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# 52003PC0163(01)

**Amended proposal for a Directive of the European Parliament and of the Council amending Directive 2001/83/EC on the Community code relating to medicinal products for human use (presented by the Commission pursuant to Article 250 (2) of the EC Treaty) /\* COM/2003/0163 final - COD 2001/0253 \*/**

  

Amended proposal for a DIRECTIVE OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL amending Directive 2001/83/EC on the Community code relating to medicinal products for human use (presented by the Commission pursuant to Article 250 (2) of the EC Treaty)

2001/0253 (COD)

Amended proposal for a DIRECTIVE OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL amending Directive 2001/83/EC on the Community code relating to medicinal products for human use

(Text with EEA relevance)

1. Background

Proposal sent to the Council and Parliament COM(2001) 404 final -2001/0253(COD)under Article 175(1)

of the EC Treaty: 26 November 2001

Opinion of the European Economic and Social Committee: 18 September 2002

Position of the European Parliament - first reading: 23 October 2002

2. Objective of the Commission proposal

Regulation 2309/93 makes provision for the evaluation of the Community procedures for the authorisation and supervision of medicinal products which entered into force in 1995. In the light of the experience acquired from 1995 to 2000, and the Commission's analysis in its report "on the operation of the procedures for granting marketing authorisations for medicinal products" (COM (2001) 606 final, 23.10.2001), it appeared necessary to adapt Regulation 2309/93 and Directives 2001/83/EC and 2001/82/EC on the Community code relating to medicinal products for human use and for veterinary use.

Generally speaking, four main objectives are particularly relevant:

(1) to guarantee a high level of public health protection, particularly by providing patients, as swiftly as possible, with innovative and reliable products and by increasing market surveillance by reinforcing monitoring and pharmacovigilance procedures;

(2) to complete the internal market in pharmaceutical products while taking account of the implications of globalisation, and to establish a regulatory and legislative framework that favours the competitiveness of the European pharmaceuticals sector;

(3) to meet the challenges of the future enlargement of the European Union;

(4) to rationalise and simplify the system, thus improving its overall consistency and visibility, and the transparency of procedures.

Lastly, with regard to veterinary medicinal products, the proposals intend to specifically address the problem of availability of such medicinal products.

3. Commission opinion on Parliament's amendments

3.1. Amendments accepted by the Commission: 2, 13, 24, 25, 33, 35, 42, 43, 44, 47, 48, 50, 57, 58, 61, 67, 68, 70, 82, 83, 84, 88, 89, 93, 97, 110, 120 (first part), 125, 130 and 158.

The Commission can accept the following amendments with the wording proposed by the European Parliament.

- Amendment 2, which introduces into recital 2 the reference to a "safe" movement of medicinal products:

"Recital 2:

Community legislation is a major milestone in the achievement of the objective of the free and safe movement of medicinal products for human use and the elimination of obstacles to trade in such products. However, in the light of the experience acquired, new measures have proved necessary to eliminate the remaining obstacles to free movement."

- Amendment 13, that deletes in the definition of "radionuclide kit" the word "radionuclide". To maintain coherence with certain provisions of the Directive, it is necessary to align the provisions of Article 6(2) and of Article 7:

"Title of Article 1, point 8:

8) Kit.

Article 6(2):

2. The authorisation referred to in paragraph 1 shall also be required for radionuclide generators, kits, radionuclide precursor radiopharmaceuticals and industrially prepared radiopharmaceuticals.

"Article 7:

A marketing authorisation shall not be required for a radiopharmaceutical prepared at the time of use by a person or by an establishment authorised, according to national legislation, to use such medicinal products in an approved health care establishment exclusively from authorised radionuclide generators, kits or radionuclide precursors in accordance with the manufacturer's instructions."

- Amendment 24 reinforcing the means to respond to the threat of bioterrorist attacks:

"Article 5

1. Without prejudice to Regulation [(EEC) No 2309/93], a Member State may, in accordance with legislation in force and to fulfil special needs, exclude from the provisions of this Directive medicinal products supplied in response to a bona fide unsolicited order, formulated in accordance with the specifications of an authorised health care professional and for use by an individual patient under his direct personal responsibility.

2. Member States may temporarily authorise the distribution of an unauthorised medicinal product in response to the suspected or confirmed spread of a pathogen which could cause harm.

Without prejudice to paragraph 1, Member States must lay down provisions removing criminal, civil and administrative liability from marketing authorisation holders, manufacturers and health professionals for any consequences resulting from the use of a medicinal product other than for the authorised indications or from the use of an unauthorised medicinal product, when such use is recommended by a competent authority in response to the suspected or confirmed spread of pathogenic agents which could cause harm. Such provisions shall apply whether or not national or Community authorisation has been issued."

- Amendment 25 regarding the documents to be submitted by the applicant on the constituents of the medicinal product:

"Article 8(3)(c):

c) Qualitative and quantitative particulars of all the constituents of the medicinal product, including the reference to its international non-proprietary name (INN) recognised by the WHO, where an INN for the medicinal product exists, or a reference to the relevant chemical name;"

- Amendment 33, according to which an applicant has to submit documents to proof that he/she will be able to meet certain pharmacovigilance obligations:

"Article 8(3)(n):

n) Proof that the applicant has the services of a qualified person responsible for pharmacovigilance and has equipment for the notification of any adverse reaction suspected of occurring either in the Community or in a third country."

- Amendment 35 that clarifies that the data protection period of 11 years constitutes the maximum time:

"Article 10(1), second subparagraph:

The ten-year period referred to in the first subparagraph shall be extended to a maximum of eleven years if, during the first eight years of those ten years, the marketing authorisation holder obtains an authorisation for one or more new therapeutic indications which, during the scientific evaluation prior to their authorisation, are held to bring a significant clinical benefit in comparison with existing therapies."

- Amendment 42, according to which the summary of the product characteristics shall contain certain information in the prescribed order:

"Article 11, introductory sentence:

The summary of the product characteristics shall contain, in the order indicated below, the following information:."

- Amendment 43, that reintroduces "major incompatibilities" into the summary of the product characteristics in the section on pharmaceutical particulars:

"Article 11(6), point 6.1a:

6.1a major incompatibilities."

- Amendment 44, that reintroduces a provision according to which homeopathic products authorised or registered before December 1993 do not need to be updated according to the new legislation:

"Article 13(1):

1. Member States shall ensure that homeopathic medicinal products manufactured and placed on the market within the Community are registered or authorised in accordance with Articles 14, 15 and 16, except where such medicinal products are covered by a registration or authorisation issued in accordance with national legislation up to 31 December 1993. Each Member State shall take due account of the registrations and authorisations issued by other Member States."

