The United States Pharmacopeia is a non-profit organization based in Rockville, MD. The stated purpose of the USP is to "...promote the public health by establishing state-of-the-art standards to ensure the quality of medicines and other health care technologies." USP publishes the USP-NF (United States Pharmacopeia and National Formulary) and sells reference standards for use in testing to determine if a substance meets USP requirements.
The USP-NF is a compendium of monographs containing requirements and test procedures for food and drug substances. A typical drug substance monograph consists of the following:
- molecular structure
- chemical formula/molecular weight
- Required potency to be considered USP grade
- Packaging and storage requirements
- Labeling requirements
- List of USP reference standards needed for testing the drug
- Complete text describing test methods, or references to test methods described in a general chapter (such as how to measure pH) or already part of another monograph (eg. the monograph for tobramycin sulfate refers to the tobramycin monograph for most tests) Typical tests include identification, pH, residue on ignition, heavy metals, and assay (purity). Additional tests would be included for a solution, ointment, suspension or solid dosage form of a drug.
In addition to drug and food additive monographs, the USP-NF also contains General Chapters (descriptions of common analytical procedures and the apparatus used for a given type of procedure) and reagent monographs. The book itself is more than 2500 pages and is published every five years, however, it is considered to be "continuously revised" to keep up with rapid changes in the pharmaceutical industry. This is accomplished through a somewhat open process. Proposals for new monographs or changes to existing monographs can be submitted to USP by anyone (although you better work for an academic institution, a food company, or a pharmaceutical company in order to be taken seriously). These proposals are given a preliminary review by USP and then published in the bi-monthly Pharmacopeial Forum. Although USP has its own laboratories, it does not have the resources to evaluate all proposals. It therefore relies heavily on industry to evaluate proposed changes and provide feedback to USP. It is in the best interest of those in industry to keep up to date with proposals in the Pharmacopeial Forum and perform laboratory evaluations of any changes that affect their products, because if there are no objections, USP publishes the new or revised monograph in one of its periodic Supplements. Monographs in a Supplement are considered to replace existing monographs in the large book, and then it is essentially the law in the US. This is because the Code of Federal Regulations references the USP in numerous places (A general definition of "drug" refering to the USP is in 21 CFR Chapter 9 section 321, numerous specific references appear in other parts of 21 CFR.), effectively making a publication by a private orginization part of Federal law and enforceable by the FDA.
USP Reference Standards are drug and food substances that have been extensively tested in order to establish their purity and appropriate handling procedures. USP currently sells about 3400 different standards. The purpose and use of USP standards is described in General Chapter < 11 >. Although the USP states that characterization of reference standards is carried out by the USP Drug Research and Testing Laboratory and by the FDA, it is likely that the actual standard material is submitted by a corporation involved in the manufacture and sale of the substance. USP and FDA are probably only verifying data submitted by the manufacturer rather than being the original source of data.
In recent years it has become common for drug companies to market products globally. This has added new wrinkles to the process of getting a product approved for sale, because the regulatory agencies in each country tend to refer to different compendia when evaluating drugs. Although the USP, Japanese Pharmacopeia (JP), British Pharmacopeia (BP), and European Pharmacopeia (EP) are all well known, requirements and test methods vary significantly among them. An attempt has been made to reduce redundant work and confusion by working with the International Conference on Harmonization (ICH) to come up with compendial requirements that are similar from one pharmacopeia to the next. This process has been very slow, so in most cases a globally marketed product must still be tested to show compliance with multiple compendia. Other countries with published pharmacopeias include Argentina, Austria, Belgium, Brazil, China, Croatia, Czech Republic, Denmark, Egypt, Finland, France, Germany, Greece, Hungary, India, Indonesia, Italy, Lithuania, Mexico, Norway, Pakistan, Poland, Portugal, Romania, Russian Federation, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey, Ukraine, and Yugoslavia. Many of the pharmacopeias from these countries rely heavily on the USP, JP, BP, and EP .
USP24/NF19, published by USP, Inc.
http://www.usp.org, the official USP web site
http://www.who.int, The World Health Organization