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20042009{JURI}Committee on Legal Affairs
2005/0227(COD)
{12/07/2006}17.7.2006
OPINION
of the {JURI}Committee on Legal Affairs
for the {ENVI}Committee on the Environment, Public Health and Food Safety
on the proposal for a regulation of the European Parliament and of the Council on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004
(COM(2005)0567 C60401/2005 2005/0227(COD))
Draftswoman (*): Hiltrud Breyer
(*) Enhanced cooperation between committees - Rule 47 of the Rules of Procedure
PA_Legam
SHORT JUSTIFICATION
The Commissions proposal seeks to regulate placing on the European market of products based on gene therapy, cell therapy and tissue engineering. These products are of growing importance for modern medicine and can potentially help a lot of patients, but some serious health risks might occur in case of improper regulation. Especially in the area of tissue engineering no harmonised European approach exists.
In general, the Commissions proposal is welcome by all stakeholders but the public debate and discussion in Parliament committees has shown that there are some points that urgently need clarification to make the proposal legally consistent, to exclude controversial interpretations, to make the proposal coherent with the current legislation and to safeguard Parliament's rights. This is why the Committee on Legal Affairs proposes a number of amendments.
1. The rights of the Parliament in the comitology procedure.
The Commissions proposal foresees to delegate almost all important questions to the comitology procedure. In such a highly political issue it is important to safeguard Parliament's rights. The Parliament should have the right to examine and to block such decisions. It is unacceptable that Art. 8 of this proposal refers to the comitology procedure although the Commission has not even submitted to the Parliament a draft of adequate technical requirements. The European institutions have just reached a new agreement on the comitology procedure which is a step forward in balancing their powers. In the meantime, a proposed amendment introduces a procedure strengthening Parliament's role.
2. Legal safety on the issue of subsidiarity.
There is broad agreement that the European Union should not harmonise the legislation on the use of human embryos and human embryonic stem cells. The Commission proposes to safeguard the legislative right of the Member States in Article 28(2). However, this provision is not adequate and may be challenged in the Court of Justice, as it causes serious problems with regard to the legal basis of the proposal. It can not be excluded that the proposed Regulation constitutes a complete harmonisation. Therefore, the proposed Art. 28(2) would be an alien substance and breach of Community law would not be excluded.
The Committee therefore proposes to exclude embryonic stem cells from the scope of the Regulation in Article 1. It would make clear that there will be no harmonization in these delicate areas. In addition, the wording of Art. 28(2) of the proposal should be changed to underline that Member States, acting on the basis of Art. 30 TEC can further ban or limit the use, the sale, the placing on the market of human and animal cells as well as the use of medicinal products which contain, consist or are derived from such cells.
3. To make the proposal coherent with the current EU legislation, some technologies that are banned in other European legislation should also not get authorisation under the current Commissions proposal.
Regardless of the competence of the Member States there should not be any compromises regarding human rights and constitutional law, even if progress in some areas is rapid. The principle of the non-commercialization of the human body has to be respected. The integrity of the person is protected under the Oviedo Convention and the Charter of Fundamental Rights. The production of human-animal hybrids or chimeras constitutes a breach of the principle of the integrity of the person and of the principle of inviolability of human dignity. Interventions in the human germ line are explicitly named in the Oviedo Convention as endangering human dignity. Products which intervene in the human germ line are excluded from clinical trials in Directive 2001/20/EC and are non patentable according to Directive 98/44/EC as are also human-animal hybrids being against ordre public.
4. To insure the voluntary and unpaid donation of human tissues and cells the Directive 2004/23/EC must be amended.
Straight in connection with advanced therapies which are subject to rapid development and for products of which the human tissue and cells are increasingly needed, the principle of the non-commercialization of the human body requires Member States to ensure the voluntary and unpaid donation and procurement of human cells and tissues. Therefore the Directive 2004/23/EC must be amended for the purposes of the suggested Regulation.
AMENDMENTS
The Committee on Legal Affairs calls on the Committee on the Environment, Public Health and Food Safety, as the committee responsible, to incorporate the following amendments in its report:
Text proposed by the CommissionAmendments by ParliamentAmendment 1
TITLE
Proposal for a Regulation of the European Parliament and of the Council on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004Proposal for a Regulation of the European Parliament and of the Council on advanced therapy medicinal products and amending Directive 2001/83/EC, Regulation (EC) No 726/2004 and Directive 2004/23/ECJustification
The title of the proposal need to be changed, as Directive 2004/23/EC is also amended (see amendment 45).
Amendment 2
RECITAL 6
(6) The regulation of advanced therapy medicinal products at Community level should not interfere with decisions made by Member States on whether to allow the use of any specific type of human cells, such as embryonic stem cells, or animal cells. It should also not affect the application of national legislation prohibiting or restricting the sale, supply or use of medicinal products containing, consisting of or derived from these cells.(6) Legislation in force in Member States concerning the use of certain types of cells, such as embryonic stem cells, varies considerably. The regulation of advanced therapy medicinal products at Community level should not interfere with decisions made by Member States on whether to allow the use of any specific type cells. It should also not affect the application of national legislation prohibiting or restricting the sale, supply or use of medicinal products containing, consisting of or derived from these cells. Moreover, it is impossible to assess when, if ever, research on these cells will reach the stage at which commercial products made from these cells could be placed on the market. In order to respect the basic principles and the proper functioning of the internal market and to ensure legal certainty, this Regulation should apply only to products made of cells, for which marketing is feasible in the near future and which do not raise major controversies. Justification
The legal base of this regulation (Article 95 TEC) is a single market harmonisation measure. It is not designed to cover situations in which significant national legislative differences are intended to remain (c.f. ECJ Case C-376/98). It is therefore necessary to exclude from the scope of this regulation products using materials which are controversial and for which differing Member States legislative provisions are intended to remain. In any case, products using these materials are unlikely to be ready to be placed on the market in the foreseeable future.