- Amendment 47 on the dossier to be submitted for a simplified registration of a homeopathic medicinal product:

"Article 15, second indent:

- dossier describing how the homeopathic stock or stocks is/are obtained and controlled, and justifying its/their homeopathic use, on the basis of an adequate bibliography,"

- Amendment 48 on certain particulars to be submitted in an application for simplified registration of a homeopathic medicinal product. It is acceptable to delete the reference to the method of dilution.

"Article 15, third indent:

- manufacturing and control file for each pharmaceutical form and a description of the method of potentisation,"

- Amendment 50, introducing a correction in the reference to Article 8(3):

"Article 18

Where a Member State is informed in accordance with point (l) of Article 8(3) that another Member State has authorised a medicinal product which is the subject of a marketing authorisation application in the Member State concerned, it shall reject the application unless it has been submitted in compliance with Articles 27 to 39."

- Amendments 57 and 58 on the invalidity of a marketing authorisation where the authorised product is not effectively marketed:

"Article 24(2) and (3):

2. Any authorisation which is not followed within three years of its issue by the actual placing on the market of the authorised product in the authorising Member State shall cease to be valid.

The competent authority may, in exceptional circumstances and on public health grounds, grant a derogation from the provisions of the previous subparagraph. The derogation shall be duly justified.

3. When an authorised product previously placed on the market in the authorising Member State is no longer actually present on the market for a period of three consecutive years, the authorisation for that product shall cease to be valid.

The competent authority may, in exceptional circumstances and on public health grounds, grant a derogation from the provisions of the previous subparagraph. The derogation shall be duly justified."

- Amendment 61 according to which the rules of procedure of the co-ordination group are to be made public:

"Article 27(3):

3. The coordination group shall draw up, its own Rules of Procedure, which shall enter into force after a favourable opinion of the Commission. These Rules of Procedure shall be made public."

- Amendment 67, which is intended to ensure that the Committee appoints a rapporteur when the arbitration procedures are examined:

"Article 32(2):

2. In order to consider the matter, the Committee shall appoint one of its members to act as the rapporteur. The Committee may also appoint individual experts to advise it on specific questions. When appointing experts, the Committee shall define their tasks and specify the time-limit for the completion of these tasks."

- Amendment 68 according to which the committee shall specify the time limit for explanations by the applicant:

"Article 32(3), first subparagraph:

3. Before issuing its opinion, the Committee shall provide the applicant or the marketing authorisation holder with an opportunity to present written or oral explanations within a time-limit which it shall specify."

- Amendment 70 which reduces the time limit for the Commission to prepare a draft decision from 30 to 15 days:

"Article 33, first subparagraph:

Within 15 days of the receipt of the opinion the Commission shall prepare a draft of the decision to be taken in respect of the application, taking into account Community law."

- Amendment 82 including into the package leaflet a specific invitation to consult health-care professionals in certain situations:

"Article 59(1)(e), indent (viii):

viii) a specific invitation to consult the doctor or the pharmacist, as appropriate, for any clarification on the use of the product;"

- Amendment 83 which adds the manufacturer's contact details to the information which must be included in the package leaflet:

"Article 59(1)(f), indent via):

via) the name and address of the manufacturer;"

- Amendment 84 on an assessment of the legibility and clarity of package leaflets:

"Article 59(3):

3. The legibility, clarity and ease of use for patients of the package leaflet shall be assessed in consultation with target patient groups."

- Amendment 88 on information on the manufacturer of a vial:

"Article 66(3), fourth indent:

- the name and address of the manufacturer,"

- Amendment 89 on the labelling of homeopathic medicinal products:

"Article 68

Without prejudice to the provisions of Article 69, homeopathic medicinal products shall be labelled in accordance with the provisions of this title and shall be identified by a reference on their labels, in clear and legible form, to their potentised nature."

- Amendment 93 changing the heading of Title VII:

"Title VII:

Wholesale distribution of medicinal products "

- Amendment 97 which extends the application of Title VII to all homeopathic medicinal products by deleting the words "with the exception of those referred to in Article 14(1)":

"Article 85

The provision of this Title shall apply to homeopathic medicinal products."

- Amendment 110 on clarifying the notion of advertising in the context of professional and scientific meetings:

"Article 95

The provisions of Article 94(1) shall not prevent hospitality being offered, directly or indirectly, at events for purely professional and scientific purposes; such hospitality shall always be strictly limited to the main scientific objective of the meeting; it must not be extended to persons other than health professionals."

- The first part of amendment 120 clarifying how to calculate when the periodic safety update reports have to be presented:

"Article 104(6):

6, Unless other requirements have been laid down as a condition of the granting of authorisation, or subsequently as indicated in the guidelines referred to in Article 106(1), reports of all adverse reactions shall be submitted to the competent authorities in the form of a periodic safety update report, either immediately upon request or periodically as follows: six monthly for the first two years after the medicinal product was first placed on the market, annually for the subsequent two years, and thereafter at three-yearly intervals. The periodic safety update reports shall include a scientific evaluation of the benefits and risks of the medicinal product."

- Amendment 125 on the possibility of unannounced inspections by the competent authorities:

"Article 111(1), second subparagraph:

The competent authority may also carry out unannounced inspections at the premises of manufacturers of active substances used as starting materials, or at the premises of marketing authorisation holders whenever it considers that there are serious grounds for suspecting non-compliance with the principles and guidelines of good management practice referred to in Article 47. These inspections may also be carried out at the request of a Member State, the Commission or the Agency."

- Amendment 130 according to which the Rules of Procedure of the Standing Committee shall be made publicy:

"Article 121(5):

5. The Standing Committee shall adopt its own rules of procedure, which shall be made public."

- Amendment 158 according to which in the name of a homeopathic medicinal product, the scientific names can be supplemented, but not be replaced by an invented name:

"Article 69(1), first indent:

- the scientific name of the stock or stocks followed by the degree of dilution, making use of the symbols of the Pharmacopoeia used in accordance with Article 1(5); if the homeopathic medicinal product is composed of two or more stocks, the scientific names of the stocks on the labelling may be supplemented by an invented name."

3.2. Amendments accepted in part or principle by the Commission: 3, 5, 8, 11, 12, 14, 15, 18, 27, 30, 31, 32, 36, 46 (first part), 51, 52, 53 (first part), 55, 60, 63, 66, 69, 71 (second part), 80, 85, 86, 91, 92 (second part), 94, 95, 98, 99, 104, 106, 108, 114, 116 (first part), 121, 122, 140, 151, 156, 159, 167, 168, 185, 186 and 191.

The Commission can accept in principle the following amendments:

- Amendment 3 introducing into recital 3 a reference to the high level of public health protection:

"Recital 3:

It is therefore necessary to align the national laws, regulations and administrative provisions which contain differences with regard to the basic principles in order to promote the operation of the internal market, while realising a high level of human health protection."

