Compendial testing ingredients

III. COMPENDIAL TESTING FOR FORMULATED PRODUCTS AND ACTIVE INGREDIENTS... 

Test and chemistry documents auto or mech. equipment to move ingredients Change to alternative equipment of same design and operating principles 1 of the same or different capacity1 Application/compendial release requirements Notification of change and submission of updated batch records Stability first production batch LT data reported in AR... 

Numerous specifications and control measures are employed to determine final product quality, the first of which is ensuring adequate quality of excipients and active ingredients. Excipient testing ensures compliance with compendial specifications, as well as specifications determined during development of the fill material and/ or shell formulation. Among these are limiting values for trace impurities, especially peroxides, aldehydes, some metals, and ionic salts. 

Identification tests for pure drug substances can be different from those for formulated products. Many times, tests for the specific counterion drug substance will be performed on the active ingredient. These tests are very general and oftentimes can follow official compendial methods. 

Excipients are pharmaceutical ingredients that are used in product formulations. Each serves a specific purpose (i.e, binder, disintegrant, or pH adjustment) for the proper performance of the dosage form. Most of the excipients used in product formulations are compendial items [United States Pharmacopeia (USP), European Pharmacopeia (EP), etc.], and therefore, they are widely used and understood and there is usually no requirement to perform stability tests for them. Many are also used in the food industry. In addition, since the excipient s function in the product is not directly linked to efficacy, its need for tight stability control is less critical. For these two reasons, it is seldom necessary to organize a formal stability program or database for excipients. 

Specifications and Methods for Drug Product Ingredients. If the information is not specified in the drug substance section, this section should include a description of tests and specifications for all active ingredients. The specifications for all ancillary products included in the drug product should be provided as well. Information on all excipients, including process gases and water, should be included and should include a list of compendial excipients (and their citations) and tests and specifications for noncompendial excipients. 

Content uniformity is a measurement of the variation in the active ingredient from one unit to the next. As drug products are manufactured, excipients and fillers are added. Factors such as densities, particle sizes, and particle shapes may contribute to the differences in uniformity. Therefore, uniformity is necessary to assure the individual unit conforms to compendial acceptance criteria of content uniformity. More information on the requirements of this test can be found in USP/NF General Chapter < 905 >. These are similar to the requirements of the European and Japanese Pharmacopeia. Typically, 10 tablets are analyzed and the average and %RSD are reported. The procedure usually is an HPLC test however, UV and other methods. 

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