RECOMMENDATION FOR SECOND READING on the Council common position for adopting a regulation of the European Parliament and of the Council on medicinal products for paediatric use and amending Regulation (EEC) No 1768/92, Directive 2001/20/EC, Directive 2001/83/EC and Regulation (EC) No 726/2004

8.5.2006 - (15763/3/2005 – C6‑0087/2006 – 2004/0217(COD)) - ***II

Committee on the Environment, Public Health and Food Safety
Rapporteur: Françoise Grossetête

DRAFT EUROPEAN PARLIAMENT LEGISLATIVE RESOLUTION

on the Council common position for adopting a regulation of the European Parliament and of the Council on medicinal products for paediatric use and amending Regulation (EEC) No 1768/92, Directive 2001/20/EC, Directive 2001/83/EC and Regulation (EC)

No 726/2004

(15763/3/2005 – C6‑0087/2006 – 2004/0217(COD))

(Codecision procedure: second reading)

The European Parliament,

–   having regard to the Council common position (15763/3/2005 – C6‑0087/2006),

–   having regard to its position at first reading[1] on the Commission proposal to Parliament and the Council (COM(2004)0599)[2],

–   having regard to the amended Commission proposal (COM(2005)0577)[3],

–   having regard to Article 251(2) of the EC Treaty,

–   having regard to Rule 62 of its Rules of Procedure,

–   having regard to the recommendation for second reading of the Committee on the Environment, Public Health and Food Safety (A6‑0171/2006),

