(1)

Regulation (EC) No 3223/94 lays down, pursuant to the outcome of the Uruguay Round multilateral trade negotiations, the criteria whereby the Commission fixes the standard values for imports from third countries, in respect of the products and periods stipulated in the Annex thereto.

(2)

In compliance with the above criteria, the standard import values must be fixed at the levels set out in the Annex to this Regulation,

(1)

The refunds on white sugar and raw sugar exported in the natural state were fixed by Commission Regulation (EC) No 757/2001 (3), as amended by Regulation (EC) No 794/2001 (4).

(2)

It follows from applying the detailed rules contained in Regulation (EC) No 757/2001 to the information known to the Commission that the export refunds at present in force should be altered to the amounts set out in the Annex hereto,

(1)

Article 18 of Regulation (EC) No 2038/1999 provides that the difference between quotations or prices on the world market for the products listed in Article 1(1)(d) of that Regulation and prices for those products within the Community may be covered by an export refund.

(2)

Article 3 of Commission Regulation (EC) No 2135/95 of 7 September 1995 laying down detailed rules of application for the grant of export refunds in the sugar sector (3), provides that the export refund on 100 kilograms of the products listed in Article 1(1)(d) of Regulation (EC) No 2038/1999 is equal to the basic amount multiplied by the sucrose content, including, where appropriate, other sugars expressed as sucrose; the sucrose content of the product in question is determined in accordance with Article 3 of Commission Regulation (EC) No 2135/95.

(3)

Article 21(3) of Regulation (EC) No 2038/1999 provides that the basic amount of the refund on sorbose exported in the natural state must be equal to the basic amount of the refund less one-hundredth of the production refund applicable, pursuant to Council Regulation (EEC) No 1010/86 of 25 March 1986 laying down general rules for the production refund on sugar used in the chemical industry (4), as last amended by Commission Regulation (EC) No 1888/2000 (5), to the products listed in the Annex to the last mentioned Regulation;

(4)

According to the terms of Article 21(1) of Regulation (EC) No 2038/1999, the basic amount of the refund on the other products listed in Article 1(1)(d) of the said Regulation exported in the natural state must be equal to one-hundredth of an amount which takes account, on the one hand, of the difference between the intervention price for white sugar for the Community areas without deficit for the month for which the basic amount is fixed and quotations or prices for white sugar on the world market and, on the other, of the need to establish a balance between the use of Community basic products in the manufacture of processed goods for export to third countries and the use of third country products brought in under inward processing arrangements.

(5)

According to the terms of Article 21(4) of Regulation (EC) No 2038/1999, the application of the basic amount may be limited to some of the products listed in Article 1(1)(d) of the said Regulation.

(6)

Article 18 of Regulation (EC) No 2038/1999 makes provision for setting refunds for export in the natural state of products referred to in Article 1(1)(f) and (g) and (h) of that Regulation; the refund must be fixed per 100 kilograms of dry matter, taking account of the export refund for products falling within CN code1702 30 91and for products referred to in Article 1(1)(d) of Regulation (EC) No 2038/1999 and of the economic aspects of the intended exports; in the case of the products referred to in the said Article (1)(f) and (g), the refund is to be granted only for products complying with the conditions in Article 5 of Regulation (EC) No 2135/95; for the products referred to in Article 1(1)(h), the refund shall be granted only for products complying with the conditions in Article 6 of Regulation (EC) No 2135/95.

(7)

The refunds referred to above must be fixed every month; they may be altered in the intervening period.

(8)

Application of these quotas results in fixing refunds for the products in question at the levels given in the Annex to this Regulation.

(9)

The measures provided for in this Regulation are in accordance with the opinion of the Management Committee for Sugar,

(1)

Article 10 of Regulation (EEC) No 1766/92 provides that the rates of duty in the Common Customs Tariff are to be charged on import of the products referred to in Article 1 of that Regulation. However, in the case of the products referred to in paragraph 2 of that Article, the import duty is to be equal to the intervention price valid for such products on importation and increased by 55 %, minus the cif import price applicable to the consignment in question. However, that duty may not exceed the rate of duty in the Common Customs Tariff.

(2)

Pursuant to Article 10 (3) of Regulation (EEC) No 1766/92, the cif import prices are calculated on the basis of the representative prices for the product in question on the world market.

