ABSTRACT
All FDA-approved drugs products must meet the quality requirements described in the U.S. Pharmacopeia (USP) (1,2). If a drug product is to be manufactured elsewhere in the world but marketed in the United States, compliance with existing USP-NF monographs is crucial. Non-compliance may result in the FDA blocking entry of the product into the U.S. market or removing the product from the market. For other markets compliance with USP standards is not binding. For
example, the European Pharmacopoeia (Ph. Eur.) has jurisdiction in Europe, the Japanese Pharmacopeia in Japan, etc. Another compendium that serves as a worldwide reference is the International Pharmacopeia (IntPh), which is published by the World Health Organisation (WHO). But the degree of specificity of the various pharmacopeias with respect to setting specifications for drug products varies considerably. Unlike the USP, Ph. Eur., for example, does not include individual monographs of drug products, so applicants have to develop their own methods. As a result, the USP provides a valuable source of information for the European as well as the American pharmaceutical industry, with monographs for drug products that include dissolution methods with test result specifications. In practice, development of biopharmaceutical procedures regarding the choice of apparatus, dissolution media, agitation speed, and even acceptance criteria is often greatly influenced by the USP monograph, if one exists. With the addition of more and more USP monographs over the years, the USP has faced mounting criticism in Europe that the monographs do not follow a clear structure that is primarily based on the drug substance but also reflects the required biopharmaceutical properties of the drug product. In order to meet these goals, alternative attempts have been undertaken to implement Biopharmaceutical Classification Scheme (BCS) concepts in dissolution method development for the characterization of multi-source drug products (3). Although standard apparatus compliant with USP, JP, and Ph. Eur. are used, the media pH, volume, and stirring rate have been adjusted to address biopharmaceutical issues. However, these methods have only recently been accepted by the WHO (4), and to date have only been developed for a limited number of compounds. For these reasons and because of the legal status of the USP for the United States and the fact that USP is a recognized standard in many countries, following an available USP monograph, which describes dissolution test conditions for the intended drug product, continues to be the recommended procedure at the time of writing.