1.  Approves the common position as amended;

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

Council common position	Amendments by Parliament
Amendment 1 RECITAL 5
(5) While taking into account the fact that the regulation of medicinal products must be fundamentally aimed at safeguarding public health, this aim must be achieved by means that do not impede the free movement of safe medicinal products within the Community. The differences between the national legislative, regulatory and administrative provisions on medicinal products tend to hinder intra-Community trade and therefore directly affect the operation of the internal market.	(5) While taking into account the fact that the regulation of medicinal products must be fundamentally aimed at safeguarding public health, this aim must be achieved by means that do not impede the free movement of safe medicinal products within the Community. The differences between the national legislative, regulatory and administrative provisions on medicinal products tend to hinder intra-Community trade and therefore directly affect the operation of the internal market. Any action to promote the development and authorisation of medicinal products for paediatric use is therefore justified with a view to preventing or eliminating these obstacles. Article 95 of the Treaty is therefore the proper legal basis.
Justification
Article 95 constitutes the basis for this Regulation and should therefore be specified.
Amendment 2 RECITAL 8
(8) It is appropriate to create a scientific committee, the Paediatric Committee, within the European Medicines Agency, hereinafter ‘the Agency’, with expertise and competence in the development and assessment of all aspects of medicinal products to treat paediatric populations. To this end, the Paediatric Committee should be independent from the pharmaceutical industry. The Paediatric Committee should be primarily responsible for the scientific assessment and agreement of paediatric investigation plans and for the system of waivers and deferrals thereof; it should also be central to various support measures contained in this Regulation. In its work, the Paediatric Committee should consider the potential significant therapeutic benefits for the paediatric patients involved in the studies or the paediatric population at large including the need to avoid unnecessary studies. The Paediatric Committee should follow existing Community requirements, including Directive 2001/20/EC, as well as International Conference on Harmonisation (ICH) guideline E11 on the development of medicinal products for the paediatric population, and it should avoid any delay in the authorisation of medicinal products for other populations deriving from the requirements for studies in the paediatric population.	(8) It is appropriate to create a scientific committee, the Paediatric Committee, within the European Medicines Agency, hereinafter ‘the Agency’, with expertise and competence in the development and assessment of all aspects of medicinal products to treat paediatric populations. The rules on scientific committees of the Agency, as laid down in Regulation (EC) No 726/2004, should apply to the Paediatric Committee. Members of the Paediatric Committee should therefore not have financial or other interests in the pharmaceutical industry which could affect their impartiality, should undertake to act in the public interest and in an independent manner, and should make an annual declaration of their financial interests. The Paediatric Committee should be primarily responsible for the scientific assessment and agreement of paediatric investigation plans and for the system of waivers and deferrals thereof; it should also be central to various support measures contained in this Regulation. In its work, the Paediatric Committee should consider the potential significant therapeutic benefits for the paediatric patients involved in the studies or the paediatric population at large including the need to avoid unnecessary studies. The Paediatric Committee should follow existing Community requirements, including Directive 2001/20/EC, as well as International Conference on Harmonisation (ICH) guideline E11 on the development of medicinal products for the paediatric population, and it should avoid any delay in the authorisation of medicinal products for other populations deriving from the requirements for studies in the paediatric population.
Justification
Within the ‘better regulation’ context, reference should be made to principles already adopted in other legislation which must apply under this Regulation, notably as regards the independence of members of the committee.
Amendment 3 RECITAL 10
(10) The introduction of the paediatric investigation plan in the legal framework concerning medicinal products for human use aims at ensuring that the development of medicinal products that are potentially to be used for the paediatric population becomes an integral part of the development of medicinal products, integrated into the development programme for adults. Thus, paediatric investigation plans should be submitted early during product development, in time for studies to be conducted in the paediatric population before marketing authorisation applications are submitted. It is appropriate to set a deadline for the submission of a paediatric investigation plan in order to ensure early dialogue between the sponsor and the Paediatric Committee. As the development of medicinal products is a dynamic process dependent on the result of ongoing studies, provision should be made for modifying an agreed plan where necessary.	(10) The introduction of the paediatric investigation plan in the legal framework concerning medicinal products for human use aims at ensuring that the development of medicinal products that are potentially to be used for the paediatric population becomes an integral part of the development of medicinal products, integrated into the development programme for adults. Thus, paediatric investigation plans should be submitted early during product development, in time for studies to be conducted in the paediatric population, where appropriate, before marketing authorisation applications are submitted. It is appropriate to set a deadline for the submission of a paediatric investigation plan in order to ensure early dialogue between the sponsor and the Paediatric Committee. Furthermore, early submission of a paediatric investigation plan, combined with the submission of a deferral request as described below, will avoid delaying the authorisation for other populations. As the development of medicinal products is a dynamic process dependent on the result of ongoing studies, provision should be made for modifying an agreed plan where necessary.
