Preparation Of Hazardous Drugs Research Articles

A comparative study of contamination in three closed systems for the preparation of hazardous drugs through simulations with fluorescein

ObjectiveThe objective of this study was to compare the environmental contamination generated during the preparation of cytostatic agents using three different methods through simulations using fluorescein, and the time required for preparation of each method. MethodA comparative study of the processing of fluorescein mixtures using three types of closed systems was conducted at the centralized unit for hazardous drugs of the Pharmacy Department of a General Teaching Hospital. Environmental contamination was detected in critical points of connection, and in splashes produced at any other points. The main variable was qualitative detection of contamination through ultraviolet light when three methods were compared (method A: ChemoClave®, method B: SmartSite® valve and Texium® connector, method C: PhaSealTM with BD luer extension). A final number of 60 mixtures were prepared to detect differences of at least 5%. ResultsQualitative contamination at the critical points during preparation, was seen in groups A and B for every mixture that was processed. No contamination at all in critical points was seen in any of the mixtures prepared using PhaSealTM. Statistically significant differences were found between arms A and C (p < 0.001) and arms B and C (p < 0.001); no differences were found between arms A and B. ConclusionsThe combination of PhaSealTM system in conjunction with the BD luer extension for administering hazardous drugs from a tree modality system has been shown to be the system with the lowest level of contamination during processing without increasing the time required for preparation of the mixture.

A Systematic Approach to Evaluating Closed System Drug-Transfer Devices During Drug Product Development

The use of Closed System Drug-Transfer Devices (CSTDs) has increased significantly in recent years due to NIOSH and USP recommendations to use them during preparation of hazardous drugs. Mechanistic and material differences between CSTDs and traditional in-use components warrant an assessment of their impact on product quality and dosing accuracy. Using a combination of prevalent CSTDs with biologic molecules, we performed an extensive assessment of the effect of using CSTDs for dose preparation and observed no negative impact on product quality attributes. Additionally, we found that the CSTD hold-up volume is 2 to 4-fold higher than conventional in-use components and exhibited a strong dependence on the CSTD brand used. We also found that the CSTD brand and dosing volume have a major influence on dosing accuracy with suboptimal protein recovery at very low dosing volumes. We identified entrapment of product in the CSTD spike as the root cause for this sub-optimal recovery and found that flushing the CSTD spike with a brand-new syringe and not the dosing syringe aided in complete protein recovery. Taken together we present a systematic approach to evaluate the risks and impact of CSTD to drug product quality, dose preparation, and dosing accuracy.

Patterns and characteristics associated with surface contamination of hazardous drugs in hospital pharmacies.

The surface contamination levels of 5 commonly used hazardous drugs in hospital pharmacies are summarized, identifying practice patterns associated with contamination. Contamination testing data were compiled to evaluate surface contaminants of 5 hazardous drugs (docetaxel, paclitaxel, cyclophosphamide, ifosfamide, and 5-fluorourcil). Data from 5,842 wipes over 6 years were collected from 338 hospital pharmacies. The contamination level for each drug was categorized as nondetectable (ND; ≤10 ng/ft2), low (between 10 and ≤100 ng/ft2), medium (between 100 and ≤1,000 ng/ft2) or high (>1,000 ng/ft2). Surface exposures for each drug were summarized based on location, contamination at first and subsequent wipe events, and the use of a closed system transfer device (CSTD). The majority of contamination results corresponded to locations at or near hazardous drug preparation, but also occurred in areas where hazardous drugs were not prepared. There was a higher incidence of contamination levels (high, medium, and low, respectively) at first wipe event (10.2%, 17.4%, and 17.7%) compared to subsequent wipe events (5.8%, 12.2%, and 13.6%) (p < 0.0001). There was a lower incidence of contamination levels at institutions that used CSTDs (6.3%, 12.8%, and 14.4%) compared to institutions that did not use CSTDs (14.2%, 17.9%, and 17.3%) (p < 0.0001). The majority of highest contamination levels corresponded to locations where hazardous drugs were prepared. While the rate of contamination was lower at subsequent wipe events and at institutions that used CSTDs, contamination was not completely eliminated in either scenario.

Comparative study of preparation of hazardous drugs with different closed-system drug transfer devices by means of simulation with fluorescein.

