Aspects of quality management: Accuracy in dosing antineoplastic drugs

Abstract

Introduction. When preparing parenteral antineo plastic preparations, different production techniques are used in hospital pharmacies or oncologic wards. National and International regulations and quality standards define the requirements for drug produc tion, independent of the methods that are used.

Materials and Methods. In the present study we compared the precision of a weight-controlled dosing system supported by production and docu mentation software to a conventional volume-con trolled dosing method. The weight-controlled method, where one technician produces the applica tions software-leaded with a connected electronic balance, includes an automatic online control and documentation of each procedure step. The pharma cists role in the production process is reduced to the endcontroller before distributing the drugs. The vol ume-controlled method, mostly used in Germany, is based on dose analogous volume calculation as mea sured by syringes. Lack of automatic control and documentation requires the pharmacist as a control ler at every step of production. To determine the difference in dosing accuracy of both methods, we measured and calculated the deviations of the real from the target doses/masses for both methods.

Results. With our weight-controlled method, every single dosage and the cumulative dose for one drug of one patients therapy lay within a 5% deviation limit of the required dose. Without validation of syringe volume and consideration of galenic factors, our volume-controlled method does not consistently meet the deviation limit of 10% required in the pharmacopoeia.

Conclusion. The weight-controlled method is superior in dosing accuracy to the conventional method, because syringe-volume deviations, densities of drug solutions, overfillings and other factors are not considered in the volume-controlled method. Only with great expense in manual documentation, the volume-controlled method correspond to the guidelines in Chapters 1, 4, and 5 of the "Guidelines for Good Manufacturing Practice of the European Communities," where requirements on quality assur ance systems, documentation and production are described.