Justification
The purpose of the amendment is to ensure that marketing authorisations for medicinal products for adults are not delayed while at the same time taking due account of the importance of the specific paediatric studies which applicants will be obliged to conduct.
Amendment 4 RECITAL 24
(24) It is essential to ensure that pharmacovigilance mechanisms are adapted to meet the specific challenges of collecting safety data in the paediatric population, including data on possible long-term effects. Efficacy in the paediatric population may also need additional study following authorisation. Therefore, an additional requirement for applying for a marketing authorisation that includes the results of studies conducted in compliance with an agreed paediatric investigation plan should be an obligation for the applicant to indicate how he proposes to ensure the long-term follow-up of possible adverse reactions to the use of the medicinal product and efficacy in the paediatric population. Additionally, where there is a particular cause for concern, provision should be made for the possibility of requiring the applicant to submit and implement a risk management system and/or perform specific post-marketing studies as a condition for the granting of the marketing authorisation.	(24) It is essential to ensure that pharmacovigilance mechanisms are adapted to meet the specific challenges of collecting safety data in the paediatric population, including data on possible long-term effects. Efficacy in the paediatric population may also need additional study following authorisation. Therefore, an additional requirement for applying for a marketing authorisation that includes the results of studies conducted in compliance with an agreed paediatric investigation plan should be an obligation for the applicant to indicate how he proposes to ensure the long-term follow-up of possible adverse reactions to the use of the medicinal product and efficacy in the paediatric population. Additionally, where there is a particular cause for concern, the applicant should submit and implement a risk management system and/or perform specific post-marketing studies as a condition for the granting of the marketing authorisation.
Justification
Where there are particular concerns, applicants must be required to submit an appropriate risk management plan.
Amendment 5 RECITAL 26
(26) For products falling within the scope of the requirement to submit paediatric data, if all the measures included in the agreed paediatric investigation plan are complied with, if the product is authorised in all Member States and if relevant information on the results of studies is included in product information, a reward should be granted in the form of a 6‑month extension of the supplementary protection certificate created by Council Regulation (EEC) No 1768/92.	(26) For products falling within the scope of the requirement to submit paediatric data, if all the measures included in the agreed paediatric investigation plan are complied with, if the product has received a marketing authorisation in all Member States and if relevant information on the results of studies is included in product information, a reward should be granted in the form of a 6-month extension of the Supplementary Protection Certificate created by Council Regulation (EEC) No 1768/92. Any decisions by Member States’ authorities concerning the setting of prices for medicinal products or their inclusion in the scope of national health insurance schemes should have no bearing on the granting of this reward.
Justification
It is important to encourage the availability of medicinal products for paediatric use throughout the territory of the EU. Moreover, applicants must not be penalised by administrative delays on the part of certain national authorities.
Amendment 6 RECITAL 35 a (new)
	(35a) Council Directive 76/769/EEC of 27 July 1976 on the approximation of the laws, regulations and administrative provisions of the Member States relating to restrictions on the marketing and use of certain dangerous substances and preparations1 prohibits the placing on the market for use by the general public of substances or preparations containing substances classified as carcinogenic, mutagenic or toxic for reproduction, category 1 or 2, pursuant to Council Directive 67/548/EEC of 27 June 1967 on the approximation of laws, regulations and administrative provisions relating to the classification, packaging and labelling of dangerous substances2.
	______________________________ 1 OJ L 262, 27.9.1976, p. 201. Directive as last amended by Directive 2005/90/EC of the European Parliament and of the Council (OJ L 33, 4.2.2006, p. 28).
	2 OJ L 196, 16.8.1967, p. 1. Directive as last amended by Commission Directive 2004/73/EC (OJ L 152, 30.4.2004, p. 1).
Justification
New amendment due to a new fact (Rule 62(2d)). Recent research has revealed the use of a substance that is toxic to reproduction as an excipient in more than 100 medicinal products. Community law prohibits the sale to the general public of substances that are carcinogenic, mutagenic or toxic to reproduction. While an exemption from this provision for cosmetic products has been overcome, medicinal products are still exempted. While it may be justified to use such substances as active substances, there is no justification to do so for excipients, all the more that alternatives are available.
