Legislative Decree 2/18/97 n. 44
Legislative Decree 18 February 1997, n. 44
"Implementation of Directive 93/39/EEC, amending Directives 65/65/EEC, 75/318/EEC and 75/319/EEC relating to medicinal products"
published in the Official Gazette no. 54 of 6 March 1997 – Ordinary Supplement n. 49
(Correction of the Official Gazette no. 84 of 11 April 1997)
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THE PRESIDENT OF THE REPUBLIC
Having regard to articles 76 and 87 of the Constitution;
Given the law of 6 February 1996, n. 52, and in particular articles 1 and 34 and annex A;
Having regard to directive 93/39/EEC, of the Council of 14 June 1993, which amends directives 65/65/EEC, 75/318/EEC and 75/319/EEC relating to medicinal products;
Given the legislative decree 29 May 1991, n. 178;
Given the legislative decree 30 December 1992, n. 541;
Given the regulation (EEC) n. 2309/93, of the Council of 22 July 1993, which establishes the Community procedures for the authorization and supervision of medicinal products for human and veterinary use and which establishes a European Medicines Evaluation Agency;
Given the resolution of the Council of Ministers, adopted in the meeting of 14 February 1997;
On the proposal of the President of the Council of Ministers and the Minister of Health, in agreement with the Ministers of Foreign Affairs, of Justice and of the Treasury;
EMANATE
the following legislative decree:
Article 1
1. In the legislative decree 29 May 1991, n. 178, as modified by the legislative decree 30 December 1992, n. 541, the following changes were made:
a) in article 7:
1) after paragraph 3, the following is inserted:
“3-bis. For the purposes of the investigations referred to in this article, the Ministry of Health - Department for the evaluation of medicinal products and pharmacovigilance - may make use of the personnel of the Higher Institute of Health, of the Higher Institute for Prevention and Safety at Work, as well as of local health units, according to the required professionals.";
2) paragraph 5 is replaced by the following:
“5. The personnel who carry out the checks referred to in this article are due a fee, including the mission allowance, to be established by decree of the Minister of Health, in agreement with the Minister of the Treasury, to be issued no later than sixty days from the date of entry into force of this decree.";
b) in article 8:
1) paragraph 1 is replaced by the following:
“1. No medicinal specialty can be placed on the market without having obtained an authorization from the Ministry of Health or a community authorization pursuant to Regulation (EEC) n. 2309/93 of the Council of 22 July 1993”;
2) in paragraph 2, line, between the words: "on the market" and the word: "must", the following are inserted:
", which must be established in the Community territory,";
3) in paragraph 2, letter e), the following words are added at the end:
“; if necessary, the reasons for the precautionary and safety measures to be adopted for the conservation of the product, for its administration to patients and for the elimination of residues, together with an indication of the potential risks that the product presents for the environment.";
4) in paragraph 3, letter f) is replaced by the following:
“f) copy of each authorisation, obtained in another Member State of the European Union or in a third country, to place the medicinal product in question on the market, together with the list of Member States where an application for authorization is being examined; copy of the summary of product characteristics proposed by the applicant or approved by the competent authorities of the Member State; copy of the label proposed by the applicant or approved by the competent authorities of the Member State, as well as, in the event of refusal of authorisation, both in a Member State and in a third country, a copy of the detailed documentation containing the reasons for the refusal. The information referred to in this letter is updated regularly.";
5) in paragraph 4:
a) the words: "The documents referred to in numbers 2 and 3" are replaced by the following: "The documents referred to in letters b) and c)";
b) the following sentence is added at the end: "Each of the documents referred to in paragraph 3, letter c), must include the report of an expert drawn up and presented in compliance with the provisions of Community provisions;".