(3)

Regulation (EC) No 1249/96 lays down detailed rules for the application of Council Regulation (EEC) No 1766/92 as regards import duties in the cereals sector.

(4)

The import duties are applicable until new duties are fixed and enter into force. They also remain in force in cases where no quotation is available for the reference exchange referred to in Annex II to Regulation (EC) No 1249/96 during the two weeks preceding the next periodical fixing.

(5)

In order to allow the import duty system to function normally, the representative market rates recorded during a reference period should be used for calculating the duties.

(6)

Application of Regulation (EC) No 1249/96 results in import duties being fixed as set out in the Annex to this Regulation,

(1)

Article 11 of Regulation (EC) No 3072/95 provides that the rates of duty in the Common Customs Tariff are to be charged on import of the products referred to in Article 1 of that Regulation; whereas, however, in the case of the products referred to in paragraph 2 of that Article, the import duty is to be equal to the intervention price valid for such products on importation and increased by a certain percentage according to whether it is husked or milled rice, minus the cif import price provided that duty does not exceed the rate of the Common Customs Tariff duties.

(2)

Pursuant to Article 12(3) of Regulation (EC) No 3072/95, the cif import prices are calculated on the basis of the representative prices for the product in question on the world market or on the Community import market for the product.

(3)

Regulation (EC) No 1503/96 lays down detailed rules for the application of Regulation (EC) No 3072/95 as regards import duties in the rice sector.

(4)

The import duties are applicable until new duties are fixed and enter into force; whereas they also remain in force in cases where no quotation is available from the source referred to in Article 5 of Regulation (EC) No 1503/96 during the two weeks preceding the next periodical fixing.

(5)

In order to allow the import duty system to function normally, the market rates recorded during a reference period should be used for calculating the duties.

(6)

Application of Regulation (EC) No 1503/96 results in import duties being fixed as set out in the Annexes to this Regulation,

(1)

Article 27(1) of Regulation (EC) No 2200/96 provides for an intervention threshold to be fixed if the market in a product listed in Annex II thereto is suffering or at risk of suffering from imbalances giving or liable to give rise to too large a volume of withdrawals. Such a development might cause budget problems for the Community.

(2)

Commission Regulation (EC) No 931/2000 (3)fixes intervention thresholds for cauliflowers, peaches, nectarines and table grapes for the 2000/01 marketing year. The conditions laid down in the abovementioned Article 27 are still met for those products and consequently intervention thresholds should be fixed for cauliflowers, peaches, nectarines and table grapes for the 2001/02 marketing year.

(3)

The intervention threshold for each of those products should be fixed on the basis of a percentage of the average production intended for consumption in the natural state over the last five marketing years for which data are available. The period to be taken into account for assessing an overrun of the intervention threshold must also be established for each product.

(4)

Pursuant to the abovementioned Article 27, an overrun of the intervention threshold gives rise to a reduction in the Community withdrawal compensation in the marketing year following the overrun. The implications of this overrun for each of the products in question should be determined and a reduction proportional to the size of the overrun should be fixed.

(5)

The measures provided for in this Regulation are in accordance with the opinion of the Management Committee for Fresh Fruit and Vegetables,

(1)

Article 9(4) of Regulation (EC) No 2201/96 provides for aid to be granted to storage agencies for the quantities of sultanas, currants and dried figs that they buy in and for the actual duration of storage.

(2)

Article 2 of Commission Regulation (EC) No 504/97 of 19 March 1997 laying down detailed rules for the application of Council Regulation (EC) No 2201/96 as regards the system of production aid for products processed from fruit and vegetables (3), as last amended by Regulation (EC) No 1607/1999 (4), lays down the dates of the marketing years.

(3)

The storage aid for unprocessed dried grapes and unprocessed dried figs from the 2000/01 marketing year should be fixed and, to that end, account should be taken of Article 7 of Commission Regulation (EC) No 1622/1999 of 23 July 1999 laying down detailed rules for applying Council Regulation (EC) No 2201/96 as regards the scheme for the storage of unprocessed dried grapes and unprocessed dried figs (5)and of the fact that the storage aid is to be calculated on the basis of the technical cost of storage and of financing the buying-in price paid for the products.

