I. The Bill for the revision of community procedures concerning the authorization of drugs and the reform of the European Agency for Drug Assessment.

The antecedent facts
A radical revision of pharmaceutical procedures in the European Community was completed in the course of 1993 and the European Agency for Drug Assessment was formed in accordance with the (EEC) regulation n. 2309/93 the same year. Hence the by-laws concerning drugs, that had been first established in 1965 seemed improved. This does not mean that the by-laws were free of lacunae and errors. Europe is developing and in constant evolution. Though it has not been completely consolidated, it is however in an advanced stage of development and is well defined in its basic institutional aspects. On the other hand, another important step and expansion hoped for was made in the course of 2001: the Codification of the European Pharmaceutical Legislature. However, owing to the very nature of the developing model, once the Codification process was completed, a new revision proved to be necessary.

It was the amendment made by the 2000 Reviewing Committee that took on the final shape of a bill in 2001, passing for a Proposal for a Directive to amend Directive 2001/82/EC, which defines the amendment a community code concerning veterinary drugs and a BILL targeted at defining community procedures in the field of authorizations, supervision and drug control directed at drugs for human and veterinary use and which forms the European Agency for drug assessment. Hence on January 1 1995 the new community procedures for the authorization and control of drugs were enforced. At the heart of the said measure, the European Agency for Drug Assessment followed various objectives such as sharing the potential of the scientific knowledge of member states, with the special intention of guaranteeing a high degree of protection of public health, the free circulation of pharmaceutical products and the access of European citizens to new generation drugs. These objectives will continue to have legal power for the following five years. The EEC regulation n. 2309/93 had foreseen the possibility of developing the above mentioned procedures. General measures concerning the marketing of drugs for human use, definitely included in Directive (2001/83/EC), in accordance with what is established in the community code concerning drugs for human use, also proved to be necessary.

The challenges
The progress of international and European results, that of science at large and the developments underway in biotechnology, genetic treatment and innovations in the field of genomic drugs and experiments related with the xenogenetic somatic treatment require a compulsory adjustment of the current non specific legislature and respective authorization procedures concerning marketing for the future. Scientific globalization must go hand in hand with the globalization of prescribed practices. No prescribed development in the sphere of drug authorization can set aside these premises. The issue’s global importance must be considered. The very nature and purpose of drugs boast an absolutely international dimension. Besides, the European Union’s expansion that compels all the institutions to review their operational regulations must also be considered.

The new regulation’s legal basis
The European Commission, in presenting its new bill that changes drug authorizing procedures and reorganizes the structure and workings of the European Agency for Drug Assessment, specially justifies the same proposal’s legal basis. This explanation was equally necessary and useful. It is an absolutely vital aspect from an institutional viewpoint. The EEC regulation n. 2309/93, in accordance with which the Agency was formed and a centralized drug authorizing procedure was introduced, was adopted on the basis of article 235 of the EC Treatise, though in 1993 it did not contemplate any special competence. Hence resorting to the “window article 235” proved to be particularly important in conferring the Community additional competences in the above mentioned spheres. The Commission, when it presented its new proposal, believed that all reference to article 235 was unnecessary, given the existence of a tailor-made legal basis. For this reason, its proposal is based on article 95, letter b and article 152, paragraph 4 of the EC Treatise. Article 95, which foresees resorting to the combined decision procedure established in article 251, represents the legal basis to implement the objectives announced in article 14 of the Treatise. Among these, the free circulation of goods (article 14, paragraph 2) and, in detail, of the drugs for human and veterinary use, must be mentioned.

Amendments

1.Changes in protocol procedures
The European Commission, after ordering a report for outside assessment and having performed its analysis concerning the experience acquired, found itself in a rather complex situation concerning legislative procedures. The need to improve authorization procedures concerning drug marketing in the EC and to change certain administrative aspects of the European Agency for Drug Assessment was extremely clear. No doubt it was not believed necessary to make substantive changes in the EC regulation n. 2309/93, except for certain corrections made to special operational regulations and adjustments in view of scientific and technical evolution and the European Union’s future expansion. The same report revealed the need to preserve intact the previously defined general principles concerning a centralized procedure. On the other hand, Directive 2001/83/EC, which established a community code concerning drugs for human use (22), and Directive 2001/82/EC, which defined a community code concerning drugs for veterinary use (23), were adopted.

