The European Pharmacopeia

Within the European Union, the official pharmacopeia is the European Pharmacopeia Ph. Eur.) from the Council of Europe. In most countries it is used as such, in some other countries it constitutes the basis for the national version of the pharmacopeia. The official texts of the Ph. Eur. are published in English and French. Translations in other languages may be prepared by the signatory states of the European Pharmacopeia Convention. In case of doubt or dispute, the English and French versions are alone authoritative. 

The monographs of the Ph. Eur. are legally enforced in the countries being signatories to the Convention on the Elaboration of a European Pharmacopeia. The terminology used in the marketing authorization dossiers must be identical to that of the Ph. Eur. Likewise, raw materials, preparations, dosage forms of medicines and, if necessary, containers, must comply with the requirements of the Ph. Eur. 

The quality standards of the Ph. Eur. have, therefore, an impact on the quality of medicines, which goes far beyond the European region. In absence of a description of 

The new European Directives 2001/82/EC and 2001/83/EC on medicines for human use and veterinary use maintain the mandatory character of the Ph. Eur. monographs in the preparation of dossiers for marketing authorization of medicines, which was instituted in the first directive. Directive 75/318/EEC in 1975. It means that the monographs of the Ph. Eur. must therefore be updated to keep pace with products on the market, with scientific progress, and with regulatory developments. 

The Ph. Eur. defines requirements for purity and activity for a wide range of radiopharmaceutical products, whether they are used for therapeutic or diagnostic purposes. 

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Quality Control. Because fine chemicals are sold according to specifications, adherence to constant and strict specifications, at risk because of the batchwise production and the use of the same equipment for different products ia multipurpose plants, is a necessity for fine chemical companies. For the majority of the fine chemicals, the degree of attention devoted to quahty control (qv) is not at the discretion of the iadividual company. This is particularly the case for fine chemicals used as active iagredients ia dmgs and foodstuffs (see Fine chemicals, standards). Standards for dmgs are pubHshed ia the United States Pharmacopeia (USP) ia the United States (6) and the European Pharmacopeia ia Europe (7). 

Specifications for hGH products are defined by the governmental licensing authorities, eg, the U.S. Pood and Dmg Administration. Draft monographs for hGH have been prepared by both the EnitedStates Pharmacopia and the European Pharmacopeia commissions and should be formally adopted by 1995. These specifications are suitable for biosynthetic hGH. The much less purified pituitary-derived hGH has virtually disappeared from commercial production. An international reference standard for pituitary-derived hGH (lot 80/505) has been used for caUbration, particularly for bioassay purposes. A highly purified biosynthetic hGH standard (lot 88/624) has been prepared and should be formally adopted by 1995, or before. 

The European Pharmacopoeia (Ph. Eur.) has also adopted some of the apparatus designs (12) described in the USP, with some minor modifications in the specifications. Small but persistent differences between the two have their origin in the fact that the American metal processing industry, unlike the European, uses the imperial rather than the metric system. In the European Pharmacopeia, official dissolution testing apparatus for special dosage forms (medicated chewing gum, transdermal patches) have also been incorporated (Table 2 provides an overview of apparatus in Ph. Eur.). 

Borka L. Review on crystal polymorphism of substances in the European Pharmacopeia. Pharm Acta Helv 1991 66 16-22. 

U. Rose, In situ degradation A new concept for system suitability in monographs of the European Pharmacopeia./. Pharm. Biomed. Anal. 18 (1998), 1-14. 

Borka, L. (1995). Crystal polymorphism and related phenomena of substances in the European Pharmacopeia. An updated review for fasciculae 13 to 19. Pharmeuropa, 7, 586-93. [241]... 

Results of a survey of asbestos fibers in consumer cosmetic talc powders from Italian and international markets using electron microscopy, electron diffraction, and energy dispersive x-ray analysis showed that asbestos was detected in 6 of 14 talc samples from the European Pharmacopeia (Paoletti et al. 1984). Chrysotile was identified in 3 samples, 2 samples contained tremolite asbestos and anthophyllite asbestos, and 1 sample contained chrysotile and tremolite asbestos. The authors noted that, in all talc powders analyzed, fibrous talc particles frequently were present that were morphologically similar to amphibole asbestos fibers. Counting fibers as particles with aspect ratio >3 1 and width < 3 m, the percentages of particles that were asbestos fibers ranged from <0.03% to 0.13% for 4 samples, and were 18% to 22% for the other 2 samples. Paoletti et al. (1984) noted that the European Pharmacopeia, at that time, had not established analytical quality control of asbestos contamination. 

The purpose of a pharmacopeia and particularly of the European Pharmacopeia is to promote public health by providing common standards recognized by health authorities and all those concerned with the quality of medicines. Such standards are to be of appropriate quality as a basis for the safe use of medicines by patients and consumers. Their existence facilitates the free movement of medicinal products in Europe and ensures the quality of medicinal products exported from Europe. 

As noted previously the status of the European Pharmacopeia is based on the existence of an international convention created under the aegis of the Council of Europe.f The primary characteristics and goals of the European Pharmacopeia are described in this convention. The following chapters present its evolution in the area of the quality of medicines to fullfil the needs of European and International Harmonization for both regulatory authorities and industries. 

The European Pharmacopeia plays an important role, not only for well known products manufactured for many years but also for new types of medicines by ... 

