Pharmacopoeia: European

H. Bohme and K. Hartke, Europaisches Arzneibuch Band I and Band 11, Kommentar (European Pharmacopoeia, Volume I and Volume II Commentary), Third edition. Wissensehaftliehc Vcrlags-gescllschaft mbH, Stuttgart, and Govi-Verlag, Frankfurt/M., 1983. 

Osterreichisches Arzneibuch (Austrian Pharmacopoeia), 2 volumes, 1981 First Supplement 1983. European Pharmacopoeia. Second edition 1980-1992. 

The guideline on chiral active substances states that particular attention should be paid to identity and stereochemical purity. It states that specifications for a racemate should include a test to show that the substance is indeed a racemate and this is a position supported by the requirements of the European Pharmacopoeia for drug substance monographs [16]. 

European Pharmacopoeia technical guide for elaboration of monographs 2 ed. Pharmeuropa, Special Issue, November 1996. 

The ability to remove particulates has made RO indispensable in the production of ultra-pure water for microchip washing. Its ability to remove large molecules enables it to produce pyrogen-free water for the pharmaceuticals industry. In the USA and elsewhere RO is permitted for producing the water used in making up injectable preparations. The European Pharmacopoeia still insists on distillation for this, but the larger amounts of water needed for ampoule washing, etc. are often purified by RO. 

Pharmacopoeia publications provide a final important source of information for the pharmaceutical industry, regulatory authorities, and the healthcare professions. These are concerned with establishing quality standards. These publications include monographs that define specifications for the purity and identity of established pharmaceutical ingredients, both active and non-active, together with recognised analytical methods that may be used to evaluate them. The most relevant are the United States Pharmacopoeia (USP) and the European Pharmacopoeia (Ph.Eur). 

OMCL Official Medicines Control Laboratories Ph. Eur. European Pharmacopoeia... 

Certification Certification of suitability of Monographs of the European Pharmacopoeia... 

Analytical methods and specifications must be established and validated so as to define and control the quality and purity of the raw materials, intermediates and the finished product. For many standard chemical raw materials, the development of specifications will not be necessary as they are already published in US and European pharmacopoeia (for example, standards for water, organic solvents and various excipients). The ultimate objective of these activities is to be able to manufacture the drugs required for clinical trials in accordance with good manufacturing practice (GMP). 

British Pharmacopoeia (1993) London Her Majesty s Stationery Office. (The British Pharmacopoeia contains edited versions of the monographs for immunological products that appear in the European Pharmacopoeia.)... 

Recognizing these problems, UK food regulatory authorities have generally abandoned the use of quantitative microbial counts as enforceable standards of food quality. Despite this, the European Pharmacopoeia has introduced both quantitative and qualitative mierobial standards for non-sterile medicines, which might become enforceable in some member states. It prescribes varying maximum total microbial levels and exclusions of particular species according the routes of administration. The British Pharmacopoeia has now ineluded these tests, but suggest they should be used... 

British Pharmacopoeia (1993). f European Pharmacopoeia (1997). SSoper Davies(1990). 

Both the British and European pharmacopoeias indicate that it is necessaiy to conduct control tests which confirm the adequacy of the facilities by sampling of air and surfaces and carrying out control tests using samples known to be sterile. In reahty, this means... 

Specific details of the sterility testing of parenteral products, ophthalmic and other non-injectable preparations, catgut, surgical dressings and dusting powders will be found in the British and European pharmacopoeias. 

Guidance concerning the extent of testing required is also given in the Technical Guide for the elaboration of monographs (1996) of the European Pharmacopoeia. These guidelines are specifically addressed to the establishment of reference substances for pharmacopoeial use. 

The monographs of the European Pharmacopoeia describe a so-called test for related substances which is intended to control the level of impurities. Reference substances may be used in this test in order to ensure the system suitability and/or to control the content of related substances. 

It is policy of the Commission of the European Pharmacopoeia to minimize the use of reference substances/preparations since the production, maintenance and distribution of chemical reference substances is a costly and time-consuming undertaking. Therefore the decision to establish a reference substance shoidd not be taken lightly and consideration should be given to other approaches which could be adopted to avoid the use of reference substances. A number of strategies can be employed to reduce the need for reference substances. 

The laboratory of the European Pharmacopoeia applies the method specific approach (inter-laboratory study) as has been previously described (Technical Guide for the Elaboration of Monographs 1996). 

The European Pharmacopoeia prepares a protocol which must be strictly followed by the participants of the collaborative trial to assign the content. The protocol usually requires ... 

The European Pharmacopoeia Commission has adopted the policy that the value assigned to a reference substance as a result of an inter-laboratory trial should have an uncertainty not greater than a predetermined value. The following formula (Equation 5.1) may be used to calculate the estimated approximate imcertainty ... 

In the specific case of the European Pharmacopoeia reference substances, it is considered that the recommendation in the ISO guidelines, to give the uncertainty value with the assigned value on the label of the CRS, is not relevant because of the following reasons ... 

The potencies of some antibiotics described in the European Pharmacopoeia are determined by microbiological assay (Microbiological Assay of Antibiotics 2.7.2... 

The procedure employed for the establishment of the chemical reference substances used in these assays has been previously published (Sandrin et al. 1997). The CRSs for the microbiological assays of antibiotics are first submitted to the chemical tests of the monograph. If the results are satisfactory, a collaborative microbiological assay is carried out, using the International Standard as calibrator. Thus, these reference substances are considered to be secondary reference substances since they are calibrated against existing standards. Potency is expressed in International Units. If an International Standard does not exist, European Pharmacopoeia Units are used. 

Where the CRS is to be employed as a verification material in general methods published in the European Pharmacopoeia, then like a CRS used as an assay standard, the extent of testing is considerable. It is desirable that several collaborating laboratories test the proposed substances using a variety of techniques to ascertain that its purity as adequate. An appropriate number of collaborating laboratories will also participate, after the substance has been deemed suitable, in the study to establish a value by the measurement of the essential property of the substance using an appropriate instrument. 

Since the CRSs and BRPs are officially certified by the European Pharmacopoeia Commission, which adopts the reports establishing their suitability for the intended use, it should be noted that neither certificates of analysis nor data which are not relevant to the use of the substances as defined by the Ph. Eur. monograph, are provided with the reference products or substances. Information required for the correct use of the chemical reference substance or biological reference preparation is provided. The label on the vials or ampoules gives ... 

A catalogue is issued three times a year, after each session of the European Pharmacopoeia Commission, where new and replacement batches of chemical reference substances or biological reference preparations are adopted. This catalogue indicates for each substance or preparation ... 

Both the catalogue and material Safety Data Sheets are available on request or may be obtained from the web site of the European Pharmacopoeia. 

However, the establishment of a new endotoxin standard by the World Health Organization is a recent example of successful international collaboration between the World Health Organization, the United Stated Pharmacopoeia and the European Pharmacopoeia (Poole et al. 1997). Thus this standard is available from any of these organizations to be employed as a reference in the harmonized Limulus Amoebocyte Lysate test. 

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