Hence it was considered necessary to update all references made in (EEC) regulation n. 2309/93 to the Directives codified and also to the new proposal. On the basis of the premises there emerged the Bill of the European Parliament and Council, which defined community procedures on the topic of authorizations, supervision and drug control, concerning drugs for human and veterinary use and, in accordance with this, formed the European Agency for Drug Assessment. The hoped for amendments do not concern the general orientation and outline of EC regulation n. 2309/93 and though, as a principle, the only objective is to introduce a series of improvements that are in accordance with the acquired experience concerning the system’s workings, there is no doubt that the text will have to undergo many adjustments. Concerning the method followed, the Commission first spoke of “Adjustment”, then moved to the term “Adaptation” and lastly chose the most radical one - total “Derogation” of the regulation that formed the system. The latter was replaced with a new act inspired by the current regulation though inclusive of all the new amendments and adaptations to the measures codified. Considering the formal problems the Commission had to face, it is no doubt acceptable to resort to the regulation’s total Derogation. However what does not appear consistent is the attribution of a “new” draft to the new text; this can cause confusion in the history of legislature. The new regulation’s title and considerations must declare that it is derogating the 1993 regulation and amending authorization procedures and the Agency’s structure and duties. The fact that a new regulation is approved does not certainly authorize us to deny history. Though it has long been repeated, the new regulation does not form the European Agency for Drug Assessment, which was instead formed in 1993. This mere formal and legislatively consistent correction is simple and the hope is that it is corrected during its legislative processing. In the first place the correction of the new proposal’s title, which could be called “Bill of amendment for the community procedures concerning the authorization, supervision and control of drugs related to drugs for human and veterinary use and the European Agency for drug assessment is reorganized” stands out as a necessity.

2. The decision concerning the prices is updated
The new proposal strictly declares that the present regulation‘s measures will not compromise member state authorities’ competences in fixing drug prices, nor those related with the inclusion of the latter in the application of national sickness fund systems or in social security systems for health, economic and social reasons. In particular, member states will reserve the right to choose, among the points stated in the marketing authorization, the therapeutic specifications and the sizes of the packages their respective social security institutions will respect”. As things stand the matter of the so-called “parallel importations” remains to date unsolved and the application of the EC’s court of law concerning the need for a community measure must wait. At the same time market segmentation in the pharmaceutical sector will continue.

3. Authorization procedures
The proposal specifies that the centralized procedure must continue to be compulsory for drugs produced with biotechnological procedures. The main amendment involves the obligation to apply this procedure to all the new active principles that can be released in the community market (article 3, paragraph 1 and appendix I, point 3). It specifies that the centralized procedure is optional for further drugs that can be a therapeutic innovation, and as an additional feature, it proposes to allow access to the procedures to drugs which, despite not being “innovative”, can be an advantage to the society or to patients, if authorized at a community level. This is especially the case of certain drugs whose distribution is not subject to a medical prescription (article 3, paragraph 2). Lastly, the proposal specifies to offer member states the possibility of nationally authorizing the over the counter drugs authorized by the community; they must only respect the agreements established throughout the community. The manufacturers of the so-called counter drugs have hence the possibility of choosing between existent procedures (centralized and decentralized) in order to obtain marketing authorizations (article 3, paragraph 3). The centralized procedure amends the procedure concerning petitions in case of contest on the part of the requesting party of the Commission’s scientific report, in order to optimize this procedure’s effectiveness and to better safeguard the requesting party’s position (article 9, paragraph 1 and article 55, second paragraph of paragraph 1). The centralized procedure for veterinary drugs: most of the previously mentioned points are also present in the proposal’s section concerning veterinary drugs, which we shall not discuss in this chapter. As explained, they want to extend the centralized procedure that enables to obtain a marketing authorization in the community market; it will be issued by the Commission following the assessment of the European Agency for Drug Assessment. Concerning the remaining drugs, from 1998 the mutual recognition procedure is compulsory to obtain a marketing authorization in more than one member state. This procedure is based on the assessment made by the member state, called “Reference member state”, which has issued a marketing authorization whose validity must be duly recognized by the “member states involved” in the same authorization request. The latter, however, in practice do not recognize it. The outcome of this procedure has proved to be absolutely negative in recent years. It is also necessary to recall that the so-called decentralized procedure is in the implementation stage.