6) in paragraph 5, the following sentence is added at the end: "Without prejudice to the legislation relating to the protection of industrial and commercial property, if there are particular reasons for the protection of public health, recognized by the Single Medicines Commission, the provisions of this paragraph also apply to medicinal specialties essentially similar to a product not yet on the market in Italy provided that it has already been on the market for at least ten years in a member state of the European Union.";
7) in paragraph 9 the words are eliminated: "or described in the scientific literature referred to.";
c) Article 9 is replaced by the following:
“Art. 9
Procedure for issuing the authorisation.1. Without prejudice to the provisions of articles 9-bis and 12-bis, the Ministry of Health adopts its own decisions on the application for marketing authorization within the term of two hundred and ten days from the submission of the application itself.
2. When the Ministry of Health invites the applicant to regularize the application or integrate the documentation, the term referred to in paragraph 1 starts from the date on which the requested complementary data are provided.
3. Before granting the authorisation, the Ministry of Health:
a) verifies the conformity of the documentation presented by the applicant with the provisions contained in article 8, complying, in the examination, with the criteria indicated in the directives and recommendations of the European Community;
b) ascertains that the manufacturer is able to produce and control the medicinal product according to the methods described in the documentation pursuant to article 8, paragraph 3, letters a) and b);
c) may submit the medicinal product, the relative raw materials and possibly the intermediate products or other constituents to the control of the Higher Institute of Health pursuant to legislative decree 30 June 1993, n. 267, to ascertain the suitability of the control methods used by the manufacturer and described in the documentation;
d) acquires the opinion of the Single Medicines Commission, which is also required to draw up, in accordance with Community legislation, an evaluation report and to formulate any observations on the dossier with regard to the results of analytical, pharmaco-toxicological and clinical trials of the medicine concerned; the evaluation report is updated, at the request of the competent Department of the Ministry of Health, by the Single Drug Commission whenever new information relevant to the evaluation of the quality, safety or efficacy of the medicinal product in question is received.
4. The authorization decree approves the labels, which must bear, among other things, the authorization number, and the leaflets of the medicines, as well as the summaries of the product characteristics referred to in article 8, paragraph 3, letter d).
5. The Ministry of Health sends the European Medicines Evaluation Agency (EMEA) a copy of the authorization referred to in paragraph 4, accompanied by the summary of product characteristics.
6. The Ministry of Health, on the proposal of the Higher Institute of Health, having consulted the Single Drug Commission and the Higher Health Council, adopts the annual control program of the compositions of medicinal products, the implementation of which is entrusted to the Higher Institute of Health.";
d) after article 9 the following article is inserted:
“Art. 9-bis
Mutual recognition of authorisations.1. When receiving an application for marketing authorization pursuant to article 9 of directive 75/319/EEC and subsequent amendments, the Ministry of Health decides on the application in compliance with the procedure and deadlines established by Community legislation.
2. When, during the preliminary investigation of an application for authorization submitted after 31 December 1997 pursuant to article 8, paragraph 2, the Ministry of Health is informed, pursuant to article 8, paragraph 3, letter f), that another Member State has authorized the medicinal product covered by the application, it immediately requests the authority of the Member State which issued the authorization to send it the evaluation report. Within ninety days of receiving the evaluation report, the Ministry of Health recognizes the decision of the first Member State and the summary of product characteristics approved by it or, if it deems that the authorization of the medicinal product presents a risk to public health, activates the procedure envisaged by articles 10 and following of directive 75/319/EEC and subsequent amendments.
3. For applications for authorization presented between 1 January 1995 and 31 December 1997, the activation of the procedure referred to in paragraph 2 is optional.”;
e) in article 11:
1) paragraph 2 is replaced by the following:
"2. To obtain the renewal of the authorisation, the holder must submit an application to the Ministry of Health, no later than the ninetieth day prior to the expiry date, attaching the list of all the modifications to the original authorization authorized by the Ministry of Health or, in any case, approved pursuant to article 12-bis, paragraph 4, as well as a detailed report of the cases of presumed adverse reactions. In the absence of the report, which must be accompanied by a suitable scientific evaluation and sales data, the renewal cannot take place. For the purposes of evaluating the application, the Ministry of Health takes into account, in particular, the pharmacovigilance data.";
2) paragraph 4 is replaced by the following:
“4. The renewal of the authorization refers to the original authorization of a medicinal product and to all the modifications of said authorisation, as identified by Regulation (EC) n. 542/95, of the Commission, of 10 March 1995, which occurred up to the date of renewal; the non-renewal of an authorization entails, unless otherwise determined by the minister, the automatic forfeiture of all modifications of the same authorized by the Ministry of Health, or approved pursuant to article 12 bis, paragraph 4.";
f) the following articles are inserted after article 12:
“Art. 12-bis
Minor changes to authorisations.1. Notwithstanding the provisions of article 12, paragraph 1, for minor modifications of the marketing authorizations issued by the Ministry of Health, listed in Annex I, the provisions of this article shall apply.