(4)

The measures provided for in this Regulation are in accordance with the opinion of the Management Committee for Processed Fruit and Vegetables,

(a)

EUR 0,1446 per day and per tonne net weight until 28 February 2002 and EUR 0,1185 per day and per tonne net weight from 1 March 2002 for dried grapes;

(b)

EUR 0,1328 per day and per tonne net weight for dried figs.

(1)

Commission Regulation (EC) No 931/2000 (3)fixes the intervention thresholds for the 2000/01 marketing year at238 200tonnes for peaches and83 200tonnes for nectarines. Under Article 3 of that Regulation, if the quantity of peaches or nectarines withdrawn in the period between 1 March 2000 and 28 February 2001 exceeds the threshold fixed, the Community withdrawal compensation laid down in Annex V to Regulation (EC) No 2200/96 for the 2001/02 marketing year is to be reduced in proportion to the size of the overrun based on the production used to calculate the relevant threshold.

(2)

The information supplied by the Member States indicates that251 515tonnes of peaches and117 961tonnes of nectarines were withdrawn in the 2000/01 marketing year.

(3)

Consequently, the Community withdrawal compensation set by Regulation (EC) No 2200/96 for the 2001/02 marketing year must be reduced by 0,57 % for peaches and 4,18 % for nectarines.

(4)

Article 3 of Regulation (EC) No 931/2000 lays down that the consequences of an overrun of the threshold are to apply in the following marketing year. The reduction in the Community withdrawal compensation for peaches and nectarines should thereofe apply in the 2001/02 marketing year.

(5)

The measures provided for in this Regulation are in accordance with the opinion of the Management Committee for Fresh Fruit and Vegetables,

—

EUR 11,65 per 100 kilograms net for peaches,

—

EUR 13,33 per 100 kilograms net for nectarines.

(1)

Article 18(1) and (2) of Regulation (EEC) No 1785/81 provides that the differences between the prices in international trade for the products listed in Article 1(1)(a), (c), (d), (f), (g) and (h) of that Regulation and prices within the Community may be covered by an export refund where these products are exported in the form of goods listed in the Annex to that Regulation. Commission Regulation (EC) No 1520/2000 of 13 July 2000 laying down common implementing rules for granting export refunds on certain agricultural products exported in the form of goods not covered by Annex I to the Treaty and the criteria for fixing the amount of such refunds (3), as amended by Regulation (EC) No 2390/2000 (4), specifies the products for which a rate of refund should be fixed, to be applied where these products are exported in the form of goods listed in Annex I to Regulation (EC) No 2038/1999.

(2)

In accordance with Article 4(1) of Regulation (EC) No 1520/2000, the rate of the refund per 100 kilograms for each of the basic products in question must be fixed for each month.

(3)

Article 18(3) of Regulation (EC) No 2038/1999 and Article 11 of the Agreement on Agriculture concluded under the Uruguay Round lay down that the export refund for a product contained in a good may not exceed the refund applicable to that product when exported without further processing.

(4)

The refunds fixed under this Regulation may be fixed in advance as the market situation over the next few months cannot be established at the moment.

(5)

The commitments entered into with regard to refunds which may be granted for the export of agricultural products contained in goods not covered by Annex I to the Treaty may be jeopardized by the fixing in advance of high refund rates. It is therefore necessary to take precautionary measures in such situations without, however, preventing the conclusion of long-term contracts. The fixing of a specific refund rate for the advance fixing of refunds is a measure which enables these various objectives to be met.

(6)

It is necessary to ensure continuity of strict management taking account of expenditure forecasts and funds available in the budget.

(7)

The measures provided for in this Regulation are in accordance with the opinion of the Management Committee for Sugar,

(1)

Article 31(1) of Regulation (EC) No 1255/1999 provides that the difference between prices in international trade for the products listed in Article 1 (a), (b), (c), (d), (e), and (g) of that Regulation and prices within the Community may be covered by an export refund. Whereas Commission Regulation (EC) No 1520/2000 of 13 July 2000 laying down common implementing rules for granting export refunds on certain agricultural products exported in the form of goods not covered by Annex I to the Treaty, and criteria for fixing the amount of such refunds (3), as amended by Regulation (EC) No 2390/2000 (4), specifies the products for which a rate of refund should be fixed, to be applied where these products are exported in the form of goods listed in the Annex to Regulation (EC) No 1255/1999.