Amendment3
RECITAL 7 A (new)
(7a) This Regulation fully respects the prohibition on making the human body and its parts as such a source of financial gain, as set out as an inalienable minimum safeguard in the Charter of Fundamental Rights of the European Union and further underlined by the European Parliament in its resolutions of 10 March 2005 on the trade in human egg cells1 and of 26 October 2005 on patents for biotechnological inventions2. To that end, it is necessary to ensure that the donation of tissues and cells is voluntary and unpaid and that their procurement is carried out on a non-profit basis. Voluntary and unpaid tissue and cell donations also contribute to high safety standards for tissues and cells and therefore to the protection of human health.
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1 OJ C 320 E, 15.12.2005, p. 251.
2 Texts Adopted of that date, P6_TA(2005)0407.Justification
Rapid developments in biotechnology and biomedicine must not be allowed to compromise the protection of fundamental rights. These rights of which one of the most important one is the right to the integrity of the person are laid down in the Oviedo Convention as well as in the Charter of Fundamental Rights. These standards should be met especially for tissue- and cell-based advanced therapy medicinal products as highly innovative new products. In this context, voluntary and unpaid donation as well as procurement on a non-profit basis are the key principles that should be imperatively respected in the Community.
Amendment 4
RECITAL 7 B (new)
(7b) Directive 2001/20/EC1 prohibits gene therapy trials that result in modifications to a subject's germ line genetic identity. Directive 98/44/EC2 provides that processes for modifying the human germ line genetic identity are to be regarded as unpatentable. To ensure legal consistency, this Regulation should prohibit any authorisation of products that modify the germ line genetic identity of human beings. By way of exception, the prohibition of authorisation should not apply to products intended to treat cancers of the gonads.
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1 Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the Member States relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use (OJ L 121, 1.5.2001, p. 34).
2 Directive 98/44/EC of the European Parliament and of the Council of 6 July 1998 on the legal protection of biotechnological inventions (OJ L 213, 30.7.1998, p. 13).Justification
As Articles 1 and 13 of the Oviedo Convention make it clear, human dignity is compromised when the inheritance of genetic identity is altered. Products which are neither properly subject to clinical trials under Directive 2001/20/EC nor legally patentable under Directive 98/44/EC should not be eligible for authorisation under this Regulation. Nevertheless, products for the treatment of cancer of the gonades should be permitted to have European marketing authorisation.
Amendment 5
RECITAL 7 C (new)
(7c) This Regulation should prohibit any authorisation of products derived from human-animal hybrids or chimeras or containing tissues or cells originating or derived therefrom. This provision should not exclude the transplantation of somatic animal cells or tissues to the human body for therapeutic purposes, in so far as it does not interfere with the germ line.Justification
The physical and mental integrity of the person and human dignity must be respected, as underlined in Articles 1 and 3 of the Charter of fundamental rights of the European Union. The creation of human-animal hybrids or chimeras is a threat to the right to integrity of a person and a violation of human dignity. Therefore, no authorisation for products containing or originating from human-animal hybrids or chimeras should be granted under this Regulation. However, the Xenotransplantation for therapeutic purposes should not be excluded, as far as it does not interfere with the germ line.
Amendment 6
RECITAL 9
(9) The evaluation of advanced therapy medicinal products often requires very specific expertise, which goes beyond the traditional pharmaceutical field and covers areas on the borderline to other sectors such as biotechnology and medical devices. For this reason, it is appropriate to create, within the Agency, a Committee for Advanced Therapies, which the Committee for Medicinal Products for Human Use of the Agency should consult on the assessment of data related to advanced therapy medicinal products, before issuing its final scientific opinion. In addition, the Committee for Advanced Therapies may be consulted for the evaluation of any other medicinal product which requires specific expertise falling within its area of competence.(9) The evaluation of advanced therapy medicinal products often requires very specific expertise, which goes beyond the traditional pharmaceutical field and covers areas on the borderline to other sectors such as biotechnology and medical devices. For this reason, it is appropriate to create, within the Agency, a Committee for Advanced Therapies, which should be responsible for preparing a draft opinion on the quality, safety and efficacy of each advanced therapy medicinal product for final approval by the Committee for Medicinal Products for Human Use of the Agency. In addition, the Committee for Advanced Therapies should be consulted for the evaluation of any other medicinal product which requires specific expertise falling within its area of competence.Justification
Due to a highly specific and unique character of the advanced therapy medicinal products, a new Committee for Advanced Therapies is established within EMEA and composed of experts having specific qualifications or experience in this highly innovative and quickly developing field. Therefore, the new structure should be responsible for drafting an opinion on the quality, safety, and efficacy of products for the final approval by the CHMP. Furthermore, the committee should be consulted for the evaluation of other products under its competence.
Amendment 7
RECITAL 9 A (new)
(9a) The Committee for Advanced Therapies should provide advice to the Committee for Medicinal Products for Human Use on whether a product falls within the definition of an advanced therapy medicinal product.Justification
Due to its specific expertise in advanced therapy medicinal products, the Committee for Advanced Therapies should assist the CHMP in its classification task of whether a product is or is not an advanced therapy medicinal product.