- Amendments 5 and 32 on the necessity to fulfil the relevant ethical criteria for all clinical trials submitted for a new medicinal product. Bearing in mind that these criteria have already been made obligatory by Directive 2001/20/EC, a similar provision in Directive 2001/83/EC is redundant. However, a recital can be introduced to refer to these ethical criteria:

"Recital 10a:

There is a need to provide for the ethical requirements of Directive 2001/20/EC of the European Parliament and the Council 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 to apply to all medicinal products authorised within the Community. In particular, with respect to clinical trials conducted outside the Community on medicinal products destined to be authorised within the Community, at the time of the evaluation of the application for authorisation, it will be verified that these trials were conducted respecting the principles of good clinical practice and the ethical requirements equivalent to the provisions of this Directive."

- Amendments 8 and 140 introduce a recital to justify the proposed provision to allow patients to obtain information on certain prescription medicinal products with regard to three illnesses. Rewording is required to ensure consistency with Recital 16, already proposed by the Commission, which relates to this same provision:

"Recital 16:

As part of the proper use of medicinal products, the rules on packaging should be adapted to take account of the experience acquired.

Recital 16a:

Patients legitimately need and expect information on medicinal products. With regard to medicinal products which require a prescription, in order to meet these needs and expectations, strict conditions must be applied to authorisation to access information on certain medicinal products in the interest of the patients. This information must not be in the form of advertising or direct promotion of medicinal products subject to prescription."

- Amendment 11 on further clarifications of the definition of a medicinal product. A reformulation is needed to refer, in addition to pharmacological action, to immunological and metabolic action. This addition helps to better specify the definition of medicinal product and is in line with Article 1(2)(a) of Council Directive 93/42/EEC on medical devices:

"Article 1, point 2 b:

b) Any substance or combination of substances which may be used in human beings either with a view to making a medical diagnosis or to restoring, correcting or modifying physiological functions by exerting a pharmacological, immunological or metabolic action."

- Amendment 12 deleting certain parts in the definition of a homeopathic medicinal product. A rewording is needed to reintroduce the reference to homeopathic stocks, which are an important step in producing a homeopathic medicinal product.

"Article 1, point 5

5) Homeopathic medicinal product:

Any medicinal product prepared from substances called homeopathic stocks in accordance with a homeopathic manufacturing procedure described by the European Pharmacopoeia or, in absence thereof, by the pharmacopoeias currently used officially in the Member States. A homeopathic medicinal product may contain a number of principles."

- Amendment 14 introducing a definition of the local representative. A rewording is necessary to bring the notion in line with the wording already used in the text of the directive:

"Article 1, point 18a)

18a) Representative of the marketing authorisation holder:

The person, commonly known as local representative, designated by the marketing authorisation holder to represent him in the Member State concerned. Any delegation of activities to this person by the market authorisation holder shall not relieve the latter of his legal responsibility."

- Amendment 15 introducing a definition of the risk/benefit balance. A rewording is necessary to distinguish between the effects on the patient and on the environment:

"Article 1, points 28, 29 and 30:

(28) Risks related to use of the medicinal product

- any risk relating to the quality, safety and efficacy of the medicinal product as regards the health of patients;

(29) Risks related to the environment

- any risk of unwanted effects on the environment;

(30) Risk/benefit balance:

An evaluation of the positive therapeutic effects of the medicinal product in relation to the risks as defined above."

- Amendment 18 on the situation that a given product could fulfil the definition of different regulatory regimes. In order to improve the legal certainty, the provision of Article 2(2) needs to be maintained. But its objective can be clarified by amending Recital 7. A rewording of this recital allows equally taking account of amendments 20, 21, 22 and 23 on the exclusion of food, food supplements, medical devices and cosmetics from the scope of Directive 2001/83/EC. While it is unnecessary to add a provision in the operative part of the Directive, the underlying idea can be stated in a recital:

"Recital 7:

Particularly as a result of scientific and technical progress, the definitions and scope of Directive 2001/83/EC should be clarified in order to achieve high standards for the quality, safety and efficacy of medicinal products for human use. In order to take account, both of the emergence of new therapies and of the growing number of so-called "borderline" products between the medicinal product sector and other sectors, the definition of "medicinal product" should be modified so as to avoid any doubt as to the applicable legislation, when a product, whilst fully falling within the definition of a medicinal product, may also fall within the definition of other regulated products. With the same objective to clarify situations, where a given product comes under the definition of a medicinal product, but could also fulfil the definition of other regulated products, it is necessary, in case of doubt and in order to provide legal certainty, to state explicitely which provisions have to be complied with. Where a product comes clearly under the definition of other product categories, in particular food, food supplements, medical devices or cosmetics, this Directive does not apply. It is also worth taking advantage of this opportunity to improve the consistency of the terminology of pharmaceutical legislation."

- Amendments 27 and 30 on certain particulars and documents to be submitted with an application for marketing authorisation to be part of the dossier in all cases. The words "if applicable" are deleted so as to make the requirement applicable in all cases.

"Article 8(3)(g):

g) Reasons for any precautionary and safety measures to be taken for the storage of the medicinal product, its administration to patients and for the disposal of waste products, together with an indication of any potential risks presented by the medicinal product for the environment."

- Amendment 31 requiring the applicant to submit detailed information on pharmacovigilance and on risk-management systems. A rewording is necessary since risk-management systems are not necessary for all medicinal products:

"Article 8(3), point ia:

ia) A detailed description of the pharmacovigilance and, where appropriate, of the risk-management system which the applicant will introduce."

- Amendment 36 allowing an abridged application for a generic product in a Member State even if the reference product has not been authorised in that particular Member State, but only in another Member State. As this exception is intrinsically linked to the provision of Article 10(1), it should be introduced into this same paragraph rather than constituting a separate paragraph:

"Article 10(1), second indent:

The first indent shall also apply, if the reference medicinal product has not been authorised in the Member State where the application for the generic medicinal product is submitted. In this case, the applicant has to indicate in the application the name of the Member State where the reference medicinal product is or has been authorised. On request of the competent authority of the Member State where the application is submitted, the competent authority of the other Member State shall transmit within a period of one month, a copy of the dossier and of the marketing authorisation of the reference medicinal product."

- The first part of Amendment 46 on the sufficient degree of dilution. Where it can be accepted to replace the term "dilution" by "potentisation" a rewording is needed to keep the word "active principles" in line with the Directive's terminology.

"Article 14(1), third indent:

there is a sufficient degree of potentisation, which involves a sequential series of dilutions or succussions, to guarantee the safety of the medicinal product; in particular, the medicinal product may not contain either more than one part per 10 000 of the mother tincture or more than 1/100th of the smallest dose used in allopathy with regard to active substances whose presence in an allopathic medicinal product results in the obligation to submit a doctor's prescription."

