product by the marketing authorisation holder could lead to safety issues being missed, in particular if the company is not transparent about possible safety concerns. Finally, the public list of medicinal product subject to additional monitoring provided for in Article 23 of Regulation (EC) No 726/2004 will include certain medicinal products subject to post-authorisation safety conditions. Those products will be included in the list, following consultation with the Pharmacovigilance Risk Assessment Committee, only if the Commission or a Member States' competent authorities make a request. Therefore, competent authorities will have to decide on a case-by-case basis whether to make public the fact that products are subject to strengthened surveillance.
Revised version (Article 82 ):
For all supplies of medicinal products to a person authorized or entitled to supply medicinal products to the public in the Member State concerned, the authorized wholesaler must enclose a document that makes it possible to ascertain: — the date, — the name and pharmaceutical form of the medicinal product, — the quantity supplied, — the name and address of the supplier and consignor, — batch number of the medicinal products at least for products bearing the safety features referred to in point (o) of Article 54. Member States shall take all appropriate measures to ensure that persons authorized or entitled to supply medicinal products to the public are able to provide information that makes it possible to trace the distribution path of every medicinal product.
Article 83 
The provisions of this Title shall not prevent the application of more stringent requirements laid down by Member States in respect of the wholesale distribution of: — narcotic or psychotropic substances within their territory, — medicinal products derived from blood, — immunological medicinal products, — radiopharmaceuticals.
Article 84 
The Commission shall publish guidelines on good distribution practice. To this end, it shall consult the Committee for Medicinal Products for Human Use and the Pharmaceutical Committee established by Council Decision 75/320/EEC ( 29 ).
Article 85 
This Title shall apply to homeopathic medicinal products.
Article 86 
1. For the purposes of this Title, ‘advertising of medicinal products’ shall include any form of door-to-door information, canvassing activity or inducement designed to promote the prescription, supply, sale or consumption of medicinal products; it shall include in particular: — the advertising of medicinal products to the general public, — advertising of medicinal products to persons qualified to prescribe or supply them, — visits by medical sales representatives to persons qualified to prescribe medicinal products, — the supply of samples, — the provision of inducements to prescribe or supply medicinal products by the gift, offer or promise of any benefit or bonus, whether in money or in kind, except when their intrinsic value is minimal, — sponsorship of promotional meetings attended by persons qualified to prescribe or supply medicinal products, — sponsorship of scientific congresses attended by persons qualified to prescribe or supply medicinal products and in particular payment of their travelling and accommodation expenses in connection therewith. 2. The following are not covered by this Title: — the labelling and the accompanying package leaflets, which are subject to the provisions of Title V, — correspondence, possibly accompanied by material of a non-promotional nature, needed to answer a specific question about a particular medicinal product, — factual, informative announcements and reference material relating, for example, to pack changes, adverse-reaction warnings as part of general drug precautions, trade catalogues and price lists, provided they include no product claims, — information relating to human health or diseases, provided that there is no reference, even indirect, to medicinal products.
Article 87 
1. Member States shall prohibit any advertising of a medicinal product in respect of which a marketing authorization has not been granted in accordance with Community law. 2. All parts of the advertising of a medicinal product must comply with the particulars listed in the summary of product characteristics. 3. The advertising of a medicinal product: — shall encourage the rational use of the medicinal product, by presenting it objectively and without exaggerating its properties, — shall not be misleading.
Article 88 
1. Member States shall prohibit the advertising to the general public of medicinal products which: (a) are available on medical prescription only, in accordance with Title VI; (b) contain substances defined as psychotropic or narcotic by international convention, such as the United Nations Conventions of 1961 and 1971. 2. Medicinal products may be advertised to the general public which, by virtue of their composition and purpose, are intended and designed for use without the intervention of a medical practitioner for diagnostic purposes or for the prescription or monitoring of treatment, with the advice of the pharmacist, if necessary. 3. Member States shall be entitled to ban, on their territory, advertising to the general public of medicinal products the cost of which may be reimbursed. 4. The prohibition contained in paragraph 1 shall not apply to vaccination campaigns carried out by the industry and approved by the competent authorities of the Member States. 5. The prohibition referred to in paragraph 1 shall apply without prejudice to Article 14 of Directive 89/552/EEC. 6. Member States shall prohibit the direct distribution of medicinal products to the public by the industry for promotional purposes.
Article 88a 
Within three years of the entry into force of Directive 2004/726/EC, the Commission shall, following consultations with patients' and consumers' organisations, doctors' and pharmacists' organisations, Member States and other interested parties, present to the European Parliament and the Council a report on current practice with regard to information provision — particularly on the Internet — and its risks and benefits for patients. Following analysis of the above data, the Commission shall, if appropriate, put forward proposals setting out an information strategy to ensure good-quality, objective, reliable and non-promotional information on medicinal products and other treatments and shall address the question of the information source's liability.
Article 89 
1. Without prejudice to Article 88, all advertising to the general public of a medicinal product shall: (a) be set out in such a way that it is clear that the message is an advertisement and that the product is clearly identified as a medicinal product; (b) include the following minimum information: — the name of the medicinal product, as well as the common name if the medicinal product contains only one active substance, — the information necessary for correct use of the medicinal product, — an express, legible invitation to read carefully the instructions on the package leaflet or on the outer packaging, as the case may be. (b) include the following minimum information: — the name of the medicinal product, as well as the common name if the medicinal product contains only one active substance, — the information necessary for correct use of the medicinal product, — an express, legible invitation to read carefully the instructions on the package leaflet or on the outer packaging, as the case may be. 2. Member States may decide that the advertising of a medicinal product to the general public may, notwithstanding paragraph 1, include only the name of the medicinal product or its international non-proprietary name, where this exists, or the trademark if it is intended solely as a reminder.
