Qualified impurities, list

An impurities analytical procedure should be described adequately so that any qualified analyst can readily reproduce the method. The description should include the scientific principle behind the procedure. A list of reagents and equipment, for example, instrument type, detector, column type, and dimensions, should be included. Equipment parameters, for example, flow rate, temperatures, run time, and wavelength settings, should be specified. How the analytical procedure is carried out, including the standard and sample preparations, the calculation formulae, and how to report results, should be described. A representative chromatogram with labeled peak(s) should be included in the procedure. 

Table 8 lists additives and the possible impurities they might present. The limits for these impurities were taken from manufacturers specification bulletins. To compound Table 8, products of pharmacopeial grade (USP, BP, Ph. Eur., DAB) were selected from qualified suppliers (Merck, Aldrich, Sigma, Fluka, EMS, Riedel deHaen). 

The profile of impurities in a new drug substance may change for a variety of reasons, such as process scale-up changes, synthetic route changes, and changes made to key intermediates. ICH decision trees help classify, qualify, and select limits for new molecular entities (NMEs). If an impurity exceeds the qualification threshold listed below in Table 3 (ICFI Q3A(R)), studies are needed to qualify that impurity in drug substances. 

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