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Pharmaceutical Technology Regulatory Sourcebook October 2020 33 informational general chapter <1857> Ultraviolet- Visible Spectroscopy–Theory and Practice). There is an exception to this rule, with USP <1225> (ICH [International Council for Harmo- nization] Q2(R1)) on Analytical Procedure Vali- dation (12, 13) that is considered mandatory by regulators. Analysis requirements in monographs. When phar- macopoeias were first widely published in the 19th century, the aim was that pharmacists would conduct analysis in their premises. Therefore, tests were relatively simple, but as the pharmaceutical industry and analytical science have developed, both molecules and analytical procedures have become more complex. Modern monographs for simple substances have become hybrid in nature and may be a mixture of classical and non-classical analytical techniques. The pharmacopoeias assume that the individu- als conducting the analytical procedures are com- petent analysts and that they are trained in the GMP regulations and good documentation prac- tice as interpreted by the organization for which they work. In addition, there is an unwritten as- sumption regarding the ethical and cultural behav- ior expected from those involved in all aspects of analysis and testing including review. In addition, they are required to interpret the minimalist re- quirements in the monograph and translate them into a working method. Lack of training and experience is at the heart of many data integrity failures. USP <1029> on Good Documentation Guidelines (14) has a number of requirements for review and approval of docu- ments, including second person review of analyti- cal testing that is consistent with FDA GMP in 21 Code of Federal Regulations (CFR) 211.194(a)(8) (15). However, given the importance of the second person review in ensuring complete and accurate results and data integrity, this requirement should be in the General Notices rather than an infor- mational general chapter, as demonstrated in the following example. Methenamine mandelate USP monograph The USP monograph for methenamine mandelate illustrates the problem of ensuring data integrity in pharmacopeial testing. The monograph speci- fies a number of tests, and their interrelationships with General Chapters and the General Notices are shown in Figure 2. Note that the LOD test for methenamine mandelate is to dry over silica gel for 18 hours. However, as this is not a common test for LOD, we have selected the most frequently used LOD method (oven drying) described in USP <731> (16) for illustrative purposes using the betamethasone valerate monograph later in this article. It will become apparent that interpretation of a compendial monograph is not a simple and straightforward task. For the interpreted analytical procedure for the identification test by infrared spectroscopy (IR), for example, there are two mandatory and two in- formational general chapters that should be taken into consideration as follows: • USP <197> Spectroscopic Identification Tests • USP <854> Mid Infra-Red Spectroscopy • USP <1854> Mid Infra-Red Spectroscopy– Theory and Practice • USP <1058> Analytical Instrument Qualification. In addition, there are the following sections of the General Notices that must be considered when all tests in the methenamine mandelate monograph are implemented (11):