(2)

In accordance with the first subparagraph of Article 4 (1) of Regulation (EC) No 1520/2000, the rate of the refund per 100 kilograms for each of the basic products in question must be fixed for each month.

(3)

Article 4(3) of Regulation (EC) No 1520/2000 provides that, when the rate of the refund is being fixed, account should be taken, where necessary, of production refunds, aids or other measures having equivalent effect applicable in all Member States in accordance with the Regulation on the common organisation of the market in the product in question to the basic products listed in Annex A to that Regulation or to assimilated products.

(4)

Article 11(1) of Regulation (EC) No 1255/1999 provides for the payment of aid for Community-produced skimmed milk processed into casein if such milk and the casein manufactured from it fulfil certain conditions.

(5)

Commission Regulation (EC) No 2571/97 of 15 December 1997 on the sale of butter at reduced prices and the granting of aid for cream, butter and concentrated butter for use in the manufacture of pastry products, ice-cream and other foodstuffs (5), as last amended by Regulation (EC) No 635/2000 (6), lays down that butter and cream at reduced prices should be made available to industries which manufacture certain goods.

(6)

It is necessary to ensure continuity of strict management taking account of expenditure forecasts and funds available in the budget.

(7)

The measures provided for in this Regulation are in accordance with the opinion of the Management Committee for Milk and Milk Products,

(1)

Pursuant to Article 10 of Regulation (EEC) No 1600/92, the requirements of the Azores and Madeira for rice are to be covered in terms of quantity, price and quality by the mobilization, on disposal terms equivalent to exemption from the levy, of Community rice, which involves the grant of an aid for supplies of Community origin. This aid is to be fixed with particular reference to the costs of the various sources of supply and in particular is to be based on the prices applied to exports to third countries.

(2)

Commission Regulation (EEC) No 1696/92 (3), as last amended by Regulation (EEC) No 2596/93 (4), lays down common detailed rules for implementation of the specific arrangements for the supply of certain agricultural products, including rice, to the Azores and Madeira. Commission Regulation (EEC) No 1983/92 of 16 July 1992 laying down detailed rules for implementation of the specific arrangements for the supply of rice products to the Azores and Madeira and establishing the forecast supply balance for these products (5), as last amended by Regulation (EC) No 1683/94 (6), lays down detailed rules which complement or derogate from the provisions of the aforementioned Regulation.

(3)

As a result of the application of these detailed rules to the current market situation in the rice sector, and in particular to the rates of prices for these products in the European part of the Community and on the world market the aid for supply to the Azores and Madeira should be set at the amounts given in the Annex.

(4)

The measures provided for in this Regulation are in accordance with the opinion of the Management Committee for Cereals,

(1)

Pursuant to Article 3 of Regulation (EEC) No 1601/92, the requirements of the Canary Islands for rice are to be covered in terms of quantity, price and quality by the mobilisation, on disposal terms equivalent to exemption from the levy, of Community rice, which involves the grant of an aid for supplies of Community origin. This aid is to be fixed with particular reference to the costs of the various sources of supply and in particular is to be based on the prices applied to exports to third countries.

(2)

Commission Regulation (EC) No 2790/94 (3), as last amended by Regulation (EC) No 1620/1999 (4), lays down common detailed rules for implementation of the specific arrangements for the supply of certain agricultural products, including rice, to the Canary Islands.

(3)

As a result of the application of these detailed rules to the current market situation in the rice sector, and in particular to the rates of prices for these products in the European part of the Community and on the world market, the aid for supply to the Canary Islands should be set at the amounts given in the Annex.

(4)

The measures provided for in this Regulation are in accordance with the opinion of the Management Committee for Cereals,

(1)

The amounts of the representative prices and additional duties applicable to the import of white sugar, raw sugar and certain syrups are fixed by Commission Regulation (EC) No 1411/2000 (5), as last amended by Regulation (EC) No 740/2001 (6).

(2)

It follows from applying the general and detailed fixing rules contained in Regulation (EC) No 1423/95 to the information known to the Commission that the representative prices and additional duties at present in force should be altered to the amounts set out in the Annex hereto,

(1)

The corrective amount applicable to the refund on malt was fixed by Commission Regulation (EC) No 624/2001 (3).