- Amendment 51 on ways to make information on marketing authorisations available to the general public. A rewording is necessary as neither the marketing authorisation nor the summary of the product characteristics contain any confidential information whose publication could be objected by the authorisation holder:

"Article 21(3):

3. The competent authorities shall make publicly available without delay the marketing authorisation together with the summary of the product characteristics for each medicinal product which it has authorised."

- Amendment 52 and the first part of amendment 53 on making publicly available the assessment report and the scientific reasoning. The contents of these amendments can be integrated in Article 21(4), second subparagraph which has to be reformulated:

"Article 21(4), second subparagraph:

The competent authorities shall make publicly accessible without delay the assessment report, together with the reasons for their opinion, after deletion of information of a commercially confidential nature."

- Amendment 55 specifying the specific obligations under which a conditional marketing authorisation may be granted. The provision needs to be reworded as the specific mechanism could concern other issues than those explicitly listed:

"Article 22, first subparagraph:

In exceptional circumstances, and following consultation with the applicant, authorisation may be granted subject to a requirement to introduce specific procedures, in particular concerning product safety, notification of the relevant authorities of any incident related to its use and any action to be taken. Such authorisation may be granted only for objective, verifiable reasons. The maintenance of the authorisation is bound to the annual reassessment of these requirements."

- Amendment 60 stressing the applicant's responsibility that the submitted data is correct and has not been falsified. A rewording is necessary since criminal sanctions cannot be foreseen in Directive 2001/83/EC dealing with pharmaceutical legislation.

"Article 26, third subparagraph:

The applicant or marketing authorisation holder is responsible for the veracity of the documents and the data submitted by him."

- Amendment 63 which shall clarify the notion of "serious potential risk to public health". The provision has to be reformulated as it needs to be clarified that the guidelines are to be adopted by the Commission.

"Article 29(1a):

1a. Guidelines to be adopted by the Commission shall define a serious potential risk to public health."

- Amendment 66 which reinforces the arbitration procedures. The Commission accepts the Parliament's amendment turning the current option to refer a matter to the Agency into an obligation, in the cases of referral where a Community interest is involved. However, to give full effect to such an obligatory referral it is necessary to clarify that such referral leads to a scientific opinion followed by a Commission decision as foreseen in Articles 33 and 34. For reasons of coherence, this similar clarification has to be introduced in the two other provisions on referral procedures. The referral procedure under Article 31 envisages inter alia changes of the marketing authorisation in order to take account of pharmacovigilance information. If this procedure is to be reinforced, Article 116 needs to be aligned so as to allow the competent authorities to take all necessary decisions, including, alongside the suspension and revocation, the variation of a marketing authorisation.

"Article 29(3) :

3. If the Member States fail to reach an agreement within the 60-day period laid down in paragraph 2, the Agency shall be immediately informed, with a view to the application of the procedure under Articles 32, 33 and 34. The Agency shall be provided with a detailed statement of the matters on which the Member States have been unable to reach agreement and the reasons for their disagreement. A copy shall be forwarded to the applicant.

Article 30(1) :

1. If two or more applications submitted in accordance with Articles 8 and Articles 10 to 11 have been made for marketing authorisation for a particular medicinal product, and if Member States have adopted divergent decisions concerning the authorisation of the medicinal product or its suspension or withdrawal, a Member State, the Commission or the applicant or the marketing authorisation holder may refer the matter to the Committee on Human Medicinal Products, hereinafter referred to as "the Committee", for application of the procedure laid down in Articles 32, 33 and 34.

Article 31(1), first subparagraph:

1. The Member States or the Commission or the applicant or the marketing authorisation holder shall, in specific cases where the interests of the Community are involved, refer the matter to the Committee for application of the procedure laid down in Articles 32, 33 and 34 before any decision is reached on a request for a marketing authorisation or on the suspension or withdrawal of an authorisation, or on any other variation to the terms of a marketing authorisation which appears necessary, in particular to take account of the information collected in accordance with Title IX.

"Article 116:

The competent authorities shall suspend, revoke or vary an authorisation to place a medicinal product on the market if the view is taken that the product is harmful under normal conditions of use, or that it lacks therapeutic efficacy, or that the risk/benefit balance is not positive under the authorised conditions of use, or that its qualitative and quantitative composition is not as declared. Therapeutic efficacy is lacking when it is concluded that therapeutic results cannot be obtained from the medicinal product.

An authorisation shall also be suspended, revoked or varied where the particulars supporting the application as provided for in Article 8 or Articles 10 to 11 are incorrect or have not been amended in accordance with Article 23, or where the controls referred to in Article 112 have not been carried out. "

- Amendment 69 which cuts down the deadline within which the Agency has to transmit the final opinion to the Commission from 30 to 15 days. A rewording is necessary to keep the reference to the marketing authorisation holder:

"Article 32(5), first subparagraph:

Within 15 days of its adoption, the Agency shall forward the final opinion of the Committee to the Member States, to the Commission and to the applicant or the marketing authorisation holder together with a report describing the assessment of the medicinal product and stating the reasons for its conclusions."

- The second part of amendment 71 on the report to be drawn up on the functioning of the Directive. A rewording is necessary to include the Council alongside the European Parliament:

"Article 38(2):

2. No later than [date], the Commission shall publish a report on the experience acquired on the basis of the procedures described in this Chapter and shall propose any amendments which may be necessary to improve those procedures. This report shall be forwarded to the European Parliament and to the Council."

- Amendment 80 which adds the competent authorities to the list of those to whom patients may report adverse reactions. However, this needs to be reworded in order to specify which competent authorities are being referred to:

"Article 59(1)(d):

d) a description of the adverse reactions which may occur under normal use of the medicinal product and, if necessary, the action to be taken in such a case; the patient should be expressly asked to communicate any adverse reaction which is not mentioned in the package leaflet to his doctor or pharmacist and the authority responsible for pharmacovigilance;"

- Amendment 85 on assessments to be carried out on mock-ups of the outer packaging with target patient groups. However, a rewording of this provision is necessary in order to align it with point (j) of Article 8(3), as proposed by the Commission, according to which the applicant only has to provide mock-ups, but no specimens.

"Article 61(1):

1. One or more mock-ups of the outer packaging and the immediate packaging of a medicinal product, together with the draft package leaflet, shall be submitted to the authorities competent for authorising marketing when the marketing authorisation is requested. The results of assessments carried out in cooperation with target patient groups shall also be provided to the competent authority."

- Amendment 86 sets out how and in what languages the leaflet should be drawn up, with a view to ensuring legibility. A subparagraph regarding the possibility that several languages might be used needs to be added.

"Article 63(2):

2. The package leaflet must be written and designed to be clear and understandable enabling the users to act appropriately, when necessary with the help of health professionals. The package leaflet must be clearly legible in the official language or languages of the Member State where the medicinal product is placed on the market.

The first subparagraph shall not prevent the package leaflet from being printed in several languages, provided that the same information is given in all the languages used."

