This site is intended for health professionals only
Cytotoxic and hazardous drug compounding is a technical challenge because it is necessary to implement correct aseptic technique to maintain product sterility while also minimising potential occupational and environmental exposure owing to the deleterious effects of this class of drugs.1
Healthcare personnel are also in danger of exposure to hazardous drugs and their effects at all contact points, including point of manufacture, transport, distribution, receipt, storage, preparation, administration, and waste handling. Pharmacists and nurses risk particular exposure to cytotoxic agents during preparation and administration.
What is considered hazardous?
Drugs that meet one or more of the following criteria should be handled as hazardous:
Harmful effects from workplace exposure to these agents were first described in the 1970s by Falck and colleagues.2 Risks associated with handling of these agents include mutagenesis and damage to DNA, and a possible increase in the risk of cancer and infertility.3–8
Routes of exposure
The most commonly identified routes of exposure and contamination are absorption through direct skin contact, inhalation, ingestion, and needlestick injuries.
Personal protective equipment
The use of personal protective equipment (PPE) when handling hazardous drugs has been recommended since the 1980s by The Occupational Safety and Health Administration (OHSA). PPE for hazardous drug handling includes:
Safety standards and guidelines
As awareness of the routes of exposure increased, safety standards have been published from technical institutes and professional bodies. These include: Occupational Safety and Health Administration, 19999National Institute for Occupational Safety and Health (NIOSH), 200410
United States Pharmacopeia USP 79711 American Society of Health System Pharmacists, 200612 Infusion Nurses Society, 200613 and International Society of Oncology Pharmacy Practitioners, 2007.14
A newer proposed standard – USP 800 – is to provide standards to protect personnel and the environment when handling hazardous drugs and is intended to define processes to provide containment of hazardous materials to as low a limit as possible (www.usp.org/usp-nf/notices/compounding-notice).
Observational studies have demonstrated surface contamination with these agents, and contamination outside of the preparation area/biological safety cabinet,15–17 and workers are likely to come in to contact with contaminated surfaces when not wearing PPE. The presence of hazardous drugs in the urine of healthcare workers has also shown that systemic absorption is a possibility, as shown by Sessink and colleagues in 1992.18
A study by Boccellino and colleagues has also demonstrated that doxorubicin can penetrate nitrile gloves.19
Minimising any environmental contamination is therefore vital to safeguard healthcare professionals against exposure to hazardous drugs.
Closed system transfer devices
Closed system transfer devices are playing an increasing role as part of the approach to reduce exposure of personnel to hazardous agents.
A closed-system transfer device is defined as: a drug transfer device that mechanically prohibits the transfer of environmental contaminants into the system and the escape of hazardous drug or vapour concentrations outside the system. The system must be airtight and leakproof. 10,14 Both the NIOSH and USP 797 standards recommend the use of CSTDs, in conjunction with PPE, when preparing and administering chemotherapy.
Studies have demonstrated the effectiveness of CSTDs in decreasing surface contamination and reducing exposure. Siderov and colleagues20 performed a pre- and post-intervention study in which chemical contamination was tested at baseline, five and 12 months after the introduction of a CSTD. Cyclophosphamide was used as a surrogate marker for all cytotoxic drugs. After five months, contamination was reduced in 13 of the 22 sites sampled with four of these samples showing undetectable levels of contamination. After 12 months, surface contamination was reduced in 75% of sample sites. The total contamination of surfaces tested was reduced by 68%.
Sessink and colleagues published data from a study of 22 US hospital pharmacies showing that the implementation of a CSTD reduced surface contamination significantly.21 Using a CSTD compared with the standard preparation techniques resulted in a significant reduction in levels of surface contamination for all drugs tested (cyclophosphamide, isosfamide and 5-Fluorouracil (5-FU); 95%, 90% and 65%, respectively).
Evaluating a CSTD in the workplace setting is important to validate the effectiveness of the product. A study by Sessink and Clark22 evaluated the effectiveness of the EquaShield CSTD in an ambulatory cancer chemotherapy infusion centre between June 2010 and August 2011.22The cancer centre has approximately 16,500 chemotherapy visits per year and has a dedicated pharmacy for chemotherapy preparation.
The Equashield system comprises a double-membrane for drug transfers and a two-chambered syringe (having a distal chamber for air and a proximal chamber for liquid), which is airtight. The connector has dual needles to allow for air and liquid exchange.
Methods and results
Twelve areas were tested for contamination with cyclophosphamide and 5-FU: within the pharmacy, infusion areas and offices. Initial wipe sampling results demonstrated environmental contamination with cyclophosphamide in a number of departments. One site was contaminated with 5-FU, which might be a result of the higher detection limit for the analysis of 5-FU compared with cyclophosphamide.
The final sampling results were obtained one year after implementation of the CSTD and demonstrated a contamination-free environment. Implementation of the CSTD had eliminated surface contamination at the ambulatory infusion centre.22
In combination with other personal protective measures, CSTDs can prevent leakage or accidental discharges during and after administration of chemotherapeutic agents and hazardous drugs, thereby protecting healthcare staff from accidental exposure.