Detergents and disinfectants currently used in hospital pharmacies : Abilities for removing and degrading cytotoxic drugs

G.J. Sewell Professor of Clinical Pharmacy and Consultant
Hospital Pharmacist, Kingston University and Plymouth Hospitals Trust, UK
Président de l’ISOPP

Introduction
The effective removal of cytotoxic residues from workstation surfaces during cleaning is not often considered. Ideally, removing cytotoxic contamination involves the physical removal of drug contamination from a surface and drug breakdown into less toxic compounds. Cytotoxic drugs represent a diverse range of chemical structures and no single agent is known to deactivate all the cytotoxic drugs currently used. Therefore, decontamination is limited to the mechanical removal from a non-disposable surface to a disposable surface i.e. by wiping the working surface with a cleaning agent. NIOSH recommends that all surfaces are decontaminated according to a protocol, which includes an appropriate deactivation agent if available [1]. The agent used should ideally demonstrate removal/breakdown of biological and chemical contamination [1]. Currently, the most common practice in the UK consists of surface wiping with water, with or without a detergent with thorough rinsing, followed by wiping with 70% alcohol.

In 1985, the International Agency for Research on Cancer (IARC) included cytotoxic drugs in its program for the treatment of contaminated waste [2], and oxidation was suggested as a method for degrading these compounds. Studies carried out to investigate the efficacy of oxidising agents used in hospitals showed sodium hypochlorite (5.25%) was >99.96% efficient at degrading several drugs including cyclophosphamide and doxorubicin. Liquid hydrogen peroxide (30%) was also effective [3] [4].

The aim of this study was to examine systems remove and deactivate cytotoxic contamination from surfaces. Decontamination may be defined as the use of physical and/or chemical means to render a surface or item safe for handling, use or disposal. This can refer to both chemical and biological decontamination, which are both important in the safe dispensing of cytotoxic drugs. Decontamination is generally a combination of cleaning (to physically remove surface contamination) and disinfection/sterilisation (which are antimicrobial processes).

This pilot study investigated the effects of two decontamination technologies currently in practice : i) vaporised hydrogen peroxide (VHP®) and ii) liquid detergents, on three marker cytotoxic drugs (cyclophosphamide, 5-FU, doxorubicin).

Methods :
Removal and/or decontamination of the three marker cytotoxic drugs were evaluated in three phases using decontamination technologies currently available in the pharmaceutical and healthcare environments ;

  • Phase I investigated the physical removal of contamination by detergents and wipes.
  • Phases II and III investigated the effectiveness of detergents and Vaporised Hydrogen Peroxide (VHP®) in degrading cytotoxic drugs,. respectively.

Major components of the acidic detergent formulations used were hyroxyacetic acid (CIP 220), phosphoric and citric acid (CIP 200), Citric acid (Cage-Klenz). The neutral formulations such as Renu-Klenz and NpH-Klenz and the alkaline formulation Criti-Klenz contain high levels of surfactants whereas the remaining alkaline formulations were potassium hydroxide, sodium hypochlorite (CIP 150) and potassium hydroxide (CIP 100) based.

In Phase I studies, the test cytotoxics (50ul) were applied to polypropylene surfaces as solutions at typical pharmaceutical concentrations. Detergent diluted according to the manufacturer’s recommendation was added at equal volume (50ul) and the surface subjected to 1, 2, or 3 wipes. Residual drug was then recovered from the surface and quantified by liquid chromatography (LC).
For Phase II studies, the drug solutions were mixed with the detergents in equal volumes (100ul) and incubated at room temperature for periods of up to 60 minutes. The mixture was then diluted in LC mobile phase and remaining drug quantified by LC assay.
The Phase III studies were conducted in a flexible film isolator and VHP was introduced in controlled cycles using a VHP generator. Polypropylene surfaces coated with the test drugs were exposed for different time periods and then remaining drug was recovered and assayed by LC.

In each case, drug recovery and LC assays were fully validated. The assays were designed to eliminate any interference from detergents or VHP.

Results

- Phase1 :
All detergents tested were effective in removing all 3 drugs on wipes. Doxorubicin was more persistent when alkali detergents were used, requiring up to 3 wipes before residual drug was below the limit of quantification. Detergents proved more effective than water for injection or IMS in removing 5-FU when the diluent was 0.9% sodium chloride.
- Phase II :
Of the 3 test drugs only doxorubicin was degraded significantly, and then only by the alkaline detergents. Deactivation half-lives ranged from 5.5 to 34 minutes.
- Phase III :
Exposure to VHP did not degrade 5-FU or cyclophosphamide. Degradation of doxorubicin was dependant on the pH of the diluent used and ranged from 43% degradation (water diluent, pH 5.9) to 92% with buffer pH 2.25 as diluent.

Conclusion
The effectiveness of the different decontamination procedures followed the outcomes predicted from the basic chemistry of the 3 test cytotoxic drugs. The key factors are clearly the main route(s) of drug degradation (oxidation or hydrolysis) and effect of pH on drug ionization and solubility. This study also demonstrates the importance of validating decontamination techniques and suggests that further work is required with a wider range of drugs to assess the potential of standard decontamination methods.

[2World Health Organisation. Laboratory Decontamination and Destruction of Carcinogens in Laboratory Wastes ; Some Antineoplastic Agents. International Agency for Research on Cancer ; Lyon, France, 1985 ; IARC publication no : 73 2004

[3Castegnaro M, De Meo M.D, Laget M, Michelon J, Garren L, Sportouch M.H, and Hansel S. Chemical Degradation of Wastes of Antineoplastic Agents. 2 : Six Anthracyclines : Idarubicin, Doxorubicin, Epirubicin, Pirarubicin, Aclarubicin and Daunorubicin. International Archives of Occupational Environmental Health 1997 ;70:378-84

[4Hansel S, Castegnaro M, Sportouch M.H, De Meo M.D, Milhavet J.C, Laget M, and Dumenil G. Chemical Degradation of Wastes of Antineoplastic Agents : Cyclophosphamide, Ifosfamide and Melphalan. International Archives of Occupational Environmental Health 1997 ;69:109-14

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