Amendment 8
RECITAL 10
(10) The Committee for Advanced Therapies should gather the best available Community expertise on advanced therapy medicinal products. The composition of the Committee for Advanced Therapies should ensure appropriate coverage of the scientific areas relevant to advanced therapies, including gene therapy, cell therapy, tissue-engineering, medical devices, pharmacovigilance and ethics. Patient associations and surgeons with scientific experience of advanced therapy medicinal products should also be represented.(10) The Committee for Advanced Therapies should gather the best available Community expertise on advanced therapy medicinal products. The composition of the Committee for Advanced Therapies should ensure appropriate coverage of the scientific areas relevant to advanced therapies, including gene therapy, cell therapy, tissue-engineering, medical devices, pharmacovigilance and ethics. Patient associations and physicians with scientific experience of advanced therapy medicinal products should also be represented.Justification
For the sake of being more precise it is necessary to apply the technical term.
Amendment 9
RECITAL 14
(14) As a matter of principle, human cells or tissues contained in advanced therapy medicinal products should be procured from voluntary and unpaid donation. Voluntary and unpaid tissue and cell donations are a factor which may contribute to high safety standards for tissues and cells and therefore to the protection of human health.deletedJustification
This recital shall be deleted as a consequence to the introduction of a new recital 7(a) and new Articles 3(a) and 28(a).
Amendment 10
RECITAL 16
(16) The manufacture of advanced therapy medicinal products should be in compliance with the principles of good manufacturing practice, as set out in Commission Directive 2003/94/EC of 8 October 2003 laying down the principles and guidelines of good manufacturing practice in respect of medicinal products for human use and investigational medicinal products for human use. Furthermore, guidelines specific to advanced therapy medicinal products should be drawn up, so as to properly reflect the particular nature of their manufacturing process.(16) The manufacture of advanced therapy medicinal products should be in compliance with the principles of good manufacturing practice, as set out in Commission Directive 2003/94/EC of 8 October 2003 laying down the principles and guidelines of good manufacturing practice in respect of medicinal products for human use and investigational medicinal products for human use, and adapted, where necessary, to reflect the specific nature of the products. Furthermore, guidelines specific to advanced therapy medicinal products should be drawn up, so as to properly reflect the particular nature of their manufacturing process.Justification
Advanced Therapy medicinal products have specific characteristics that differ greatly from traditional medicinal products. That leads to important differences in their manufacturing process (e.g. in Article 11.4. the GMP Directive requires that sample batches of finished products should be kept for 1 year after expiry date. It is, however, difficult to consider expiry dates for certain classes of ATMPs).
Amendment 11
RECITAL 28
(28) Directive 2001/83/EC and 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 European Medicines Agency should therefore be amended accordingly,(28) Directive 2001/83/EC, 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 European Medicines Agency and Directive 2004/23/EC should therefore be amended accordingly,Justification
This is a consequential amendment to the introduction of Article 28(a) (new) modifying Directive 2004/23/EC on tissues and cells.
Amendment 12
ARTICLE 1 A (new)
Article 1a
ExclusionsThis Regulation shall not apply to any advanced therapy medicinal products that contain or are derived from human embryonic and foetal cells, primordial germ cells and cells derived from those cells.
Justification
The legal base of this regulation (Article 95 TEC) is a single market harmonisation measure. It is not designed to cover situations in which significant national legislative differences are intended to remain (c.f. ECJ Case C-376/98).
Amendment 13
ARTICLE 2, PARAGRAPH 1, POINT (D), INDENT 1 A (new)
- its cellular or tissue part contains viable cells or tissues; orJustification
For the purposes of this Regulation, the most important criterion when defining a combined advanced therapy medicinal product should be the viability of its cellular or tissue part. For the patient's safety and the high standards of the evaluation of a product, a combined product should be always classified as an advanced therapy medicinal product when it contains viable tissues or cells.
Amendment 14
ARTICLE 2, PARAGRAPH 1, POINT (D), INDENT 2
its cellular or tissue part must be liable to act upon the human body with action that cannot be considered as ancillary to that of the devices referred to. its cellular or tissue part containing non-viable cells or tissues must be liable to act upon the human body with action that can be considered as primary to that of the devices referred to.Justification
A combined product should always be considered as advanced therapy medicinal product when it contains non-viable cells or tissues which act upon human body in a manner that is considered as primary to the action of the device part of the product concerned.
Amendment 15
ARTICLE 2, PARAGRAPH 1, POINT (D A) (new)
(da) chimera means:- an embryo into which a cell of any non-human life form has been introduced; or- an embryo of any non-human life form into which a human cell has been introduced; or- an embryo that consists of cells of more than one embryo, foetus or human being;Justification
This definition is introduced for the purpose of Article 3(c)(new) of the present Regulation.
Amendment 16
ARTICLE 2, PARAGRAPH 1, POINT (D B) (new)
(db) hybrid means:- a human ovum that has been fertilised by a sperm of a non-human life form;- an ovum of a non-human life form that has been fertilised by a human sperm;- a human ovum into which the nucleus of a cell of a non-human life form has been introduced;- an ovum of a non-human life form into which the nucleus of a human cell has been introduced; or- a human ovum or an ovum of a non-human life form that otherwise contains haploid sets of chromosomes from both a human being and a non-human life form.Justification
This definition is introduced for the purpose of Article 3(c) of the present Regulation. Source: Canadian assisted human reproduction act 2004.
