Stability tests, article/carrier mixtures

StabUity of the article/carrier mixture can be established in conjimction with the homogeneity assays of nonsolutions. Separate stabdity tests will, of course, be required for solutions. Formal stability trials sufficient to show long-term sta-bdity of the mixtures are not required rather, stabdity shoidd be estabhshed for a period that encompasses the period of use of the article/carrier mixture. Period of use shoidd be defined as whichever of the foUowing two time periods is longer, the time between preparation of the mixture and final administration of that mixture to the test system, or the time between preparation of the mixture and the analysis of the mixture as required by 58.113(a)(2). Often the period between preparation and analysis may be longer than the period between preparation and last administration to the test system. 

A reasonable interpretation of 58.113(c) should not require expiration dating of containers of article/carrier mixtures when the mixtures wiU be used on the date of preparation unless a component of the mixture has an extremely short (e.g., less than 8 hr) period of stability. This section does not require that an expiration date appear on feeders that are filled with article/ diet mixtures on the date the mixture is prepared and are presented to the test animals on that same day. 

The requirements of 58.113(a) substantially changed the state of the art for the conduct of nonclinical laboratory studies. Prior to the promulgation of GLP regulations, analytical tests to establish the homogeneity and stability of article/carrier mixtures were not routine, nor were tests to determine the concentration of test and control articles in the mixtures used to deliver test and control articles to test systems. 

Tests to establish the stability and homogeneity of article/carrier mixtures as well as the periodic concentration analyses of the mixtures must be conducted in full compliance with the GLP regulations. 

Third, for each substance (or article) that is mixed with a carrier (solvent or other medium) 1) the uniformity or concentration shall be determined, 2) the solubility shall be determined (EPA only), and 3) the stability in the mixture shall be determined. Expiration dates shall be clearly shown and (EPA only) the device used to formulate the mixture shall not interfere with the integrity of the test. 

Documentation and the same type of procedures are important for mixtures of articles with carriers. In addition, procedures for each test or control article that is mixed with a carrier, appropriate analytical methods shall be conducted to determine the uniformity and stability of the mixture and the concentration of the test or control article in the mixture. In GLP studies, these assays should incorporate validated methods. SOPs need to define general ranges for standard parameters used for analytical acceptability. 

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