(2)

On the basis of today's cif prices and cif forward delivery prices, taking foreseeable developments on the market into account, the corrective amount at present applicable to the refund on malt should be altered,

(1)

The corrective amount applicable to the refund on cereals was fixed by Commission Regulation (EC) No 623/2001 (3), as amended by Regulation (EC) No 803/2001 (4).

(2)

On the basis of today's cif prices and cif forward delivery prices, taking foreseeable developments on the market into account, the corrective amount at present applicable to the refund on cereals should be altered.

(3)

The corrective amount must be fixed according to the same procedure as the refund. It may be altered in the period between fixings,

(1)

Council Directive 65/65/EEC of 26 January 1965 on the approximation of provisions laid down by law, regulation or administrative action relating to medicinal products (4)requires that applications for authorisation to place a medicinal product on the market should be accompanied by a dossier containing particulars and documents relating to the results of tests and clinical trials carried out on the product. Council Directive 75/318/EEC of 20 May 1975 on the approximation of the laws of Member States relating to analytical, pharmaco-toxicological and clinical standards and protocols in respect of the testing of medicinal products (5)lays down uniform rules on the compilation of dossiers including their presentation.

(2)

The accepted basis for the conduct of clinical trials in humans is founded in the protection of human rights and the dignity of the human being with regard to the application of biology and medicine, as for instance reflected in the 1996 version of the Helsinki Declaration. The clinical trial subject's protection is safeguarded through risk assessment based on the results of toxicological experiments prior to any clinical trial, screening by ethics committees and Member States' competent authorities, and rules on the protection of personal data.

(3)

Persons who are incapable of giving legal consent to clinical trials should be given special protection. It is incumbent on the Member States to lay down rules to this effect. Such persons may not be included in clinical trials if the same results can be obtained using persons capable of giving consent. Normally these persons should be included in clinical trials only when there are grounds for expecting that the administering of the medicinal product would be of direct benefit to the patient, thereby outweighing the risks. However, there is a need for clinical trials involving children to improve the treatment available to them. Children represent a vulnerable population with developmental, physiological and psychological differences from adults, which make age- and development- related research important for their benefit. Medicinal products, including vaccines, for children need to be tested scientifically before widespread use. This can only be achieved by ensuring that medicinal products which are likely to be of significant clinical value for children are fully studied. The clinical trials required for this purpose should be carried out under conditions affording the best possible protection for the subjects. Criteria for the protection of children in clinical trials therefore need to be laid down.

(4)

In the case of other persons incapable of giving their consent, such as persons with dementia, psychiatric patients, etc., inclusion in clinical trials in such cases should be on an even more restrictive basis. Medicinal products for trial may be administered to all such individuals only when there are grounds for assuming that the direct benefit to the patient outweighs the risks. Moreover, in such cases the written consent of the patient's legal representative, given in cooperation with the treating doctor, is necessary before participation in any such clinical trial.

(5)

The notion of legal representative refers back to existing national law and consequently may include natural or legal persons, an authority and/or a body provided for by national law.

(6)

In order to achieve optimum protection of health, obsolete or repetitive tests will not be carried out, whether within the Community or in third countries. The harmonisation of technical requirements for the developmentof medicinal products should therefore be pursued through the appropriate fora, in particular the International Conference on Harmonisation.

(7)

For medicinal products falling within the scope of Part A of the Annex to Council Regulation (EEC) No 2309/93 of 22 July 1993 laying down Community procedures for the authorisation and supervision of medicinal products for human and veterinary use and establishing a European Agency for the Evaluation of Medicinal Products (6), which include products intended for gene therapy or cell therapy, prior scientific evaluation by the European Agency for the Evaluation of Medicinal Products (hereinafter referred to as the‘Agency’), assisted by the Committee for Proprietary Medicinal Products, is mandatory before the Commission grants marketing authorisation. In the course of this evaluation, the said Committee may request full details of the results of the clinical trials on which the application for marketing authorisation is based and, consequently, on the manner in which these trials were conducted and the same Committee may go so far as to require the applicant for such authorisation to conduct further clinical trials. Provision must therefore be made to allow the Agency to have full information on the conduct of any clinical trial for such medicinal products.