Article 90 
The advertising of a medicinal product to the general public shall not contain any material which: (a) gives the impression that a medical consultation or surgical operation is unnecessary, in particular by offering a diagnosis or by suggesting treatment by mail; (b) suggests that the effects of taking the medicine are guaranteed, are unaccompanied by adverse reactions or are better than, or equivalent to, those of another treatment or medicinal product; (c) suggests that the health of the subject can be enhanced by taking the medicine; (d) suggests that the health of the subject could be affected by not taking the medicine; this prohibition shall not apply to the vaccination campaigns referred to in Article 88(4); (e) is directed exclusively or principally at children; (f) refers to a recommendation by scientists, health professionals or persons who are neither of the foregoing but who, because of their celebrity, could encourage the consumption of medicinal products; (g) suggests that the medicinal product is a foodstuff, cosmetic or other consumer product; (h) suggests that the safety or efficacy of the medicinal product is due to the fact that it is natural; (i) could, by a description or detailed representation of a case history, lead to erroneous self-diagnosis; (j) refers, in improper, alarming or misleading terms, to claims of recovery; (k) uses, in improper, alarming or misleading terms, pictorial representations of changes in the human body caused by disease or injury, or of the action of a medicinal product on the human body or parts thereof.
Article 91 
1. Any advertising of a medicinal product to persons qualified to prescribe or supply such products shall include: — essential information compatible with the summary of product characteristics; — the supply classification of the medicinal product. Member States may also require such advertising to include the selling price or indicative price of the various presentations and the conditions for reimbursement by social security bodies. 2. Member States may decide that the advertising of a medicinal product to persons qualified to prescribe or supply such products may, notwithstanding paragraph 1, include only the name of the medicinal product, or its international non-proprietary name, where this exists, or the trademark, if it is intended solely as a reminder.
Article 92 
1. Any documentation relating to a medicinal product which is transmitted as part of the promotion of that product to persons qualified to prescribe or supply it shall include, as a minimum, the particulars listed in Article 91(1) and shall state the date on which it was drawn up or last revised. 2. All the information contained in the documentation referred to in paragraph 1 shall be accurate, up-to-date, verifiable and sufficiently complete to enable the recipient to form his or her own opinion of the therapeutic value of the medicinal product concerned. 3. Quotations as well as tables and other illustrative matter taken from medical journals or other scientific works for use in the documentation referred to in paragraph 1 shall be faithfully reproduced and the precise sources indicated.
Article 93 
1. Medical sales representatives shall be given adequate training by the firm which employs them and shall have sufficient scientific knowledge to be able to provide information which is precise and as complete as possible about the medicinal products which they promote. 2. During each visit, medical sales representatives shall give the persons visited, or have available for them, summaries of the product characteristics of each medicinal product they present together, if the legislation of the Member State so permits, with details of the price and conditions for reimbursement referred to in Article 91(1). 3. Medical sales representatives shall transmit to the scientific service referred to in Article 98(1) any information about the use of the medicinal products they advertise, with particular reference to any adverse reactions reported to them by the persons they visit.
Article 94 
1. Where medicinal products are being promoted to persons qualified to prescribe or supply them, no gifts, pecuniary advantages or benefits in kind may be supplied, offered or promised to such persons unless they are inexpensive and relevant to the practice of medicine or pharmacy. 2. Hospitality at sales promotion events shall always be strictly limited to their main purpose and must not be extended to persons other than health-care professionals. 3. Persons qualified to prescribe or supply medicinal products shall not solicit or accept any inducement prohibited under paragraph 1 or contrary to paragraph 2. 4. Existing measures or trade practices in Member States relating to prices, margins and discounts shall not be affected by paragraphs 1, 2 and 3.
Article 95 
The provisions of Article 94(1) shall not prevent hospitality being offered, directly or indirectly, at events for purely professional and scientific purposes; such hospitality shall always be strictly limited to the main scientific objective of the event; it must not be extended to persons other than health-care professionals.
Article 96 
1. Free samples shall be provided on an exceptional basis only to persons qualified to prescribe them and on the following conditions: (a) the number of samples for each medicinal product each year on prescription shall be limited; (b) any supply of samples shall be in response to a written request, signed and dated, from the prescribing agent; (c) those supplying samples shall maintain an adequate system of control and accountability; (d) each sample shall be no larger than the smallest presentation on the market; (e) each sample shall be marked ‘free medical sample — not for sale’ or shall show some other wording having the same meaning; (f) each sample shall be accompanied by a copy of the summary of product characteristics; (g) no samples of medicinal products containing psychotropic or narcotic substances within the meaning of international conventions, such as the United Nations Conventions of 1961 and 1971, may be supplied. 2. Member States may also place further restrictions on the distribution of samples of certain medicinal products.
Article 97 
1. Member States shall ensure that there are adequate and effective methods to monitor the advertising of medicinal products. Such methods, which may be based on a system of prior vetting, shall in any event include legal provisions under which persons or organizations regarded under national law as having a legitimate interest in prohibiting any advertisement inconsistent with this Title, may take legal action against such advertisement, or bring such advertisement before an administrative authority competent either to decide on complaints or to initiate appropriate legal proceedings. 2. Under the legal provisions referred to in paragraph 1, Member States shall confer upon the courts or administrative authorities powers enabling them, in cases where they deem such measures to be necessary, taking into account all the interests involved, and in particular the public interest: — to order the cessation of, or to institute appropriate legal proceedings for an order for the cessation of, misleading advertising, or — if misleading advertising has not yet been published but publication is imminent, to order the prohibition of, or to institute appropriate legal proceedings for an order for the prohibition of, such publication, 2. even without proof of actual loss or damage or of intention or negligence on the part of the advertiser. 3. Member States shall make provision for the measures referred to in the second subparagraph to be taken under an accelerated procedure, either with interim effect or with definitive effect. It shall be for each Member State to decide which of the two options set out in the first subparagraph to select. 4. Member States may confer upon the courts or administrative authorities powers enabling them, with a view to eliminating the continuing effects of misleading advertising the cessation of which has been ordered by a final decision: — to require publication of that decision in full or in part and in such form as they deem adequate, — to require in addition the publication of a corrective statement. 5. Paragraphs 1 to 4 shall not exclude the voluntary control of advertising of medicinal products by self-regulatory bodies and recourse to such bodies, if proceedings before such bodies are possible in addition to the judicial or administrative proceedings referred to in paragraph 1.
