Rational and safe transfer and mixture of medication

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There are numerous highly effective products available to enable the safe handling of injectable medicines. But could expertise be a more cost-effective route to the same goal?

Simon Ogden
DipClinPharm MRPharmS MPS(NZ)

Principal Pharmacist Technical Services

Oweikumo Eradiri
PhD MPSN MRPharmS MIPharmM

Lead Clinical Pharmacist Medication Safety and Research

Richard Needle
PhD MRPharmS

Chief Pharmacist
Colchester Hospital University NHS Foundation Trust
UK

Innovations in safe intravenous (IV) technologies could have potential for rationalisation of pharmacy’s involvement in preparing injectable medicines and an improvement in safety in exposure to and contamination of medication during handling and administration. However, before embracing the use of these products, a thorough organisational cost-benefit analysis is recommended.

Over the past few years there have been quite a few innovations in reconstitution, mixing and transfer systems. For example, currently on the market – with regard to needle-free, closed system, vial-access devices – are the Tevadaptor (Teva), PhaSeal (Carmel), Codan Cyto (Codan), Genie (ICU Medical), MixJect (West Pharmaceuticals) and Ultrasite dispensing-pin (B Braun) products. These vial-access products are all designed to protect the operator from hazardous drugs during their preparation and reduce the risk of product contamination.

Traditional methods of reconstitution and withdrawal from a vial involve using a needle and equalisation of pressure differentials; if procedures are carried out incorrectly this can lead to needlestick injury and the release of vapours and aerosols causing accidental exposure to the hazardous drug.

Also available are needle-free infusion access devices, infusion sets and IV access devices, all working in a similar manner.  Most of these devices are claimed by their manufacturers to exhibit greater barrier properties for preventing microbiological transfer than conventional IV systems.

Another key marketing element for all these products is that they are needle-free and designed to reduce the rate of needlestick injury, which has been reported as being as high as 11 to 14 injuries per 100 hospital beds per year in the UK (although it may be up to 10 times more prevalent due to marked underreporting).

So, in summary, all of the products for reconstitution, mixing and transfer of medication are promoted by their manufacturers as being leakproof, convenient and efficient to use, and as reducing the risks of drug exposure, needlestick injury, and product contamination during usage.

Organisations such as the UK Health and Safety Executive,[1] the US National Institute for Occupational Safety and Health,[2] the United States Pharmacopeia[3] and other organisations[4-7] have recommended the use of specialised IV equipment to help protect the healthcare worker from exposure to hazardous drugs and to protect the integrity of the drug itself. This stance is supported by a study by Kromhout et al[8 ]highlighting the point that the most likely risk to oncology nurses from cytotoxic drugs is when the infusion and IV system are being set up for administration, where the technology has not changed significantly. A study by Elder and Paterson[9] concludes that safety-engineered sharps devices, dependent on type, are likely to be successful in preventing injury and should be considered as part of any sharps injury prevention programme.

These systems could quite easily provide a safe method for clinical staff, in a near-patient or ward-based setting, to manipulate pharmaceuticals.

In the UK considerable awareness of this issue has been raised by the National Patient Safety Agency (NPSA) Alert 20 (2007) on the safe use of injectable medicines.[10] For those injections assessed as low-risk and capable of being safely prepared in the clinical area, the NPSA recommends the use of closed systems. This is an obvious opportunity for the use of these needle-free access devices. However, the need for these IV systems to protect the product from contamination can be disputed by a number of studies challenging the notion that background air contamination is a causative factor in microbial contamination of parenteral fluids which have been manipulated in an aseptic manner in non-cleanroom conditions.[11-13] A notable finding from a study by Van Grafhorst et al[14] was that admixtures prepared from solutions in rubber-stoppered vials are significantly less prone to touch contamination than those prepared from glass ampoules. Helpfully, many pharmaceutical products are available in single-use rubber-stoppered vials.

As far as using these systems in a clinical setting for handling cytotoxics and other hazardous drugs is concerned, the prospective long-term risk of exposure to these agents via skin contact, dermal penetration and inhalation is unclear. However, it must be believed that any level of exposure is undesirable, regardless of the setting for manipulation of those products. MARCH guidelines[15,16] clearly recommend: “All personnel involved in the handling of cytotoxic agents must be given appropriate training and competency assessed in safe handling and minimizing the risk of occupational exposure. There is no substitute for good technique in minimizing the escape of aerosols and vapours during manipulations in preparation and administration of cytotoxic products. Where proprietary containment systems are used, it should be in conjunction with appropriately trained staff and suitable facilities to minimize the risk of occupational exposure”.