(8)

A single opinion for each Member State concerned reduces delay in the commencement of a trial without jeopardising the well-being of the people participating in the trial or excluding the possibility of rejecting it in specific sites.

(9)

Information on the content, commencement and termination of a clinical trial should be available to the Member States where the trial takes place and all the other Member States should have access to the same information. A European database bringing together this information should therefore be set up, with due regard for the rules of confidentiality.

(10)

Clinical trials are a complex operation, generally lasting one or more years, usually involving numerous participants and several trial sites, often in different Member States. Member States' current practices diverge considerably on the rules on commencement and conduct of the clinical trials and the requirements for carrying them out vary widely. This therefore results in delays and complications detrimental to effective conduct of such trials in the Community. It is therefore necessary to simplify and harmonise the administrative provisions governing such trials by establishing a clear, transparent procedure and creating conditions conducive to effective coordination of such clinical trials in the Community by the authorities concerned.

(11)

As a rule, authorisation should be implicit, i.e. if there has been a vote in favour by the Ethics Committee and the competent authority has not objected within a given period, it should be possible to begin the clinical trials. In exceptional cases raising especially complex problems, explicit written authorisation should, however, be required.

(12)

The principles of good manufacturing practice should be applied to investigational medicinal products.

(13)

Special provisions should be laid down for the labelling of these products.

(14)

Non-commercial clinical trials conducted by researchers without the participation of the pharmaceuticals industry may be of great benefit to the patients concerned. The Directive should therefore take account of the special position of trials whose planning does not require particular manufacturing or packaging processes, if these trials are carried out with medicinal products with a marketing authorisation within the meaning of Directive 65/65/EEC, manufactured or imported in accordance with the provisions of Directives 75/319/EEC and 91/356/EEC, and on patients with the same characteristics as those covered by the indication specified in this marketing authorisation. Labelling of the investigational medicinal products intended for trials of this nature should be subject to simplified provisions laid down in the good manufacturing practice guidelines on investigational products and in Directive 91/356/EEC.

(15)

The verification of compliance with the standards of good clinical practice and the need to subject data, information and documents to inspection in order to confirm that they have been properly generated, recorded and reported are essential in order to justify the involvement of human subjects in clinical trials.

(16)

The person participating in a trial must consent to the scrutiny of personal information during inspection by competent authorities and properly authorised persons, provided that such personal information is treated as strictly confidential and is not made publicly available.

(17)

This Directive is to apply without prejudice to Directive 95/46/EEC of the European Parliament and of the Council of 24 October 1995 on the protection of individuals with regard to the processing of personal data and on the free movement of such data (7).

(18)

It is also necessary to make provision for the monitoring of adverse reactions occurring in clinical trials using Community surveillance (pharmacovigilance) procedures in order to ensure the immediate cessation of any clinical trial in which there is an unacceptable level of risk.

(19)

The measures necessary for the implementation of this Directive should be adopted in accordance with Council Decision 1999/468/EC of 28 June 1999 laying down the procedures for the exercise of implementing powers conferred on the Commission (8),

(a)

‘clinical trial’: any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of one or more investigational medicinal product(s), and/or to identify any adverse reactions to one or more investigational medicinal product(s) and/or to study absorption, distribution, metabolism and excretion of one or more investigational medicinal product(s) with the object of ascertaining its (their) safety and/or efficacy;

This includes clinical trials carried out in either one site or multiple sites, whether in one or more than one Member State;

(b)

‘multi-centre clinical trial’: a clinical trial conducted according to a single protocol but at more than one site, and therefore by more than one investigator, in which the trial sites may be located in a single Member State, in a number of Member States and/or in Member States and third countries;

(c)

‘non-interventional trial’: a study where the medicinal product(s) is (are) prescribed in the usual manner in accordance with the terms of the marketing authorisation. The assignment of the patient to a particular therapeutic strategy is not decided in advance by a trial protocol but falls within current practice and the prescription of the medicine is clearly separated from the decision to include the patient in the study. No additional diagnostic or monitoring procedures shall be applied to the patients and epidemiological methods shall be used for the analysis of collected data;

(d)

