on the proposal for a directive of the European Parliament and of the Council amending Directive 2001/82/EC and Directive 2001/83/EC as regards variations to the terms of marketing authorisations for medicinal products

(COM(2008)0123 – C6‑0137/2008 – 2008/0045(COD))

(Codecision procedure: first reading)

The European Parliament,

–   having regard to the Commission proposal to the European Parliament and the Council (COM(2008)0123),

–   having regard to Articles 251(2) and 95 of the EC Treaty, pursuant to which the Commission submitted the proposal to Parliament (C6‑0137/2008),

–   having regard to Rule 51 of its Rules of Procedure,

–   having regard to the report of the Committee on the Environment, Public Health and Food Safety and the opinion of the Committee on Agriculture and Rural Development (A6‑0346/2008),

1.  Approves the Commission proposal as amended;

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

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

Amendment  1 Proposal for a directive – amending act Recital 6 Text proposed by the Commission Amendment (6) For reasons of public health, legal consistency and predictability for economic operators, variations to all types of marketing authorisations should be subject to harmonised rules. (6) For reasons of public health, legal consistency, reducing the administrative burden and strengthening predictability for economic operators, variations to all types of marketing authorisations should be subject to harmonised rules. Amendment  2 Proposal for a directive – amending act Recital 6 a (new) Text proposed by the Commission Amendment   (6a) The possibility of filing a single application for one or more identical changes to the terms of a number of marketing authorisations must be extended to all the types of change in order to simplify and optimise the procedures. Justification It is important to extend to the other categories of change this possibility of submitting a single application for one or more identical changes made to the terms of several marketing authorisations granted by the same competent authority. This system would lighten the administrative burden considerably, facilitate consideration of applications and benefit patients by the simultaneous implementation of accepted changes. Amendment  3 Proposal for a directive – amending act Recital 6 b (new) Text proposed by the Commission Amendment   (6b) It is necessary to revisit current administrative procedures as laid down in Regulation (EC) No 1084/2003 and Commission Regulation (EC) No 1085/2003of 3 June 2003 concerning the examination of variations to the terms of a marketing authorisation for medicinal products for human use and veterinary medicinal products falling within the scope of Council Regulation (EEC) No 2309/931 (Variations Regulations), with a focus, in particular, on simplifying administrative procedures.   1 OJ L 159, 27.6.2003, p.24. Amendment  4 Proposal for a directive – amending act Recital 6 c (new) Text proposed by the Commission Amendment   (6c) As regards extensions of marketing authorisations, the possibility should be left open, on the basis of arguments presented, of submitting a complete, separate application for authorisation for a medicinal product that has already been authorised under another name and with a different product characteristic summary. Justification Under the current system, Regulations (EC) No 1084/2003 (recital 8) and No 1085/2003 (recital 6) provide for the possibility, in the case of an extension of a marketing authorisation, of filing a complete, separate request for authorisation for a medicinal product that has already been authorised, but under another name and with a different product characteristic summary. It is essential that this possibility should be retained. Some names of medicines have strong associations to a certain pathology, and it could have a damaging effect on patients if the same name were kept when the pathology treated by the medicine had changed completely. Amendment  5 Proposal for a directive – amending act Article 1 – point 1 Directive 2001/82/EC Article 10 – paragraph 3   Text proposed by the Commission Amendment (1) Article 10(3) is replaced by the following: deleted “3. By way of derogation from Article 11, the Commission shall establish a list of substances essential for the treatment of equidae and for which the withdrawal period shall be not less than six months according to the control mechanisms laid down in Decisions 93/623/EEC and 2000/68/EC.   This 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 89(2a).”   