• The specifications in monographs of pharmacopoeias are intended to be applicable to drug substances, excipient and finished products from different producers. Although the monographs contain the essential tests that provide verification of the suitability of the product for use, the monographs do not attempt to control unique aspects of individual products. ► Consequently, drug substance and finished product specifications in marketing authorizations of individual products may be based on the requirements of a relevant pharmacopoeia, but may also contain additional tests or tighter acceptance criteria
    This is particularly true of finished product specifications for the release of batches of products onto the market (release specifications are used in Europe, but not in the USA). For these, tighter acceptance criteria may be required at the time of release to ensure that the product remains within specification during its shelf–life. Since samples tested by an independent laboratory are often obtained from the marketplace, the shelf–life acceptance criteria in pharmacopoeias provide a suitable means by which the quality of medicinal products can be judged.
  • Pharmacopoeial monographs for medicinal products provide good models upon which the testing of non– pharmacopoeial products should also be based when a general check of their quality is required. Typical pharmaceutical specifications for dosage forms include the following types of tests to provide assurance of their quality, safety and efficacy: ► Identity test to confirm the identity of the active ingredient(s) and, if appropriate other important constituents (e.g. preservatives)
  • 1. 2. 3. 4. 5. Assay of the active ingredient(s) and, if appropriate other constituents Homogeneity (e.g. uniformity of content for tablets and capsules) Release of the active ingredient from the formulation Drug–related impurities and other contaminants Microbiological tests (e.g. sterility tests for injectable and ophthalmic products Pharmacopoeias contain useful chemical, physical and microbiological information about drug substances, excipient and dosage forms. Examples include molecular structures and formulae, relative molecular masses, melting and boiling points, spectroscopic data and solubility in various solvents.
  • Pharmacopoeial methods should always be considered when the testing of pharmacopoeial articles is required. Even if the test methods in the marketing authorization differ from those in the relevant pharmacopoeia, the article must also comply with the standards of the pharmacopoeia, including the use of the pharmacopoeial test methods, if it is covered by a monograph in the pharmacopoeia. ► In most circumstances, pharmacopoeial methods can be assumed to be valid for the materials covered by the monographs. This is because they are intended for use by a wide variety of laboratories, sometimes on an infrequent basis.
  • One of the criteria for the selection of the methods is that they should be robust. Nevertheless, it is good practice to carry out additional tests (e.g. a recovery test) to demonstrate that the method is suitable for the sample. ► If a test method is required for a pharmaceutical product for which there is no pharmacopoeial monograph, it may be possible to use or adapt the test methods in a monograph of a similar material. In these circumstances, however, relevant validation tests should be carried out, such as recovery, precision, robustness, selectivity and/or specificity and (for trace amounts, e.g. impurities) limits of detection and quantification, to provide confidence in the suitability of the adapted method.
  • Pharmacopoeial monographs generally do not rely on a single analytical technique, but instead contain a number of tests based on different analytical methodologies (e.g. identity tests that use spectroscopic techniques and colour reactions, tests for impurities using chromatographic techniques and assays using a non–selective titrimetry or UV spectrophotometric technique). Pharmacopoeial authorities consider that this approach provides the optimum level of assurance about the quality of the product.
    For many substances and products it is possible to combine the identity test, tests for impurities and assay into a single chromatographic test. Indeed, many manufacturers, including those of pharmacopoeial products, adopt this approach for economic reasons. For similar reasons, an independent laboratory may choose to develop a single chromatographic test to check identity, impurities and assay in surveillance programme that involve large numbers of samples. However, it is important to weigh the cost benefits of this approach against the risks of failure to detect sub– standard products (e.g. those that contain impurities not detected by the single test).
  • Pharmacopoeial monographs may contain, in addition to product–specific test methods, a number of general tests applicable to a wide variety of materials in the pharmacopoeia. Examples of these are melting and boiling point determination, heavy metals test, sulfated ash test (test for residue on ignition in the USP), disintegration testing of solid dose products, tests for microbial contamination, preservative efficacy tests, sterility tests and the Karl Fischer determination of moisture. These pharmacopoeial methods have been accepted as standard test methods and, consequently, can be applied by laboratories to a wide range of non– pharmacopoeial materials, provided appropriate validation has been carried out.