WRITTEN QUESTION E-1752/96 by Graham Watson (ELDR) to the Commission (3 July 1996)

Subject: Committee for Proprietary Medicinal Products

Which of the criteria specified in Article 8 of Directive 75/319/EEC ((OJ L 147, 9.6.1975, p. 13. )) was the basis for the consideration by the Committee for Proprietary Medicinal Products on 17-18 October and 26-27 October 1995? Does the Commission consider that this was or was not an Article 12 (of Directive 75/319/EEC) referral? If so why? If not, why not?

Joint answer to Written Questions E-1750/96, E-1751/96, E-1752/96, E-1753/96, E-1754/96, E-1755/96, E-1756/96, E-1757/96 and E-1758/96 given by Mr Bangemann on behalf of the Commission (5 September 1996)

The Honourable Member has raised a series of questions relating to the considerations of the committee for proprietary medicinal products in relation to the safety of combined oral contraceptives containing desogestrol and gestodene.

During its meeting on 17 to 19 October 1995, the attention of the scientific committee for human medicines within the European agency for the evaluation of medicinal products, the committee for proprietary medicinal products (CPMP), was drawn to three unpublished studies suggesting an increased (although still rare) risk of venous thromboembolism associated with third generation oral contraceptives. The products are those containing 'third generation' progestogens (desogestrel, gestodene and norgestimate) with low oestrogen levels, and seven products from three companies are marketed in Member States.

The studies included a multinational study carried out for the World health organisation, a cohort study based on record linkage carried out by Prof. H. Jick, and a transnational study carried out by Prof. W.O. Spitzer.

Not all of these studies had been available to all the members of the CPMP prior to the issue being raised. The results of these studies have not been made available to the Commission for publication. However, it is understood that they are to be published in medical journals.

A preliminary discussion and oral exchange between the members of the CPMP and the investigators involved in the three studies took place during the meeting of 17-19 October 1995. Members thereafter analysed the available data and a special meeting of the CPMP was convened on 26 October 1995. At this meeting, the CPMP considered that, in view of the benefit and risk re-assessment, it was not appropriate to withdraw combined oral contraceptives containing gestodene or desogestrel. The three companies concerned were requested to provide further data to be reviewed by the committee within six months.

The CPMP again considered this issue on 16, 17 and 18 April 1996 in the light of further studies and submissions made be the companies concerned. Following that consideration it was concluded that, 'from a public health point of view, there was no evidence that the major benefits or risks are different for desogestrel or gestodene containing oral contraceptives. For the individual there may, however, be benefits in quality of life. Factors other than the 'generation' of the pill used, such as heredity and immobilisation also have an important role for the occurrence of venous thromboembolic events'.

Regarding effects on myocardial infarction, the committee considered 'the requested pooled analyses of acute myocardial infarction have not yet been performed and currently available data do not allow a conclusion that desogestrel or gestodene containing oral contraceptives have an advantage over levonorgestrel containing oral contraceptives in this respect'.

The medicinal products in question are authorised by the authorities of the Member States and in response to the concerns raised, all Member States initiated an information campaign, either directly to healthcare professionals or to the public in regard to the correct usage of such products. Neither the Member States nor the companies concerned requested that this matter be considered in accordance with Article 12 of Directive 75/319/EEC as amended ((OJ L 214, 24.8.1993. )), and therefore this procedure was not followed and the timetable prescribed in Article 13 of the same directive does not apply.

Article 8 of Directive 75/319/EEC is the article which establishes the committee for proprietary medicinal products, and provides that it is part of the European agency for the evaluation of medicinal products.