- Amendment 91 which replaces the statement "without approved therapeutic indications" on the label, and, where appropriate, in the package leaflet for homeopathic medicinal products registered under the simplified registration procedure, with the statement "without specific therapeutic indications". However, this needs to be reworded to make it clear that a registered homeopathic medicinal product cannot have any therapeutic indication whatsoever, neither general, nor specific:

"Article 69(1), eleventh subparagraph:

- homeopathic medicinal product "without therapeutic indications".

- The second part of amendment 92 sets out a period of protection for data provided in the context of an application for a change of classification of a medicinal product. However, it needs to be reworded to limit the duration of the period of protection and to clarify it. Therefore, a new Article 74a should be added:

"Article 74a

Where a change of classification of a medicinal product has been authorised on the basis of significant pre-clinical tests and clinical trials, the competent authority shall not refer to the results of those tests or trials when examining an application by another applicant for or holder of marketing authorisation for a change of classification of the same substance for two years after the initial change was authorised."

- Amendment 94 lays down a requirement for distributors importing in parallel a medicinal product originating from another Member State to inform the holder of the marketing organisation of their intention. However, rewording is needed to clarify the provision and to add a requirement to also inform the competent authorities in the Member State to which the product will be imported. A new paragraph 2a must be added to Article 76:

"Article 76(2a):

2a. Any distributor, not being the marketing authorisation holder, who imports a product from another Member State shall notify the marketing authorisation holder and the competent authority in the Member State to which the product will be imported of his/her intention to import it."

- Amendment 95 lays down a requirement for the marketing authorisation holder and, within the limits of their responsibilities, the distributors to provide suitable supplies. However, rewording is needed to include this provision in Article 81, which already lays down public service obligations. It is also necessary to exclude pharmacists from this obligation, and to limit it to the needs of patients in the Member State where the supplies are kept. The application of the principles of proportionality and protection of public health, and the fact that such provisions must be implemented in compliance with the rules of the EC Treaty should also be taken into account. A new subparagraph has therefore been inserted into Article 81 after the first subparagraph and the second subparagraph has been reworded:

"Article 81:

With regard to the supply of medicinal products to pharmacists and persons authorised or entitled to supply medicinal products to the public, Member States shall not impose upon the holder of a distribution authorisation which has been granted by another Member State, any obligation, in particular public service obligations, more stringent than those they impose on persons whom they have themselves authorised to engage in equivalent activities.

The holder of a marketing authorisation for a medicinal product and the distributors of the said medicinal product in a Member State shall, within the limits of their responsibilities, ensure appropriate supplies of that medicinal product so that the needs of patients in the Member State in question are covered.

The arrangements for implementing this Article should, moreover, be justified on grounds of public health protection and be proportionate in relation to the objective of such protection, in compliance with the Treaty rules, particularly those concerning the free movement of goods and competition."

- Amendment 98, which introduces into the wording of Title VIII the concept of "information". However, rewording appears appropriate in order to refer to "information" in general and not only to "Communication of information":

"Title VIII

ADVERTISING AND INFORMATION".

- Amendment 99, which is intended to make the definition of advertising more precise by distinguishing it from information. However, rewording is needed to clarify this provision. Information is already defined in Article 88(2), as proposed by the Commission:

"Article 86(1), introductory sentence:

1. For the purposes of this Title, "advertising of medicinal products" shall include any form of door-to-door information, canvassing activity or inducement designed to promote the prescription, supply, sale or consumption of medicinal products; it shall include in particular:"

- Amendment 104, which stipulates certain topics to be covered by the report to be submitted by the Commission on the experience with the pilot-case on information to patients. It needs to be reworded though, in particular to clarify that the list is not exhaustive:

"Article 88(7a):

7a. The evaluation of the information pilot project shall include, among other things:

- overall quality of the information presented,

- accuracy of the information,

- dissemination of the information,

- accessibility of the information."

- Amendments 106 and 191 on the reference to the international non-proprietary name. A rewording is necessary to combine the wording of both amendments :

"Article 89(2):

2. Member States may decide that the advertising of a medicinal product to the general public may, notwithstanding paragraph 1, include only the name of the medicinal product or its international non-proprietary name, where this exists, or the trademark if it is intended solely as a reminder."

- Amendment 108 allowing a reference to the trademark in advertising under certain conditions. A rewording is necessary to align the provisions with the one covering the advertising of a medicinal product to the general public (Article 89(2)) :

"Article 91(2):

2. Member States may decide that the advertising of a medicinal product to persons qualified to prescribe or supply such products may, notwithstanding paragraph 1, include only the name of the medicinal product, or its international non-proprietary name, where this exists, or the trademark, if it is intended solely as a reminder."

- Amendment 114, which makes it compulsory for Member States to take measures to require doctors and other health care professionals to report adverse reactions. Rewording is needed to make such a provision obligatory, while maintaining the wording of the Commission's proposal:

"Article 101, paragraph 2:

The Member States shall impose specific requirements on doctors and other health care professionals, in respect of the reporting of suspected serious or unexpected adverse reactions."

- The first part of amendment 116 which lays down a requirement to publish information concerning pharmacovigilance. Rewording is needed to avoid referring to the Register and to preserve wording that is more accessible to public:

"Article 102, paragraph 2:

2. Member States shall ensure that suitable information collected within this system is communicated to the other Member States and the Agency. This information shall be recorded in the database referred to in point (j) of the second paragraph of Article 51 of Regulation (EEC) 2309/93 and shall be permanently and immediately accessible to the public."

- Amendment 121 on the communication of pharmacovigilance information by the authorisation holder to the public:

"Article 104(8):

8. The marketing authorisation holder shall not be authorised to communicate information on pharmacovigilance issues to the public without the consent of the competent authority."

- Amendments 122 and 159 impose an obligation on the holder of a marketing authorisation to inform the competent authorities of any imminent cessation of sales or withdrawal of a medicinal product from the market. Rewording is needed to bring this provision into line with the measure set out in the proposal for a Regulation amending Regulation 2309/93:

"Article 104a:

The marketing authorisation holder shall notify the competent authorities of any imminent temporary or definitive cessation of sales of a medicinal product. He/ she shall ensure that, except in exceptional circumstances, the notification is carried out at least two months prior to the cessation of sales of the product."

- Amendment 151 on the classification of a medicinal product by the reference Member State in the case of a mutual recognition procedure. However, a rewording is necessary to make clear that the classification remains part of the summary of the product characteristics:

"Article 11, point 10

10) Classification in accordance with Article 70(1). The classification by the reference Member State shall be taken seriously into account when the mutual recognition procedure referred to in Articles 27 to 39 for obtaining marketing authorisation for a medicinal product is applied."