Amendment 17
ARTICLE 3
Where an advanced therapy medicinal product contains human cells or tissues, the donation, procurement and testing of those cells or tissues shall be made in accordance with the provisions laid down in Directive 2004/23/EC.Where an advanced therapy medicinal product contains human cells or tissues, the donation, procurement and testing of those cells or tissues shall be made in accordance with the provisions laid down in Directive 2004/23/EC. The Committee for Medicinal Products for Human Use of the European Medicines Agency, hereinafter the Agency, shall verify the assurances (or the documentation) of the holder of the marketing authorisation with regard to the voluntary and unpaid donation of tissues and cells as laid down in Directive 2004/23/EC.
Amendment 18
ARTICLE 3 A (new)
Article 3a
Prohibition of commercialisation of the human body and its parts as such
Where an advanced therapy medicinal product contains human tissues or cells, every stage of the authorisation procedure shall be carried out in accordance with the principle of non-commercialisation of the human body or its parts as such. To that end, and for the purposes of this Regulation, Member States shall ensure that:
- the donation of human cells and tissues is voluntary and unpaid and is made of the donor's free will without payment except compensation; and
- the procurement of tissues and cells as such is carried out on a non-profit basis.Justification
Rapid developments in biotechnology and biomedicine must not undermine the protection of fundamental rights. These rights, of which a very important one is the person's integrity, are laid down in the the patenting directive, the Oviedo Convention and the Charter of Fundamental Rights.
Amendment 19
ARTICLE 3 B (new)
Article 3b
Prohibition of products modifying the human germ line.
No authorisation shall be granted for products which modify the germ line genetic identity of human beings, except for those intended to treat cancers of the gonads.Justification
As Articles 1 and 13 of the Oviedo Convention make it clear, human dignity is compromised when the inheritance of genetic identity is altered. Products which are neither properly subject to clinical trials under Directive 2001/20/EC nor legally patentable under Directive 98/44/EC should not be eligible for authorisation under this Regulation, with the exclusion of cancer treatment.
Amendment 20
ARTICLE 3 C (new)
Article 3c
Prohibition of products derived from human-animal hybrids or chimeras
No authorisation shall be granted for products derived from human-animal hybrids or chimeras or containing tissues or cells originating or derived therefrom.
This provision shall not preclude the transplantation of somatic animal cells or tissues to the human body for therapeutic purposes, in so far as it does not interfere with the germ line.Justification
The physical and mental integrity of the person and human dignity must be respected, as underlined by the Charter of fundamental rights of the EU. The creation of human-animal hybrids or chimeras is a breach of the right to integrity of a person and a violation of human dignity. In addition, the Directive 98/44/EC on the legal protection of biotechnological inventions stresses that the production of chimeras from germ cells is excluded from patentability. Therefore, no authorisation under this regulation should be granted to products containing or derived from such tissues and cells.
Amendment 21
ARTICLE 5, PARAGRAPH -1 (new)
The Commission shall, in accordance with the procedure referred to in Article 26(2), amend Directive 2003/94/EC to take into account the specific characteristics of advanced therapy medicinal product and, especially, tissue engineered products.Justification
Advanced therapy medicinal products have specific characteristics that differ greatly from traditional medicinal products. That leads to important differences in their manufacturing process (e.g. Article 11.4. of the GMP Directive requires that sample batches of finished products should be kept for 1 year after the expiry date. It is, however, difficult to consider expiry dates for certain classes of ATMPs).
Amendment 22
ARTICLE 7 A (new)
Article 7a
Specific requirements for products containing animal cells
In addition to the requirements laid down in this Regulation and the Annexes hereto, products containing non-human cells or tissues shall be authorised only where it is guaranteed that they will not give rise to problems relating to the identification of endogen retroviruses in the external cells and in the recipients, the possible creation of new viruses, possible immune reactions or the possible development of cancer.Or. {EN}en
Justification
The legal base of this regulation (Article 95 TEC) is a single market harmonisation measure. It is not designed to cover situations in which significant national legislative differences are intended to remain (c.f. ECJ Case C-376/98). It is therefore necessary to exclude from the scope of this regulation products using materials which are ethically controversial and for which differing Member States legislative provisions are intended to remain. In any case, products using these materials are unlikely to be ready to be placed on the market in the foreseeable future.
Amendment 23
ARTICLE 9, PARAGRAPH 2
2. The rapporteur or co-rapporteur appointed by the Committee for Medicinal Products for Human Use pursuant to Article 62 of Regulation (EC) No 726/2004 shall be a member of the Committee for Advanced Therapies. This member shall also act as rapporteur or co-rapporteur for the Committee for Advanced Therapies.2. The rapporteur or co-rapporteur appointed by the Committee for Medicinal Products for Human Use pursuant to Article 62 of Regulation (EC) No 726/2004 shall be a member of the Committee for Advanced Therapies, shall be proposed by the Committee for Advanced Therapies and shall possess specific expertise in relation to the product concerned. This member shall also act as rapporteur or co-rapporteur for the Committee for Advanced Therapies.Justification
In order to ensure the highest level of expertise, the rapporteur and co-rapporteur appointed by the CHMP should be proposed by the Committee for Advanced Therapies and should have specific expertise for the relevant product.
Amendment 24
ARTICLE 9, PARAGRAPH 3
3. The advice given by the Committee for Advanced Therapies under paragraph 1 shall be sent to the chairman of the Committee for Medicinal Products for Human Use in a timely manner so as to ensure that the deadline laid down in Article 6(3) of Regulation (EC) No 726/2004 can be met.