The 3rd Edition was published in 1996, and an annual supplement is published in midyear (supplement 1998 in 1997, supplement 1999 in 1998, supplement 2000 in 1999). All new editions of the European Pharmacopeia now include the year their texts entered into force in their titles this should make them easier to use. Each supplement is cumulative and replaces the previous... 

This introductory chapter summaries the characteristics of the legalities of the European Pharmacopeia and gives the principal definitions. It explains the legal significance of each part of the Pharmacopeia and the role of each section of a monograph. This chapter is essential reading when reference must to be made to a monograph of the European Pharmacopeia. 

The ICH guideline on impurities is also integrated into the technical guide, and the guideline on residual solvents has been integrated into a general chapter of the European Pharmacopeia. 

The role of the production section is described in the General Notices. The requirement described in this section applies primarily to the manufacturers of the substance in question and to the body of inspectors responsible for checking compliance with the prescriptions of the European Pharmacopeia or with the information given in the licensing dossier. 

In recent years, the European Pharmacopeia Commission has elaborated a policy of replacing the use of animals in quality control testing of medicines in parallel with the application of the corresponding Convention of the Council of Europe. A sizeable program has been set up to apply the 3-R concept (refine, reduce, replace). To this end, the Council of Europe, represented by the EDQM, and the Commission of the European Communities are now working on an extensive standardization programme to set up collaborative studies to ... 

It should be noted that this chapter and the previous EEC guideline published in 1991 on authorised terms for dosage forms, routes of administration and containers were revised together by the European Pharmacopeia Commission at the request of the Commission of the European Communities. 

Thus, both tasks were carried out in parallel and coherently on the one hand, the revision of all the monographs of the European Pharmacopeia and on the other hand, the revision of the Community guideline on authorized terms. 

In addition, compilers of the European Pharmacopeia have been asked to add a production section to the monographs for specific substances. The production section gives key points but not all the details that refer to a specific manufacturer. In addition to the production section in specific monographs, general concepts in line with new ICH guidelines are also identified. Such details are described in the application for a Certificate of Suitability by each manufacturer (see above). 

The European Pharmacopeia Commission is very attentive to updating its monographs. Revisions can be made at any time if a pharmaeopeial or licensing authority requests a particular change. The European Pharmacopeia Commission has defined its criteria for revision of monographs when ... 

The European Pharmacopeia is elaborated by a Commission made up of national delegations from regulatory authorities, with decisions requiring a unanimous vote by the delegations. (Today, the Convention has been signed by 27 European countries including all EU members and by the EU Commission itself Nine other European and eight Non-European countries are also observers.)... 

The monographs are elaborated by the groups of experts appointed by the European Pharmacopeia Commission based on proposals by the national delegations. The experts participating in this work are from industry, universities, and national control laboratories. 

The European Pharmacopeia has progressively been replacing the national pharmacopeias. Nevertheless, we need to emphasize the major role played by the national pharmacopeia secretariats in the elaboration of the common European work. Indeed, they are in the best position to identify national needs and to organize ... 

Finally, the national secretariats play an important role in providing information at the national level on how European rules are elaborated, and any national text is prepared and revised in compliance with the European Pharmacopeia. 

The European Pharmacopeia is a common supranational document that supersedes any national texts for the signatory parties. A common implementation date is adopted by the European Pharmacopoiea Commission for each supplement/edition (or individual text for rapid revision) that enters into force by means of a resolution of the Council of Europe/Public Health Committee. 

Although the signatory parties are bound by the texts and specifications of the European Pharmacopeia published by the Coimcil of Europe, they are free to implement then in ways that are compatible with their technical, legal, and administrative regulations. Thus, different procedures are used in different countries. 

The certification procedure is a complement and bridge between the public standards described in the European Pharmacopeia and the need to prepare a file for licensing. This procedure is a result of much common discussion and agreement among the partners concerned. It was in fact made to measure its collaboration not only with the European regulatory authorities so that they could rely on it totally and recognize unreservedly its validity but also with the industries so that they could be absolutely sure of the protection of industrial property. 

On the basis of the data collected during the elaboration of the monograph and the specific data provided by a specific manufacturer on a specific substance, the Certificate of Suitability certifies that both types of data make it possible to conclude that the quality of the substance corresponds to the quality defined in the European Pharmacopeia monograph. 

In principle, a certificate can be granted for any substance (active substances, excipients) such as organic or inorganic substances, substances produced by fermentation as indirect gene products, and products with risk of TSE for which a monograph published in the European Pharmacopeia exists. Excluded, however, are biological substances such as proteins, products obtained from human tissues, vaccines, blood products, and preparations. 

This is an internal guide for professionals of the European Pharmacopeia and for the secretariat to make the monograph style more uniform in English and French, the two official languages of the Council of Europe. The aim is to provide the means of drafting clear, unambiguous texts. The style, which will appear in the 4th Edition, is more telegraphic than that used in the 3rd Edition. 

Although both procedures have the same aim and require dossiers with exactly the same contents, the certification procedure is especially designed to cover substances for which there is a monograph in the European Pharmacopeia, whereas the European Drug... 

The fundamental goal of the European Pharmacopeia is to promote the harmonization of standards for medicinal products in the member states and in view of... 

The European Pharmacopeia contains a number of general monographs that cover categories of products defined by the ... 

Charton, E. Hormones the role of the european pharmacopeia. Alternatives to animals in the development and control of biological products for human and veterinary use. Dev. Biol. Standardisation (Basel, Karger) 1999, 101, 159-167. 

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