Article 98 
1. The marketing authorization holder shall establish, within his undertaking, a scientific service in charge of information about the medicinal products which he places on the market. 2. The marketing authorization holder shall: — keep available for, or communicate to, the authorities or bodies responsible for monitoring advertising of medicinal products, a sample of all advertisements emanating from his undertaking together with a statement indicating the persons to whom it is addressed, the method of dissemination and the date of first dissemination, — ensure that advertising of medicinal products by his undertaking conforms to the requirements of this Title, — verify that medical sales representatives employed by his undertaking have been adequately trained and fulfill the obligations imposed upon them by Article 93(2) and (3), — supply the authorities or bodies responsible for monitoring advertising of medicinal products with the information and assistance they require to carry out their responsibilities, — ensure that the decisions taken by the authorities or bodies responsible for monitoring advertising of medicinal products are immediately and fully complied with. 3. The Member States shall not prohibit the co-promotion of a medicinal product by the holder of the marketing authorisation and one or more companies nominated by him.
Article 99 
Member States shall take the appropriate measures to ensure that the provisions of this Title are applied and shall determine in particular what penalties shall be imposed should the provisions adopted in the execution of Title be infringed.
Article 100 
Advertising of the homeopathic medicinal products referred to in Article 14(1) shall be subject to the provisions of this Title with the exception of Article 87(1). However, only the information specified in Article 69(1) may be used in the advertising of such medicinal products.
Article 101 
The Member States shall take all appropriate measures to encourage doctors and other health care professionals to report suspected adverse reactions to the competent authorities. The Member States may impose specific requirements on doctors and other health-care professionals in respect of the reporting of suspected serious or unexpected adverse reactions.
Amendment rationale: Context of the proposal 1.1. Grounds for and objectives of the proposal Medicinal products contribute considerably to the health of EU citizens. The discovery, development and effective use of medicinal products improve quality of life, reduce the length of time spent in hospital and save lives. Medicinal products can, however, also have adverse effects and adverse drug reactions present an important public health burden in the Community. It is estimated that 5% of all hospital admissions are due to an adverse drug reaction, 5% of all hospital patients suffer an adverse drug reaction and adverse drug reactions are the fifth most common cause of hospital death. Some adverse reactions will only be detected after a medicine has been authorised and the full safety profile of medicinal products can only be known once they have entered the market. Pharmacovigilance rules are therefore necessary for the protection of public health in order to prevent, detect and assess adverse effects of medicinal products. Community rules so far adopted have made a major contribution to the achievement of the objective that medicinal products authorised to be placed on the Community market are continuously monitored as regards their safety. However, in the light of the experience acquired and following an assessment by the Commission of the Community system of pharmacovigilance, it has become clear that new measures are necessary to improve the operation of the Community rules on the pharmacovigilance of medicinal products for human use. Therefore, the proposals aim at the strengthening and rationalizing the Community pharmacovigilance system of medicinal products for human use through the amendment of the two legal acts governing this field, with the overall objectives of better protecting public health, ensuring proper functioning of the internal market. and simplifying the current rules and procedures. The specific objectives are: - Providing for clear roles and responsibilities for the key responsible parties and clear obligations against which they perform their roles; - Rationalising EU decision-making on drug safety issues in order to deliver measures that are equally and fully implemented for all relevant products and across the Community with a view to preventing unnecessary patient exposure to risks; - Strengthening medicines safety transparency and communication to increase the understanding and trust of patients and health professionals in the safety of medicines and improve the penetration of key warnings; - Strengthening companies' pharmacovigilance systems, allowing companies to improve their systems constantly while reducing administrative burden; - Ensuring the proactive and proportionate collection of high quality data relevant to the safety of medicines through risk management and structured data collection in the form of post authorisation safety studies, together with rationalised single case and periodic reporting of suspected adverse reactions; - Involving stakeholders in pharmacovigilance including through direct patient reporting of suspected adverse reactions and inclusion of patients and heath-care professionals in decision-making. - Simplification of the current Community pharmacovigilance procedures with consequent efficiency gains for both the pharmaceutical industry and medicines regulators. 1.2. General context Pharmacovigilance is defined as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects of medicinal products. The Community has had legislation on medicinal products on pharmacovigilance since 1965. Until now there has been no systematic review of the Community pharmacovigilance legislation, its operation and its effect on protecting public health. Therefore, in 2004 the Commission services launched an independent study into the functioning of the Community pharmacovigilance system. The independent report together with a subsequent broad public consultation revealed several shortcomings. 1.3. Existing provisions in the area of the proposal Harmonised Community rules on the pharmacovigilance of medicinal products for human use are laid down in: - 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[1], as regards medicinal products authorized by the Commission in accordance with the procedure of that Regulation (the so-called "centralised procedure"); and - Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use[2], as regards general rules on medicinal products for human use and specific rules for medicinal products authorised by the Member States. While the rules are broadly the same in substance, there are certain divergences and various provisions are duplicated in the two legal texts. It is appropriate to rationalise and simplify this by laying down all general rules in the Community code on medicinal products for human use (Directive 2001/83/EC), and cross-referring to them in the regulation governing the centralised procedure (Regulation (EC) No 726/2004), with specific provisions for centrally authorised products only when justified. 1.4. Consistency with the other policies and objectives of the Union The proposals are consistent with the overall objective of the Community legislation on medicinal products for human use, which is to remove disparities between national provisions in order to ensure the proper functioning of the internal market for such products, while at the same time safeguarding a high level of protection of public and human health. They are also consistent with Article 152(1) of the Treaty establishing the European Community, which provides that a high level of human health protection shall be ensured in the definition and implementation of all Community policies and activities. The proposal is equally consistent with the Commission patient safety initiative[3] and the Commission work to stimulate innovation in the pharmaceutical sector, through the 7th Framework programme in general and the Innovative Medicines Initiative[4] in particular. The proposal is also consistent with Community projects which aim to develop and validate the use of innovative information technology tools to identify medicines adverse events.
