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Automated compounding devices (ACDs) for the preparation of parenteral nutrition admixtures are widely used by pharmacists in hospitals and other health care settings. They are designed to streamline the labor-intensive processes involved in the compounding of these multiple-component formulations by automatically delivering the individual nutritional components in a predetermined sequence under computerized control. Parenteral nutrition admixtures often contain 20 or more individual additives representing as many as 50 or more individual components (e.g., 15 to 20 crystalline amino acids, dextrose monohydrate, and lipids; 10 to 12 electrolyte salts; 5 to 7 trace minerals; and 12 vitamins). Thus, the ACDs can improve the accuracy and precision of the compounding process compared to the traditional, manual compounding methods. Pharmacists should consult the general information chapter Validation of Compendial Methods 1225 for verification parameters to be considered when evaluating an ACD.
The accuracy of an ACD can be determined in various ways to ensure that the correct quantities of nutrients, electrolytes, or other nutritional components are delivered to the final infusion container. Initially, the ACD is tested for its volume and weight accuracy. For volume accuracy, a suitable volume of Sterile Water for Injection, which represents a typical additive volume (e.g., 40 mL for small-volume range of 1 to 100 mL; or 300 mL for large-volume range of 100 to 1000 mL), is programmed into the ACD and delivered to the appropriate volumetric container. The pharmacist then consults Volumetric Apparatus 31 for appropriate parameters to assess the volumetric performance of the ACD. For gravimetric accuracy, the balance used in conjunction with the ACD is tested using various weight sizes that represent the amounts typically used to deliver the various additives. The pharmacist consults Weights and Balances 41 for acceptable tolerances of the weights used. In addition, the same volume of Sterile Water for Injection used to assess volumetric accuracy is then weighed on the balance used in conjunction with the ACD. For example, if 40 mL of water was used in the volumetric assessment, its corresponding weight should be about 40 g (assuming the relative density of water is 1.0). In addition, during the use of the ACD, certain additives, such as potassium chloride (corrected for density differences) can also be tested in the same manner as an in-process test.
Finally, additional tests of accuracy may be employed that determine the content of certain ingredients in the final volume of the parenteral nutrition admixture. Generally, pharmacy departments do not have the capability to routinely perform chemical analyses such as analyses of dextrose or electrolyte concentrations. Consequently, hospital or institutional laboratories may be called upon to perform these quality assurance tests. However, the methods in such laboratories are often designed for biological, not pharmaceutical, systems. Thus, their testing procedures must be verified to meet the USP requirements stated in the individual monograph for the component being tested. For example, under Dextrose Injection, the following is stated: It contains not less than 95.0 percent and not more than 105.0 percent of the labeled amount of C6H12O6·H2O. The hospital or institutional chemistry laboratories have to validate their methods to apply to this range and correct for their typical measurement of anhydrous dextrose versus dextrose monohydrate. Similar ranges and issues exist, for example, for injections of calcium gluconate, magnesium sulfate, potassium chloride, and so forth. The critical point is the use of USP references and possible laboratory procedural differences.
The intermediate precision of the ACD can be determined on the basis of the day-to-day variations in performance of the accuracy measures. Thus, the pharmacist must keep a daily record of the above-described accuracy assessments and review the results over time. This review must occur at least at weekly intervals to avoid potentially clinically significant cumulative errors over time. This is especially true for additives with a narrow therapeutic index, such as potassium chloride.