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Pharmaceutical Technology Regulatory Sourcebook October 2020 31 Examples are taken from the United States Pharmacopeia (USP), but the principles apply to all pharmacopoeias. Understanding pharmacopoeias The GMP regulations define the requirements for the manufacturing, testing, and distribution of APIs and finished pharmaceutical products. However, there are no details about how to test; test methods are the role of the pharmacopeial standards for generic materials. Pharmacopoeias provide the monographs that contain standards for excipients, APIs, and, in some instances, finished pharmaceutical products that for all samples tested within shelf life have to be met for compliance with legal quality standards. Pharmacopoeias in various countries are pub- lished to control the quality of pharmaceutical products. Each API, excipient, or finished product is defined in a pharmacopeial monograph contain- ing the standard, which presents the outline of the analytical procedures used to test with the accep- tance criteria. In addition, certified reference ma- terials are identified for use as reference standards for use in testing. It must be remembered that the acceptance crite- ria relate to the sample tested, not the batch. Hence pharmacopeial acceptance criteria are not suitable or intended to be for batch release (10). The original intention of the pharmacopeial monograph was to allow the practicing pharmacist to test pharmaco- peial items to assess their quality. The use of simple classical analytical procedures, such as volumetric procedures (e.g., titrations), visual appearance, color tests for identity, and gravimetric procedures (e.g., loss on drying [LOD] or loss on ignition), continue to be used in monographs today. Many of these tests rely on observations made by the performer of the test which, in the current data integrity en- vironment, may be subject to manipulation. In the 1890 edition of USP (7 t h edition), the monograph for whiskey has similar simple tests for quality to that of modern ethyl alcohol USP for appearance, specific gravity for strength as well as tests for impurities and common adulteration. Ethyl alcohol, in the 42 nd (2020) edition of the USP, still has tests and specifications for specific grav- ity and non-volatile residue based upon classical analytical techniques. The non-volatile residue test is based on the same evaporative method of 130 years earlier, although the acceptance criterion is now 100 times smaller. Structure of the USP The USP primarily consists of the following sec- tions, illustrated in Figure 1: • General notices and requirements for analysis • Monographs for excipients and APIs and fin- ished pharmaceutical products • General chapters that divide into mandatory (numbered <1000) and informational or strong guidance (numbered >1000) • Reference standards and reagents. General notices and requirements. Most users of the USP will focus their attention on the General Chapters; however, the General Notices and Requirements section (better known as the General Notices) presents the basic assumptions, definitions, and default conditions for the interpretation and application of the USP and the Na- tional Formulary (NF). The requirements stated in the General Notices apply to all articles (e.g., standards, tests, assays, and other specifications), otherwise known as the compendia in the USP, and to all general chapters unless specifically stated otherwise (11).