The level of environmental contamination generated during preparation and administration of hazardous drugs using different valve closed-systems and their combinations was compared. The actual impact on the overall time of preparation of cytostatics and the economic cost of the different modalities were also compared. Comparative study of the preparation of fluorescein mixtures with different modalities of valve closed-system combinations. Environmental contamination was detected in critical points of connection, and in splashes produced at any other points. The main variable was qualitative detection of contamination by splashes through ultraviolet light when modalities with or without a connector were compared. A final number of 160 mixtures were prepared to detect differences of at least 5%. Splashes were produced in 7 preparations without a connector (p = 0.015). No significant differences (p = 0.445) were detected either in the use of a supporting vial spike vs an anchoring spike, or in the ChemoCLAVE® system vs valve systems with Fleboflex® solutions. Contamination at any critical point was produced in all preparations. The use of a supporting vial spike, syringe connector and bag solution with Luer connection was the most efficient modality. A syringe connector is needed to guarantee a closed system. Anchoring spikes do not show higher advantages as compared with supporting vial spikes. Fleboflex® solutions with Luer bags are more efficient than ChemoCLAVE® and show similar safety. However, connections of these closed systems are not leak-tight, and it is therefore important to continue studies of contamination of the different closed system transfer devices.

Cost savings realized by use of the PhaSeal® closed-system transfer device for preparation of antineoplastic agents

Medication cost is a major factor associated with increasing health care costs in the United States. Expenditures for prescription drugs in 2013 are estimated to be $283.7 billion. Closed system transfer devices are widely used for preparation of hazardous drugs. Reports indicate the Phaseal(®) closed system transfer device maintains sterility in vials for 7 days, suggesting the unused portion of single-use vials could be salvaged. This study was done to determine whether using a closed system transfer device to extend the beyond-use date of single-use vials of antineoplastic medications would result in a measurable cost saving. A list of 25 drugs available in single-use vials, with a chemical stability of at least 48 hours, was compiled. Use of these agents was recorded during a 50-day period in April through June 2012. Use from a total of 296 vials of 21 antineoplastic agents was recorded. After allowing for the initial use of each vial, the mean potential percentage of drug waste was calculated to be 57.03%. Actual savings during the study period was $96,348.70. The pharmacy avoided nearly half of the potential waste and saved a mean of 29% of each vial. The cost-saving during the study period represents a $703,047.67 annual saving; which more than offsets the $106,556.55 the pharmacy spent for the Phaseal(®) system in 2012. In addition to being a protective measure to reduce exposure to hazardous agents, use of the Phaseal(®) system results in a reduction in drug waste, and a noticeable cost saving for antineoplastic agents.

Evaluation of surface contamination with cyclophosphamide following simulated hazardous drug preparation activities using two closed-system products

Purpose. A preliminary investigation was conducted to evaluate and compare the effectiveness of two closed-system products in preventing contamination of typical pharmacy workplace surfaces with cyclophosphamide during simulated hazardous drug preparation activities in a controlled laboratory setting.Methods. Two separate trials simulating hazardous drug compounding using cyclophosphamide were performed with two different closed-system products. Prior to each trial, work area surfaces of the biological safety cabinet (BSC) workbench, the BSC airfoil and front grill, and the floor below the BSC were cleaned, and wipe samples were collected and analyzed to determine, if present, levels of cyclophosphamide. Following each trial, wipe samples were collected from the work area surfaces to determine the hazardous drug containment effectiveness of each closed-system product.Results. Cyclophosphamide was not detected on work area surfaces prior to each trial. Low levels were detected on the BSC workbench surface following both trials.Discussion. Based on the limited number of samples obtained during this preliminary study and the determination of the presence of the chemical of interest on the drug vials, no statistical evaluation was performed to compare the relative effectiveness of the two systems tested. Work practices and procedures regarding product operation may affect hazardous drug containment and worker safety. Further study and statistical analyses are needed.

