Strasbourg, 8 January 1997     Restricted

    CM(97)13

     For consideration at the 581st meeting

    of the Ministers' Deputies

    (13-16 January 1997, A level, item 11.2)

EVALUATION AND ORGANISATION OF THE EUROPEAN DEPARTMENT FOR THE QUALITY OF MEDICINES

        Reinforcement of upper management

The composition of the Secretariat of the European Pharmacopoeia, which remained practically unchanged from 1973 to 1990 (19 countries and only 23 agents), was the subject of an important development plan which followed the decisions taken at the end of 1990 by the Committee of Ministers (see document CM (90) 223) so that the European Pharmacopoeia could rise to the challenges at the European and now the world level (see Appendix 1 for table summarising recruitment). In addition, in connection with the closer and closer ties being developed with the European Union, this Department has been made responsible for setting up a European network of Official Medicines Control Laboratories. As a result, for administrative reasons, its name had to be changed from the Secretariat of the European Pharmacopoeia to the European Department for the Quality of Medicines (1995) (see organisation chart in Part II, "Organisation and function of EDQM").

The Secretariat of the European Pharmacopoeia, which until 1993 was a single administrative unit made up of one A5 and four A4 agents responsible for the various tasks of a scientific secretariat, has undergone real change over the last three years, leading to the creation of four divisions, together constituting the European Department for the Quality of Medicines.

The European Department for the Quality of Medicines (EDQM) was structured in 1994 to give four divisions.

The activities of each division are as follows:

_    Division I - Preparation of chapters and monographs of the European Pharmacopoeia

_    Division II - Publications of the EDQM

_    Division III - Laboratory

_    Division IV - European network of official medicines control laboratories and biological standardisation.

Consisting of 23 agents in 1990 (1 A5 and 4 A4), it now comprises 63 permanent posts (2 upper management posts, 1 A6 and 1 A5, for 21 agents at grades A2, A3, A4, LT3 and 40 agents at grades B and C) and 5 to 10 temporary posts, the number of which depends on the workload.

The matter of middle management in this department has taken on increasing importance.

Indeed, the considerable expansion of the Department (threefold increase in staff and activities) has increased managerial needs and responsibilities (need for management of personnel and multiplication of tasks within each division). The 5-year development plan, presented in document CM (90) 223 which described the creation of 63/64 posts, has been carried out, resulting in the creation of 22 B, 4 C, 12 A2/A3 and 1 LT3 posts. These new posts have enabled a start to be made in achieving the Department's goals (see summary table in Appendix 3) but they will require a proper managerial framework to be completely effective.

No upper management posts have been created since the A6 post in 1992 and it is therefore proposed to make up for this lack of managers by creating three upper management posts at the A5 level for the heads of Divisions II, III and IV.

The restructuring of the EDQM around these four divisions should continue for the years to come in order to adjust the needs and qualifications for the various posts, taking account of the changes in the activities of the Department.

The simultaneous creation of these three posts is proposed for the following reasons:

_    to ensure that the structure of the Department is balanced, that each of its functions develops simultaneously and that the four divisions, which are interdependent, potentiate and interact with each other;

_    to respond to the qualitative as well as quantitative increase in the responsibilities of the managers of the three divisions, namely:

     Division II: Publications of the EDQM

    - qualitative: activities have become more diversified; this requires taking initiatives and assuming new responsibilities for the organisation, management, promotion and supervision of the sales of the Pharmacopoeia and related publications.

    - quantitative: increased activity due to the growth of other sections of the EDQM.

     Division III: Laboratory

    - qualitative: the scientific contribution of the laboratory has increased with the needs of the European Pharmacopoeia Commission and the creation of the European network of Official Medicines Control Laboratories.

    - quantitative: management of four scientific administrators and fifteen laboratory technicians.

     Division IV: European network of Official Medicines Control Laboratories and biological standardisation.

    - qualitative: organisation of European exchanges on the quality control of medicines at the highest level of responsibility; development of the Division; management of the budget for co-operation with the European Community.

    - quantitative: setting up a service to co-ordinate a network of about 90 OMCLs.

The details of the development of the various areas of activity of the European Department for the Quality of Medicines are described below.

A. Division II

Division II is responsible for producing scientific publications. Created in 1994 and structured since then, this Division's activities have increased ten-fold over the last few years thanks to the new organisation that has been set up. The considerable increase in the EDQM's receipts originates in this Division; this growth is due to the multiplication of publications and to the launching of publicity campaigns, which increases contacts with users; the interaction of these phenomena causes them to spiral upwards.