Special procedures
The Quick assessment procedure meets the patient’s need to access, as fast as possible, certain innovative treatment. The requesting party may request that the assessment and related decision are supplied faster and given priority compared to other procedures. The procedure of temporary authorization refers to the concrete case of drugs backed by studies that can prove that they may benefit patients and which are approved by the risk/benefit ratio, considering the often serious pathology for which they are specified. The proposal foresees the issue of the one-year temporary authorization within the terms of the written conditions and they are subject to annual reassessments. In the same manner the Agency’s intervention on a community scale is proposed in the sphere of programmes for carefully gauged problems established by certain pharmaceutical cases (article 73) concerning drugs for human use included in the regulation’s applicational sphere.

4. Authorization and supervision
Each authorization request for a drug for human use must include the data and documentation required by the laws in force. The proposal expressly states that the said data and documentation will bear in mind the exclusive and community nature of the authorization request and, especially, the use of one name for the drug. The request must be duly accompanied by the payment to the Agency of the request’s assessment tax. The Agency will see that the Commission’s report for drugs for human use is issued within a term of two hundred days from the receipt of any valid request. Any marketing authorization issued in accordance with the regulation must be considered valid within the community. The above mentioned authorization will confer, in each member state, the same rights and obligations conferred by a marketing authorization issued by any member state. Drugs for human use thus authorized will be registered in the Community’s Register of drugs and they will be assigned a number that must be duly printed on the packaging. The authorization will have an unlimited duration. All authorizations that are not followed by effective marketing of the drug for human use within the community, within the two years following their issue, will be cancelled. Drugs for human use authorized in accordance with specifications in the regulation will benefit of a ten-year protective period.

The Commission’s report and resolution project

In case of a report that approves issuing the authorization to market the drug, the following documents will be annexed to the report:

a) a brief outline of the product’s features;

b) a detailed explanation of the conditions or restrictions that can be applied to the distribution or use of the drug in question, including the conditions of the drug’s administration to the sick,

c) the draft of the label and explanatory leaflet’s text proposed by the requesting party;

d) the report of the assessment.

The Agency will publish the drug assessment report drafted by the Commission for drugs for human use.

The Commission’s decision making context is also adjusted.

The Commission proposes to subject its decision making to a consulting procedure, should the project presented by the Commission be in accordance with the Agency’s scientific report, or to a management procedure concerning the above mentioned decision in all other cases. In both cases, the terms to reduce the consultation stages in member states are adjusted (articles 10 and 77). The Commission is obliged to prepare a resolution project concerning the request within a term of thirty days from the receipt of the report.

5. Responsibility and supervision
The accordance of the authorization will not compromise the civil and penal responsibility of the manufacturer nor of the owner of the marketing authorization in accordance with the international right in force in the member states. The authorities appointed to supervise will be the competent authorities for the State or member states that have requested the manufacturing authorization. The supervising authorities will check, on the community’s behalf, that the owner of the authorization to market the drug for human use and the authorized manufacturer or importer within the community’s territory comply with the requirements. Following the consultation with the member states concerned the Commission may require an inspector of the supervising authority to inspect again the owner of the marketing authorization, the manufacturer or importer. This inspector will be duly accompanied by two inspectors of the member states outside the contentious affair or, as an alternative, by two experts appointed by the Commission for Drugs for human use. .

6. Drug control
The proposal specifies that the owner of an authorization to market a drug for human use is obliged to have at his disposal, permanently and constantly, a person endowed with the appropriate competences, who is responsible in the field of drug control. The company will develop detailed relations concerning the presumed collateral effects produced both inside and outside the community by resorting to the competence of a Health Service professional. Instead member states will act in such a manner that all the serious collateral effects of any drugs are immediately recorded and the Agency and the owner of the authorization to market the drug are informed about them.