- Amendment 156, which is intended to make the definition of a generic medicinal product more precise. However, this needs to be reworded to take into account the scientific definition commonly accepted by the Member States within the informal "notice to the applicant" group:

"Article 10(2)(b):

b) generic medicinal product shall mean a medicinal product which has the same qualitative and quantitative composition in active principles and the same pharmaceutical form, and whose bioequivalence with the reference medicinal product has been demonstrated by appropriate bioavailability tests. The different salts, esters, ethers, isomers, mixtures of isomers, complexes or derivatives of an active substance are considered as the same active substance, unless they differ significantly in properties with regard to safety and/or efficacy. The various solid immediate-release oral pharmaceutical forms are deemed to be one and the same pharmaceutical form. Bioavailability studies may not be required of the applicant if he/she can demonstrate that the product meets the criteria of Annex I."

- Amendments 167 and 168 explicitly set out that the provisions for generic medicinal products also cover similar biological medicinal products. Such medicinal products cannot always be considered to be generic medicinal products under the definition in Article 10(2)(b), but are nonetheless not required to provide a full dossier. Relevant studies which take the place of bioavailability studies must be included in the dossier. The amendment needs to be reworded so that it reflects the conditions for such medicinal products, in particular by adding a paragraph on them to Article 10:

"Article 10(3a):

3a. Where a biological medicinal product which is similar to a reference biological product does not meet certain conditions in the definition of generic medicinal products, the results of appropriate pre-clinical tests and clinical trials related to these conditions must be provided. The results of other tests and trials from the reference medicinal product's dossier shall not be provided."

- Amendments 185 and 186 which change the period of validity of the marketing authorisation. The European Parliament proposes that the Commission's proposal to abolish the requirement of five-yearly renewal be amended. It is proposed that a requirement to renew the first marketing authorisation after five years be introduced. After this renewal, the marketing authorisation would be considered to be valid indefinitely. Recital 13 and Article 24(1) are therefore amended. Rewording is needed to more precisely set out the context of the first evaluation and to avoid increasing the amount of time needed to complete such a procedure:

"Recital 13:

Marketing authorisations for new medicinal products must initially be limited to five years' validity. After the first renewal, the marketing authorisation shall be considered to be valid indefinitely. Furthermore, any authorisation not used for three consecutive years, that is, it has not led to the actual placing on the market of a medicinal product during that period, should be considered invalid in order, in particular, to avoid the administrative burden linked to maintaining such authorisations.

Article 24(1):

1. Without prejudice to paragraphs 2 and 3, authorisation shall be valid for five years.

This authorisation may be renewed after five years on the basis of a comparative reassessment of the risk/benefit balance. When, after five years, the marketing authorisation is renewed, the holder shall provide a consolidated version of the dossier on the quality, safety and efficacy of the medicinal product which includes all the modifications made during its five years of validity.

The application for renewal shall be submitted to the competent authority at least six months before the authorisation's validity lapses.

After this renewal, the marketing authorisation shall be valid indefinitely."

3.3. Amendments not accepted by the Commission: 1, 4, 6, 8, 9, 10, 16, 19, 26, 28, 29, 34, 38, 39, 40, 41, 45, 46 (second part), 49, 53 (second part), 54, 56, 59, 62, 64, 65, 71 (first sentence), 72, 73, 74, 75, 76, 77, 78, 79, 81, 87, 92 (first part), 96, 100, 101, 102, 103, 105, 107, 111, 113, 115, 116 (second part), 117, 118, 119, 120 (second part), 123, 124, 126, 127, 129, 131, 132, 134, 135, 136, 141, 153, 154, 155, 157, 172, 173, 176, 179, 181, 182, 189, 190, 196, 198 and 202.

- The Commission does not accept amendment 1, which defines medicinal products as opposed to other consumer goods. Specifying this is not necessary to make the provisions in the proposal clearer, nor does it reflect any of its provisions.

- The Commission does not accept amendment 4, which introduces a specific reference to the objectives set out in Articles 152 and 153 of the EC Treaty. This reference is not justified from a legal point of view, as the Commission's proposal is based on Article 95 of the EC Treaty.

- The Commission does not accept amendment 6, which states in a recital that the quality requirements for medicinal products are different according to whether the medicinal product is intended for adults or for children. This cannot be accepted, as there can be no difference between quality, safety and efficacy requirements for medicinal products depending on their target population.

- The Commission does not accept amendments 8 and 9, which set out the provisions concerning providing patients with information. The proposed recitals do not reflect the contents of the provision on information in Article 88(2).

- The Commission does not accept amendment 10, which introduces a recital on the environmental classification of medicinal products. This recital is not reflected by any measure in the proposal.

- The Commission does not accept amendments 16 and 73, which lay down a requirement for generic medicinal products authorised by the Member States to be identified with the same denomination. This provision cannot be applied since these measures are also applicable to generic medicinal products authorised under national procedures.

- The Commission does not accept amendment 19, which grants the Agency the power to determine the scope of the proposed Directive. Firstly, this must be the prerogative of the national authorities entrusted with applying it. Secondly, and within the framework of the mutual recognition procedure, if several Member States are in disagreement, the Agency's corresponding scientific committee will issue an opinion in the context of arbitration proceedings.

- The Commission does not accept amendment 26, which adds to Article 8, on the requirements for preparing the dossier for the application for authorisation, a requirement for an assessment of the risk/benefit balance in respect of the release of the product as waste into the environment. This provision already exists and is included under paragraph 3, point g of the same Article.

- The Commission does not accept amendment 28, which introduces a reference to all tests, regardless of who carried them out. The provision in the proposal is intended to cover all tests and trials which are necessary and useful for the application for authorisation, without specifying who carries them out. There is no need for this reference.

- The Commission does not accept amendment 29, which introduces requirements to, firstly, specify the tests for adults and for children, and secondly, provide for tests comparing the new medicinal product to be authorised with existing medicinal products in the same therapeutic class This requirement cannot be a part of the assessment with a view to granting marketing authorisation. Such assessments must be based solely on the criteria of quality, safety and efficacy. The competent authorities in Member States compare efficacy in order to determine the price and the amount refunded. Such assessments should only be carried out in such a context.

- The Commission does not accept amendments 34, 39, 134 and 202, which introduce the possibility of conducting the tests and trials needed for authorisation, submitting the application for authorisation, and authorising generic medicinal products during the ten-year period of data protection. It is also proposed that the application of "Bolar" type clauses be extended to cover generic medicinal products, the submission of the application for authorisation and of samples, the granting of authorisation, and exports during the period in which the reference medicinal product is covered by a patent or a supplementary protection certificate. These derogations from the rights deriving from the protection of data and from intellectual property rights are detrimental to the balance proposed by the Commission in its original proposal. It is important to maintain this balance between a ten-year period of data protection for innovative medicinal products and a "Bolar" type clause for generic medicinal products in order to allow the tests and trials needed for authorisation to be carried out during the period in which they are protected by intellectual property rights. As for the last part of amendment 34, which introduces a reference to medicinal products which are biosimilar to biological medicinal products, the principle of referring to this type of product is acceptable but should be specified directly in Article 10.