Article 102 
In order to ensure the adoption of appropriate and harmonised regulatory decisions concerning the medicinal products authorised within the Community, having regard to information obtained about adverse reactions to medicinal products under normal conditions of use, the Member States shall operate a pharmacovigilance system. This system shall be used to collect information useful in the surveillance of medicinal products, with particular reference to adverse reactions in human beings, and to evaluate such information scientifically. Member States shall ensure that suitable information collected within this system is communicated to the other Member States and the Agency. The information shall be recorded in the database referred to in point (l) of the second subparagraph of Article 57(1) of Regulation (EC) No 726/2004 and shall be permanently accessible to all Member States and without delay to the public. This system shall also take into account any available information on misuse and abuse of medicinal products which may have an impact on the evaluation of their benefits and risks.
Amendment rationale: Context of the proposal 1.1. Grounds for and objectives of the proposal Medicinal products contribute considerably to the health of EU citizens. The discovery, development and effective use of medicinal products improve quality of life, reduce the length of time spent in hospital and save lives. Medicinal products can, however, also have adverse effects and adverse drug reactions present an important public health burden in the Community. It is estimated that 5% of all hospital admissions are due to an adverse drug reaction, 5% of all hospital patients suffer an adverse drug reaction and adverse drug reactions are the fifth most common cause of hospital death. Some adverse reactions will only be detected after a medicine has been authorised and the full safety profile of medicinal products can only be known once they have entered the market. Pharmacovigilance rules are therefore necessary for the protection of public health in order to prevent, detect and assess adverse effects of medicinal products. Community rules so far adopted have made a major contribution to the achievement of the objective that medicinal products authorised to be placed on the Community market are continuously monitored as regards their safety. However, in the light of the experience acquired and following an assessment by the Commission of the Community system of pharmacovigilance, it has become clear that new measures are necessary to improve the operation of the Community rules on the pharmacovigilance of medicinal products for human use. Therefore, the proposals aim at the strengthening and rationalizing the Community pharmacovigilance system of medicinal products for human use through the amendment of the two legal acts governing this field, with the overall objectives of better protecting public health, ensuring proper functioning of the internal market. and simplifying the current rules and procedures. The specific objectives are: - Providing for clear roles and responsibilities for the key responsible parties and clear obligations against which they perform their roles; - Rationalising EU decision-making on drug safety issues in order to deliver measures that are equally and fully implemented for all relevant products and across the Community with a view to preventing unnecessary patient exposure to risks; - Strengthening medicines safety transparency and communication to increase the understanding and trust of patients and health professionals in the safety of medicines and improve the penetration of key warnings; - Strengthening companies' pharmacovigilance systems, allowing companies to improve their systems constantly while reducing administrative burden; - Ensuring the proactive and proportionate collection of high quality data relevant to the safety of medicines through risk management and structured data collection in the form of post authorisation safety studies, together with rationalised single case and periodic reporting of suspected adverse reactions; - Involving stakeholders in pharmacovigilance including through direct patient reporting of suspected adverse reactions and inclusion of patients and heath-care professionals in decision-making. - Simplification of the current Community pharmacovigilance procedures with consequent efficiency gains for both the pharmaceutical industry and medicines regulators. 1.2. General context Pharmacovigilance is defined as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects of medicinal products. The Community has had legislation on medicinal products on pharmacovigilance since 1965. Until now there has been no systematic review of the Community pharmacovigilance legislation, its operation and its effect on protecting public health. Therefore, in 2004 the Commission services launched an independent study into the functioning of the Community pharmacovigilance system. The independent report together with a subsequent broad public consultation revealed several shortcomings. 1.3. Existing provisions in the area of the proposal Harmonised Community rules on the pharmacovigilance of medicinal products for human use are laid down in: - 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[1], as regards medicinal products authorized by the Commission in accordance with the procedure of that Regulation (the so-called "centralised procedure"); and - Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use[2], as regards general rules on medicinal products for human use and specific rules for medicinal products authorised by the Member States. While the rules are broadly the same in substance, there are certain divergences and various provisions are duplicated in the two legal texts. It is appropriate to rationalise and simplify this by laying down all general rules in the Community code on medicinal products for human use (Directive 2001/83/EC), and cross-referring to them in the regulation governing the centralised procedure (Regulation (EC) No 726/2004), with specific provisions for centrally authorised products only when justified. 1.4. Consistency with the other policies and objectives of the Union The proposals are consistent with the overall objective of the Community legislation on medicinal products for human use, which is to remove disparities between national provisions in order to ensure the proper functioning of the internal market for such products, while at the same time safeguarding a high level of protection of public and human health. They are also consistent with Article 152(1) of the Treaty establishing the European Community, which provides that a high level of human health protection shall be ensured in the definition and implementation of all Community policies and activities. The proposal is equally consistent with the Commission patient safety initiative[3] and the Commission work to stimulate innovation in the pharmaceutical sector, through the 7th Framework programme in general and the Innovative Medicines Initiative[4] in particular. The proposal is also consistent with Community projects which aim to develop and validate the use of innovative information technology tools to identify medicines adverse events.