Hence the decision-making procedure and that of adopting emergency measures by the Commission in order to increase speed and efficiency will be modified. In practice, it is proposed to increase the frequency of updated periodical reports concerning safety, to enlarge the criteria of information on collateral effects, to generalize the use of a common and international terminology in the field of drug control, to strengthen the Agency’s functions of coordination and control and to generalize the use of a database related to the acquired information.

7. The European Agency for drug assessment
Article 49 re-forms the European Agency for Drug Assessment. The Agency basically continues to maintain the competences conferred to it when it was formed. The Agency will coordinate the scientific resources supplied by member states, with special reference to the assessment, supervision and control of drugs. The Agency’s duty will be to supply member states and community institutions the best consulting service possible concerning issues associated with the assessment of the quality, safety and effectiveness of drugs for human or veterinary use presented to it, in accordance with what was arranged by the community legislation in the field of drugs. The Agency will have the charter of a juridical person.

The organizational structure
The amendments made to the regulations concerning the Agency refer on the one hand to the responsibilities conferred to the latter and, on the other hand, to the adjustment of its administrative and scientific structures to the new duties and the Union’s future expansion. The Agency’s regulatory principles are not amended nor are its administrative structure and general workings, since the experience has proved that the solutions adopted in 1993 were more than satisfactory. The Agency, in accordance with article 50, will comprise:

a) the Committee for drugs for human use, in charge of preparing the Agency’s relations concerning any matter that regards the assessment of drugs for human use;

b) the Committee for drugs for veterinary use, in charge of preparing the Agency’s relations concerning any issue related with the assessment of drugs for veterinary use;

c) the Committee for orphan drugs; and possibly

d) the Committee for homeopathic drugs], should a special measure be approved at a later date;

e) a Secretary in charge of supplying technical, administrative and scientific assistance to the Committees and of supervising the appropriate coordination of the latter’s work;

f) an Executive Manager who will perform the duties specified in article 57;

g) a Governing body whose duty is defined in articles 58, 59 and 60;

h) an Advisory Committee whose roles are specified in article 59.

The member of the governing body, the members of the advisory committee, the members of the committees and the spokesmen and experts who take part in the meetings or work groups will have to declare, at each meeting, their special interests that can compromise their objective judgement with regard to the points listed in the agenda. The executive manager will be appointed by the governing body on the proposal of the Commission for a 5-year period that is renewable. He will hold the post of the Agency’s legal representative.

The scientific committees
Both the traditional committees are maintained - the one related to drugs for human use and the one related to drugs for veterinary use. The above mentioned committees will depend on the Agency and will create the Agency’s relations concerning any matter regarding the acceptability of the papers presented within the centralized procedure, the authorization, amendments, the suspension or withdrawal of the authorization to market a drug for human use and in the field of drug control. The proposal specifies that the composition of the Scientific Committees competent in the sphere of a centralized procedure must be changed (article 5); (a representative for each competent authority) to bear in mind the future expansion. In order to maintain a suitable group of scientific representatives, the possibility of appointing additional members by means of cooptation was introduced (article 54). Th regulation also states the committee’s faculty to form work groups or groups of experts, and to delegate certain tasks to these groups (article 50, paragraph 2 and 3). Special attention is given to the creation of a permanent work group inside the committee, which is responsible for the development and subsequent adoption of scientific relations with companies and consulting services provided. These proposals of the Commission seem reasonable. However the many questions raised can involve different answers.

Spokesmen
The regulation specifies that both the members of the Committees and the experts responsible for the assessment of the drugs will rely on the experience and the scientific resources listed by the national marketing authorizing bodies. Each Committee will see to the development of its own rules of procedure. The committees will appoint, among their members, a spokesman and coordinator of the assessment procedure. The committee will have the faculty to appoint another member as an additional spokesman. The report will reflect the stand taken by the majority of members. Member states will supply the Agency with the names of the national experts who have substantiated experience in the field of drug assessment, who will be allowed to participate in the work groups or in the groups of experts belonging to the Committee of Drugs for human use or to the Committee for Drugs for veterinary use, together with a report of their respective qualifications and special field of expertise. The committees composition will be made public.