Justification The amendments concerned here (6-16), which are of a purely legal nature, are intended solely to bring Directive 2001/82/EC into line with the relevant new comitology procedure (the regulatory procedure with scrutiny). They are not directly related to the subject of the proposal, that is to say, changes to marketing authorisations. They already appear, moreover, in the Commission’s ‘all-inclusive’ proposal (COM(2008)0071 – 2008/0032(COD)) and are consequently redundant in this proposal. They should therefore be deleted. Amendment  6 Proposal for a directive – amending act Article 1 – point 2 Directive 2001/82/EC Article 11 – paragraph 2 - subparagraph 3   Text proposed by the Commission Amendment (2) In Article 11(2), the third subparagraph is replaced by the following: deleted “However, the Commission may modify these specific withdrawal periods. Those measures, designed to amend non-essential elements of this Directive, shall be adopted in accordance with the regulatory procedure with scrutiny referred to in Article 89(2a).”   Amendment  7 Proposal for a directive – amending act Article 1 – point 3 Directive 2001/82/EC Article 13 – paragraph 1 - subparagraph 4   Text proposed by the Commission Amendment (3) In Article 13(1), the fourth subparagraph is replaced by the following: deleted “However, the ten-year period provided for in the second subparagraph shall be extended to 13 years in the case of veterinary medicinal products for fish or bees or other species designated 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 89(2a).”   Amendment  8 Proposal for a directive – amending act Article 1 – point 4 Directive 2001/82/EC Article 17 – paragraph 1 - subparagraph 2   Text proposed by the Commission Amendment (4) In Article 17(1), the second subparagraph is replaced by the following: deleted “If it appears justified in the light of new scientific evidence, the Commission may adapt points (b) and (c) of the first subparagraph. Those measures, designed to amend non-essential elements of this Directive, shall be adopted in accordance with the regulatory procedure with scrutiny referred to in Article 89(2a).”   Amendment  9 Proposal for a directive – amending act Article 1 – point 7 Directive 2001/82/EC Article 50a – paragraph 2   Text proposed by the Commission Amendment (7) Article 50a (2) is replaced by the following: deleted “2. The Commission shall adopt any amendments which may be necessary to adapt the provisions of Paragraph 1 to take account of scientific and technical progress.   Those measures, designed to amend non-essential elements of this directive, shall be adopted in accordance with the regulatory procedure with scrutiny referred to in Article 89(2a).”   Amendment  10 Proposal for a directive – amending act Article 1 – point 8 Directive 2001/82/EC Article 51 - paragraph 1   Text proposed by the Commission Amendment (8) In Article 51, the first subparagraph is replaced by the following: deleted “The principles and guidelines of good manufacturing practice for veterinary medicinal products referred to in Article 50(f) shall be adopted by the Commission in the form of a Directive addressed to the Member States. Those measures, 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 89(2a).”   Amendment  11 Proposal for a directive – amending act Article 1 – point 9 Directive 2001/82/EC Article 67 – point a a   Text proposed by the Commission Amendment (9) In Article 67, point (aa) is replaced by the following: deleted “(aa) veterinary medicinal products for food-producing animals.   However, Member States may grant exemptions from this requirement according to criteria established by the Commission. The establishment of those criteria, a 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 89(2a).   Member States may continue to apply national provisions until either:   – the date of application of the decision adopted in accordance with the first subparagraph; or   – 1 January 2007, if no such decision has been adopted by 31 December 2006;”   Amendment  12 Proposal for a directive – amending act Article 1 – point 10 Directive 2001/82/EC Article 68 – paragraph 3   Text proposed by the Commission Amendment (10) Article 68(3) is replaced by the following: deleted “3. The Commission shall adopt any amendments to the list of substances referred to in paragraph 1.   Those measures, designed to amend non-essential elements of this Directive, shall be adopted in accordance with the regulatory procedure with scrutiny referred to in Article 89(2a).”   Amendment  13 Proposal for a directive – amending act Article 1 – point 11 Directive 2001/82/EC Article 75 – paragraph 6   Text proposed by the Commission Amendment (11) Article 75(6) is replaced by the following: deleted “6. The Commission may amend paragraph 5 in the light of the experience gained from its operation.   Those measures, designed to amend non-essential elements of this Directive, shall be adopted in accordance with the regulatory procedure with scrutiny referred to in Article 89(2a).”   Amendment  14 Proposal for a directive – amending act Article 1 – point 12 Directive 2001/82/EC Article 79   Text proposed by the Commission Amendment (12) Article 79 is replaced by the following: deleted “Article 79   The Commission shall adopt any amendments which may be necessary to update Articles 72 to 78 to take account of scientific and technical progress.   