The publication of the European Pharmacopoeia (first and second editions) was formerly entrusted to a publisher outside the Council of Europe. Over time, it became clear that it was indispensable to have direct contact with our users, given the scientific and regulatory nature of the pharmacopoeial texts. It also became clear that having an outside editor between the European Pharmacopoeia and its users (despite our good relations with this editor) was generating little revenue for the Council and constituted a barrier that worked against the proper development of the European Pharmacopoeia. The Council of Europe (Secretariat of the European Pharmacopoeia) therefore decided to be its own publisher for the newsletter Pharmeuropa. As this experience was positive (see Appendix 5 comparing the revenue generated by the sales of the 2nd Edition and Pharmeuropa See footnote 1 ) the EDQM decided to extend this approach to the new publications that were planned.

The Division was initially involved in the following activities:

_    Elaboration of the style guide for European Pharmacopoeia texts

_    Proof-reading of scientific texts prepared by Divisions I, III and IV

_    Preparation and marketing of the forum publication Pharmeuropa (four issues per year: 395 pages in 1993, 417 in 1994, 612 in 1995).

and as restructuring has progressed, with the addition of junior scientific staff, it has added the following new publications:

_    First publication in CD-ROM form of the entire 2nd Edition in December 1994, with yearly updates. This operation, completed within extremely tight deadlines, thanks to the personal involvement of an A4 and a newly recruited A2, turned out to be truly successful, beyond our most optimistic projections (see generated revenue in Appendix 5);

_    Prepublication (since 1995) of texts adopted by the European Pharmacopoeia Commission at each of its three sessions per year. This operation makes scientific texts available to users as soon as they are adopted, which facilitates the preparation of licensing dossiers for pharmaceutical products before the texts enter into force (12 to 18 months after adoption);

_    Publication of the 3rd Edition of the European Pharmacopoeia in June/July 1996. The obsolete format and structure of the 2nd Edition, which included texts more than 15 years old, had hindered the international recognition of the European Pharmacopoeia. Division II has played an essential role in the scientific preparation of the texts (revision of 2000 pages in each official language of the Council of Europe) with the support of temporary staff. This operation also has been a success;

_     Publication of study reports from the biological standardisation programme;

_    Publication of the handbook of the Official Medicines Control Laboratories (OMCL), an essential data base for the network co-ordinated by Division IV;

_     Publication of a newsletter (three times a year) for the OMCLs;

_     Publication of proceedings of conferences and scientific seminars.

In addition, Division II organises and supervises sales and promotional activities for the European Pharmacopoeia and other publications; it handles many of the contacts with users, on both technical and commercial matters.

The Division, currently headed by an A4 administrator, has insufficient managerial staff to properly supervise its personnel. In addition to the A4 in charge, it includes one A4 responsible for the preparation of the newsletter Pharmeuropa and of electronic publications (CD-ROM, data base), one A2/A3, two A2, one B4 and two B3 agents. It employs temporary staff to help during periods of intense activity and also to help with the new responsibilities due to the multiplication and diversification of activities and to the closer relationship with the European Union (exchange of data).

B. Division III

Division III corresponds to the laboratory. Its activities are more traditional but they have developed considerably in the three years since it moved to the new premises in the Meinau and since investments were made to improve laboratory equipment. Furthermore, microbiological, biological and immunological sections have been created. Since its creation, the laboratory has been headed by an A4 administrator, who initially supervised four B grade technicians. Over the last six years, the laboratory's capacity has been multiplied by four and there are now four full or part-time scientific administrators (two A3 and two A2) and fifteen technicians (B3, B4, B5 and B6).

The expansion in the laboratory's activities and the increase in its staff require a reinforcement of its managerial staff to ensure that its work is properly planned and co-ordinated.

The expansion of the laboratory has made it possible to:

_    prepare more reference substances (550 in 1992 . 750 in 1995) and monitor these substances to ensure their quality and thus the credibility of products distributed by the Council of Europe;

_    carry out the scientific analyses necessary for the elaboration and revision of monographs, thus accelerating work at a time when experts from industry are contributing less and less volunteer work owing to restructuring and mergers in international companies. Scientific work requiring costly equipment is, however, sub-contracted to outside laboratories, for example, nuclear magnetic resonance (NMR) analyses are carried out by the Université de Strasbourg.

C. Division IV

The Division is in charge of the activities recently defined within the framework of co-operation with the Commission of the European Communities. Its role has grown and become decisive now that the European Union is involved in licensing (accession of the European Union to the Convention on the Elaboration of a European Pharmacopoeia in 1994, creation of the European Agency for the Evaluation of Medicinal Products in 1995, setting up of the European network of official control laboratories for medicines for human and veterinary use in May 1994/95). This new area of activity for the EDQM was created and expanded to respond to the need for the European Pharmacopoeia to be taken into account as new European regulations on medicines are developed. This division has a supplementary budget coming from a special account to which the Commission of the European Communities contributes.