The Agency’s arbitrary competence
Those requesting an authorization in the sphere of the decentralized procedure will have to resort to arbitration should the member states in question prove unable to solve the drug-related situation.

The Commission adds that the companies could feel obliged to support the expense of resorting to arbitration, something they can avoid by withdrawing the request. No doubt, these expenses will be compensated for by the fact that the companies will be allowed to market a drug subject to the arbitration procedure in the member states that have showed themselves in favour of the product, something that will enable the companies to recover the investment expenses faster than at present. This is possible. However the industries and hospital administrations should ask themselves of this potential economic advantage is such to compensate for the social alarm that could be produced should patients make sure that no member state, in the sphere of the mutual recognition procedure, consents to authorize a certain drug in its own territory, as it could be a danger to public health. This would be hard to explain.

8. Additional functions
The proposal specifies that the Agency will be given additional functions, most of which are outside the sphere of drug assessment. The intention is to systematically strengthen and develop the companies’ scientific advice during the research and development stages of the new drugs, in a new stage that by far preceded the marketing authorization procedure (article 51, letter 1). The Commission believes that this aspect is of vital importance, especially with reference to the new treatments and the drugs obtained with biotechnological procedures. This will encourage the development of small and average size companies involved in the above mentioned sectors. The Commission rightly believes that it is absolutely essential to establish real cooperation based on mutual respect between these companies and the authorities appointed to assess future drugs. In the past the Agency already supplied this type of service with encouraging results. This task will be assigned to a Permanent Work Group, to enable companies to resort more extensively to this type of service. In the same manner, the Agency’s participation in the performance, in a community scale, of programmes for carefully gauged problems. is also proposed.

II. Amendment to Directive 2001/83/EC, which defines a community code for drugs for human use

Besides revising drug recording procedures and the regulation that formed the Agency, it was believed necessary to adapt the general measures concerning the marketing of drugs for human use definitely included in Directive (2001/83/EC), which defines a community code for drugs for human use. The above mentioned Directive had the credit of codifying and collecting in just one text the many community legislation texts on the subject of drugs for human use (31 codified texts). There exists a clear intention to simplify administrative and legislative procedures. It also introduces a series of measures directed at rationalizing and speeding up the marketing authorization procedures of drugs for human use. The new proposal recognizes the need to adopt new measures in order to remove the obstacles to free circulation; they however still remain with the special purpose of encouraging the workings of inside markets. The community legislation represents an undoubtedly important lap in view of this objective’s implementation. We must keep in mind that the values recognized in the treatise require constant balance. The defence of public health proceeds hand in hand with the free market. If a product is considered a danger to public health in one country, it is absolutely unacceptable that the community law can allow it to be marketed in another state and the other way round. Since the conflict and assessment vary from country to country, it becomes a necessary measure to automatically and immediately appeal to the Agency during a compulsory arbitration procedure. It is up to the Commission to make this happen.

11. The decentralized procedure and the mutual recognition procedure
These procedures’ sphere of application is interrelated with that of the centralized procedure. Any drug that is not strictly subject to the centralized procedure will be automatically subject to the decentralized procedure or the mutual recognition one, as long as it is directed at the markets of more member states (46). These procedures still represent an option for other drugs that can be a therapeutic innovation, and can be applied to over the counter drugs. To this end, it is necessary to inform that these procedures can be applied to over the counter drugs whose reference drug was authorized by a centralized procedure. The mutual recognition procedure and the decentralized procedure are clearly defined in this new proposal. These are two diverse procedures whose application is directed at overcoming the mutual mistrust existent, through future mutual recognition. On the one hand it proposes to maintain the mutual recognition procedure’s general principles intact, in accordance with the terms specified in the current regulation for those drugs that already have a marketing authorization in member states and whose owner however hopes to extend the distribution to other member states (article 28, paragraph 1 and 2). On the other hand, it follows a new decentralized procedure for drugs that are not as yet authorized in the Community (article 28, paragraph 1 and 3). In order to guarantee the transparency of procedures, as in the case of the centralized procedure, it proposes that the assessment reports and the authorizations accompanied by an outline of the characteristics of the drugs authorized by the centralized or mutual recognition procedure are placed at the disposal of those concerned (article 21).