Amendment 7 RECITAL 35 b (new)
	(35b) Given the special risks that substances classified as carcinogenic, mutagenic or toxic for reproduction, category 1, 2 and 3, pursuant to Directive 67/548/EEC may entail for human health, their use in medicinal products as constituents of excipients or as constituents of the outer covering should be prohibited. A substance classified in category 3 may be used as a constituent of excipients or as a constituent of the outer covering in medicinal products if the substance has been evaluated by the Committee for Medicinal Products for Human Use and found acceptable for use in medicinal products.
Justification
The use of CMR substances as excipients has led to very elevated exposure to such substances. This is particularly problematic for pregnant women, as it may contribute to the increase of genital malformations observed in new-born boys. The use of CMR substances category 1 and 2 should be prohibited in excipients or in the outer covering of medicinal products. In analogy to the cosmetics legislation, CMR substances category 3 may only be allowed if they have been assessed to be safe (see also justification to amendment 6).
Amendment 8 ARTICLE 3, PARAGRAPH 2
2. Save where otherwise provided for in this Regulation, Regulation (EC) No 726/2004 shall apply to the Paediatric Committee.	2. Save where otherwise provided for in this Regulation, Regulation (EC) No 726/2004 shall apply to the Paediatric Committee, including the provisions on the independence and impartiality of its members.
Justification
Within the ‘better regulation’ context, reference should be made to principles already adopted in other legislation which must apply under this Regulation, notably as regards the independence of members of the committee.
Amendment 9 ARTICLE 5, PARAGRAPH 1
1. When preparing its opinions, the Paediatric Committee shall use its best endeavours to reach a scientific consensus. If such a consensus cannot be reached, the Paediatric Committee shall adopt an opinion consisting of the position of the majority of the members. The opinion shall mention the divergent positions, with the grounds on which they are based.	1. When preparing its opinions, the Paediatric Committee shall use its best endeavours to reach a scientific consensus. If such a consensus cannot be reached, the Paediatric Committee shall adopt an opinion consisting of the position of the majority of the members. The opinion shall mention the divergent positions, with the grounds on which they are based. The opinion shall be made public.
Justification
Partial reinstatement of amendment 22 from first reading, adopted on 7 September 2005. It is important to ensure that the position of the Paediatric Committee is made public.
Amendment 10 ARTICLE 16, PARAGRAPH 1
1. In the case of the applications referred to in Articles 7 and 8, the paediatric investigation plan shall be submitted with a request for agreement, unless otherwise justified, not later than upon completion of the human pharmaco-kinetic studies in adults specified in Section 5.2.3 of Part I of Annex I to Directive 2001/83/EC, so as to ensure that an opinion on use in the paediatric population of the medicinal product concerned can be given at the time of the assessment of the marketing authorisation or other application concerned.	1. In the case of the applications for marketing authorisation referred to in Articles 7 and 8 or the applications for waiver referred to in Articles 11 and 12, the paediatric investigation plan or the application for waiver shall be submitted with a request for agreement, except in duly justified cases, not later than upon completion of the human pharmaco-kinetic studies in adults specified in Section 5.2.3 of Part I of Annex I to Directive 2001/83/EC, so as to ensure that an opinion on use in the paediatric population of the medicinal product concerned can be given at the time of the assessment of the marketing authorisation or other application concerned.
Justification
The purpose of the amendment is to ensure that marketing authorisations for medicinal products for adults are not delayed while at the same time taking due account of the importance of the specific paediatric studies which applicants will be obliged to conduct.
Amendment 11 ARTICLE 25, PARAGRAPH 3
3. Within 30 days following receipt of a request for re-examination pursuant to paragraph 2, the Paediatric Committee, having appointed a new rapporteur, shall issue a new opinion confirming or revising its previous opinion. The opinion shall be duly reasoned and a statement of reasons for the conclusion reached shall be annexed to the new opinion, which shall become definitive.	3. Within 30 days following receipt of a request for re-examination pursuant to paragraph 2, the Paediatric Committee, having appointed a new rapporteur, shall issue a new opinion confirming or revising its previous opinion. The rapporteur shall be able to question the applicant directly. The applicant may also offer to be questioned. The rapporteur shall inform the Paediatric Committee without delay in writing about details of contacts with the applicant. The opinion shall be duly reasoned and a statement of reasons for the conclusion reached shall be annexed to the new opinion, which shall become definitive.
Justification
The rapporteur shall act as representative of the Committee and keep it informed about contacts with the applicant. (Reinstates amendment 41 adopted at first reading on 7 September 2005.)
Amendment 12 ARTICLE 34, PARAGRAPH 1, INTRODUCTORY PART
1. In the following cases, the applicant shall detail, in addition to the normal requirements for post marketing monitoring, the measures to ensure the follow-up of efficacy and of possible adverse reactions to the paediatric use of the medicinal product:	1. In the following cases, the applicant shall detail the measures to ensure the follow-up of efficacy and of possible adverse reactions to the paediatric use of the medicinal product:
Justification