2. To make a minor modification, the applicant is required to send the Ministry of Health a notification accompanied by the documentation demonstrating the fulfillment of the conditions set out in Annex I, by all the printed documents modified as a result of the request.
3. If several changes are to be made to a single authorisation, a notification must be submitted for each desired change and each notification must contain a reference to the others submitted. The sending of a single notification is sufficient when the modification of the marketing authorization necessarily entails other changes; in this case, the notification must illustrate the relationship between the main modification and the consequent ones.
4. After thirty days from the date of the note from the Ministry of Health acknowledging the regularity of the notification without any further communication, the notified modification is considered approved.
5. In the case envisaged in paragraph 3, second sentence, together with the main amendment, the consequent amendments are understood to be approved within the time limit referred to in paragraph 4, provided that they have been clearly specified in the notification.
6. When the changes concern the summary of product characteristics, the labeling or the package leaflet, the interested party is required to send the Ministry of Health a copy of the updated texts within thirty days of the approval referred to in paragraph 4.
7. The modifications deriving from the application of this article are communicated by the interested parties to the Ministry of Health and to the national federations of the orders of surgeons and dentists and pharmacists and published, at the expense of the interested parties, in the Official Gazette of the Italian Republic, second part, on the basis of the model prepared by the Ministry itself. The Ministry of Health publishes the list of changes made in the Official Gazette of the Italian Republic every six months.
8. With regard to medicinal products governed by articles 20 and 22, the procedure referred to in this article does not apply for the minor modifications referred to in numbers 11, 12, 13, 14, 15, 16, 17, 24 and 25 of Annex I.
9. Amendments and additions to Annex I are adopted by decree of the Minister of Health, taking into account any amendments to Annex I to Regulation (EC) no. 542/95.
Article 12-ter
Restrictive variations of authorizations for security reasons.1. Notwithstanding the provisions of article 12-bis, if the holder of the marketing authorization notifies a modification motivated by safety reasons, consisting in the reduction of the therapeutic indications or in the reduction of the dosage, or in the addition of contraindications or warnings, he must immediately adopt the same modification, on a provisional basis, if no objections are raised by the Ministry of Health within the following twenty-four working hours.";
g) in article 14:
1) in paragraph 2, letter e), the following words are added at the end:
“taking into account the need to adopt generally accepted scientific methods.”;
2) paragraph 7 is replaced by the following:
“7. With the decree which provides, upon renunciation of the holder, the revocation of the marketing authorization of a medicinal specialty or which provides for a modification of said authorization, the Ministry of Health, when this is not prevented by reasons of public health, grants a deadline for the withdrawal from the market of the medicinal product object of revocation or modification. In the event of modifications approved pursuant to article 12-bis, paragraph 4, disposal of the stocks of the medicinal product subject to modification is permitted, unless otherwise determined by the Ministry of Health for the need to protect public health.";
h) Article 19 is replaced by the following:
“Art. 19
Failure to place and withdraw from the market a medicinal product1. If a medicinal product is not placed on the market in the national territory within sixty days from the effective start date of the authorization issued by the Ministry of Health, the person responsible for placing it on the market is required to notify the Ministry of Health of the delay in marketing and, subsequently, of the effective start of the same.
2. The person responsible for placing it on the market has the obligation to immediately notify the Ministry of Health and the competent health authorities of other possibly interested Member States of any initiative aimed at withdrawing the product from the market or suspending its marketing. In such an event, the Ministry of Health shall suspend the authorisation.".