- The Commission does not accept amendment 38, which lays down a requirement to provide appropriate tests and trials if one or more of the active principles in a generic medicinal product is changed. There is no need for this reference as the modified provision already makes this a requirement.

- The Commission does not accept amendment 40, which introduces an additional period of three-years data protection for data submitted with regard to authorising new indications for a medicinal product, which has already been authorised. The provision would lead to a disproportionate extension of the data protection period and would provoke, in addition, disharmonisation between generic medicines and the reference products, which would obtain these protected new indications. The amendment needs to be considered together with the second part of amendment 92, which the Commission has accepted and which provides for a protection of data submitted with regard to changing the classification of an already authorised medicinal product.

- The Commission does not accept amendment 41, which reduces of period of time required to establish a "well-established medicinal use" from ten years to eight years. There is no justification for such a reduction. To the contrary, given that scientific literature replaces pre-clinical tests and clinical trials, a ten-year period is indispensable.

- The Commission does not accept amendment 45, which extends the option of simplified registration to homeopathic products administered by any route of administration that is described in the Pharmacopoeia or is used officially in the Member States. Such an extension of the simplified registration procedure is not justified. It must be limited to homeopathic medicinal products administered orally or externally. The risk related to other routes of administration must be accompanied by proven efficacy.

- The Commission does not accept the second part of amendment 46, which grants the Commission the option of adapting to technical progress the conditions which apply to homeopathic medicinal products which are eligible for the simplified registration procedure. These provisions are already included in the Commission's proposal. There is therefore no need to repeat them in this provision.

- The Commission does not accept amendment 49, which reduces of period of time required to draw up an assessment report from the 120 days proposed by the Commission to 90 days. It must be ensured that the amount of time for assessing the medicinal product is sufficient, and for this reason, the 120-day period must be maintained.

- The Commission does not accept the second part of amendment 53, which lays down a requirement to state the grounds for each indication of the medicinal product being assessed when publishing the assessment report. There is no need to stipulate such a requirement as this practice is already followed by the competent authorities.

- The Commission does not accept amendment 54, which lays down a requirement to publish the authorisation granted, the summary of product characteristics, the assessment report and the comments on this report for each medicinal product authorised. This provision is already set out in the proposed Directive.

- The Commission does not accept amendment 56, which introduces a requirement to take account of scientific and technical progress, after authorisation, and Community law. There is no need for such a reminder as Community law or scientific developments are to be taken into account for all medicinal products which are already authorised.

- The Commission does not accept amendments 59, 131 and 157, which lay down a requirement for the Commission to conduct studies comparing new medicinal products authorised by the Commission and examining the application of Council Directive 89/105/EEC relating to the transparency of measures regulating the prices of medicinal products for human use and their inclusion in the scope of national health insurance systems. Such studies, though desirable, do not fall within the scope of legislation on authorisation, surveillance and pharmacovigilance of medicinal products.

- The Commission does not accept amendment 62, which extends the scope of the mutual recognition procedure to homeopathic medicinal products registered under the simplified procedure. There is no need to specify this as Article 39 of the proposal for a Directive already sets out in detail the provisions of the mutual recognition procedure which apply to this kind of medicinal product.

- The Commission does not accept amendments 64 and 65, which make it obligatory to inform the Agency's scientific committee when Member States have arrived at different decisions regarding the authorisation, suspension, withdrawal or requests to harmonise the summary of characteristics of a medicinal product. These procedures must not appear to be automatic. Discretion is needed to verify their usefulness on a case-by-case basis. Not allowing this would risk creating an excessive number of procedures which the Agency would not be able to process.

- The Commission does not accept the first sentence of amendment 71, which introduces a requirement for the Commission to take account of the need to standardise the procedures which apply to pre-clinical tests and clinical trials in the context of the general report on the application of the mutual recognition procedure. Legislation which specifically addresses the harmonisation of national procedures for conducting these tests already exists (Directive 2001/20/EC relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use).

- The Commission does not accept amendment 72, which replaces the term "common name" with "international non-proprietary name" in the context of information which must obligatorily be included on the packaging. There is no need for this provision since the definition of "common name" in Article 1 already refers to "international non-proprietary name".

- The Commission does not accept amendment 74, which requires an obligatory blank space to be left on the packaging of the medicinal product for stating the dosage. The space on the external packaging of medicinal products is already quite limited. Requiring additional space would result in a reduction of the space available for other obligatory information.

- Commission does not accept amendments 75, 76 and 103, which require the competent authorities to set up a website containing information on the medicinal product and to include its address on the packaging and the package leaflet. Pharmaceutical legislation makes no provision for any requirement to publish information on websites.

- The Commission does not accept amendment 77, which requires a warning concerning disposal of unused medicinal products or waste materials from medicinal products to be placed on the packaging. This requirement is already set out in a provision of the proposed Directive.

- The Commission does not accept amendment 78, which lays down a requirement to include certain information on the packaging or the package leaflet in braille, or certain typefaces, or in other formats, on request. This requirement would be disproportionate with regard to the goal to be achieved and could be detrimental to the normal format for the indications. The prescribing agent and the pharmacist must be capable of providing blind or visually impaired patients with the necessary information in an appropriate form.

- The Commission does not accept amendment 79, which sets out certain requirements for the competent authorities in the Member States with regard to creating a database and making the data it contains accessible to all patients. Such provisions are the responsibility of the Member States, which decide on the best means for guaranteeing access to certain information for all patients. The proposal for a regulation amending Regulation 2309/93 already provides for the creation of a database on all medicinal products authorised by the Community and by the Member States.

- The Commission does not accept amendment 81, which sets out a requirement to state on the packaging that the medicinal product was authorised recently and asking for all adverse reactions to be reported. The date on which a medicinal product was authorised is already to be stated on the packaging, and asking for adverse reactions to be reported should apply to all medicinal products, not only to new ones. Moreover, specifically asking for reports solely on such medicinal products could call into question the fact that they have undergone a full assessment and authorisation procedure.

- The Commission does not accept amendment 87, which modifies the wording of the purpose of the guidelines on the legibility of the information on the label and in the package leaflet. There is no need for such a change, as the goal of the Commission's proposal is already clearly to check the legibility of the packaging and the leaflets.

- The Commission does not accept the first part of amendment 92, which lays down a requirement for the competent authorities to examine the classification of the medicinal product during the authorisation procedure. Such a provision is already set out in the Commission's proposal.

- The Commission does not accept amendments 96 and 132, which impose obligations on pharmacists. Pharmaceutical legislation does not set out in detail the provisions governing pharmacists' professional activity.

