WRITTEN QUESTION E-2335/96 by Hiltrud Breyer (V) to the Commission (27 August 1996)

Subject: BSE and medicinal products

1. Is the safety of the raw materials used guaranteed throughout the EU?

2. What is the status of official recommendations? To what extent are manufacturers of medicinal products bound by them?

3. In which pharmaceutical products is beef fat used?

4. What other substances derived from cattle are used in the manufacture of medicinal products and for which products?

5. Is it possible to identify from the instruction leaflet with medicinal products which raw materials derived from cattle have been used and their origin?

6. Does the Commission know whether in Great Britain in particular the same safety precautions are used for raw materials derived from cattle as in the Federal Republic of Germany, for example including in the production of gelatine?

Answer given by Mr Bangemann on behalf of the Commission (16 October 1996)

1. The quality of raw materials used by the pharmaceutical industry is guaranteed by several provisions in Community law. The specifications and controls carried out on each batch of raw materials are evaluated as part of the procedure for granting an authorization to place a finished (medicinal) product on the market. ((Council Directive 65/65/EEC of 26 January 1965 on the approximation of provisions laid down by law, regulation or adminstrative action relating to proprietary medicinal products (OJ L 22, 9.2.1965), as last amended by Directive 93/39/EEC. Council Directive 75/319/EEC of 20 May 1975 on the approximation of provisions laid down by law, regulation or administrative action relating to proprietary medicinal products (OJ L 147, 9.6.1975), as last amended by Directive 93/93/EEC). Council Directive 75/318/EEC of 20 May 1975 on the approximation of provisions laid down in the laws of Member States relating to analyticalm pharmaco-toxicological and clinical standards and protocols in respect of the testing of proprietary medicinal products (OJ L 147, 9.6.1975), as last amended by Commission Directive 91/507/EEC (OJ L 270, 26.9.91). Council Regulation (EEC) No 2309/93 of 22 July 1993 laying down Community procedures for the authorization and supervision of medicinal products for human and veterinary use and establishing a European Agency for the Evaluation of Medicinal Products (OJ L 214, 24.8.1993). )) The batches of raw materials used by a manufacturer must be checked by his quality control service and 'good manufacturing practice' ((Commission Directive 91/356/EEC of 13 June 1991 laying down the principles and guidelines of good manufacturing practice for medicinal products for human use (OJ L 193, 17.7.1991). )) recommends checks on the producers of these raw materials.

In addition, two guidelines on measures to minimize the risk of agents which cause spongiform encephalopathies being transmitted via medicinal products were adopted by the Committee for Proprietary Medicinal Products in 1992. Both guidelines, covering medicinal products for human and veterinary use, are implemented by pharmaceutical firms on the one hand and the national and Community authorities which authorize the medicinal products on the other.

The safety of raw materials, including those derived from cattle, whatever their geographical origin, is thus guaranteed by this set of provisions.

2. Clearly, the above-mentioned Directives and Regulations are legally binding. The same is true of the guidelines referred to in these texts. The other guidelines are intended for guidance or reference. When manufacturers conform to them, which is in practice always the case, they must demonstrate that they are applying them correctly and the authorities may decide to carry out inspections. Were manufacturers to choose not to conform to them, that is if they wished to apply different measures, they would have to prove that these measures were at least as effective as those recommended by the guidelines, so as to achieve the same objectives with regard to product safety, quality and efficacy. Since in practice this is very difficult and likely to considerably slow down marketing authorization procedures and compromise their outcome, manufacturers choose to apply all the guidelines in full.

3. It is impossible to provide an exhaustive list of these products. The most common are tablets (if they contain magnesium stearate or other stearic derivatives), gelatine capsules (if they contain gelatine), serums and vaccines, certain antidiabetic products (glucagon), products containing heparin (anticoagulants) and products containing collagen (creams).

4. As a general rule, the following substances derived from cattle may be contained in certain medicinal products: gelatine, heparin, pepsin, glycerine, stearic acid and products derived therefrom, collagen, thrombin, glucagon, vasopressin and blood products.

5. This is not one of the requirements of Article 7(1) of Council Directive 92/27/EEC of 31 March 1992 on the labelling of medicinal products for human use and on package leaflets. ((OJ L 113, 30.4.1992. )) The marketing authorization holder may nevertheless include this information on a voluntary basis, provided that it is not presented as an element of a promotional nature (Article 7(3) of the same Directive).

The application to obtain a marketing authorization must, on the other hand, always give the qualitative and quantitative particulars of all the constituents of the medicinal product and a description of the control methods employed by the manufacturer (Article 4 of Directive 65/65/EEC, as above).

6. Commission Decision 96/362/EC ((OJ L 139, 12.6.1996. )) of 11 June 1996 sets the standards with respect to bovine spongiform encephalopathy (BSE) for the production of tallow and gelatine and some related products in the United Kingdom. Other materials derived from cattle slaughtered in the United Kingdom and intended for use in medicinal products cannot be exported.

Furthermore, the Commission has been advised by all Community marketing authorization holders and applicants having received a favourable opinion from the Committee for Veterinary Medicinal Products or the Committee for Proprietary Medicinal Products that the medicinal products concerned do not contain tissues of United Kingdom origin.

There are no equivalent Community production standards to ensure inactivation of these agents in other Member States. The Commission is not fully informed about any national standards applied by Germany, and cannot therefore make comparisons.