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Economics of cytotoxic preparation


Recent research shows that careful planning of the preparation of cytotoxic injections can result in significant cost-savings with no loss of product integrity

Johan Vandenbroucke
Central Pharmacy
Ghent University

When cost-savings are sought, inevitably questions arise about the way in which expensive medicines such as cytotoxic agents are prepared and whether more economical approaches might be possible. Cytotoxic injections need to be prepared in response to demand so that the doses can be tailored to individual requirements. However, when planning a cytotoxic reconstitution service a number of factors need to be taken into account. Some of the reconstituted products do not have long shelf lives. In some centres, good aseptic practice demands that vials and ampoules are not shared between patients. As a result of working within these constraints, there is often a significant amount of wastage of cytotoxic drugs.
One approach to more economical provision of cytotoxic injections is dose-banding (see page 31 in HPE 51 – article by Graham Sewell), which is associated with quality and safety benefits and reduces wastage. An alternative approach might be to design a scheme that allows use of surplus reconstituted cytotoxic injections for other patients, instead of discarding these amounts. Clearly, this could only be done if the shelf lives of the reconstituted products are long enough, if the processes and equipment can guarantee sterility during the requisite period and if national laws and local guidelines permit such a procedure.
In defining the shelf-life/expiry time for a reconstituted cytotoxic injection the following factors must be taken into account:

  • The shelf life/expiry time of the (reconstituted) drug regarding its physical and chemical properties.
  • The internal procedures of the hospital and hospital pharmacy.
  • The level of safety/quality assurance for the sterility of the product because of the ‘hardware’ such as the location, equipment, air quality of the clean room and use of special devices.
  • The level of safety/quality assurance for the sterility of the product because of the ‘software’ such as the training, education and skills of personnel.
  • National laws or guidelines.

Given that cytotoxic doses are individually tailored, on many occasions there will be a quantity of surplus material in the vial after the dose has been prepared. The pharmacist then has three options:

  • Discard the rest of the vial after each individual preparation.
  • Discard the rest of the vial at the end of the day.
  • Use the vials until the expiry time of the product.

In practice, the decision will involve consideration of the way in which the product will be used and a detailed risk analysis. The recent finding that a closed system transfer device (PhaSeal) exhibits very low susceptibility to microbial contamination (two-three orders of magnitude lower than needle stick/comparator products) means that the third option is now a realistic possibility.[1]


We modelled the financial impact of these three scenarios using the observed patterns of drug use in the centralised preparation unit at the Ghent University Hospital over a two-month period (July–August 2006).[2] The basis of each calculation is described in Table 1.
All calculations were based on products available on the Belgian market at the time. For each vial used it was assumed that one transfer device (PhaSeal Protector) of appropriate size would be used.
Expiry times were determined by reference to published guidelines 3–6 and the guidelines for stability used at the MD Anderson Cancer Center, Houston, Texas.
The results showed that during the study period 3,086 doses were prepared comprising 39 different drug products.
The top ten most frequently-used cytotoxic agents accounted for 70% of the workload (see Table 2).


The total costs of drugs and transfer devices are shown in Table 3.


The actual income for the hospital in all three scenarios is identical in accordance with Belgian law. This law allows reimbursement from the government to the hospital of the amount of drug administered to the patient, calculated as full vials as close as possible to that amount (eg, if a patient requires a dose of 173mg of drug x and the vials of drug x containing 100, 50 and 10mg are available, the hospital is reimbursed for 1 of 100mg, 1 of 50mg and 3 of 10mg, making a total of 180mg).
Thus, from the Government perspective, the cost is as shown in scenario 1.
Scenario 2 was associated with a saving of 65103 Euros (7.5%) and scenario 3 with a saving of 117,970 Euros (13.5%) compared with scenario 1 for that two-month period.
A more detailed analysis shows that a large proportion of the savings related to a group of relatively expensive drugs, few of which were in the overall top ten for usage (see Table 4). Given that in 2006 the use of monoclonal antibodies was not yet standard in therapeutic schemes, the results of a similar exercise today would show even greater differences between the different scenarios.


This study showed that significant savings can be made by using vials of cytotoxic agents until the end of their expiry times. We estimate that since the introduction of this procedure in our hospital savings of 300,000 to 700,000 Euros per year have been made.


In the past manufacturers have often arbitrarily assigned shelf lives of 24 hours to reconstituted products, arguing that sterility cannot be guaranteed after this time. In recent years the stability of reconstituted cytotoxic injections has been well-researched[3–16] and it is clear that longer shelf lives are possible. Today, several generic companies have performed in-house stability studies on their products and now use these stability data (after reconstitution/after first puncture/final dilution) as part of their marketing strategy.
However, if products are to be conserved over longer periods, aseptic procedures must be of the highest calibre. Validated procedures to ensure that the contents of vials remain sterile and that sterility can be guaranteed until the expiry date are essential. In this connection the microbiological integrity of transfer devices becomes an important issue.
Our results also show that the cost of the closed system transfer device, allowing better security for the manipulators and the product itself, is a small proportion of the overall costs – only 2.2– 4.3% of the cost of the drugs.
The possible savings could also be an additional argument for investing in a better work-setting (such as a clean room and flow cabinets) and devices to ensure the safe and sterile handling of cytotoxic drugs.
We recognise that national laws or guidelines in some countries may preclude the use of cytotoxic injections in the way described in scenario 3, and therefore the savings that we described could not be obtained everywhere.

1. De Prijck K, et al. Letters in Applied Microbiology 2008;47:543–548.
2. Vandenbroucke J, & Robays H. EJHP 2008;14:37–42.
3. Wood MJ, Allwood MC, et al. The cytotoxic handbook 4th ed.Oxford: Radcliffe Medical Press; 2002.
4. Trissel LA. American Society of Health-System Pharmacists; 1994.
5. B Braun container compatibility database [homepage on the internet]. Melsungen: Available from:
6. Stabilis international database [homepage on the internet]. Nancy:Available from:
7. Brooke D, Bequette RJ, et al. Am J Hosp Pharm 1973;30:134–7.
8. El Aatmani M, Poujol S, et al. Am J Health-Syst Pharm 2002;59:1351–6.
9. Cytostatica monographies from the oncology workgroup of ADKA. Krankenhauspharmazie. 1999;20:97–102.
10. Thiesen J, Krämer I. Pharm World Sci 1999;21:137–41.
11. Xu Q, Zhang Y, et al. J Am Pharm Assoc 1999;39:509–13.
12. Trittler R, Heni J, et al. Krankenhauspharmazie 2000;21(7):375–6.
13. Zhang Y, Trissel LA. Ann Pharmacother 2006;40:1082–5.
14. Krämer I, Thiesen J. J Onc Pharm Pract1999;5:75–82.
15. ABPI Medicines Compendium. Summary of product characteristics for Herceptin. Roche Products Limited. Electronic Medicines Compendium. Available from:
16. Dine T, Luyckx M, et al. Int J Pharmaceutics 1991;77:279–85.

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