- The Commission does not accept amendment 100, which lays down an obligation for advertising to be consistent with all the information which accompanies the marketing authorisation or is related to it. Advertising is to be checked only on the basis of a summary of the product's characteristics which reflects the scientific assessment as approved by the competent authority.

- The Commission does not accept amendments 101, 102, 173, 182 and 198, which either delete or amend the Commission's proposal regarding the provision of information to patients regarding prescription medicinal products for certain conditions, subject to certain requirements and controls, and for a three-year trial period. The Commission is of the opinion that its proposal should be maintained in order to ensure that patients are provided with certain information which is legitimate but limited solely to certain conditions during the first stage of trials. For the same reasons, the Commission does not accept amendment 113 which introduces a new chapter on the provision of information, and which would make it possible to provide comparative information on all authorised medicinal products, diseases or therapies.

- The Commission does not accept amendment 105, which reforms what information should be brought to the attention of patients in the context of advertising for certain medicinal products. This provision is not appropriate in the context of advertising for non-prescription medicinal products.

- The Commission does not accept amendment 107, which replaces the term "state of health" with "health" in the provisions with which advertising must comply. The original terminology in the Commission's proposal was more precise.

- The Commission does not accept amendment 111, which extends the possibilities of co-promotion to co-marketing activities by the holder of the marketing authorisation and one or more companies nominated by him/her. Co-promotion can in no way cover the placing on the market of the medicinal product. This is to be done solely by the holder of the marketing authorisation, who is in all cases solely responsible for this activity.

- The Commission does not accept amendment 115, which asks a specific service of the Commission to put forward legislative proposals on pharmacovigilance. The distribution of work and services within the Commission is the responsibility of the Commission itself.

- The Commission does not accept the second part of amendment 116, nor amendments 123 and 124, which provide for access to pharmacovigilance information on authorised medicinal products. This information on authorised medicinal products is already referred to in point e) of the second paragraph of Article 51 of Regulation 2309/93, as provided for in the second paragraph of Article 102 and amended by the first part of amendment 116.

- The Commission does not accept amendment 117, which sets out an obligation to provide guaranteed public financing for activities related to pharmacovigilance. Decisions on financing national pharmacovigilance activities lie solely within the competence of Member States.

- The Commission does not accept amendment 118, which deletes the reference to exceptional circumstances for cases where electronic communication of pharmacovigilance data is not possible. This provision must be maintained and, as proposed by the Commission, limited solely to exceptional circumstances.

- The Commission does not accept amendment 119, which also includes patients as a source of information on adverse reactions that is forwarded directly to the holder of the marketing authorisation. Such direct communication between patients and marketing authorisation holders would not result in reliable and potentially usable information. Such information must be filtered by health professionals or by officials from the competent authority.

- The Commission does not accept the second part of amendment 120, which defines the areas of competence for the Agency's pharmacovigilance working group. This group is not explicitly created by Regulation 2309/93 and, as a result, no legal obligations can be laid down. As for the last part of the amendment, which sets out that all periodic safety update reports must be accessible to the public in a Register, the obligation to provide public access is already set out in Article 102(2).

- The Commission does not accept amendment 126, which lays down an obligation to consider the scientific assessment of the risk/benefit balance to be the first stage in the analysis of the medicinal product's relative efficacy. The purpose of a risk/benefit balance is, and must continue to be, to scientifically assess the benefits and the risks of the medicinal product in question on an individual basis, and not to compare that medicinal product with others.

- The Commission does not accept amendment 127, which lays down a requirement for the competent authorities to inform the prosecuting authorities if they find that data submitted by an applicant has been falsified. Such provisions do not fall under pharmaceutical law, but rather under Member States' administrative or criminal law.

- The Commission does not accept amendment 129, which introduces four new Articles requiring Member States to apply the criteria of independence, transparency and data protection in national activities concerning authorisation and scientific assessment. In the Commission's opinion, these are areas of national competence, and pharmaceutical law relates to the procedures regarding marketing authorisation, surveillance and pharmacovigilance for medicinal products, not to the internal administrative rules of each Member State.

- The Commission does not accept amendments 135 and 136, which lay down a specific requirement to take appropriate consideration of the sexes, particularly in clinical trials. The criteria of differences between the sexes is already taken into account in the scientific guidelines prepared with regard to the international harmonisation of the guidelines that the Community applies to its evaluation procedures.

- The Commission does not accept amendment 141, which introduces a recital regarding three objectives which must underlie all national policies concerning the control of social expenditure. The main aims of the pharmaceutical legislation are already expressed in the recitals of the Commission's proposal.

- The Commission does not accept amendments 153 and 154, which propose that a new category of medicinal product, "herbal health product", be introduced. There is no need to add such a category of products to the legislation. The new proposal on traditional herbal-based medicinal products already includes the definitions for this type of medicinal product.

- The Commission does not accept amendment 155, which removes the requirement to include the various strengths, pharmaceutical forms, routes of administration and forms of presentation of the same medicinal product in the same marketing authorisation. This clarification is needed from a legal point of view.

- The Commission does not accept amendment 172, which adds a recital referring to the pharmacovigilance data collected by the agencies of third countries and by the World Health Organisation. This recital is not reflected by any measure in the proposed Directive.

- The Commission does not accept amendment 176, which adds a new requirement with regard to the documents to be included in applications for marketing authorisations regarding "long-term tests" for medicinal products for long-term treatment. This wording is too vague. Medicinal products must, in all cases, undergo tests which are appropriate for the use for which they are authorised.

- The Commission does not accept amendment 179, which introduces an option for the Member States to lay down specific rules on the evaluation of homeopathic medicinal products. Such a derogation cannot be accepted. The legislation already allows for this, but limits it to the rules which apply to pre-clinical tests and clinical trials.

- The Commission does not accept amendment 181, which replaces Article 94 with a text that makes stricter the conditions under which medicinal products may be promoted to persons qualified to prescribe or supply them. Nevertheless, the proposed wording is too restrictive and makes such promotion impracticable.

- The Commission does not accept amendments 189 and 190, which lay down a requirement to refer to clinical information using natural frequencies in the relevant part of the summary of product characteristics and to include the research designs. The summary of product characteristics, which contains the results of the scientific assessment, is not the appropriate place for this information.

- The Commission does not accept amendment 196, which introduces a specific exception to patent rights, allowing for the production of medicinal products intended for export to third countries, at the request of the authorities of the third country in question, when it is covered by a patent. First, as drafted, this amendment does not meet the strict conditions on possible exceptions to patent rights set by the WTO Agreement on Trade Related Intellectual Property Rights. Secondly, such provision does not have a place in the legislation governing the placing on the market of medicinal products within the Community.

4. Amended proposal

Pursuant to Article 250(2) of the EC Treaty, the Commission amends its proposal in the aforementioned terms.

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