Within the ‘better regulation’ context, reference should be made to principles already adopted in other legislation which must apply under this Regulation, notably as regards pharmacovigilance.
Amendment 13 ARTICLE 34, PARAGRAPH 2, SUBPARAGRAPH 1
2. Where there is particular cause for concern, the competent authority may require, as a condition for granting marketing authorisation, that a risk management system be set up or that specific post-marketing studies be performed and submitted for review. The risk management system shall comprise a set of pharmacovigilance activities and interventions designed to identify, characterise, prevent or minimise risks relating to medicinal products, including the assessment of the effectiveness of those interventions.	2. Granting marketing authorisation for a paediatric indication shall be subject to the setting-up of a risk management system by the firm concerned. If necessary, the competent authority may also require specific studies to be performed. The risk management system shall comprise a set of pharmacovigilance activities and interventions designed to identify, characterise, prevent or minimise risks relating to medicinal products, including the assessment of the effectiveness of those interventions.
Justification
Reinstatement of Amendment 47 adopted at first reading on 7 September 2005. A risk management system should be set up systematically for medicinal products with a paediatric indication.
Amendment 14 ARTICLE 34, PARAGRAPH 2 a (new)
	2a. In addition to the provisions contained in paragraphs 1 and 2, the provisions on pharmacovigilance as laid down in Regulation (EC) No 726/2004 and in Directive 2001/83/EC must apply to marketing authorisations for medicinal products which include a paediatric indication.
Justification
Within the ‘better regulation’ context, reference should be made to principles already adopted in other legislation which must apply under this Regulation, notably as regards pharmacovigilance.
Amendment 15 ARTICLE 36, PARAGRAPH 3
3. Where the procedures laid down in Directive 2001/83/EC have been used, the six‑month extension of the period referred to in paragraph 1 shall be granted only if the product is authorised in all Member States.	3. Where the procedures laid down in Directive 2001/83/EC have been used, the six‑month extension of the period referred to in paragraph 1 shall be granted only if the product has received a marketing authorisation in all Member States.
Justification
It is important to encourage the availability of medicinal products for paediatric use throughout the territory of the EU. Moreover, applicants must not be penalised by administrative delays on the part of certain national authorities.
Amendment 16 ARTICLE 43, PARAGRAPH 1, SUBPARAGRAPH 2
By ….***, the Agency shall make the inventory public and shall update it regularly.	The Agency shall make the inventory public in the second year at the earliest and not later than ….*** and shall update it regularly.
Amendment 17 ARTICLE 45, PARAGRAPH 3 a (new)
	3a. In consultation with the Agency, the Commission shall draw up guidelines to establish assessment criteria for the significance of studies for the purposes of applying paragraph 3.
Justification
In this context, it is for the Commission to decide, based on the Agency’s scientific expertise, which studies are considered necessary and/or relevant.
Amendment 18 ARTICLE 52, POINT 2 Article 7, paragraph 4 a (new) (Regulation (EEC) No 1768/92)
	4a. Notwithstanding paragraph 4, for five years following the entry into force of Regulation (EC) No .../...*[paediatric regulation], the application for an extension of the duration of a certificate already granted shall be lodged not later than six months before the expiry of the certificate. _______________ * Note to OJ: please insert number of this Regulation.
Justification
The introduction of this transitional clause is important in so far as there are currently medicinal products whose certificate is due to expire but which may be important for the paediatric population.
Amendment 19 ARTICLE 54, POINT 1 a (new) Article 117, paragraph 1, point (d a) (new) (Directive 2001/83/EC)
	1a) In Article 117(1) of Directive 2001/83/EC, the following point shall be added:
	‘(da) it contains substances that are carcinogenic, mutagenic or toxic to reproduction as listed in Annex I to Council Directive 67/548/EEC1 as constituents of excipients or as constituents of the outer covering.
	_______________________ 1 OJ L 196, 16.8.1967, p. 1. Directive as last amended by Commission Directive 2004/73/EC (OJ L 152, 30.4.2004, p. 1).’
Justification
Medicinal products containing CMR substances in excipients or in outer covering should be withdrawn from the market. Alternative medicinal products for the same treatment are available. Manufacturers could then apply to vary the authorisation so as to continue to sell a varied medicinal product that does not contain CMR substances in excipients and outer covering. Alternative substances are widely available and in use (see also justification to amendments 6 and 7).
Amendment 20 ARTICLE 54, POINT 1 b (new) Annex 1, point 3.2.2.4 (a) (Directive 2001/83/EC)
	1b) In Annex I, point 3.2.2.4 (a) of Directive 2001/83/EC, the following paragraph shall be added:
	‘Substances classified as carcinogenic, mutagenic or toxic for reproduction, category 1, 2 and 3, pursuant to Directive 67/548/EEC1 must not be used as constituents of excipients or constituents of the outer covering of medicinal products. A substance in category 3 may be used if the substance has been evaluated by the Committee for Medicinal Products for Human Use and found acceptable for use in medicinal products.
	____________________________ 1 OJ L 196, 16.8.1967, p. 1. Directive as last amended by Commission Directive 2004/73/EC (OJ L 152, 30.4.2004, p. 1).’
Justification
It is necessary to avoid that CMR substances are used as excipients or in outer coverings in the future. It therefore needs to be specified in the control of excipients that such substances must not be used (see also justifications to amendments 6 and 7).