‘investigational medicinal product’: a pharmaceutical form of an active substance or placebo being tested or used as a reference in a clinical trial, including products already with a marketing authorisation but used or assembled (formulated or packaged) in a way different from the authorised form, or when used for an unauthorised indication, or when used to gain further information about the authorised form;

(e)

‘sponsor’: an individual, company, institution or organisation which takes responsibility for the initiation, management and/or financing of a clinical trial;

(f)

‘investigator’: a doctor or a person following a profession agreed in the Member State for investigations because of the scientific background and the experience in patient care it requires. The investigator is responsible for the conduct of a clinical trial at a trial site. If a trial is conducted by a team of individuals at a trial site, the investigator is the leader responsible for the team and may be called the principal investigator;

(g)

‘investigator's brochure’: a compilation of the clinical and non-clinical data on the investigational medicinal product or products which are relevant to the study of the product or products in human subjects;

(h)

‘protocol’: a document that describes the objective(s), design, methodology, statistical considerations and organisation of a trial. The term protocol refers to the protocol, successive versions of the protocol and protocol amendments;

(i)

‘subject’: an individual who participates in a clinical trial as either a recipient of the investigational medicinal product or a control;

(j)

‘informed consent’: decision, which must be written, dated and signed, to take part in a clinical trial, taken freely after being duly informed of its nature, significance, implications and risks and appropriately documented, by any person capable of giving consent or, where the person is not capable of giving consent, by his or her legal representative; if the person concerned is unable to write, oral consent in the presence of at least one witness may be given in exceptional cases, as provided for in national legislation.

(k)

‘ethics committee’: an independent body in a Member State, consisting of healthcare professionals and non-medical members, whose responsibility it is to protect the rights, safety and wellbeing of human subjects involved in a trial and to provide public assurance of that protection, by, among other things, expressing an opinion on the trial protocol, the suitability of the investigators and the adequacy of facilities, and on the methods and documents to be used to inform trial subjects and obtain their informed consent;

(l)

‘inspection’: the act by a competent authority of conducting an official review of documents, facilities, records, quality assurance arrangements, and any other resources that are deemed by the competent authority to be related to the clinical trial and that may be located at the site of the trial, at the sponsor's and/or contract research organisation's facilities, or at other establishments which the competent authority sees fit to inspect;

(m)

‘adverse event’: any untoward medical occurrence in a patient or clinical trial subject administered a medicinal product and which does not necessarily have a causal relationship with this treatment;

(n)

‘adverse reaction’: all untoward and unintended responses to an investigational medicinal product related to any dose administered;

(o)

‘serious adverse event or serious adverse reaction’: any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability or incapacity, or is a congenital anomaly or birth defect;

(p)

‘unexpected adverse reaction’: an adverse reaction, the nature or severity of which is not consistent with the applicable product information (e.g. investigator's brochure for an unauthorised investigational product or summary of product characteristics for an authorised product).

(a)

the informed consent of the parents or legal representative has been obtained; consent must represent the minor's presumed will and may be revoked at any time, without detriment to the minor;

(b)

the minor has received information according to its capacity of understanding, from staff with experience with minors, regarding the trial, the risks and the benefits;

(c)

the explicit wish of a minor who is capable of forming an opinion and assessing this information to refuse participation or to be withdrawn from the clinical trial at any time is considered by the investigator or where appropriate the principal investigator;

(d)

no incentives or financial inducements are given except compensation;

(e)

some direct benefit for the group of patients is obtained from the clinical trial and only where such research is essential to validate data obtained in clinical trials on persons able to give informed consent or by other research methods; additionally, such research should either relate directly to a clinical condition from which the minor concerned suffers or be of such a nature that it can only be carried out on minors;

(f)

the corresponding scientific guidelines of the Agency have been followed;

(g)

clinical trials have been designed to minimise pain, discomfort, fear and any other foreseeable risk in relation to the disease and developmental stage; both the risk threshold and the degree of distress have to be specially defined and constantly monitored;

(h)

the Ethics Committee, with paediatric expertise or after taking advice in clinical, ethical and psychosocial problems in the field of paediatrics, has endorsed the protocol; and

(i)

the interests of the patient always prevail over those of science and society.