Article 102a 
The management of funds intended for activities connected with pharmacovigilance, the operation of communication networks and market surveillance shall be under the permanent control of the competent authorities in order to guarantee their independence.
Amendment rationale: Context of the proposal 1.1. Grounds for and objectives of the proposal Medicinal products contribute considerably to the health of EU citizens. The discovery, development and effective use of medicinal products improve quality of life, reduce the length of time spent in hospital and save lives. Medicinal products can, however, also have adverse effects and adverse drug reactions present an important public health burden in the Community. It is estimated that 5% of all hospital admissions are due to an adverse drug reaction, 5% of all hospital patients suffer an adverse drug reaction and adverse drug reactions are the fifth most common cause of hospital death. Some adverse reactions will only be detected after a medicine has been authorised and the full safety profile of medicinal products can only be known once they have entered the market. Pharmacovigilance rules are therefore necessary for the protection of public health in order to prevent, detect and assess adverse effects of medicinal products. Community rules so far adopted have made a major contribution to the achievement of the objective that medicinal products authorised to be placed on the Community market are continuously monitored as regards their safety. However, in the light of the experience acquired and following an assessment by the Commission of the Community system of pharmacovigilance, it has become clear that new measures are necessary to improve the operation of the Community rules on the pharmacovigilance of medicinal products for human use. Therefore, the proposals aim at the strengthening and rationalizing the Community pharmacovigilance system of medicinal products for human use through the amendment of the two legal acts governing this field, with the overall objectives of better protecting public health, ensuring proper functioning of the internal market. and simplifying the current rules and procedures. The specific objectives are: - Providing for clear roles and responsibilities for the key responsible parties and clear obligations against which they perform their roles; - Rationalising EU decision-making on drug safety issues in order to deliver measures that are equally and fully implemented for all relevant products and across the Community with a view to preventing unnecessary patient exposure to risks; - Strengthening medicines safety transparency and communication to increase the understanding and trust of patients and health professionals in the safety of medicines and improve the penetration of key warnings; - Strengthening companies' pharmacovigilance systems, allowing companies to improve their systems constantly while reducing administrative burden; - Ensuring the proactive and proportionate collection of high quality data relevant to the safety of medicines through risk management and structured data collection in the form of post authorisation safety studies, together with rationalised single case and periodic reporting of suspected adverse reactions; - Involving stakeholders in pharmacovigilance including through direct patient reporting of suspected adverse reactions and inclusion of patients and heath-care professionals in decision-making. - Simplification of the current Community pharmacovigilance procedures with consequent efficiency gains for both the pharmaceutical industry and medicines regulators. 1.2. General context Pharmacovigilance is defined as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects of medicinal products. The Community has had legislation on medicinal products on pharmacovigilance since 1965. Until now there has been no systematic review of the Community pharmacovigilance legislation, its operation and its effect on protecting public health. Therefore, in 2004 the Commission services launched an independent study into the functioning of the Community pharmacovigilance system. The independent report together with a subsequent broad public consultation revealed several shortcomings. 1.3. Existing provisions in the area of the proposal Harmonised Community rules on the pharmacovigilance of medicinal products for human use are laid down in: - 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[1], as regards medicinal products authorized by the Commission in accordance with the procedure of that Regulation (the so-called "centralised procedure"); and - Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use[2], as regards general rules on medicinal products for human use and specific rules for medicinal products authorised by the Member States. While the rules are broadly the same in substance, there are certain divergences and various provisions are duplicated in the two legal texts. It is appropriate to rationalise and simplify this by laying down all general rules in the Community code on medicinal products for human use (Directive 2001/83/EC), and cross-referring to them in the regulation governing the centralised procedure (Regulation (EC) No 726/2004), with specific provisions for centrally authorised products only when justified. 1.4. Consistency with the other policies and objectives of the Union The proposals are consistent with the overall objective of the Community legislation on medicinal products for human use, which is to remove disparities between national provisions in order to ensure the proper functioning of the internal market for such products, while at the same time safeguarding a high level of protection of public and human health. They are also consistent with Article 152(1) of the Treaty establishing the European Community, which provides that a high level of human health protection shall be ensured in the definition and implementation of all Community policies and activities. The proposal is equally consistent with the Commission patient safety initiative[3] and the Commission work to stimulate innovation in the pharmaceutical sector, through the 7th Framework programme in general and the Innovative Medicines Initiative[4] in particular. The proposal is also consistent with Community projects which aim to develop and validate the use of innovative information technology tools to identify medicines adverse events.
Revised version (Article 105 ):
The management of funds intended for activities connected with pharmacovigilance, the operation of communication networks and market surveillance shall be under the permanent control of the national competent authorities in order to guarantee their independence in the performance of those pharmacovigilance activities. The first paragraph shall not preclude the national competent authorities from charging fees to marketing authorisation holders for performing those activities by the national competent authorities on the condition that their independence in the performance of those pharmacovigilance activities is strictly guaranteed.