2. Legislative decree 29 May 1991, n. 178, most recently amended by paragraph 1, the following attachment is added:
"Annex I
(article 12-bis)
MINOR CHANGES TO A MARKETING AUTHORIZATION
1. Changing the content of the manufacturing authorization.
Conditions to be met: attach the production authorization (the applicant must be the authorization holder).
2. Change of name of the medicinal product.
Conditions to be fulfilled: any confusion with the names of other existing medicinal products must be avoided: if it is a common name, the change must take place in the following order: from the common name to the invented name or to the DCI.
3. Change of name or business name or business name or address of the Marketing Authorization Holder.
Conditions to be satisfied: the holder of the authorization must be the same individual or the same company.
4. Replacement of an excipient with another equivalent (excluding vaccine adjuvants and excipients of biological origin). Conditions to be satisfied: identity of the functional characteristics, no change of the dissolution modalities for the solid forms.
5. Deleting a colorant or replacing one colorant with another.
Conditions to be met: the proposed colorant must comply with the ministerial decree of 27 February 1996, n. 209.
6. Addition, removal or substitution of a flavour.
Conditions to be met: the proposed flavoring must comply with the provisions of the legislative decree of 25 January 1992, n. 107.
7. Change in the weight of the tablet coating or capsule shell.
Conditions to be met: no change in the dissolution methods.
8. Change in the qualitative composition of the primary packaging material.
Conditions to be fulfilled: The proposed container material must be at least equivalent to the approved material with respect to the relevant properties and the change must not affect sterile products.
9. Deleting an indication.
Conditions to be fulfilled: The safety of the prolonged use of the medicinal product has not given rise to concern from the point of view of pharmacovigilance, preclinical safety or qualitative characteristics. The operation must be justified.
10. Deleting an administration route.
Conditions to be fulfilled: The safety of the prolonged use of the medicinal product has not given rise to concern from the point of view of pharmacovigilance, preclinical safety or qualitative characteristics.
11. Change of the manufacturer of the active substance.
Conditions to be met: the specifications, synthesis and quality control procedures must be identical to those already approved, otherwise a certificate from the European Pharmacopoeia must be sent attesting the suitability of the new active substance.
12. Minor modification of the manufacturing process of active substances.
Conditions to be fulfilled: specifications must not be adversely affected; there should be no changes in physical properties, new impurities or changes in the level of impurities requiring further safety studies.
13. Batch size of the active substance.
Conditions to be fulfilled: Batch data must indicate that the change does not affect the suitability of production or the physical properties.
14. Modification of the specifications relating to the active substance.
Conditions to be fulfilled: the specifications must be strengthened or new tests or new limits must be introduced.
15. Minor change in the production of the medicinal product.
Conditions to be fulfilled: the specifications relating to the medicinal product must not be adversely affected; the new process must give rise to an identical product as regards quality, safety and efficacy.
16. Changing the batch size of the finished product.
Condition to be fulfilled: the modification must not affect the suitability of the production.
17. Modification of the specifications relating to the medicinal product.
Conditions to be met: Specifications need to be strengthened or new tests and limits introduced.
18. Synthesis or recovery of excipients not part of the Pharmacopoeia, but described in the original documentation.
Conditions to be fulfilled: Specifications must not be adversely affected, no new impurities or changes in the level of impurities requiring further safety studies must occur, no changes in physico-chemical properties must result.
19. Modification of the specifications relating to the excipients contained in a medicinal product (excluding adjuvants for vaccines and excipients of biological origin).
Conditions to be met: Specifications need to be strengthened or new tests and limits introduced.
20. Extension of the period of validity of the product envisaged at the time of authorisation.
Conditions to be met: stability studies must have been carried out to be attached to the approved protocol at the time of release of the marketing authorization; the studies must indicate that the agreed shelf life specifications are still met; the duration of validity must not exceed five years.
