International pharmacopeia

Note The limits are related to the method used for the determination LO = light obscuration particle count test, M = microscopic particle count test, IP = International Pharmacopeia. 

In accordance with Article 41 of its Constitution, the WHO published a first edition of the International Pharmacopeia in 1952. Because no official national representatives were part of the Commission, the... 

In 1960, at the general assembly of the International Pharmaceutical Federation (FIP), the obsolescence of various national pharmacopeial methods for assaying pharmaceutical enzymes was demonstrated. An international commission on pharmaceutical enzymes was created to deal with this unsatisfactory situation and develop improved assay methods and guidelines for the preparation of pharmaceutical enzyme reference materials. The Center for Standards has a coordination function in organizing collaborative enzyme assays between academic, industrial, and national pharmaceutical control laboratories and in distributing FIP pharmaceutical enzyme standards. Since 1960, many FIP assay methods and standard preparations have been adopted by national and international pharmacopeias, such as the European Pharmacopoeia. The ultimate goal is to provide official, preferentially nonempirical, standardized assay methods by which comparison of commercially available pharmaceutical enzymes is made possible. The most desirable situation would be an international uniformity of enzyme standards and assay methods, which would allow physicians and clinicians to unambiguously compare the potencies of commercially available enzyme products. 

The sources of infrared spectra are quite numerous, some of which contain specific information on drugs and pharmaceuticals and others which have data on compounds indirectly related to them. Sadtler Research Laboratories, Inc. (1969) have compiled collections of pharmaceutical, steroid, and biochemical spectra. The pharmaceutical collection contains 850 infrared and 1500 ultraviolet reference spectra of drugs, medicinals, and pharmaceutical compounds compiled from the latest editions of the U.S.P., British Pharmacopeia, International Pharmacopeia, National Formulary, and New and Nonofficial Drugs. The steroid collection contains the infrared spectra of 750 steroids and related compounds. The biochemical collection consists of 2(X)0 infrared spectra and 650 ultraviolet spectra. The American Petroleum Institute and the Manufacturing Chemists Association also have collections of spectra available. (The address is given in the References to this Chapter.)... 

Professor Aboul-Enein is a member of the World Health Organization (WHO) advisory panel on international pharmacopeia and pharmaceutical preparations, and he is a Fellow of the Royal Society of Chemistry (UK). He received his B.Sc. degree (1964) in pharmacy and pharmaceutical chemistry from Cairo University, Cairo, Egypt, and his M.Sc. (1969) and Ph.D. (1971) degrees in pharmaceutical and medicinal chemistry from the University of Mississippi, Oxford, USA. Professor Aboul-Enein s current research interests are in the field of pharmaceutical and biomedical analysis and drug development, with a special emphasis on chiral chromatography, ion-selective electrodes and other separation techniques. 

United States Pharmacopeia. Reference standards are requited in many USP and NF tests, and in a few FCC tests. The USPC distributes such standards domestically and has authorized international distribution by a number of organizations or companies. There are well over 1000 USP Reference Standards, including several for melting points, and also specimens of narcotics and other controlled substances. New standards are constantly under development as needed in various USP, NF, and FCC testing methods. 

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. 

In 1949 the World Health Organization adopted the biological activity of 1 mg of an oil solution containing 0.025 p.g of crystalline D as the analytical standard for vitamin D. This standard was discontinued in 1972. USP uses crystalline cholecalciferol as a standard (80). Samples of reference standard may be purchased from U.S. Pharmacopeia Convention, Inc., Reference Standards Order Department, 12601, Twinbrook Parkway, Rockville, Maryland 20852. One international unit of vitamin D activity is that activity demonstrated by 0.025 ]1 of pure crystalline (7 -vitamin D. One gram of vitamin D3 is equivalent to 40 x 10 lU or USP units. The international chick unit (ICU) is identical to the USP unit. 

Excipients should be listed in the composition using their Ph Eur name (or one from another national pharmacopeia from an EEA member state), the International Nonproprietary Name, or an exact scientific designation, other than for materials such as preservatives or coloring agents which can be identified by an E-number. Third country pharmacopeial names may be acceptable. Coloring matter is subject to the provisions of specific legislation in the EEA. 

All bioassays are comparative in nature, requiring parallel assay of a standard preparation against which the sample will be compared. Internationally accepted standard preparations of most biopharmaceuticals are available from organizations such as the World Health Organization (WHO) or the United States Pharmacopeia. 

Alternative methods are possible the three regional pharmacopeias (United States, European, and Japanese) allow an individual laboratory able to do the official method to validate an alternative method of analysis. The latter is chosen usually for speed, eonvenience, or expense but also to incorporate an existing database when a new or revised pharmaeopeial method is adopted. Under those provisions, a laboratory ean validate a method from another pharmacopeia, thereby avoiding duplication of routine work. In all three cases, only the official method could be used in eompli-ance or contest. One point of harmonization is to avoid even the more remote in-stanees of duplieative testing in addition to international produet registration. 