Article 103 
The marketing authorization holder shall have permanently and continuously at his disposal an appropriately qualified person responsible for pharmacovigilance. That qualified person shall reside in the Community and shall be responsible for the following: (a) the establishment and maintenance of a system which ensures that information about all suspected adverse reactions which are reported to the personnel of the company, and to medical representatives, is collected and collated in order to be accessible at least at one point within the Community; (b) the preparation for the competent authorities of the reports referred to in Article 104, in such form as may be laid down by those authorities, in accordance with the guidance referred to in Article 106(1); (c) ensuring that any request from the competent authorities for the provision of additional information necessary for the evaluation of the benefits and risks afforded by a medicinal product is answered fully and promptly, including the provision of information about the volume of sales or prescriptions of the medicinal product concerned; (d) the provision to the competent authorities, of any other information relevant to the evaluation of the benefits and risks afforded by a medicinal product, including appropriate information on post-authorization safety studies.
Amendment rationale: Context of the proposal 1.1. Grounds for and objectives of the proposal Medicinal products contribute considerably to the health of EU citizens. The discovery, development and effective use of medicinal products improve quality of life, reduce the length of time spent in hospital and save lives. Medicinal products can, however, also have adverse effects and adverse drug reactions present an important public health burden in the Community. It is estimated that 5% of all hospital admissions are due to an adverse drug reaction, 5% of all hospital patients suffer an adverse drug reaction and adverse drug reactions are the fifth most common cause of hospital death. Some adverse reactions will only be detected after a medicine has been authorised and the full safety profile of medicinal products can only be known once they have entered the market. Pharmacovigilance rules are therefore necessary for the protection of public health in order to prevent, detect and assess adverse effects of medicinal products. Community rules so far adopted have made a major contribution to the achievement of the objective that medicinal products authorised to be placed on the Community market are continuously monitored as regards their safety. However, in the light of the experience acquired and following an assessment by the Commission of the Community system of pharmacovigilance, it has become clear that new measures are necessary to improve the operation of the Community rules on the pharmacovigilance of medicinal products for human use. Therefore, the proposals aim at the strengthening and rationalizing the Community pharmacovigilance system of medicinal products for human use through the amendment of the two legal acts governing this field, with the overall objectives of better protecting public health, ensuring proper functioning of the internal market. and simplifying the current rules and procedures. The specific objectives are: - Providing for clear roles and responsibilities for the key responsible parties and clear obligations against which they perform their roles; - Rationalising EU decision-making on drug safety issues in order to deliver measures that are equally and fully implemented for all relevant products and across the Community with a view to preventing unnecessary patient exposure to risks; - Strengthening medicines safety transparency and communication to increase the understanding and trust of patients and health professionals in the safety of medicines and improve the penetration of key warnings; - Strengthening companies' pharmacovigilance systems, allowing companies to improve their systems constantly while reducing administrative burden; - Ensuring the proactive and proportionate collection of high quality data relevant to the safety of medicines through risk management and structured data collection in the form of post authorisation safety studies, together with rationalised single case and periodic reporting of suspected adverse reactions; - Involving stakeholders in pharmacovigilance including through direct patient reporting of suspected adverse reactions and inclusion of patients and heath-care professionals in decision-making. - Simplification of the current Community pharmacovigilance procedures with consequent efficiency gains for both the pharmaceutical industry and medicines regulators. 1.2. General context Pharmacovigilance is defined as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects of medicinal products. The Community has had legislation on medicinal products on pharmacovigilance since 1965. Until now there has been no systematic review of the Community pharmacovigilance legislation, its operation and its effect on protecting public health. Therefore, in 2004 the Commission services launched an independent study into the functioning of the Community pharmacovigilance system. The independent report together with a subsequent broad public consultation revealed several shortcomings. 1.3. Existing provisions in the area of the proposal Harmonised Community rules on the pharmacovigilance of medicinal products for human use are laid down in: - 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[1], as regards medicinal products authorized by the Commission in accordance with the procedure of that Regulation (the so-called "centralised procedure"); and - Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use[2], as regards general rules on medicinal products for human use and specific rules for medicinal products authorised by the Member States. While the rules are broadly the same in substance, there are certain divergences and various provisions are duplicated in the two legal texts. It is appropriate to rationalise and simplify this by laying down all general rules in the Community code on medicinal products for human use (Directive 2001/83/EC), and cross-referring to them in the regulation governing the centralised procedure (Regulation (EC) No 726/2004), with specific provisions for centrally authorised products only when justified. 1.4. Consistency with the other policies and objectives of the Union The proposals are consistent with the overall objective of the Community legislation on medicinal products for human use, which is to remove disparities between national provisions in order to ensure the proper functioning of the internal market for such products, while at the same time safeguarding a high level of protection of public and human health. They are also consistent with Article 152(1) of the Treaty establishing the European Community, which provides that a high level of human health protection shall be ensured in the definition and implementation of all Community policies and activities. The proposal is equally consistent with the Commission patient safety initiative[3] and the Commission work to stimulate innovation in the pharmaceutical sector, through the 7th Framework programme in general and the Innovative Medicines Initiative[4] in particular. The proposal is also consistent with Community projects which aim to develop and validate the use of innovative information technology tools to identify medicines adverse events.