21. Change of shelf life after opening the package.
Condition to be fulfilled: Studies must demonstrate that the agreed shelf life specifications are still met.
22. Change in shelf life after reconstitution.
Conditions to be fulfilled: Studies must demonstrate that the agreed shelf life specifications of the reconstituted product are still met.
23. Change in storage conditions.
Conditions to be met: stability studies must have been carried out to be attached to the approved protocol at the time of release of the marketing authorization; the studies must indicate that the agreed shelf life specifications are still met.
24. Change of test procedures related to the active substance.
Conditions to be fulfilled: The results of the validation tests must indicate that the new test procedures are at least equivalent to the previous ones.
25. Change in drug testing procedures.
Conditions to be fulfilled: the specifications relating to the medicinal product must not be adversely affected; the results of the validation tests must indicate that the new test procedure is at least equivalent to the previous one.
26. Changes linked to supplements added to the Pharmacopoeia, (if reference is made in the dossiers to the "current" edition of the Pharmacopoeia; no notification is required, provided that the change is made within six months of the adoption of the monograph). Conditions to be met: the modification must be made for the sole purpose of implementing the new provisions set out in the supplement.
27. Changed testing procedures for non-pharmacopoeia excipients.
Conditions to be fulfilled: The results of the validation tests must indicate that the new test procedure is at least equivalent to the previous one.
28. Change in test procedures related to primary packaging.
Conditions to be fulfilled: the results of the validation tests must indicate that the new procedure is at least equivalent to the previous one.
29. Changed dosing device testing procedures.
Conditions to be fulfilled: the results of the validation tests must indicate that the new procedure is at least equivalent to the previous one.
30. Changing the shape of the container.
Conditions to be met: the product must not undergo quality and stability changes in the container, there must be no changes in the container-product interactions.
31. Modification of the impressions, punching or other markings (except engravings) placed on the tablets or the impressions on the capsules.
Condition to be fulfilled: The new markings must not lead to confusion with other tablets or capsules.
32. Change in size of tablets, capsules, suppositories and pessaries (ova) in the absence of changes in the quantitative composition and average mass.
Conditions to be met: there must be no change in the methods of dissolution".
Article 2
1. The national pharmacovigilance system belongs to the Department for the evaluation of medicinal products and pharmacovigilance of the Ministry of Health, hereinafter referred to as the "Department".
2. The Department, in accordance with any procedures agreed at Community level and defined by the EMEA:
a) collects and scientifically evaluates useful information for the monitoring of medicines with particular regard to adverse reactions, also taking into account data relating to the consumption of the medicines themselves;
b) collects information on the improper use of medicines, as well as on the serious abuse of the same;
c) promotes and coordinates, also in collaboration with the Higher Institute of Health, studies and research on the use of medicinal products, epidemiology, active pharmacovigilance and the interpretation of the data obtained and prepares population registers for pharmacoepidemiology;
d) adopts, assisted by the regions, measures aimed at promoting spontaneous reporting by health professionals;
e) ensures, as soon as possible and in any case within fifteen days of receipt, that notifications relating to serious adverse reactions received by the Department are brought to the attention of the EMEA and the person in charge of placing the medicinal product on the market;
f) maintain the necessary relations with the EMEA, with the national pharmacovigilance centers of the other Member States, with international bodies and with the regions;
g) arranges, in collaboration with the Single Drug Commission and the Higher Health Council, for the preparation of the annual report to Parliament of the Ministry of Health on pharmacovigilance;
h) provides the EMEA and the national pharmacovigilance centers of the other Member States with information on modifications, suspensions or withdrawals of the authorization of a medicinal product caused by reasons of public health protection. In case of suspension, determined for reasons of urgency, the information to the EMEA is given, at the latest, within the first working day following the provision.
3. The Regions, individually or in agreement with each other, collaborate with the Department in the pharmacovigilance activity, providing elements of knowledge and evaluation to integrate the data received by the Department pursuant to article 4. The Regions also provide, within the scope of their competences, for the dissemination of information to healthcare personnel and for the training of operators in the field of pharmacovigilance.