3. The draft opinion given by the Committee for Advanced Therapies under paragraph 1 shall be sent to the chairman of the Committee for Medicinal Products for Human Use in a timely manner so as to ensure that the deadlines laid down in Articles 6(3) or 9(2) of Regulation (EC) No 726/2004 can be met.Justification
Due to the highly specific and unique character of the advanced therapy medicinal products, a new Committee for Advanced Therapies is established within EMEA, composed of experts having specific qualifications or experience in this highly innovative and quickly developing field. Therefore, this new structure should be responsible for drafting an opinion on the quality, safety, and efficacy of products for the final approval by the CHMP. The draft opinion should be given in a timely manner so the deadline laid down in Article 9(2) of Regulation (EC) No 726/2004 can also be met.
Amendment 25
ARTICLE 14, PARAGRAPH 2
2. The package leaflet shall reflect the results of consultations with target patient groups to ensure that it is legible, clear and easy to use.2. Where products are exclusively applied to patients by medical practitioners, the summary of product characteristics pursuant to Article 11 of Directive 2001/83/EC may be used as the package leaflet.Justification
Since the predominant majority of Advanced Therapy Medicinal Products will not come into the hands of patients but will be applied by medical practitioners directly, information about the therapy, especially in cases of autologous products, must be given to patients even before the starting material is removed. Therefore the possibility should be introduced to use the summary of product characteristics as package leaflet. Because the package will not come into the hand of patients the necessity for consultations with target patient groups could be deleted.
Amendment 26
ARTICLE 15, PARAGRAPH 2, SUBPARAGRAPH 1
2. Where there is particular cause for concern, the Commission may, on the advice of the Agency, require as part of the marketing authorisation that a risk management system designed to identify, prevent or minimise risks related to advanced therapy medicinal products, including an evaluation of the effectiveness of that system, be set up, or that specific post-marketing studies be carried out by the holder of the marketing authorisation and submitted for review to the Agency.2. Where there is particular cause for concern, the Commission shall, on the advice of the Agency, require as part of the marketing authorisation that a risk management system designed to identify, prevent or minimise risks related to advanced therapy medicinal products, including an evaluation of the effectiveness of that system, be set up, or that specific post-marketing studies be carried out by the holder of the marketing authorisation and submitted for review to the Agency.Justification
In order to ensure the effectiveness of the risk management system, the Commission should have an obligation to require necessary measures to be carried out when there is a cause for concern.
Amendment 27
ARTICLE 17, PARAGRAPH 2
2. By way of derogation from Article 8(1) of Regulation (EC) No 297/95, a 90% reduction shall apply to the fee payable to the Agency for any advice referred to in paragraph 1 and in Article 57(1)(n) of Regulation (EC) No 726/2004 in respect of advanced therapy medicinal products.2. By way of derogation from Article 8(1) of Regulation (EC) No 297/95, a 95% reduction for SMEs and 70% for other applicants shall apply to the fee payable to the Agency for any advice referred to in paragraph 1 and in Article 57(1)(n) of Regulation (EC) No 726/2004 in respect of advanced therapy medicinal products.Justification
This Regulation seeks to encourage and support SME's in the development of ATMPs. Therefore, it is necessary to introduce special fee-waivers applicable to SME's on scientific advice. The 5% of the basic fee which the SME's should cover themselves is a symbolic amount, in order to prevent any abuse of the totally gratis system. Moreover, to support the applicants which do not fall under the SME criteria and to ensure the competitiveness of the whole sector, a reduction of 70% should be applied to all companies irrespective of their size.
Amendment 28
ARTICLE 18, PARAGRAPH 1
1. Any applicant developing a product based on cells or tissues may request a scientific recommendation of the Agency with a view to determining whether the referred product falls, on scientific grounds, within the definition of an advanced therapy medicinal product. The Agency shall deliver this recommendation after consultation with the Commission.1. Any applicant developing a product based on cells or tissues may request a scientific recommendation of the Agency with a view to determining whether the referred product falls, on scientific grounds, within the definition of an advanced therapy medicinal product. The Agency shall deliver this recommendation, after consultation with the Committee for Advanced Therapies and the Commission, within 60 days after receipt of the request.Justification
The proposed amendment foresees that an applicant will get clarity on the classification of the concerned product in a timely manner, thus facilitating business planning and further development of the product.
Amendment 29
ARTICLE 19 A (new)
Article 19a
Incentives for small and medium-sized biotech enterprises
1. Manufacturers of advanced therapy medicinal products which employ not more than 500 persons and have a turnover not exceeding EUR 100 million, or a balance-sheet total not exceeding EUR 70 million, shall be eligible for all incentives which are granted to small and mediumsized enterprises as defined in Commission Recommendation 2003/361/EC1.
2. The same shall apply to enterprises in which other enterprises have an interest up to 50%, if those enterprises invest more than 15% of their annual turnover in research and development activities.
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1 OJ L 124, 20.5.2003, p. 36.Justification
For many young biotech enterprises it is difficult to meet the criteria for an SME. One of the reasons is that a purchase or sale of a patent or platform technology may generate a big oneoff turnover which exceeds the current limitations. Another reason is that many enterprises don't comply with the current criteria of independence (interests below 25 %), since they built up alliances with other companies. These problems are likely to have the greatest relevance for biotech enterprises. These companies should nevertheless enjoy more favourable financial terms.