Article 104 
1. The marketing authorisation holder shall be required to maintain detailed records of all suspected adverse reactions occurring either in the Community or in a third country. Save in exceptional circumstances, these reactions shall be communicated electronically in the form of a report in accordance with the guidelines referred to in Article 106(1). 2. The marketing authorisation holder shall be required to record all suspected serious adverse reactions which are brought to his attention by a health-care professional and to report them promptly to the competent authority of the Member State on whose territory the incident occurred, and no later than 15 days following the receipt of the information. 3. The marketing authorisation holder shall be required to record and report all other suspected serious adverse reactions which meet the notification criteria in accordance with the guidelines referred to in Article 106(1), of which he can reasonably be expected to have knowledge, promptly to the competent authority of the Member State in whose territory the incident occurred, and no later than 15 days following the receipt of the information. 4. The marketing authorisation holder shall ensure that all suspected serious unexpected adverse reactions and any suspected transmission via a medicinal product of any infectious agent occurring in the territory of a third country are reported promptly in accordance with the guidelines referred to in Article 106(1), so that the Agency and the competent authorities of the Member States in which the medicinal product is authorised are informed of them, and no later than 15 days following the receipt of the information. 5. By way of derogation from paragraphs 2, 3 and 4, in the case of medicinal products which are covered by Directive 87/22/EEC or which have qualified for the procedures laid down in Articles 28 and 29 of this Directive or which have been the subject of the procedures under Articles 32, 33 and 34 of this Directive, the marketing authorisation holder shall also ensure that all suspected serious adverse reactions occurring in the Community are reported in such a way as to be accessible to the reference Member State or to any competent authority acting as reference Member State. The reference Member State shall assume the responsibility of analysing and monitoring such adverse reactions. 6. Unless other requirements have been laid down as a condition for the granting of the marketing authorisation, or subsequently as indicated in the guidelines referred to in Article 106(1), reports of all adverse reactions shall be submitted to the competent authorities in the form of a periodic safety update report, immediately upon request or at least every six months after authorisation and until the placing on the market. Periodic safety update reports shall also be submitted immediately upon request or at least every six months during the first two years following the initial placing on the market and once a year for the following two years. Thereafter, the reports shall be submitted at three-yearly intervals, or immediately upon request. The periodic safety update reports shall include a scientific evaluation of the risk-benefit balance of the medicinal product. 7. The Commission may amend paragraph 6 in view of experience gained through its operation. That measure, 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). 8. Following the granting of a marketing authorisation, the marketing authorisation holder may request the amendment of the periods referred to in paragraph 6 in accordance with the procedure laid down by Commission Regulation (EC) No 1084/2003 ( 30 ). 9. The holder of a marketing authorisation may not communicate information relating to pharmacovigilance concerns to the general public in relation to its authorised medicinal product without giving prior or simultaneous notification to the competent authority. In any case, the marketing authorisation holder shall ensure that such information is presented objectively and is not misleading. Member States shall take the necessary measures to ensure that a marketing authorisation holder who fails to discharge these obligations is subject to effective, proportionate and dissuasive penalties.
Amendment rationale: Context of the proposal 1.1. Grounds for and objectives of the proposal Medicinal products contribute considerably to the health of EU citizens. The discovery, development and effective use of medicinal products improve quality of life, reduce the length of time spent in hospital and save lives. Medicinal products can, however, also have adverse effects and adverse drug reactions present an important public health burden in the Community. It is estimated that 5% of all hospital admissions are due to an adverse drug reaction, 5% of all hospital patients suffer an adverse drug reaction and adverse drug reactions are the fifth most common cause of hospital death. Some adverse reactions will only be detected after a medicine has been authorised and the full safety profile of medicinal products can only be known once they have entered the market. Pharmacovigilance rules are therefore necessary for the protection of public health in order to prevent, detect and assess adverse effects of medicinal products. Community rules so far adopted have made a major contribution to the achievement of the objective that medicinal products authorised to be placed on the Community market are continuously monitored as regards their safety. However, in the light of the experience acquired and following an assessment by the Commission of the Community system of pharmacovigilance, it has become clear that new measures are necessary to improve the operation of the Community rules on the pharmacovigilance of medicinal products for human use. Therefore, the proposals aim at the strengthening and rationalizing the Community pharmacovigilance system of medicinal products for human use through the amendment of the two legal acts governing this field, with the overall objectives of better protecting public health, ensuring proper functioning of the internal market. and simplifying the current rules and procedures. The specific objectives are: - Providing for clear roles and responsibilities for the key responsible parties and clear obligations against which they perform their roles; - Rationalising EU decision-making on drug safety issues in order to deliver measures that are equally and fully implemented for all relevant products and across the Community with a view to preventing unnecessary patient exposure to risks; - Strengthening medicines safety transparency and communication to increase the understanding and trust of patients and health professionals in the safety of medicines and improve the penetration of key warnings; - Strengthening companies' pharmacovigilance systems, allowing companies to improve their systems constantly while reducing administrative burden; - Ensuring the proactive and proportionate collection of high quality data relevant to the safety of medicines through risk management and structured data collection in the form of post authorisation safety studies, together with rationalised single case and periodic reporting of suspected adverse reactions; - Involving stakeholders in pharmacovigilance including through direct patient reporting of suspected adverse reactions and inclusion of patients and heath-care professionals in decision-making. - Simplification of the current Community pharmacovigilance procedures with consequent efficiency gains for both the pharmaceutical industry and medicines regulators. 1.2. General context Pharmacovigilance is defined as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects of medicinal products. The Community has had legislation on medicinal products on pharmacovigilance since 1965. Until now there has been no systematic review of the Community pharmacovigilance legislation, its operation and its effect on protecting public health. Therefore, in 2004 the Commission services launched an independent study into the functioning of the Community pharmacovigilance system. The independent report together with a subsequent broad public consultation revealed several shortcomings. 1.3. Existing provisions in the area of the proposal Harmonised Community rules on the pharmacovigilance of medicinal products for human use are laid down in: - 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[1], as regards medicinal products authorized by the Commission in accordance with the procedure of that Regulation (the so-called "centralised procedure"); and - Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use[2], as regards general rules on medicinal products for human use and specific rules for medicinal products authorised by the Member States. While the rules are broadly the same in substance, there are certain divergences and various provisions are duplicated in the two legal texts. It is appropriate to rationalise and simplify this by laying down all general rules in the Community code on medicinal products for human use (Directive 2001/83/EC), and cross-referring to them in the regulation governing the centralised procedure (Regulation (EC) No 726/2004), with specific provisions for centrally authorised products only when justified. 1.4. Consistency with the other policies and objectives of the Union The proposals are consistent with the overall objective of the Community legislation on medicinal products for human use, which is to remove disparities between national provisions in order to ensure the proper functioning of the internal market for such products, while at the same time safeguarding a high level of protection of public and human health. They are also consistent with Article 152(1) of the Treaty establishing the European Community, which provides that a high level of human health protection shall be ensured in the definition and implementation of all Community policies and activities. The proposal is equally consistent with the Commission patient safety initiative[3] and the Commission work to stimulate innovation in the pharmaceutical sector, through the 7th Framework programme in general and the Innovative Medicines Initiative[4] in particular. The proposal is also consistent with Community projects which aim to develop and validate the use of innovative information technology tools to identify medicines adverse events.