The mutual recognition procedure is based on the assessment made by a member state called “reference member state”, which has granted a marketing authorization of regulations recognized by the “member states involved” in the same authorization request. The mutual recognition procedure has not produced the hoped for effects. According to community logic, the general system must be represented by the mutual recognition of the authorizations issued by the national administrations of each nation. Since all must perform the same procedure, which for this very reason is already a community procedure, it is no doubt hoped that the possibility of cooperation between member states will be strengthened. This cooperation process is formalized through the creation of a coordination group (article 27) of the said procedure and the definition of its workings, to create the possible disagreements in the revised decentralized procedure. The cooperation between member states will be implemented before a resolution formed on the basis of the assessment conducted by one of them is adopted. Concerning the new mutual recognition or decentralization procedures, in case of a disagreement it will be possible to resort to the same process (article 29, paragraphs 1 and 2), while should an agreement not be reached in this group, according to compulsory arbitration one must appeal to the European Agency for Drug Assessment (article 29, paragraph 3). It is in short an extension of the procedure. This new administrative complexity could be acceptable if the goal was to simplify the course. It is not said that it is realistic. This coordination group will also create common outlines of the productive features of the drugs that have been authorized for over ten years. No drug can be marketed if its quality, safety and effectiveness are not previously proved. These guarantees must be respected when it is actually marketed. The new regulation must assure the safety of use for patients, market supervision and drug control. The cost/benefit ratio analysis must still be the basis of any administrative decision concerning a drug, notwithstanding the authorization procedure applied.

12. Adjusted definitions
In order to consider the introduction of new treatments available in the market and the increasing number of the so-called “borderline” products between the pharmaceutical sector and other sectors, it was considered advisable to modify the definition of drug in order to avoid doubts concerning the legislation that applies when a product fully meets the definition of drug though it also meets the definition of other authorized products too. We must distinguish between the main meaning, which showed that “this Directive will be applied when a substance or a compound met the definition of drug and the measures specified, though the substance or the compound may equally belong to the range of applications of further community regulations”. In short this means stressing the basic interpretation of the concept of drug “according to its presentation”. Notwithstanding the product’s composition, if the latter “presents itself” as a drug, this means it is a drug from a juridical viewpoint. From another perspective, any product that has an official drug authorization must be considered such notwithstanding its composition. This interpretation closes the possible dualism of the so-called called “borderline products” (sanitary products, cosmetics, biocides),which have generated divergent interpretations in the legislation in force. For this reason it is also proposed to apply the pharmaceutical legislation when a product fully meets the definition of drug, though it may also meet the definition of other authorized products too (article 2, paragraph 2).

13. The quality, safety and effectiveness criteria
The criteria that regulate the refusal, suspension or withdrawal of marketing authorizations have been adopted and harmonized so that the main assessment criteria (quality, safety and effectiveness) should combine with the concept of the risk/benefit ratio, which represents the basics of the authorization and of its preservation (articles 26, 116 and 117). It is peremptorily declared that these quality, safety and effectiveness criteria must enable to assess the risk/benefit ratio of all drugs, both when they are marketed and when they are checked. To this purpose the criteria that regulate the refusal, suspension or withdrawal of marketing authorizations are harmonized and adjusted.

Relative effectiveness
Some member states have implemented a drug effectiveness assessment in order to recognize the new drugs compared to those already present in the market. In the same manner, the Council’s conclusions concerning drugs and public health (43), adopted on June 29 2000, did not fail to stress the importance of spotting the drugs characterized by a clear added therapeutic value. The Commission on its part believes that this type of assessment must not be conducted inside the procedure that grants the marketing authorization, which offers a leading role to the basic criteria (quality, safety and effectiveness). Hence the Commission will not present any proposal on the issue right now, believing that a community act could prove useful.

14. The validity of the authorizations
The new proposal shows that the validity of marketing authorizations must not be limited to five years. The authorization will have an unlimited duration. To compensate for this, the new proposal shows increased market control. Besides, any authorization that is not translated into effective drug marketing must be considered null and void. This change will not be peacefully accepted during the legislative processing. However, there are other alternatives too.