4. The Department organizes, with the participation of the Higher Institute of Health, periodic meetings to examine with the Regions the best ways to implement collaboration in the pharmacovigilance sector.
5. For the purposes of this decree:
a) adverse side effect or adverse reaction: a noxious and unwanted reaction occurring at doses of medicinal product normally administered to man for the prophylaxis, diagnosis or therapy of a disease, or to modify a physiological function;
b) serious negative side effect or serious adverse reaction: an adverse reaction with a lethal outcome, or an adverse reaction that threatens survival, or that creates disability, incapacity or that causes or prolongs hospitalization;
c) unexpected side effect or unexpected reaction: a reaction whose nature or severity is not indicated or does not correspond to what is reported in the summary of product characteristics;
d) serious and unexpected side effect or serious and unexpected reaction: a serious and unexpected reaction.
Article 3
1. Every company that holds a marketing authorization for medicinal products must have, on a stable and continuous basis, a person in charge of the pharmacovigilance service, with a degree in medicine and surgery, in pharmacy, or in pharmaceutical chemistry and technology, or in biology or chemistry.
2. The person in charge of the pharmacovigilance service must be a separate person from the person in charge of the scientific service provided for by article 14 of the legislative decree of 30 December 1992, n. 541, but must, however, be placed in a position to use all the data of this service. The powers of the person in charge extend to all medicines whose marketing authorization is held by the company he employs, even if marketed by other companies.
3. The head of the pharmacovigilance service ensures:
a) the establishment and functioning of a system capable of ensuring that information on all alleged adverse reactions communicated to company personnel and medical-scientific representatives is collected and sorted in a single place;
b) the preparation for the competent authorities of the reports referred to in paragraph 4, according to the methods established by the Ministry of Health, which takes into account the indications of the competent international and community bodies for this purpose;
c) the transmission of a rapid and comprehensive response to any request from the competent authorities for additional information for the purpose of assessing the risks of a medicinal product, including information concerning the volume of sales of the medicinal product concerned.
4. The person responsible for placing a medicinal product on the market is required to record all cases of alleged serious adverse reactions reported by healthcare personnel and to notify them, within three days for serious and unexpected ones and within six days for the others, to the local healthcare units competent for the area, for further forwarding to the Ministry of Health - Department for the evaluation of medicinal products and pharmacovigilance. He must also keep a detailed report of all other cases of alleged adverse reactions communicated to him by the health personnel. Without prejudice to any other conditions established for the granting of the marketing authorisation, these reports must be submitted to the competent authorities, immediately upon request of the same or, in the absence of a request, every six months, during the first two years from the granting of the authorisation, and once a year in the following three years. Subsequently, the reports are sent at five-year intervals together with the application for renewal of the authorisation.
5. In the hypothesis envisaged by article 7, paragraph 5, of the legislative decree of 30 December 1992, n. 541, the obligations and fulfilments envisaged by this article extend to the owner of the company that sees to the effective marketing of the medicinal product and to the person in charge of the pharmacovigilance service employed by the same company.
Article 4
1. Physicians are required to report any presumed adverse reaction of which they become aware in the exercise of their professional activity. This obligation also applies to medicinal products undergoing clinical trials.
2. With regard to medicinal products not subject to medical prescription, the pharmacist who becomes directly aware of them is also required to report the adverse reactions referred to in paragraph 1.
3. The reports referred to in paragraphs 1 and 2 must be sent by the healthcare professionals operating in the territory to the competent local healthcare unit and by the healthcare professionals operating in public and private hospital structures to the healthcare management of the structure itself, within three days in the case of serious adverse reactions and within six days in other cases.
4. The local health units and the health directorates referred to in paragraph 3 must send the Department the reports referred to in this article and those referred to in article 3, paragraph 4, also informing the Region to which they belong and the person responsible for placing the medicinal product on the market; Reports received of serious adverse reactions must be transmitted promptly and in any case within three days and all other reports within five days.