(a)

the informed consent of the legal representative has been obtained; consent must represent the subject's presumed will and may be revoked at any time, without detriment to the subject;

(b)

the person not able to give informed legal consent has received information according to his/her capacity of understanding regarding the trial, the risks and the benefits;

(c)

the explicit wish of a subject who is capable of forming an opinion and assessing this information to refuse participation in, or to be withdrawn from, the clinical trial at any time is considered by the investigator or where appropriate the principal investigator;

(d)

no incentives or financial inducements are given except compensation;

(e)

such research is essential to validate data obtained in clinical trials on persons able to give informed consent or by other research methods and relates directly to a life-threatening or debilitating clinical condition from which the incapacitated adult concerned suffers;

(f)

clinical trials have been designed to minimise pain, discomfort, fear and any other foreseeable risk in relation to the disease and developmental stage; both the risk threshold and the degree of distress shall be specially defined and constantly monitored;

(g)

the Ethics Committee, with expertise in the relevant disease and the patient population concerned or after taking advice in clinical, ethical and psychosocial questions in the field of the relevant disease and patient population concerned, has endorsed the protocol;

(h)

the interests of the patient always prevail over those of science and society; and

(i)

there are grounds for expecting that administering the medicinal product to be tested will produce a benefit to the patient outweighing the risks or produce no risk at all.

(a)

after the commencement of the clinical trial, the sponsor may make amendments to the protocol. If those amendments are substantial and are likely to have an impact on the safety of the trial subjects or to change the interpretation of the scientific documents in support of the conduct of the trial, or if they are otherwise significant, the sponsor shall notify the competent authorities of the Member State or Member States concerned of the reasons for, and content of, these amendments and shall inform the ethics committee or committees concerned in accordance with Articles 6 and 9.

On the basis of the details referred to in Article 6(3) and in accordance with Article 7, the Ethics Committee shall give an opinion within a maximum of 35 days of the date of receipt of the proposed amendment in good and due form. If this opinion is unfavourable, the sponsor may not implement the amendment to the protocol.

If the opinion of the Ethics Committee is favourable and the competent authorities of the Member States have raised no grounds for non-acceptance of the abovementioned substantial amendments, the sponsor shall proceed to conduct the clinical trial following the amended protocol. Should this not be the case, the sponsor shall either take account of the grounds for non-acceptance and adapt the proposed amendment to the protocol accordingly or withdraw the proposed amendment;

(b)

without prejudice to point (a), in the light of the circumstances, notably the occurrence of any new event relating to the conduct of the trial or the development of the investigational medicinal product where that new event is likely to affect the safety of the subjects, the sponsor and the investigator shall take appropriate urgent safety measures to protect the subjects against any immediate hazard. The sponsor shall forthwith inform the competent authorities of those new events and the measures taken and shall ensure that the Ethics Committee is notified at the same time;

(c)

within 90 days of the end of a clinical trial the sponsor shall notify the competent authorities of the Member State or Member States concerned and the Ethics Committee that the clinical trial has ended. If the trial has to be terminated early, this period shall be reduced to 15 days and the reasons clearly explained.

—

the planning of the trial does not require particular manufacturing or packaging processes;

—

the trial is conducted with medicinal products with, in the Member States concerned by the study, a marketing authorisation within the meaning of Directive 65/65/EEC, manufactured or imported in accordance with the provisions of Directive 75/319/EEC;

—

the patients participating in the trial have the same characteristics as those covered by the indication specified in the abovementioned authorisation.

(1)

Article 3 of the Council Decision concerning the conclusion of an Agreement between the European Community and Republic of Bulgaria on the reciprocal protection and control of wine names lays down that, for the purposes of Article 13 of the Agreement, the Commission is authorised to conclude the necessary acts amending the Agreement, in accordance with the procedure laid down in Article 83 of Council Regulation (EEC) No 822/87 of 16 March 1987 on the common organisation of the market in wine (2). Regulation (EEC) No 822/87 was replaced by Regulation (EC) No 1493/1999 (3), as last amended by Regulation (EC) No 2826/2000 (4).

(2)

The Commission, on behalf of the Community, and the Republic of Bulgaria have reached agreement in the form of an Exchange of Letters. That Exchange of Letters should be approved.

(3)

The Management Committee for Wine has not delivered an opinion within the time limit laid down by its Chairman,