The European Pharmacopeia and How U.S. Manufacturers Can Use It

By Mark S. Phillips, Pharm. D.
Jan. 26, 2017

On Jan. 1, 2017, the 9^th edition of the European Pharmacopoeia (Ph. Eur.) became legally binding in its 37 European member countries and the European Union. Compared to the 8^th edition, more than 50 percent of the text is new or revised. The European Pharmacopoeia is the legal and scientific benchmark for pharmacopoeia standards in Europe. It provides common quality control standards for medicines, including homeopathic medicines, active pharmaceutical ingredients and other components. The Ph. Eur is considered the equivalent to the United States Pharmacopoeia (USP), along with the inclusion of homeopathic drug monographs that in the U.S.A. appear in a separate Homeopathic Pharmacopoeia of the United States (HPUS).

The Ph. Eur. is published by the European Directorate for the Quality of Medicines & Health Care (EDQM) centered in Strasbourg, France, under the governance of the European Pharmacopoeia Commission. Established in 1964, the EDQM includes 700 experts from member countries along with other observers who work collaboratively in 72 committees. They have developed over 3,000 verified quality standards to date. The Ph. Eur. is used and recognized in more than 100 countries outside the Ph. Eur. member countries including the United States, which maintains Observer status. This allows the U.S. to participate in scientific committees and gain access to quality control methods of analysis. In an effort to harmonize, many Ph. Eur. methods of analysis are referenced in the QC Data monographs of the Homeopathic Pharmacopoeia of the United States (HPUS).

European Pharmacopoeia standards are applicable to homeopathic drug manufacturers in the United States for products intended to be exported to the European Union and the 37 EDQM member countries. For a complete list of member countries, see https://www.edqm.eu/en/list-ph-eur-members-observers. Products manufactured in the U.S. intended for export to the 100+ countries outside the E.U. that observe the E.P. will also benefit from compliance with the Ph. Eur.

The EDQM conducts assessment programs for the quality of Active Pharmaceutical Ingredients and other substances, resulting in compliant manufacturing facilities being able to issue Certificates of Suitability for their products (the equivalent of a Certificate of Analysis in the U.S.A.). The EDQM also coordinates the Official Medicines Control Laboratories (OMCL), a network of 70 independent public laboratories in 36 European and 5 non-Europe countries that are responsible for conducting market surveillance programs on medicinal products.

European Pharmacopoeia data is organized in several General Chapters as follows:

• Chapter 1 General Notices: data that applies to multiple or all Ph. Eur. monographs, definitions, storage guidelines, etc.
• Chapter 2 Methods of Analysis: information on analytical methods and apparatus
• Chapter 3 Materials for Containers and Containers: details and specifications on materials used for drug containers (e.g., glass, polypropylene) and their identification and purity tests, along with details and specifications on Pharmaceutical Containers (e.g., single dose, multi dose, air tight, etc.)
• Chapter 4 Reagents: compilation of all reagents stated in various tests in the Ph. Eur. organized alphabetically with description and specification for each
• Chapter 5 General Texts: general requirements and guidelines (e.g., viral safety of medicines, sterility tests)

Following the chapters are several general monographs, including our favorite: General Monograph 13 on Homeopathic Preparations.

General Monograph 13 on Homeopathic Preparations is composed of both general and specific data for 38 homeopathic drug products. As monographs for homeopathic preparations are published in the Ph. Eur. they replace those monographs that formerly appeared in national pharmacopoeias of European Union member countries such as the French Pharmacopoeia, the German Homeopathic Pharmacopoeia, and the British Homeopathic Pharmacopoeia.

General data includes preparation of mother tinctures, pillules for homeopathic preparations, impregnation of homeopathic pillules, and methods of preparation of homeopathic stocks and potentization. The general data has been adapted directed from the French Pharmacopoeia and the German Homeopathic Pharmacopoeia, as well as information from the British Homeopathic Pharmacopoeia that does not duplicate that from the first two sources. Specific data such as definitions, ID tests, purity tests, assays (in select monographs) and storage info are provided for the following 30 homeopathic medicines:

Acidum picrinicum	Agaricus phalloides	Allium sativum
Anacardium	Apis	Arsenicum album
Aurum chloratum natronatum	Barium chloratum	Belladonna
Cadmium sulfuricum	Calcium iodatum	Cocculus
Crocus	Cuprum aceticum	Cuprum metallicum
Ferrum metallicum	Hedera helix	Histaminum
Hydrastis canadensis	Hyoscyamus	Hypericum perforatum
Ignatia amara	Kali bichromicum	Magnesium fluoratum
Magnesium phosphoricum	Nux Vomica	Petroleum
Staphysagria	Sulfur	Urtica dioica

In addition to these 30 homeopathic monographs that also appear in the HPUS, the Ph.Eur. has monographs on many other substances. As many of those substances are also utilized for making homeopathic drug products, the HPCUS has worked closely with the Ph.Eur.’s ID tests, purity tests, and select assays to create quality standards for some HPUS monographs. As noted above, the HPUS cross-references some of the Ph.Eur. Tests methods to provide HPUS subscribers validated methods for performing certain quality control testing.

The EDQM works in coordination with the European Medicines Agency (EMA) that is responsible for the scientific evaluation and safety monitoring of pharmaceuticals for use in the European Union. Based in London at this time, the EMA publishes its own EMA Quality Guidelines to help manufacturers demonstrate quality, safety, and efficacy of pharmaceuticals as they prepare applications for marketing pharmaceuticals in the European Union, and for listing in the European Pharmacopoeia. The EMA strongly encourages applicants to follow these quality guidelines on active substance, manufacturing, impurities, analytical procedures and validation, excipients, packaging, stability, pharmaceutical development, specific types of products, and post-approval change management protocols.

The European Pharmacopoeia is available online from EDQM. For subscription information EDQM can be contacted by writing EDQM – Council of Europe, 7 allée Kastner, CS 30026, F-67081 Strasbourg, FRANCE; by telephoning + 33 3 88 41 30 30; by faxing + 33 3 88 41 27 71; or through their website https://www.edqm.eu/en/EDQM-contact-685.html. EDQM welcomes visitors by appointment with a 2-month lead time, and I hear the local cuisine is wonderful. Enjoy.