Article 105 
1. The Agency, in collaboration with the Member States and the Commission, shall set up a data-processing network to facilitate the exchange of pharmacovigilance information regarding medicinal products marketed in the Community in order to allow all competent authorities to share the information at the same time. 2. Making use of the network referred to in paragraph 1, Member States shall ensure that reports of suspected serious adverse reactions that have taken place on their territory are promptly made available to the Agency and the other Member States, and in any case within 15 days after their notification at the latest. 3. The Member States shall ensure that reports of suspected serious adverse reactions that have taken place on their territory are promptly made available to the marketing authorisation holder, and in any case within 15 days after their notification at the latest.
Amendment rationale: Context of the proposal 1.1. Grounds for and objectives of the proposal Medicinal products contribute considerably to the health of EU citizens. The discovery, development and effective use of medicinal products improve quality of life, reduce the length of time spent in hospital and save lives. Medicinal products can, however, also have adverse effects and adverse drug reactions present an important public health burden in the Community. It is estimated that 5% of all hospital admissions are due to an adverse drug reaction, 5% of all hospital patients suffer an adverse drug reaction and adverse drug reactions are the fifth most common cause of hospital death. Some adverse reactions will only be detected after a medicine has been authorised and the full safety profile of medicinal products can only be known once they have entered the market. Pharmacovigilance rules are therefore necessary for the protection of public health in order to prevent, detect and assess adverse effects of medicinal products. Community rules so far adopted have made a major contribution to the achievement of the objective that medicinal products authorised to be placed on the Community market are continuously monitored as regards their safety. However, in the light of the experience acquired and following an assessment by the Commission of the Community system of pharmacovigilance, it has become clear that new measures are necessary to improve the operation of the Community rules on the pharmacovigilance of medicinal products for human use. Therefore, the proposals aim at the strengthening and rationalizing the Community pharmacovigilance system of medicinal products for human use through the amendment of the two legal acts governing this field, with the overall objectives of better protecting public health, ensuring proper functioning of the internal market. and simplifying the current rules and procedures. The specific objectives are: - Providing for clear roles and responsibilities for the key responsible parties and clear obligations against which they perform their roles; - Rationalising EU decision-making on drug safety issues in order to deliver measures that are equally and fully implemented for all relevant products and across the Community with a view to preventing unnecessary patient exposure to risks; - Strengthening medicines safety transparency and communication to increase the understanding and trust of patients and health professionals in the safety of medicines and improve the penetration of key warnings; - Strengthening companies' pharmacovigilance systems, allowing companies to improve their systems constantly while reducing administrative burden; - Ensuring the proactive and proportionate collection of high quality data relevant to the safety of medicines through risk management and structured data collection in the form of post authorisation safety studies, together with rationalised single case and periodic reporting of suspected adverse reactions; - Involving stakeholders in pharmacovigilance including through direct patient reporting of suspected adverse reactions and inclusion of patients and heath-care professionals in decision-making. - Simplification of the current Community pharmacovigilance procedures with consequent efficiency gains for both the pharmaceutical industry and medicines regulators. 1.2. General context Pharmacovigilance is defined as the science and activities relating to the detection, assessment, understanding and prevention of adverse effects of medicinal products. The Community has had legislation on medicinal products on pharmacovigilance since 1965. Until now there has been no systematic review of the Community pharmacovigilance legislation, its operation and its effect on protecting public health. Therefore, in 2004 the Commission services launched an independent study into the functioning of the Community pharmacovigilance system. The independent report together with a subsequent broad public consultation revealed several shortcomings. 1.3. Existing provisions in the area of the proposal Harmonised Community rules on the pharmacovigilance of medicinal products for human use are laid down in: - 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[1], as regards medicinal products authorized by the Commission in accordance with the procedure of that Regulation (the so-called "centralised procedure"); and - Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community code relating to medicinal products for human use[2], as regards general rules on medicinal products for human use and specific rules for medicinal products authorised by the Member States. While the rules are broadly the same in substance, there are certain divergences and various provisions are duplicated in the two legal texts. It is appropriate to rationalise and simplify this by laying down all general rules in the Community code on medicinal products for human use (Directive 2001/83/EC), and cross-referring to them in the regulation governing the centralised procedure (Regulation (EC) No 726/2004), with specific provisions for centrally authorised products only when justified. 1.4. Consistency with the other policies and objectives of the Union The proposals are consistent with the overall objective of the Community legislation on medicinal products for human use, which is to remove disparities between national provisions in order to ensure the proper functioning of the internal market for such products, while at the same time safeguarding a high level of protection of public and human health. They are also consistent with Article 152(1) of the Treaty establishing the European Community, which provides that a high level of human health protection shall be ensured in the definition and implementation of all Community policies and activities. The proposal is equally consistent with the Commission patient safety initiative[3] and the Commission work to stimulate innovation in the pharmaceutical sector, through the 7th Framework programme in general and the Innovative Medicines Initiative[4] in particular. The proposal is also consistent with Community projects which aim to develop and validate the use of innovative information technology tools to identify medicines adverse events.