Therefore, given the precautionary principle, steps should be taken to ensure nursing staff exposure to cytotoxics is minimised by all possible means, implying that pharmacy preparation of such products is essential. NPSA Alert 20 discourages preparation of high-risk medicines in clinical areas, advocating ready-to-administer products instead.[10]

Within a pharmacy aseptic preparation facility the benefits of any safe IV system may be negated due to the level of expertise of trained staff and the specialist environment in which the item is manufactured. Staff are trained to avoid aerosol production and it is recommended that all workstations used for preparation of cytotoxics are externally ducted to prevent re-entry into the work environment of cytotoxics released as aerosols or spillages inside the workstation during preparation.

The selection and usage of any IV transfer system for preparing and administering pharmaceuticals will need thorough cost�’benefit analysis. Although the system may reduce risk of needlestick injury in a clinical and pharmacy-based setting, many products on the market meet this criteria and are not as expensive – for example, blunted needles or cannulae – and it may be that other sharps injury prevention strategies may be more beneficial.

Also, the additional cost of using a vial access device may be far outweighed by the amount of drug wasted due to vial retention. For example, trastuzumab (Herceptin® – Roche) costs £407.40 per 150 mg vial[17] and is reconstituted with 7.2 ml water for injection. The solution obtained has a concentration of 21 mg/ml and costs approximately £56.60/ml. To put the potential wastage cost into context, if just 1 ml per vial is wasted due to vial retention by using a vial access device, the excess costs could be as follows: based on a single cycle of a three-weekly dose of trastuzumab 6 mg/kg bodyweight for a 75 kg person, the dose would be 450 mg. This will require three vials and could mean an additional expense of £169.80 per patient per cycle, and maybe the needless usage of a fourth vial to ensure accurate dose volume.

So before any IV reconstitution, mixing or transfer system is used in a pharmacy or clinical setting, a full cost-benefit review will need to be done, covering aspects such as drug exposure hazard risk, the cost of device usage (both acquisition and potential drug wastage), staff competency, education and training requirements, and workload changes. â–

References
1. Health and Safety Executive. HSE information sheet MISC615. London: HSE; 2003.
2. National Institute for Occupational Safety and Health. NIOSH publication 2004-165. Atlanta (GA): NIOSH; 2004.
3. United States Pharmacopeia. USP 797. Rockville (MD): USP; 2007.
4. Royal College of Nursing. The administration of cytotoxic chemotherapy. London: RCN; 1998.
5. Oncology Nursing Society. Chemotherapy and biotherapy guidelines and recommendations for practice. Pittsburgh (PA): ONS; 2005.
6. Oncology Nursing Society. Safe handling of hazardous drugs guidelines. Pittsburgh (PA): ONS; 2003.
7. American Society of Health-System Pharmacists. Guidelines on safe handling of hazardous drugs. Bethesda (MD): ASHP; 2006.
8. Kromhout H, et al. Postulating a dermal pathway for exposure to anti-neoplastic drugs among hospital workers. Ann Occup Hyg 2000;44(7);551-60.
9. Elder A, Paterson C. Sharps injuries in UK health care. Occup Med 2006;56:566-74.
10. National Patient Safety Agency. Patient safety alert 20. London: NPSA; 2007.
11. Van Doorne H, et al. Influence of background air on microbial contamination during simulated IV admixture preparation. J Clin Pharm Ther 1994;19(3):181-7.
12. Thomas M, et al. IV admixture contamination rates. Am J Health-Syst Pharm 2005:62(22):2386-92.
13. Personal communication, Davis M to Mel Davis and Associates, Australia, September 2007.
14. Van Grafhorst JP, et al. Unexpected high risk of contamination with Staphylococci species attributable to standard preparation of syringes for intravenous drug administration in a simulation model in ICUs. Crit Care Med 2002;30(4):833-6.
15. Sewell G et al. MARCH guidelines: handling and containment from goods received to clinical areas. Leeds: Teva UK; 2007.
16. Sewell G et al. MARCH guidelines: drug preparation. Facilities and good practice. Leeds: Teva UK; 2007.
17. Joint Formulary Committee. British National Formulary 55. London: British Medical Association; 2008.