Those measures, designed to amend non-essential elements of this Directive, shall be adopted in accordance with the regulatory procedure with scrutiny referred to in Article 89(2a).”   Amendment  15 Proposal for a directive – amending act Article 1 – point 13 Directive 2001/82/EC Article 88   Text proposed by the Commission Amendment (13) Article 88 is replaced by the following: deleted “Article 88   The Commission shall adopt any changes which are necessary in order to adapt Annex I to take account of technical progress   Those measures, designed to amend non-essential elements of this Directive, shall be adopted in accordance with the regulatory procedure with scrutiny referred to in Article 89(2a).”   Amendment  16 Proposal for a directive – amending act Article 1 – point 14 Regulation 2001/82/EC Article 89   Text proposed by the Commission Amendment (14) Article 89 is amended as follows: deleted (a) The following paragraph 2a is inserted:   “2a. Where reference is made to this paragraph, Article 5a (1) to (4) and Article 7 of Decision No 1999/468/EC shall apply, having regard to the provisions of Article 8 thereof”.   (b) Paragraph 4 is replaced by the following:   “4. The rules of procedure of the Standing Committee shall be made public.”   Amendment  17 Proposal for a directive – amending act Article 2 – point 1 Regulation 2001/83/EC Article 23 b - paragraph 2 a and 2 b (new)   Text proposed by the Commission Amendment   Member States may continue to apply national provisions on variations applicable at the time of entry into force of this implementing regulation to marketing authorisations granted before 1 January 1998 to medicinal products authorised only in that Member State. Where a medicinal product subject to national provisions in accordance with this Article is subsequently granted a marketing authorisation in another Member State, the implementing regulation shall apply to that medicinal product from that date.   Where a Member State decides to continue to apply national provisions pursuant to the previous paragraph, it shall notify the Commission thereof. If a notification has not been made by [date of transposition of amending directive], the implementing regulation shall apply. Amendment  18 Proposal for a directive – amending act Article 2 – point 1 a (new) Directive 2001/83/EC Article 23 c (new)   Text proposed by the Commission Amendment   (1a) The following Article 23c shall be inserted:   “Article 23 c   The appropriate arrangements adopted by the Commission in accordance with Article 23b must take the following considerations into account:   - for practical reasons of efficiency, the possibility should be extended to all the categories of change of submitting a single application for one or more identical changes made to the terms of a number of marketing authorisations;   - as regards extensions of marketing authorisations, the possibility should be provided, on the basis of arguments in justification, of submitting a complete, separate application for authorisation for a medicinal product that has already been authorised under another name and with a different product characteristic summary.” Justification 1er- Il parait important d’étendre aux autres catégories de modifications cette possibilité de soumission d’une demande unique. 2e : Le système actuel prévoit la possibilité pour une extension de l’AMM, de présenter une demande d’autorisation complète et distincte pour un médicament qui a déjà été autorisé, mais sous une autre dénomination et avec un résumé des caractéristiques du produit différent. Il est essentiel de conserver cette possibilité. Certains noms de médicaments sont associés à une pathologie et être obligé de conserver le même nom pour une pathologie différente pourrait avoir un effet dommageable pour le patient. Amendment  19 Proposal for a directive – amending act Article 3 – paragraph 1 – subparagraph 1 Text proposed by the Commission Amendment 1. Member States shall bring into force the laws, regulations and administrative provisions necessary to comply with this Directive by [12 months after entry into force] at the latest. They shall forthwith communicate to the Commission the text of those provisions and a correlation table between those provisions and this Directive. 1. Member States shall bring into force the laws, regulations and administrative provisions necessary to comply with this Directive by [18 months after entry into force] at the latest. They shall forthwith communicate to the Commission the text of those provisions and a table showing the correlation between those provisions and this Directive. Justification The transitional period of 12 months is too short in the light of the considerable changes for many national marketing authorisations. It is therefore appropriate to extend this period to 24 months.

