Re: Proposed amendments to the EU pharmaceutical legislation

We are aware that the current pharmaceutical legislation applying to the European Medicines Evaluation Agency (EMEA) will be reviewed in the near future by the European Parliament. We would like to provide our comments and suggestions on the proposed amendments to the legislation, which we believe could better respond to the public health interest. In order to ensure the achievement of this important objective, we propose the following comments for your consideration:

Institutional location of EMEA

The EMEA is currently located within the DG Enterprise of the European Commission. This is certainly not ideal from a public health perspective, and suggests that political and industrial considerations about the development and production of medicines may be regarded as more important than their impact on health and consumers. In line with its declared objectives, the right location for EMEA would appear to be within the Public Health Directorate of the European Commission.

EMEA Board membership

The proposed new structure of the Management Board should not include representatives of the pharmaceutical industry, as this would inevitably make the EMEA more respondent to the needs of the industry at the expense of public health interests.

CPMP (Committee for Proprietary Medicinal Products) membership

Under the new legislation, there would be only one member, rather than two, per each country. However, ideally, each Member State should nominate one independent expert and one staff member from its national drug evaluation agency, to provide a broader picture that combines scientific and regulatory views.

EMEA funding

Financial support for EMEA comes from two sources: a European Community (EC) grant and the fees charged to the industry for the evaluation of dossiers and other services, which for the year 2000 represented around 70% of its total budget. This balance should be changed to increase the level of independence from the industry. Most importantly, the EC grant should be increased to allow EMEA to improve pharmacovigilance activities, clinical study inspections and to actively review drug use. The EMEA is still much smaller than the US Food and Drug Administration, although it covers almost double the population of its transatlantic cousin.

Mutual recognition

The decentralised procedure does not facilitate uniform and consistent availability of new drugs in the EU, as it leads to different outcomes in different member states. In the interest of public health, all innovative medicinal products should use the centralised procedure for marketing authorisation.

Comparative studies

For most diseases, physicians already have a range of different products available for prescription. Thus, public health needs would be better addressed by focusing on how new drugs compare with existing ones (in terms of efficacy, safety or both) based on sound scientific basis.

At present, new drugs can be evaluated for their own quality, efficacy and safety with no comparison with alternative treatments already available in the market. In those few cases where comparisons are made, the industry usually relies on demonstration of therapeutic “equivalence” or “non-inferiority”. This results in a high degree of uncertainty about the merits of the drug being tested. If legislation does not change, there will still be the possibility that new drugs approved for the EU market are indeed proven to be effective and safe on their own, but may nevertheless be potentially less effective and/or less safe than other drugs currently prescribed. Therefore, the new legislation should include the requirement that, whenever feasible, clinical studies be conducted in comparison to reference drugs, in accordance with the Helsinki Declaration to allow assessment of relative benefit. Assessment of relative benefit should become an independent criterion for marketing authorisation decisions.

Renewal of the marketing authorisation

Under the proposed new legislation, marketing authorisations would have unlimited validity, as compared with the current requirement for renewal every five years. This would definitely wipe out the opportunity to re-consider the risk-benefit profile of drugs, the role of which may have changed due to the approval of better products or to the continuous changes in the clinical scenario.

Transparency of EMEA activities

During its years of activity the EMEA has certainly improved “transparency” by establishing rules to decide on conflicts of interest and by making some of its decisions available on the website and through press releases. However, there is still room for improvement in the public health interest.

1. Drug dossiers must no longer be entirely confidential. The need to maintain full confidentiality around some aspects of drug production is indeed recognised. However, the existence of applications, pre-clinical and clinical data (in accordance with legal privacy requirements) should be made available. A positive consequence of this may be the opportunity for a more widespread debate among all interested parties (physicians, patient groups, medical bodies) about the merits of drugs, which could only benefit the public health interest.

2. All final opinions made by the Committee for Proprietary Medicinal Products (CPMP) – whether positive or negative – should be immediately made public. At present, negative opinions are withheld for two weeks in order to allow pharmaceutical companies to file an appeal. However, there is no clear reason why they should not do so publicly.

3. Information on withdrawn applications should also be made public. Pharmaceutical companies prefer to withdraw applications likely to result in negative opinions before the CPMP makes its final decision, as to avoid bad publicity. However, the public should be informed at least of the name of the product, active substance, its proposed indications and the reasons for the CPMP’s negative opinion, as potential weak aspects of new drugs should be known in order to ensure the correct and safe use of drugs when they reach the market. Furthermore, it is clearly a public health concern that these medicinal products might be prescribed in the Member States through compassionate use programs, without the prescriber and patient having the possibility to review the results of independent scientific assessment by CPMP, which lead to withdrawal of the marketing authorisation application.

4. Another important element of transparency is the information concerning the view of the minority. The EPAR (European Public Assessment Report – the final document on new drugs published when approval is granted) does mention whether a product has been approved by consensus or by majority, but does not give the minority’s viewpoint. This minority view should be reported in the EPAR and in the summary of CPMP opinion for the benefit of prescribing physicians.

5. In the new legislation it is proposed that information about prescription drugs be also made available to the public. Three chronic diseases (namely, asthma, diabetes and AIDS) have been selected for a five-year pilot period. This has the potential to put undue pressure on patients and physicians, who are already target of intense marketing activities from the pharmaceutical industry. It is suggested that this information be provided only by national regulatory agencies, which would ensure a more balanced and independent information to consumers.

Timing for assessment

There is still a strong difference between the timing allowed to the CPMP for the assessment of new drugs and the timing allowed to the industry during each procedure. Drug companies can delay submissions, stop the clock of the procedure or withdraw the dossier at any time, while the CPMP has to operate within tight deadlines, even when new data have been presented by the relevant company, which would need careful assessment in the public health interest. The new legislation does not change any of these rules for the industry. However, it further shorten the deadlines the CPMP has to adhere to, which may have a negative impact on the quality of the assessment process.

We hope the above comments offer a constructive contribution to the discussion on the new legislation in the interest and protection of public health within the European Community. We would like to offer our full support and availability should you need further clarification or more detailed information on these critical issues.

Please note that the views expressed in this letter by the undersigned should not be considered to represent the views of either the EMEA, the Committee for Proprietary Medicinal Products (CPMP) or any National Authority.

Yours sincerely

Prof. Fernando de Andres-Trelles (e-mail: fandres@agemed.es - Fax: +34.91.5961615)

Prof. Silvio Garattini (e-mail: garattini@marionegri.it - Fax: +39.02.3546277)

Dr Lars Gramstad (e-mail: lars.gramstad@legemiddelverket.no - Fax: +47.22.897799)

Prof. Magnus Johannsson (e-mail: mailto:magnus.johannsson@lyfjanefnd.is - Fax: +354.5612170)

Dr Frits Lekkerkerker (e-mail: nl-h.cpmp@nl-h.eudra.org - Fax: +31.70.3567515)

Dr Pasqualino Rossi (e-mail: p.rossi@sanita.it - Fax: +39.06.59943488)

Prof. Cristina Sampaio (e-mail: crissampaio@mail.telepac.pt - Fax: +351. 21.7987339)

Prof. Beatriz Silva Lima (e-mail: beatrizlima@netcabo.pt - Fax: +351.21.7987316)

Dr Markku Toivonen (e-mail: markku.toivonen@nam.fi - Fax: +358.9.47334350)