5. Any further methods of information are established by the Ministry of Health.
Article 5
1. For the examination of applications for authorization to market medicines and for applications for modification and renewal of authorizations issued pursuant to legislative decree 29 May 1991, n. 178, most recently amended by this decree, tariffs equal to one fifth of the amounts established by article 3 of Regulation (EC) no. 297/95 of the Council, of 10 February 1995, and subsequent updates, calculated at the official exchange rate of the ECU on the day of payment; the proof of payment must be attached to the application.
2. The tariffs in force due to the Ministry of Health for the examination of applications relating to medicinal products other than those provided for in paragraph 1 are confirmed; these tariffs are updated in the month of January of each year on the basis of the variations of the ISTAT index on the cost of living.
3. The sums deriving from the tariffs referred to in paragraph 1 are acquired in chapter XX – chapter 3629 – of the Revenue's estimates and subjected to the same regime as the tariffs referred to in article 5, paragraph 12, of the law of 29 December 1990, n. 407.
Article 6
1. For the purposes of the provisions of article 28, paragraph 1, of law no. 52, for the rationalization of the work of the Single Drug Commission, the Minister of Health, with his own decree, divides the same commission into sub-commissions, without prejudice to the total number of members.
2. Within the limits of the budget allocations, the members and experts of the Single Drug Commission may be summoned by the President of the commission itself even independently of the meetings of the commission or of the sub-commissions.
3. The members and experts of the Single Drug Commission are bound to respect and confidentiality. As part of their activity, the examination of documentation is also permitted outside the headquarters of the Ministry of Health and the EMEA.
4. The list of experts to be reported to the EMEA pursuant to article 53, paragraph 2, of Regulation no. is compiled and periodically updated by decree of the Minister of Health. 2309/EEC and that of the experts of the Single Medicines Commission who must possess the same requirements as the experts of the EMEA.
Article 7
1. The Department, within the available resources, may also make use of Universities, research institutions and hospitalization and treatment institutes of a scientific nature, through appropriate agreements.
Article 8
1. In implementation of the provisions of article 53 of Regulation (EEC) no. 2309/93, the Ministry of Health stipulates collaboration contracts with the EMEA for the evaluation of medicinal products subject to the community authorization procedure.
2. The sums disbursed by the EMEA in favor of the Ministry of Health - Department of Prevention and Medicines - relating to the services - envisaged by the contracts referred to in paragraph 1, flow to chapter XX - chapter 3629 - of the Revenue's estimates.
3. The amounts referred to in paragraph 2 are reassigned to a specific chapter under Heading 3 of the estimates of the Ministry of Health. The related budget allocation is used to cover mission expenses in Italy and abroad for Italian and foreign experts who operate within the framework of the activities envisaged in the contracts referred to in paragraph 1, as well as fees for professional services rendered on the basis of specific agreements.
4. The Minister of the Treasury is authorized to make the necessary budgetary changes with his own decrees.
Article 9
1. In article 7, paragraph 5, of the legislative decree 30 December 1992, n. 541, the words: "Until the implementation of the provisions of the European Economic Community which specify the pharmacovigilance tasks of pharmaceutical companies," are deleted.
Article 10
1. For medicinal products already authorized on the date of entry into force of this decree, the obligation of establishment in the Community territory of the person responsible for placing them on the market, provided for by article 8, paragraph 2, of legislative decree no. 178, as last amended by this decree, applies from the renewal of the authorization currently in force.
Article 11
1. The person responsible for placing medicinal products on the market and the person responsible for the pharmacovigilance service who violate the obligations referred to in article 3, paragraphs 1 and 3, are subject, unless the fact constitutes a crime, to the administrative sanction of payment of a sum from thirty million to one hundred and eighty million lire.
2. Anyone responsible for placing medicinal specialties on the market who violates the obligation referred to in article 3, paragraph 4, as well as doctors, pharmacists, health professionals and legal representatives of local health agencies and health directorates who violate the obligation to report adverse reactions referred to in article 4, are punished with a fine ranging from one million to ten million lire and with imprisonment of up to six months.