(1)    Context

A number of aspects of a medicine may change during its life cycle. Technological progress, as well as new scientific data, offer the possibility of improving existing medicinal products. These changes can relate, for example, to the manufacturing process, purification methods or the introduction of a new therapeutic indication, not to mention updating of patient information leaflets to incorporate new safety information based on reported side-effects. In addition, consolidation of the pharmaceutical industry via mergers and acquisitions gives rise to many administrative changes, such as changes to the names or addresses of pharmaceutical companies. All of these changes are known as ‘variations’ and must be reported to the competent authorities by the holders of authorisations to market medicinal products.

The pharmaceutical industry devotes a large part of its regulatory work to managing these variations. By way of example, in the case of a medium-sized company producing generic medicines and carrying a list of 400 products (including different pharmaceutical presentations and dosages), the total number of variations submitted would exceed 4 000 per year. In the case of a large company, the number would be about 19 000.

(2)    Weakness of the current system of regulatory requirements relating to changes in marketing authorisations for medicinal products

The current way of managing variations is proving increasingly inefficient and is no longer satisfactory either for the authorities or for the pharmaceutical industry as a whole.

Given that 80% of all human and veterinary medicinal products are authorised via national procedures, this revision will have a considerable impact on the pharmaceuticals market in the European Union.

The granting of purely national marketing authorisations is subject to the same regulatory requirements as marketing authorisations granted under European procedures. The regulatory requirements for changing marketing authorisations, on the other hand, are not harmonised.

Changes to purely national marketing authorisations take place in accordance with provisions specific to each Member State, which are different from the European regulatory requirements.

Any one change to products authorised under national procedures in different Member States is therefore treated in a number of different ways in terms of the dossier to be submitted and the evaluation procedure.

This situation has some undesirable repercussions:

– an unjustified additional administrative burden for the competent authorities and pharmaceutical businesses;

– logistical issues for the actual implementation of changes;

– widely differing deadlines for introducing changes to the summary of characteristics of the product and the information leaflet for healthcare personnel and patients, with a knock-on effect on the overall working of the single market in pharmaceutical products;

– for patients, since the introduction of some changes that improve the effectiveness of a medicine may be delayed or never happen at all.

(3)    Planned improvements

The rapporteur actively supports the Commission’s proposal designed to revise and simplify the variations system for the benefit of human and animal health. It must be made possible for all medicinal products, whatever procedure was applied in authorising their marketing, to be subject to the same evaluation, approval and administrative-processing criteria in the event of changes being made to them.

An optimisation of the system will, inter alia, be of long-term benefit to patients, in that it will encourage improvement of medicines and have a favourable impact on the use of the competent authorities’ resources with a consequent improvement in public health protection.

Simplifying the process of changing the terms of marketing authorisations for medicinal products will mean they are subject to the same criteria with regard to the authorisation, administrative management and supervision of the changes made, whatever the legal procedure whereby the medicinal products were licensed may have been.

For reasons of harmonisation and simplification, therefore, it is important that changes to marketing authorisations should be governed by the same regulatory requirements, whatever licensing procedure was initially used. This will bring benefits for all concerned: patients, authorities and pharmaceutical companies.

Over and above this harmonisation of all medicinal products, it is also desirable to simplify the regulatory system for handling changes to marketing authorisations, particularly in the case of minor changes whose effects on the quality, safety and effectiveness of the medicine concerned are minimal or non-existent. The Commission Regulation concerning the examination of variations to the terms of marketing authorisations for medicinal products for human use and veterinary medicinal products adopted unanimously on 10 June 2008 significantly simplifies the system.

In order to put in place an optimal regulatory system for managing changes to marketing authorisations, it is important to define precisely the different categories of change. The Commission provides for detailed lists to be drawn up for each category of change. It is important to capitalise on the experience acquired by the existing national systems. In the case of changes relating to medicinal products licensed under national procedures, some Member States have already applied a simple notification system to a large number of changes that they regard as minor, following Germany’s example. These national lists of different types of change have been used as a basis for drawing up the European lists.

The Commission proposes a number of significant improvements to the regulatory system for managing changes to marketing authorisations, also following the German example closely in the regulation. For reasons of proportionality, homeopathic medicines and traditional herbal medicines which have not received a marketing authorisation, but are subject to a simplified registration procedure, continue to be excluded from the regulation’s scope. The rapporteur welcomes this, because it avoids complicating a registration procedure which was simpler in some Member States.

Nonetheless, an additional improvement could be made to the system proposed in cases where a change relates to a number of marketing authorisations, with the possibility of a single submission covering all the marketing authorisations.

In its regulation, the Commission proposes restricting this possibility to minor Type-IA changes. However, in order to obtain the full benefit of such a measure (lighter administrative burden and greater ease in considering and simultaneously applying the change to all the products concerned), it is important that this possibility should be extended to the other categories of change: minor Type‑IB changes and major Type-II changes.

This is only proposed by the Commission in the context of the worksharing procedure described in Article 20. Where the marketing authorisations concerned were granted under a national procedure by the same Member State, there is no justification for using this worksharing procedure, which should be reserved for changes relating to marketing authorisations granted by different Member States or under different initial registration procedures. It is only in this context that there is a benefit in terms of dealing with the plethora of evaluations by different competent authorities of the same change or group of changes.

As regards extensions of marketing authorisations, the Commission proposes that the medicinal product should retain the same name as in the initial marketing authorisation (Article 19).

Under the current system, Regulations (EC) No 1084/2003 (recital 8) and No 1085/2003 (recital 6) provide for the possibility, in the case of an extension of a marketing authorisation, of filing a complete, separate request for authorisation of a medicinal product that has already been authorised, but under another name and with a different product characteristic summary.