15. Counter drugs
Among the most important and questionable amendments the new proposal means to introduce is the increased number of counter drugs launched in the market. Though the Commission, Parliament and Council largely agree concerning the validity of this measure, there exists a doubt that related effects may further aggravate the unrestrainable drop recorded in recent years in the European pharmaceutical industry’s ability to innovate. The Commission declares its objective without half measures: counter drugs represent a remarkable share of the drug market, hence it is advisable to simplify their access in the community market. The issue of counter drugs, just as that of “parallel importations”, is distorted right from the beginning by a juridical misunderstanding whose evidence can hardly be recognized. When there is a fragmented market, and prices are directly or indirectly part of it, the regulations of free competition cannot be applied to the drug. It also means forgetting that in the drug issue, economic and health policies present different answers and clearly distinct bases.

Shortened procedure
Concerning the shortened procedures of marketing authorizations, it proposes dropping the concept of “basically similar” drug, which is in practice applied to counter drugs. It thus targets at introducing a definition of counter drugs and a definition of reference drugs - counter drugs will be defined in relations to this, in view of adjusting the commonly accepted terminology (article 10, paragraph 2). In accordance with the proposal, counter drugs are defined “any drug that has the same qualitative composition regarding active principles, the same pharmaceutical form and whose biological equivalence with the reference drug has been duly proved by appropriate bioavailability studies”. The requesting party can be exempted from bioavailability studies if it can prove that the criteria, listed in appendix I, have been met. On the other hand, it harmonizes the administrative protection period of the data related to the reference drug, fixing it at ten years (article 10, paragraph 1). However it proposes that the requesting party may benefit of an additional year of data protection if the therapeutic directions meet the above mentioned conditions and are obtained during the said period of ten years (article 10, paragraph 1). The party requesting the authorization to market a counter drug may perform the tests required to present the documentation before the exclusive period expires (article 10, paragraph 4).

16. Appeal procedures
These procedures are applied when a member state cannot accept the assessment report nor the summary of the product characteristics processed by another member state (article 29), when there are divergences between the resolutions adopted by member states (article 30, paragraph 8), or when community interests are involved (article 31).

17. Supervision and control
The quality guarantees include respecting correct manufacturing practices. The current regulation concerns drugs, though it is not specifically targeted at the raw materials. This is why it proposes to extend the guarantee to the active principles used as raw materials to manufacture the drugs (article 111, paragraph 1). On the other hand it is directed at strengthening the general drug supervision measures and, in this specific case, with special reference to the European Pharmacopoeia (article 11, paragraphs 1 and 5), it proposes motivating community coordination by creating a community register of information related to correct manufacturing practices.( article 111, paragraphs 6 and 7). This will be completed with the creation of a community system of data related to manufacturing authorizations (article 40, paragraph 4). An improvement of the supervision system is proposed, based on the recognition of supervisions conducted by any member state, through a composition procedure of the possible controversies arisen between member states concerning the results of a certain supervision (article 122). In the same manner it proposes to introduce the possibility of supervision procedures wherever there are drug control problems and in third party nations (article 111, paragraph 4). In order to clearly state the responsibilities of member states and the European Commission should there be an emergency withdrawal of a drug, the proposal specifies that if it is necessary to act urgently to protect public health, the member state in question may suspend the authorization to market the drug after informing the Agency, the Commission and other member states the first day their offices are open. (Article 101).

18. Drug control
It is believed advisable to increase drug control and, more generally, the control of the market and the sanctions in case of failure to comply with the measures specified. Concerning drug control, we must keep in mind the facilitations offered by the new information technologies in order to improve the exchange of information between member states. It mostly stresses the need to adopt a preventive attitude on the drug control issue. The remarkable technical progress made both at a community and international level is recognized. Concerning the proposal to abolish the five-yearly renewal and in order to increase the system’s effectiveness, it proposes reducing the compulsory term by which periodically updated reports on the safety issue must be presented (article 104). On the other hand it also proposes that should there be urgent measures, the Commission may request member states to immediately adopt effective temporary measures (article 107). It also proposes strengthening inspections focused on the obligations of the marketing authorization’s owner (article 111). Lastly, it proposes improving the coordination between member states on the matter of drug control applied to drugs that are the object of the mutual recognition or decentralized procedures (article 104, paragraph 5). These are in short ameliorative measures. It was no doubt hoped that the Community would implement “positive drug control” measures.