Amendment 30
ARTICLE 19 B (new)
Article 19b
Reduction of the fee for marketing authorisation
1. The fee for marketing authorisation shall be reduced by 50% if the applicant can prove that there is a particular public interest in the Community in the advanced therapy medicinal product or if the return on investment to be expected from the marketing of that product is small.
2. Paragraph 1 shall also apply to fees charged by the Agency for post-authorisation activities in the first year following the granting of the marketing authorisation for the medicinal product.
3. In the case of small and medium-sized enterprises or enterprises which employ not more than 500 persons and have a turnover not exceeding EUR 100 million, or a balance-sheet total not exceeding EUR 70 million, paragraph 1 shall also apply, without any time limit, to the fees charged by the Agency for post-authorisation activities.
4. In the case of an enterprise in which other enterprises have an interest up to 50% and which invests more than 15% of its annual turnover in research and development activities, paragraph 1 shall also apply, without any time limit, to the fees charged by the Agency for post-authorisation activities.Justification
Reductions of the fee for marketing authorisations is necessary in cases of ATMPs serving public interest like orphan drugs or where the applicant is an SME. For those products and enterprises the centralised procedure is a big administrative burden which should be eased by minimised fees. The stipulated cost reductions are also necessary in case of autologous ATMPs and those for intended use because these products can only be introduced into the market to a limited extent.
Amendment 31
ARTICLE 21, PARAGRAPH 1, POINT (C)
(c) four members appointed by the Commission, on the basis of a public call for expressions of interest, two of them to represent surgeons and two of them to represent patients associations.(c) four members appointed by the Commission, on the basis of a public call for expressions of interest, two of them to represent physicians and two of them to represent patients associations.Justification
For the sake of being more precise it is necessary to apply the technical term.
Amendment 32
ARTICLE 21, PARAGRAPH 1, POINT (C) AND POINT (C A) (new)
(c) four members appointed by the Commission, on the basis of a public call for expressions of interest, two of them to represent surgeons and two of them to represent patients associations.(c) two members and two alternates appointed by the Commission, on the basis of a public call for expressions of interest and after consultation of the European Parliament, to represent physicians;(ca) two members and two alternates appointed by the Commission, on the basis of a public call for expressions of interest and after consultation of the European Parliament, to represent patients associations.Justification
In order to cover all medical fields which the advanced therapies may relate to, more general medical expertise, i.e. medical doctors, should be represented in the Committee for Advanced Therapies . In addition, by introducing alternate members, we would like to ensure a permanent representation of the groups involved. The appointment of these members and their alternates should take place in consultation with the European Parliament.
Amendment 33
ARTICLE 21, PARAGRAPH 2
2. All members of the Committee for Advanced Therapies shall be chosen for their scientific qualification or experience in respect of advanced therapy medicinal products. For the purposes of point (b) of paragraph 1, the Member States shall cooperate, under the coordination of the Executive Director of the Agency, in order to ensure that the final composition of the Committee for Advanced Therapies appropriately and in a balanced way covers the scientific areas relevant to advanced therapies, including medical devices, tissue-engineering, gene therapy, cell therapy, biotechnology, pharmacovigilance, risk management and ethics.2. All members and alternates of the Committee for Advanced Therapies shall be chosen for their scientific qualification or experience in respect of advanced therapy medicinal products. For the purposes of point (b) of paragraph 1, the Member States shall cooperate, under the coordination of the Executive Director of the Agency, in order to ensure that the final composition of the Committee for Advanced Therapies, appropriately and in a balanced way covers the scientific areas relevant to advanced therapies, including medical devices, tissue-engineering, gene therapy, cell therapy, biotechnology, pharmacovigilance, risk management and ethics.Justification
The alternate members of the Committee for Advanced therapies introduced in paragraph 1 shall comply with the same criteria of scientific qualification or experience in the field of advanced therapy medicinal products as its members.
Amendment 34
ARTICLE 23, POINT (A)
(a) to advise the Committee for Medicinal Products for Human Use on any data generated in the development of an advanced therapy medicinal product, for the formulation of an opinion on its quality, safety and efficacy;(a) to formulate a draft opinion on the quality, safety and efficacy of an advanced therapy medicinal product for final approval by the Committee for Medicinal Products for Human Use and to advise it on any data generated in the development of such a product; Justification
Due to the highly specific and unique character of the advanced therapy medicinal products, a new Committee for Advanced Therapies is established within EMEA, composed of experts having specific qualification or experience in this highly innovative and quickly developing field. Therefore, the new structure should be responsible for drafting an opinion on the quality, safety, and efficacy of products for the final approval by the CHMP. Furthermore, the committee should be consulted for the evaluation of other products under its competence.
Amendment 35
ARTICLE 23, POINT (A A) (new)
(aa) to provide advice, pursuant to Article 18, to the Committee for Medicinal Products for Human Use on whether a product falls within the definition of an advanced therapy medicinal product;Justification
Having specific expertise in advanced therapy medicinal products, the Committee for Advanced Therapies should assist the CHMP in its classification task of whether a product is or is not an advanced therapy medicinal product.
Amendment 36
ARTICLE 23, PARAGRAPH 1 A (new)
When preparing a draft opinion for final approval by the Committee for Medicinal Products for Human Use, the Committee for Advanced Therapies shall endeavour to reach a scientific consensus. If such consensus cannot be reached, the Committee for Advanced Therapies shall adopt the position of the majority of its members. The draft opinion shall mention the divergent positions and the grounds on which they are based.Justification
In order to guarantee transparency in the process of preparation of a draft opinion, a clear decision procedure should be defined within Committee for Advanced Therapies. Consequently, we suggest that a scientific consensus should be reached by its members.