Given the political and strategic necessity of rapidly developing this area of activity of the EDQM in coming months and years in response to the European Union's deepening involvement in this area and given the high level of responsibility at which international contacts must be made (notably the USA and Japan), it is necessary to provide the Division with additional managerial staff able to operate with a high level of initiative and responsibility.

Indeed, Division IV is responsible for developing the interface and symbiosis between the European Pharmacopoeia, licensing authorities, Official Medicines Control Laboratories and national inspectors of the pharmaceutical industry's production sites. Division IV has initiated several biological standardisation programmes through a contract for co-operation between the Commission of the European Communities and the Council of Europe. These programmes are aimed at establishing biological reference standards (for blood products, vaccines and biotechnology products) and developing validated and standardised methods of physicochemical analysis, some of which are intended to replace animal methods. Biological reference standards have been a source of revenue since 1994 (Appendix 7).

With the setting up of the European network of Official Medicines Control Laboratories, the Division's role has grown in importance.

_    Mutual recognition of testing by OMCLs either for pre-marketing batch release of biologicals such as vaccines and immunosera or for quality control of marketed medicines (testing for adulteration in generic products, comparison of qualities of medicines from all over the European territory, harmonisation of the expression of active ingredient content, of biological units, etc).

_    Organisation of many high level scientific seminars (about ten per year) involving manufacturers and national laboratories, persons from all over the world dealing with the quality control of high technology products (blood products, hormones, vaccines for human or veterinary use, etc).

_    In its work, Division IV pools resources from the various countries and applies the principle of subsidiarity, operating with a staff that is relatively small but high in scientific quality; it acts as a co-ordinating centre enabling the entire network to benefit from the contribution of each of its formerly isolated members (90 laboratories participate in the network, totalling about 150 experts). Its activity consists in preparing study protocols in close collaboration with project leaders selected from the network, evaluating the results, and drafting reports for publication.

_    It also promotes the European Pharmacopoeia by publicising and facilitating its use by the national control laboratories. It was also instrumental in Division III's entry into the biological area and in the installation of sophisticated methods (freeze-drying) in the service responsible for preparing and maintaining the quality of biological reference preparations.

_    Finally, in the area of biological and biotechnological products, the Division plays an essential role in developing international relations with the European licensing authorities, the United States (Food and Drug Administration), Japan and the WHO (World Health Organization).

D. Division I

Division I is responsible for the scientific preparation of the chapters and monographs of the European Pharmacopoeia. This is the most traditional activity in the Department (organisation of meetings of groups of experts, preparation of reports and scientific texts). It should be noted that the scientific work of elaborating monographs is assigned as much as possible to national rapporteurs in the groups of experts (250 experts working on a volunteer basis for the European Pharmacopoeia). Nevertheless, relying on volunteer work has its limits, and it became indispensable to develop European secretariat activities to co-ordinate these various contributions so that the monographs needed by the national and European public health authorities (European Agency for the Evaluation of Medicinal Products created in London in 1995 by the European Union) can be published. Thus additional technical working parties have been created in a wide variety of scientific areas (see Appendix 4 for the annual report of activities published in Pharmeuropa), a greater number of meetings have been organised and the scientific work carried out by the Secretariat has increased (there are now seven more A2/A3 agents working full or part-time than in 1990 when five A2/A3/A4 agents worked full or part-time).

This division, which now includes twelve A2/A3 agents, is headed by an A5 administrator who, through his duties as deputy director, is also responsible for the international harmonisation secretariat (harmonisation with the United States and Japan) as well as for the plenary sessions of the European Pharmacopoeia Commission and for three specialised groups of experts. It is essential that he be assisted in his duties by an A4 agent who could train new arrivals and co-ordinate their activities. In the event that the proposed A5 posts are created, this A4 post should become available when the A5 posts are filled.

The other A4 posts that would become vacant with the creation of the A5 posts would be used to satisfy managerial needs in other areas of the EDQM now being developed such as the certification of suitability of monographs (created in 1994, now under the direct responsibility of the Director and growing rapidly: 150 dossiers examined including 113 certificates already granted) and the preparation and dispatching service for reference substances and preparations (the sale of reference samples continues to grow: 16 000 samples in 1993, more than 20 000 in 1994, more than 25 000 in 1995, see Appendices 5 and 6).

Footnote: 1 The increase in royalties on the sales of the 2nd Edition in 1995-1996 corresponds to the balancing of accounts at the end of the contract with the printer in May 1995.