Training Course on Safe Handling and Preparation of Hazardous Drugs Offered in 2008

Training Course on Safe Handling and Preparation of Hazardous Drugs Offered in 2008

Evaluación de la calidad en el proceso de utilización de fármacos peligrosos: prescripción y preparación

To evaluate the quality of cytotoxic drug prescription based on the results of an interventional pharmaceutical program and the quality of the final product based on quality-control prior to preparation. July 2002-March 2003. Hazardous drug prescription was evaluated through an analysis of pharmaceutical interventions during therapeutical monitoring. Depending on repercussion in patients, they were classified in three categories (treatment optimization, resource optimization or criteria unification). Data obtained from manual quality control programs prior to hazardous drug preparation were evaluated. Sixty-four interventions were made (9 interventions per 100 prescriptions): 55% were classified as treatment optimization, 28% as resource optimization and 17% as criteria unification. A total of 66% of the interventions focused on treatment optimization were caused by prescription errors. Ninety-seven per cent were accepted. Out of 2,074 preparations, 1,951 were evaluated (94.9%). A 5.1% of non-evaluated preparations were due to a lack of registration and 0.8% to violations in the established protocol. Results of the interventional Pharmaceutical program show that an assisted prescription system is necessary, not only to detect prescription errors but also to prevent them. Manual controls in different stages of the process are useful and they should be complementary to other more reliable dosification controls.

Determining Sources of Workplace Contamination with Antineoplastic Drugs and Comparing Conventional IV Drug Preparation with a Closed System

Many procedures involved in the preparation and administration of hazardous drugs put health care workers at risk of exposure to these agents through leakage or accidental spills. The first objective of this study was to determine if the conventional needle/syringe technique has the potential to allow drugs to escape into the environment. The second objective was to evaluate if a closed system, PhaSeal, prevents inadvertent release of hazardous drugs. Fluorescein, a fluorescent indicator, was prepared as a dry powder and a 0.05% solution in empty drug vials. Each phase of the manipulation was photographed using UV light to visualize fluorescein leaks and spills. The procedures included reconstitution of a dry powder, drug transfer from the vial to an IV bag, simulated drug administration, and IV push administrations through an IV port. With the conventional needle/syringe technique, each phase of the manipulations resulted in visible fluorescein leakage into the environment. Fluorescein leakage ranged in size from less than 1 to 50 mm in diameter. The syringes, work surfaces, gloves, manifold ports, and IV bag ports exhibited fluorescein contamination. With PhaSeal, no leakage was observed during any phase of the manipulations. Using the conventional needle/syringe technique during preparation of a hazardous drug may lead to release of the agent into the work environment, posing a health risk to the worker. A closed system such as PhaSeal has the ability to confine hazardous drugs, substantially reducing or possibly eliminating drug exposures.

Barrier isolators as an alternative to a cleanroom.

The use of barrier isolators as an alternative to a cleanroom for the preparation of sterile products at ASHP-defined risk levels 2 and 3 and cytotoxic and hazardous drugs is described. The two isolators selected provide enclosed microenvironments. The isolator used for preparing products of risk level 2 has white acrylic and polycarbonate rigid walls that isolate the sterile product from the operator. The isolator used for preparing level 3 products and cytotoxic and hazardous drugs has epoxy-painted steel walls, a front window, and a pair of glove ports; its design theoretically prevents cross contamination between the operator and the product under preparation and between the product and the external environment. An independent contractor familiar with barrier isolators certifies the equipment every six months. A random microbiological sampling is periodically compared with a control. The isolators have been in operation since July 1998 without microbial growth in any sample tested. The barrier isolators cost more than traditional laminar-airflow hoods, but the hospital considers the barrier isolators to be more cost-effective than a cleanroom. A cost saving in supplies for cytotoxic and hazardous drug preparation as a result of a reduction in overall gown and glove use was observed. Barrier isolators offer an alternative to a cleanroom for the preparation of products at risk levels 2 and 3 and offer an aseptic, safe environment for preparing cytotoxic and hazardous agents.

Centralized preparation of hazardous drugs. A choice between isolator and laminar airflow.

In 1987, the manager of the Saint-Joseph Hospital (Paris, France) requested a reorganization of cytotoxic drug preparation. Protection for staff who handle hazardous drugs was the main concern. The conclusions drawn from a first analysis emphasize the advantages of a centralized reconstitution unit against a decentralized system. Subsequently, a workload study and an economic study (investment, maintenance, supplies, staff costs, comparative balance sheet and a 5-year simulation) were carried out, but to choose between a laminar airflow in aseptic room and an isolator in a conventional room. The selected isolator is the first of the conception: the central half-suit uses as a server, and four sleeves located on one side allow two technicians to work in a sterile and closed area without sterile garments.