It is essential that this possibility available under the present system should be retained. In some cases it can be important to register an extension of a marketing authorisation under a different name where it concerns an indication different from that initially registered in the original marketing authorisation. Some medicine names have strong associations to a certain pathology, and it could have a damaging effect on patients if the same name were kept when the pathology treated by the medicine had changed completely.

SHORT JUSTIFICATION

The draftswoman is in favour of the Commission proposal and wishes to see harmonisation of medicinal products take effect also as regards the marketing of medicinal products for human and veterinary use.

So far, only a small proportion of the medicinal products are subject to harmonized European legislation (around 20 %, i.e. those products that had received their authorisation in accordance with two accepted procedures, "centralised" and "mutual recognition"). Those products that have a purely national authorisation are not regulated by the current European legislation on variations and subsequently are dealt with through specific and varying national rules. This is both inefficient and lead to significant economic costs, in addition to affecting the proper functioning of the internal market. The present directive would grant legal basis for harmonisation and would permit for the adoption of implementing measures through comitology with regards to all types of variations.

The rapporteur is in favour of harmonisation, which will bring great benefits to both consumers and industry and would speed up the access to the latest medicines across the Member States. So far, the lack of harmonisation with regards to variations has caused great delays and inefficiency, from both an economic point of view and also as regards the needs of the veterinary medicinal sector. It is also illogical to have harmonisation for every stage in the lifecycle of a product except when it comes to changes brought to it.

Nevertheless, there is a need to be careful about the implied costs for the Member States and a proper schedule for achieving harmonisation in practice. Member States cannot be called on to change their internal regulations in order to comply with the present directive and further changes adopted through comitology in a period of time that is too short and that implies too high costs.

In accordance with the Impact Assessment conducted, the public consultation and the position papers submitted by regulatory agencies of the Member States, proposals by the draftswoman focus on several points.

Firstly, we need to achieve a schedule for harmonisation that corresponds to variations in preparedness between Member States. In the papers submitted, there have been different calls for different schedules and it is apparent that a 2-year period for transposition is preferred by a significant number of Member States. We need to take these into account as it is essential to the real implementation of harmonisation into practice.

Secondly, we need to further stress the need for Parliament supervision of legislation adopted under comitology. We need to be able to supervise the legislative process through the regulatory procedure with scrutiny.

Thirdly, the draftswoman believes Parliament should call for the simplification of the Variations Regulations. This issue was raised by several participants in the public consultation and we need to ensure that the Variations Regulations we have in place at the moment do not create unnecessary bureaucracy for the Member States, companies and the citizens.

AMENDMENTS

The Committee on Agriculture and Rural Development calls on the Committee on the Environment, Public Health and Food Safety, as the committee responsible, to incorporate the following amendments in its report:

Amendment  1 Proposal for a directive – amending act Recital 6 Text proposed by the Commission Amendment (6) For reasons of public health, legal consistency and predictability for economic operators, variations to all types of marketing authorisations should be subject to harmonised rules. (6) For reasons of public health, legal consistency, reducing the administrative burden and strengthening predictability for economic operators, variations to all types of marketing authorisations should be subject to harmonised rules. Amendment  2 Proposal for a directive – amending act Recital 6 a (new) Text proposed by the Commission Amendment   (6a) It is necessary to revisit current administrative procedures as laid down in Regulation (EC) No 1084/2003 and Commission Regulation (EC) No 1085/2003of 3 June 2003 concerning the examination of variations to the terms of a marketing authorisation for medicinal products for human use and veterinary medicinal products falling within the scope of Council Regulation (EEC) No 2309/931 (Variations Regulations), with a focus, in particular, on simplifying administrative procedures.   1 OJ L 159, 27.6.2003, p.24. Amendment  3 Proposal for a directive – amending act Article 3 – paragraph 1 – subparagraph 1 Text proposed by the Commission Amendment 1. Member States shall bring into force the laws, regulations and administrative provisions necessary to comply with this Directive by [12 months after entry into force] at the latest. They shall forthwith communicate to the Commission the text of those provisions and a correlation table between those provisions and this Directive. 1. Member States shall bring into force the laws, regulations and administrative provisions necessary to comply with this Directive by [24 months after entry into force] at the latest. They shall forthwith communicate to the Commission the text of those provisions and a correlation table between those provisions and this Directive.

PROCEDURE