Amendment 37
ARTICLE 24
The Commission shall, in accordance with procedure referred to in Article 26(2), amend Annexes I to IV in order to adapt them to scientific and technical evolution.The Commission shall, in accordance with procedure referred to in Article 26(2), amend Annexes II to IV in order to adapt them to scientific and technical evolution.Justification
Annex I contains a fundamental and substantial definition. We therefore consider that it should not be subject to any changes through comitology. Should any changes be necessary due to scientific progress, they should be adopted in codecision, fully involving the European Parliament.
Amendment 38
ARTICLE 25
Reporting
Within 5 years of entry into force of this Regulation, the Commission shall publish a general report on its application, which shall include comprehensive information on the different types of advanced therapy medicinal products authorised pursuant to this Regulation.Report and review
Within 5 years of entry into force of this Regulation, the Commission shall publish a general report on its application, which shall include comprehensive information on the different types of advanced therapy medicinal products authorised pursuant to this Regulation.
In that report, the Commission shall also assess the impact of technical progress on the application of this Regulation and, if necessary, submit a legislative proposal for a review of its scope to include novel therapies which are neither gene therapy, nor cell therapy nor tissue engineering.Justification
Scientific advances may make additional novel therapies possible which are neither gene therapy, nor cell therapy nor tissue engineering. It would be in the interest of patients for these to be included at some future date in order to allow European authorisation of the resulting products.
Amendment 39
ARTICLE 25 A (new)
Article 25a The Commission shall by no later than the end of 2007 submit a legislative proposal in order to ensure that products used for cosmetic purposes which contain human or animal cells or tissues are also covered by adequate Community legislation.Justification
Until now products used for cosmetic purposes containing human or animal cells or tissues, although already being placed on the market, are not regulated under Community law. This regulation gap needs to be closed.
Amendment 40
ARTICLE 26, PARAGRAPH 2, SUBPARAGRAPH 1
2. Where reference is made to this paragraph, Articles 5 and 7 of Decision 1999/468/EC shall apply, having regard to the provisions of Article 8 thereof.
2. Where reference is made to this paragraph, and without prejudice to Article 26a, Articles 5 and 7 of Decision 1999/468/EC shall apply, having regard to the provisions of Article 8 thereof.Justification
This is a consequential amendment to the introduction of the new Article 26(a) below.
Amendment 41
ARTICLE 26 A (new)
Article 26a
Without prejudice to the implementing measures already adopted, on 1 April 2008 at the latest, the application of the provisions of this Regulation requiring the adoption of technical rules, amendments and decisions shall be suspended. Acting on a proposal from the Commission, the European Parliament and the Council may renew the provisions concerned in accordance with the procedure laid down in Article 251 of the Treaty and, to that end, they shall review them prior to the expiry of the date referred to above.
The first paragraph shall apply until such time as it is superseded by a new agreement on comitology.Justification
This amendment is preliminary tabled until the new comitology procedure is adopted which ensures more control by the Parliament.
Amendment 42
ARTICLE 27, POINT 2
Annex, point 1 a (Regulation (EC) No 726/2004)
1a. Advanced therapy medicinal products, as defined in Regulation (EC) No [
/of the European Parliament and of the Council (Regulation on Advanced Therapy Medicinal Products)*].1a. Advanced therapy medicinal products, as defined in Regulation (EC) No [
/of the European Parliament and of the Council (Regulation on Advanced Therapy Medicinal Products)*], except for advanced therapy medicinal products for autologous or intended use which are exclusively manufactured and distributed in one Member State and for which that Member State has envisaged the national marketing authorisation procedure in accordance with the criteria of this Regulation as an alternative, for a period of five years subsequent to the granting of the marketing authorisation at national level. Afterwards an application for a single renewal within the centralised procedure shall be necessary, with the effect that, after the renewal, the national marketing authorisation will become a centralised marketing authorisation.Justification
In order to facilitate the stage of market entry for many SMEs wanting to market their product only in one member state, a marketing authorisation at national level for products marketed at national level should be rendered possible. This national marketing authorisation should be limited to a period of five years. The renewal after this first period of five years can be conducted through a centralised marketing authorisation.
Amendment 43
ARTICLE 28, POINT 2
5. This Directive and all Regulations referred to therein shall not affect the application of national legislation prohibiting or restricting the use of any specific type of human or animal cells, or the sale, supply or use of medicinal products containing, consisting of or derived from these cells. The Member States shall communicate the national legislation concerned to the Commission.5. This Directive and all Regulations referred to therein shall not affect the application of national legislation prohibiting or restricting the use of any specific type of human or animal cells, or the sale, supply or use of medicinal products containing, consisting of or derived from these cells, by virtue of the Article 30 of the Treaty establishing the European Community.Justification
As this regulation is a partially harmonizing measure, it should be made clear that Member States has the right to refer to the Article 30 of the TEC when it comes to the access of certain medicinal products to their market. With regard to the Article 95, paragraph 4 of the TEC, the obligation to communicate the national legislation concerned to the Commission is only appropriate if the community measure is a fully harmonizing one.
