(1995; 156 pages)
1. General data on the pharmaceutical sector
Currently, there are 342 licensed pharmaceutical manufacturers in France. This figure does not include approximately 35 enterprises operating as contract manufacturers without marketing authorization, nor does it include 12 manufacturing units which operate attached to pharmacies. The total number of plants (separate inspection sites) in the country is 766 (43% in the region of Paris alone).
There are 231 pharmaceutical wholesalers in the country, but only three major groups of approximately 70 establishments each make up 80% of the market. These three groups are also involved in export activities. However only 26 of the pharmaceutical wholesalers carry out export activities exclusively. La Pharmacie Centrale des Hôpitaux (Central Pharmacy for Hospitals) exports pharmaceuticals, often without registered products.* Charitable associations also export drugs often in the form of a donation.
* According to the information received after the assessment, “This activity has stopped since 1994 and La Pharmacie Centrale is not allowed to export".
2. Infrastructure and functioning
Law No. 93-5 of 4 January 1993, recognizes a central agency, Agence du Médicament, for the regulation of medicines in France. Its power is defined in Article 567.2. Decree No. 93-295 of March 1993 stipulates the status of the agency.
The agency is divided into four parts:
- la Direction de l’Administration Générale (General Administration)
- la Direction de l’Evaluation du Médicament (Drug Evaluation)
- la Direction des Laboratories et des Contrôles (Quality Control Laboratories)
- la Direction des Etudes et de l’Information Pharmaco-économiques (Studies and Pharmaco-economic information).
The Service de l’Inspection et des Etablissements pharmaceutiques (Department of Inspection and Pharmaceutical Establishments) comes directly under the Direction Générale. The Quality Control Laboratories are located in Lyon, Montpellier and Paris.
2.2.1 Drug regulation
The export of medicines is regulated by Article L 603 of the revised Law No. 92-1279, of 8 December 1992. The Law stipulates that drug manufacturing companies which intend to export are required by the Ministry of Health to have a GMP certificate in accordance with Article L.600. However, medicines destined for export are not required to be controlled or subjected to evaluation.
Article L.596-1, stipulates that not-for-profit organizations of a humanitarian nature are allowed to establish their own pharmaceutical establishments and to distribute medicines which conform to Article L.600, to similar organizations in France or to countries in the EEC. In Article 596-2, the Ministry of Health of France can authorize the collection of unused drugs for the benefit of the poor.
The percentage of pharmaceutical products on the market currently registered is less than 100%. This is because some of the products are used for the treatment of tropical diseases and parasites which do not exist in France, and hence are not registered. Since 1978, about 3500 products have been registered exclusively for export in accordance with Article L.603.*
* According to the information received after the assessment...."New products are not registered as of June 1994 and the new regulation of Law No 92 1279 of December 1992, in addition to the previous authorizations will not be valid as of June 1995. Nowadays, there is no longer any registering of Article L 603. A declaration of exportation to be completed by the producer explaining the reason why his product does not have a Free Sale Certificate (AMM) is reviewed by the Agence and transmitted to the health authorities in the importing country".
2.2.2 Quality control
The Quality Control Laboratories are responsible for the testing of the quality of medicines. Quality control testing is not undertaken during the registration of drugs for economic reasons, rather, the testing is performed through a post marketing surveillance which takes place during the first year that the product goes on the market. In 1992, 493 products were tested, especially those used in emergency conditions, as well as new drugs.
In 1992, 493 batches (three samples each) were sent for quality control testing and 80% passed the tests. Quality control tests were not performed on exported products.**
** Also..."In 1993, 565 products used in emergency conditions as well as new drugs were tested and 96% passed the tests".
Inspection is done both at central and regional level. There are no specialized production inspectors at the moment. The frequency of inspection of manufacturers is once a year in conformity with Article R5056 of the Code of Health. The majority of the inspection reports are submitted to the Regional Health Department with copies to the Chief of Inspection. Inspectors have no special instruction or control programme related to products for export.
There is a formal side-effect reporting system in conformity with Decree No. 84-402 of 24 May 1984. The Agence du Médicament through its Direction de l’Evaluation du Médicament (Drug Evaluation Agency) coordinates the activities of 30 regional centres. Pharmaceutical companies are required to report all undesirable effects related to the drugs they produce. There is also a formal system for the recall of medicines.
2.3 Operation of the WHO Certification Scheme
France accepted the Scheme in 1975 and the competent authority is the Agence du Médicament. Certificates issued by the authority include:*
* According to the information received after the assessment, ..."in accordance with the Law 92 179 of December 1992 certificates issued after June 1994 by the authority will include: Certificate of Free Sale (AMM) according to L 601 (Certificate de libre vente); Export Certificate according to L 603 (Délaration d'exportation); Certificate for legal existence of the establishement (Arreté d'ouverture d'éstablissement); Certificate of Good Manufacturing Practice (délivré par l'Inspection, non conforme OMS), not in accordance with WHO; Certificate of a Pharmaceutical Product (WHO type 1975), déliverance non systématique.
- Attestation of Free Sale (AMM) according to L.601.
- Certificate of Free Sale for product according L.603.
- Certificate for legal existence of an establishment.
- Certificate of origin testifying that the establishment is the actual manufacturer of the product.
- Certificate of Good Manufacturing Practice.
- Certificate of a Pharmaceutical Product (WHO 1975 type).
The Certificates are written in French, English and French, and Spanish. They do not contain the WHO emblem and do not mention that they are in accordance with the WHO recommendation. The Certificates include their date of issue, an official seal, and a seal on each page in cases where certificates are more than one page. The paper used has a special mark to prevent counterfeiting.
According to Article L. 603, a special responsibility is given to customs authorities to control the export of pharmaceutical products if the export is forbidden. However, the issue of a Certificate of a Pharmaceutical Product is not a condition for obtaining an export license.** Also, exporters are not interested to obtain such a certificate because importing countries do not ask for it. All certificates are issued by the Agence du Médicament, which has under its authority departments for evaluation and inspection.
** Also..."Export license no longer exists."
Manufacturers which use contract manufacturers declare their commitment during registration that they respect the requirements for registration and they audit their contract manufacturers.
In 1992, 20% of the requests made for a Certificate of a Pharmaceutical Product were rejected by the authority. During the same year, about 3000 certificates were issued for products not registered for use in the country. Requests for product certificates are sometimes rejected on the ground that documents are incomplete, the applicant has no manufacturing authorization, and does not conform to health laws.
There is a post marketing surveillance system for the quality control of pharmaceutical products approved under Article L.601 for local consumption but not for export products. In 1992, 19.3% of the products for which product certificates had been issued were rejected upon testing samples in the course of a post marketing surveillance.