One of the earliest references to USP s commitment to international harmonization may be found in the historical introduction to the 3rd revision [1] of the U.S. Pharmacopeia (1851) The new Dublin and London Pharmacopoeias were compared with our own, with a view of introducing uniformity wherever more important considerations did not seem to forbid the requisite modifications.. .. Note that uniformity for its own sake was not the sine qua non. 

Harmonization of pharmacopeial standards as a practical matter began at the International Congresses of Pharmacy between 1865 and 1910 [2], but the first formal attempt can be traced to 1902. Both USP President Horatio C. Wood, M.D., and Frederick M. Power, Ph.D., an American chemist of the Wellcome Chemical Research Laboratories of London, were appointed by the U.S. Secretary of State as delegates to represent the United States government at the International Conference for the Unification of the Formulae for Heroic Medicines, a conference of 19 countries from Europe and North America [3]. The second conference occurred in 1918. The 3rd in 1925 was attended by 31 countries from all continents except Asia and Australia. They drafted a new International Convention, which came in force in 1929. It revised the 1902 agreements on 77 heroic medicines and introduced the concept of maximum dose. It also requested that the League of Nations create a permanent secretariat of pharmacopeias [4]. Andrew G. DuMez, Ph.D., represented the USP, and was officially appointed by the U.S. Public Health Service to represent the United States at this conference [4,5]. An expert committee of the League of Nations planned a third conference for 1938, but it was never convened because of World War II [2]. 

Seeking to establish dialogues with Central and South America, the USP in 1905 responded to a request for a Spanish edition of the Pharmacopeia by contracting with Dr. Jose Guillermo Diaz, Dean and Professor of the College of Pharmacy of the University of Havana, Cuba. Support for this project may have come from a resolution adopted by the Second International Sanitary Convention of the American Republics in 1905, which read in part [3] Resolved, that a translation of this United States Pharmacopoeia into the Spanish language would prove of great benefit to the medical profession and pharmacists in each of the republics represented in this Convention. ... 

Founded in 1990, the International Conference on Harmonization (ICH) is comprised of the pharmacopeial manufacturers associations in Europe (EFPIA), Japan (JPMA), the United States (PMA), and the drug regulatory agencies in Europe (EEC), Japan (MHW), and the United States (FDA), with the International Federation of Pharmaceutical Manufacturers Association (IFPMA) serving as secretariat. Pharmacopeias are not members of the ICH, where membership is reserved for three PMAs and three regulatory agencies. Invited observers include Canada, WHO, and the European Free Trade Association (EFTA). 

The pharmacopeias have worked with the ICH process to facilitate the international environment of pharmaceutical research and product registration. On the other hand, the additional situation for compendia is that the standards which they have published now apply to all of the already marketed products. In that case a company has testing history and product history in their quality control departments. These are the most conservative elements within the pharmaceutical industry as is necessary to their task. Quality control departments are reluctant to change methods when they feel that their products are properly represented by the current of tests. Therefore, a tension is ereated between trying to develop harmonized standards, which facilitate one area of activity in the world of pharmaeeutieals, and not disturbing a satisfactory marketplace. A vast amount of progress has been made in the harmonization of phar-maeopeial methods. 

Shabir, G. A. Validation of high-performance liquid chromatography methods for pharmaceutical analysis. Understanding the differences and similarities between validation requirements of the U S Food and Drug Administration, the US Pharmacopeia and the International Conference on Harmonization. 

US Pharmacopeia 29/NationaI Formulary 24,1086, Rockville, MD, 2006, p. 2921. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use, ICH S6 Preclinical Safety Evaluation of Biotechnology-derived Pharmaceuticals, 1997. 

Figure 5.19 The official logos of the United States Pharmacopeia (left), the American Society for Testing and Materials (center), and the AO AC International (right). 

FDA, USP, and ICH U.S. Food and Drug Administration, U.S. Pharmacopeia, International Conferences on Harmonization Method validation 55,72-74... 

The Stage 4 draft and the commentary are published in the revision document of each pharmacopeia in a section entitled International Harmonization. The draft is published in its entirety. 

Abbreviations. Ab, antibody SC, subcutaneous IV, intravenous CHO HSA, human serum albumin SC, subcutaneous USP, United States Pharmacopeia AHF IU, international unit NMT, not more than Ig, immunoglobulin BHK, baby hamster kidney PEG, polyethylene glycol hGH, human growth hoimone IM, intramuscular WFI, water for injection. 

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