19. Patient Information
Drug information is an essential dimension both for the system and for the patients. Never as today have technologies been able to effectively meet this demand. The Commission proposes authorizing the information related to certain drugs, respecting the strict conditions and to the exclusive advantage of patients, meaning to meet the latter’s demands and rightful expectations. Hence member states will allow the communication of information related to certain drugs authorized for the following diseases: Acquired Immunodepression Syndrome (AIDS), asthma and chronic bronchopulmonary diseases and diabetes. This type of information will be subject to the principles of best practice adopted by the Commission, and to the creation of an ethical code for the sector. An assessment that will decide the validity of this experience will be performed in five years (article 88, paragraph 2). This information will not be interpreted as advertisements or direct advertising of prescribable drugs. I believe that it is an effective measure that should be implemented. We must not fear information so much as disinformation. The rule must be information with limited access only in exceptional cases. The Commission’s problem is that when it proposed the Directive on Advertising, it did not accept the European Parliament’s proposals, which were absolutely logical and well suited the issue. The Commission’s error was the failure to accept the differentiation between “Official Scientific Information” and “Advertising”. The regulation foresees the presence, inside the drug’s packaging, of a descriptive leaflet directed to patients. The order of the points to be printed on the leaflet is compulsory.

20. Other relevant changes
The proposal in question amends a series of other points, which, though they are not particularly innovative, are extremely relevant for the legal status of pharmaceuticals within the EU - they are the result of experience and aim at overcoming lacunae and often divergent interpretations. This is not the place for a detailed analysis of each of them. However it is important to stress that not mentioning them does not mean depriving them of the right consideration. It is only a matter of expediency and of limiting the field discussed. Basically we are enlarging on the changes to the amendments that involve the recording system. No doubt the proposal presents a series of little modifications in almost all the Drug Statute’s chapters. One of these is the problem of a factory manufacturing a sample formula. In fact it strictly states that “the owner of the marketing authorization will be responsible for the drug’s marketing”. The target is to reduce the terms that nationally grant the authorization. The new proposal also means to handle homeopathic drugs. Hence, besides the legislation of drugs based on scientific evidence, the Commission once again deals also with the sociological problems of the social requests of groups of individuals whose preference is for alternative medicine. In order to introduce an additional step to this drug category’s harmonization procedure, the proposal foresees defining a procedure limited to mutual recognition. Besides, to simplify marketing, it will be possible to use freely chosen names, always respecting certain conditions, and it is proposed to abolish the general prohibition of advertising to the public (article 100). Information and openness are generalized by extending the centralized system’s consolidated practices. The assessment report will be updated whenever new important data is available to assess the drug’s quality, safety and effectiveness.

José Luis Valverde
Docente di Diritto Comunitario Jean Monnet "europa de la Salud" (Europa della Salute) Università di Granada

References

(1) proposal of a Directive that amends Directive 2001/82/EC, which establishes a community code related to drugs for veterinary use, and a Proposal of a REGULATION that defines community procedures in the field of authorizations, supervision and drug control related to drugs for human and veterinary use and which forms the European Agency for Drug Assessment.

(2) 2001/0253(CODE) Proposal for a DIRECTIVE OF THE EUROPEAN PARLIAMENT AND COUNCIL as amendment of Directive 2001/83/EC, which establishes a community code related to drugs for human use.

(*)(To facilitate reading, reference articles refer to Directive 2001/83/EC amended by this proposal).

Procedures: Representing most of the measures required for the application of this Directive, measures of individual competence, foresees resorting to the consultative procedure specified in article 3 of the Council’s Resolution 1999/468/EC, dated June 28 1999. It defines the procedures required to practice the executive functions attributed to the Commission or as an alternative to manage the procedure specified in article 4 of the above mentioned resolution. The general decision measures, in accordance with article 2 of the above mentioned resolution, will be appropriately adopted in accordance with the regulating procedure specified in article 5 of the same. DO L 184 dated 17.7.1999, page 23.

Translated by interpres sas