Amendment 44
ARTICLE 28 A (new)
Article 2, paragraph 1 (Directive 2004/23/EC)
Article 28a
Amendment to Directive 2004/23/EC
In Article 2(1) of Directive 2004/23/EC, the second subparagraph shall be replaced by the following:
"Where such manufactured products are covered by other Community legislation, this Directive shall apply only to donation, procurement and testing. However, the donation, procurement and testing provisions of this Directive shall be without prejudice to more specific provisions contained in other Community legislation."Justification
According to the existing legislation, the donation, procurement and testing of human tissues and cells should comply with high standards of quality and safety in order to ensure a high level of health protection in the Community. Moreover, it also has to be ensured that the human body or its parts as such are not commercialised. Therefore, for the purposes of this Regulation, Member States shall have an imperative obligation to ensure voluntary and unpaid donation and to guarantee that the procurement of tissues or cells is carried out on a non-profit basis.
Amendment 45
ARTICLE 29, PARAGRAPH 1
1. Advanced therapy medicinal products which were legally on the Community market in accordance with national or Community legislation at the time of entry into force of this Regulation shall comply with this Regulation no later than 2 years after its entry into force.1. For advanced therapy medicinal products, other than tissue engineered products, which were legally on the Community market in accordance with national or Community legislation at the time of entry into force of this Regulation, an application for a marketing authorisation shall be filed no later than five years after the entry into force of this Regulation.
Justification
The envisaged Transitional period of two years is too short, since the duration of the clinical trials alone will in many cases exceed the proposed time period. Furthermore the applicant should only be responsible for the date of filing the application and not for delays due to the Agency/national competent authorities or problems during the assessment phase. Otherwise, it could deprive patients from these important new medicinal products.
Amendment 46
ARTICLE 29, PARAGRAPH 1 A (new)
1a. For tissue engineered products which are legally on the Community market in accordance with national or Community legislation at the time of entry into force of the technical requirements referred to in Article 8, an application for a marketing authorisation shall be filed no later than five years after the entry into force of the technical requirements referred to in Article 8.Justification
The envisaged Transitional period of two years is too short, since the duration of the clinical trials alone will in many cases exceed the proposed time period. Furthermore the applicant should only be responsible for the date of filing the application and not for delays due to the Agency/national competent authorities or problems during the assessment phase. Otherwise, it could deprive patients from these important new medicinal products.
Amendment 47
ANNEX II, POINT 2.2.
2.2. qualitative and quantitative composition in terms of the active substances and other constituents of the product, knowledge of which is essential for proper use, administration or implantation of the product. Where the product contains cells or tissues, a detailed description of these cells or tissues and of their specific origin shall be provided.2.2. qualitative and quantitative composition in terms of the active substances and other constituents of the product, knowledge of which is essential for proper use, administration or implantation of the product. Where the product contains cells or tissues, a detailed description of these cells or tissues and of their specific origin, including the species of animal in cases of non-human origin, shall be provided.Justification
This amendment aims at ensuring that potential recipients having various cultural considerations are duly informed before taking their decision.
Amendment 48
ANNEX III, POINT (B)
(b) A description of the active substance(s) expressed qualitatively and quantitatively, including, where the product contains cells or tissues, the statement This product contains cells of human/animal [as appropriate] origin together with a short description of these cells or tissues and of their specific origin;(b) A description of the active substance(s) expressed qualitatively and quantitatively, including, where the product contains cells or tissues, the statement This product contains cells of human/animal [as appropriate] origin together with a short description of these cells or tissues and of their specific origin, including the species of animal in cases of non-human origin;Justification
This amendment aims at ensuring that potential recipients having various cultural considerations are duly informed before taking their decision.
Amendment 49
ANNEX IV, POINT (A), POINT (III)
(iii) where the product contains cells or tissues, a description of those cells or tissues and of their specific origin;(iii) where the product contains cells or tissues, a description of those cells or tissues and of their specific origin, including the species of animal in cases of non-human origin;Justification
This amendment aims at ensuring that potential recipients having various cultural considerations are duly informed before taking their decision.
PROCEDURE
TitleProposal for a regulation of the European Parliament and of the Council on advanced therapy medicinal products and amending Directive 2001/83/EC and Regulation (EC) No 726/2004ReferencesCOM(2005)0567 C60401/2005 2005/0227(COD)Committee responsibleENVIOpinion by Date announced in plenaryJURI23.3.2006Enhanced cooperation date announced in plenary18.5.2006Drafts(wo)man Date appointedHiltrud Breyer19.4.2006Previous drafts(wo)manDiscussed in committee30.5.200622.6.2006Date adopted13.7.2006Result of final vote+:
:
0:13
8
1Members present for the final voteMaria Berger, Carlo Casini, Monica Frassoni, Giuseppe Gargani, Piia-Noora Kauppi, Katalin Lévai, Hans-Peter Mayer, Aloyzas S a k a l a s , D a n i e l S t r o ~, D i a n a W a l l i s , R a i n e r W i e l a n d , T a d e u s z Z w i e f k a S u b s t i t u t e ( s ) p r e s e n t f o r t h e f i n a l v o t e H i l t r u d B r e y e r , M a n u e l M e d i n a O r t e g a , M a r i e P a n a y o t o p o u l o s - C a s s i o t o u , M i c h e l R o c a r d S u b s t i t u t e ( s ) u n d e r R u l e 1 7 8 ( 2 ) p r e s e n t f o r t h e f i n a l v o t e S h a r o n B o w l e s , E s t h e r H e r r a n z G a r c ķ a , M i e c z y s Ba w E d m u n d J a n o w s k i , P e t e r L i e s e , M a r i a M a r t e n s , M i r o s l a v M i k o l į ai k C o m m e n t s ( a v a i l a b l e i n o n e l a n g u a g e o n l y ) . . .
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