• [1]  Texts adopted, 7.9.2005, P6_TA(2005)0331
• [2]  Not yet published in OJ.
• [3]  Not yet published in OJ.

EXPLANATORY STATEMENT

Thanks to this Regulation, medicinal products specifically intended for paediatric use will finally be able to be made available to children. In many cases, the medicines used for children are the same as those prescribed for adults. The only difference is that the doses are smaller. However, it is a well-known fact that children do not have the same metabolism as adults. This is why they need pharmaceutical forms different from those intended for adults, so as to ensure both that the medicinal products are better tolerated and that they are more effective.

We must therefore seek to ensure that this Community act is able to be implemented as soon as possible.

Your rapporteur welcomes, with some satisfaction, the common position, which both incorporates many of Parliament’s amendments and accepts the introduction of specific incentives for European research.

However, your rapporteur wishes to make some adjustments to the common position to make the regulations more pragmatic.

In the area of pharmacovigilance and as regards the independence of members of the Paediatric Committee, reference should be made to directives and regulations already adopted in order to avoid overlapping of regulatory texts.

The development of medicinal products intended for children must not be allowed to hamper the development of medicinal products for adults. Your rapporteur is therefore proposing the introduction in certain cases of a duly justified derogation. This will make it possible, on scientific grounds, for the requirement for the results of the paediatric studies to be submitted at the same time as those of the studies in adults not to apply.

It is also necessary to introduce a transitional clause under Article 52. The introduction of such a clause is important in so far as there are currently medicinal products whose certificate is due to expire but which may be important for the paediatric population. Being too restrictive at this stage would risk blocking the development of new treatments. This transitional clause will not penalise the generics industry, which will be able to benefit from new medicinal products developed in this way.

Finally, this Regulation derives its legal basis from Article 95 of the EC Treaty, and it seems inconceivable that the Council should be proposing to delete this reference.

With the introduction of this Community act, the European Union will have effective means of promoting the development of medicinal products for paediatric use and closing this current major gap in the area of public health. That will mean that our children will no longer have to depend on the good will of the research sector in the USA or Asia.

PROCEDURE

Title	Common Position adopted by the Council on 10 March 2006 with a view to the adoption of a Regulation of the European Parliament and of the Council on medicinal products for paediatric use and amending Regulation (EEC) No 1768/92, Directive 2001/20/EC, Directive 2001/83/EC and Regulation (EC) No 726/2004
References	15763/3/2005 – C6‑0087/2006 – 2004/0217(COD)
Date of first reading in EP – P number	7.9.2005	P6_TA(2005)0331
Commission proposal	COM(2004)0599 – C6‑0159/2004
Amended Commission proposal	COM(2005)0577
Date on which receipt of common position announced in plenary	16.3.2006
Committee responsible   Date announced in plenary	ENVI 27.10.2004
Rapporteur(s)   Date appointed	Françoise Grossetête 20.1.2005
Previous rapporteur(s)
Discussed in committee	3.4.2006		4.5.2006
Date adopted	4.5.2006
Outcome of final vote	+ : – : 0 :	39 2 3
Members present for final vote	Adamos Adamou, Liam Aylward, Irena Belohorská, Johannes Blokland, John Bowis, Frederika Brepoels, Chris Davies, Avril Doyle, Mojca Drčar Murko, Edite Estrela, Jillian Evans, Matthias Groote, Françoise Grossetête, Cristina Gutiérrez-Cortines, Satu Hassi, Gyula Hegyi, Marie Anne Isler Béguin, Dan Jørgensen, Christa Klaß, Eija-Riitta Korhola, Holger Krahmer, Urszula Krupa, Jules Maaten, Linda McAvan, Riitta Myller, Miroslav Ouzký, Frédérique Ries, Guido Sacconi, Karin Scheele, Carl Schlyter, Richard Seeber, María Sornosa Martínez, Antonios Trakatellis, Thomas Ulmer, Åsa Westlund, Anders Wijkman.
Substitutes present for final vote	María del Pilar Ayuso González, Sergio Berlato, Philip Bushill-Matthews, Milan Gaľa, Erna Hennicot-Schoepges, Glenis Willmott.
Substitutes under Rule 178(2) present for final vote	Elisabeth Jeggle, Lapo Pistelli
Date tabled	8.5.2006
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