Band 1, Heft 3 - Special Issue: Chemical Contamination

Purpose : At the present time, the method of choice to determine surface contamination of the workplace with antineoplastic and other hazardous drugs is surface wipe sampling and subsequent sample analysis with various analytical techniques. The purpose of this article is to review current methodology for determining the level of surface contamination with hazardous drugs in healthcare settings and to discuss recent advances in this area. In addition it will provide some guidance for conducting surface wipe sampling and sample analysis for these drugs in healthcare settings. Methods : Published studies on the use of wipe sampling to measure hazardous chemicals, including antineoplastic drugs on surfaces were reviewed. These studies include the use of well-documented chromatographic techniques for sample analysis in addition to newly evolving technology that provides rapid analysis of specific antineoplastic drugs. Results : Methodology for the analysis of surface wipe samples for hazardous drugs are reviewed, including the purposes, technical factors, sampling strategy, materials required, and limitations. The use of lateral flow immunoassay (LFIA) and fluorescence covalent microbead immunosorbent assay (FCMIA) for surface wipe sample evaluation is also discussed. Conclusions : Current recommendations are that all healthcare settings where antineoplastic and other hazardous drugs are handled include surface wipe sampling as part of a comprehensive hazardous drug-safe handling program. Surface wipe sampling may be used as a method to characterize potential occupational dermal exposure risk and to evaluate the effectiveness of implemented controls and the overall safety program. New technology, although currently limited in scope, may make wipe sampling for hazardous drugs more routine, less costly, and provide a shorter response time than classical analytical techniques now in use.

The aim of the study was to evaluate the risk of chemical cross-contamination between preparations of cytotoxic drugs performed in hospital pharmacy. Simulation of handling process errors was performed with two selected tracers, thiamine and retinol to mimic hydrophilic and lipophilic cytotoxic drugs. Four types of handling errors were simulated: errors associated with the re-use of a disposable transfer device: syringe, spike and needle and errors associated with surface contamination such as the use of a contaminated pad. The results show rates of contamination above the limit of quantification with the re-use of a syringe, a needle or a spike. For example, with the thiamine solution at 50 mg/ml final concentration, the re-use of a spike led to a contamination of approximately 100 µl equivalent to 5 mg. By contrast, the use of a surface contaminated pad failed to detect a cross-contamination. Cross-contamination related to a contamination of surface by a cytotoxic drug represents a low risk. However, the re-use of a single medical device due to handling human error led to quantifiable risk of cross-contamination. Furthermore, this type of error is very difficult to detect and may be frequent enough to have potential impact on patient.

Handling of pharmaceutical specialities is required before its distribution or administration. Unpackaging and repackaging solid oral doses (SOD) in pharmacy settings; crushing, pills fragmenting or capsules opening inside care units may expose nurses and pharmacy dispensers to chemical contamination according to three recent North American studies. In the absence of a regulatory framework the application of the “principle of precaution” implies at first an analysis of the medication circuit and then the implementation of protective measures to prevent healthcare workers from contamination. Comparison of professional recommendations published in other countries allowed us to select a group of protective methods. We gathered these technical and organisational methods to compose a matrix of recommendations intended to hospital staff involved in SOD handling. This tool aims to improve the development of good manufacturing practices (GMP). It combines the issue of personal protection with other criteria such as quality, efficiency and safety of a medication.

Objectives: The aim of this study was to evaluate environmental contamination levels from a large dataset of long-term monitoring data of 5-fluorouracil and platinum-containing drugs in pharmacies, and to investigate the contaminations over 15 years. Methods: Wipe sampling for 5-fluorouracil and platinum (marker for cis-, carbo- and oxaliplatin) was performed on-site from various surfaces in hospital and retail pharmacies with a validated sampling procedure over a period of 15 years. The 5-fluorouracil concentrations were quantified by GCMSMS and platinum concentrations by voltammetry. Statistical evaluation was performed with respect to sampling locations and years, and over the course of time. Results: Overall, 3,584 wipe samples for 5-fluorouracil and 2,955 wipe samples for platinum were analysed and contamination was detected at all surface types in all 151 examined pharmacies with ranges from ND (not detectable) to 1,725,000 pg/cm² and ND to 23,068 pg/cm², respectively. Median concentrations from the different locations ranged between ND and 4.3 pg/cm² (5-fluorouracil) and 0.2 and 1.8 pg/cm² (platinum) with highest loads inside the biological safety cabinets/isolators and storage areas. Evaluation of contamination over the course of 15 years showed a substantial decrease, especially in the years after introduction of guidance values. Conclusions: Long-term evaluation of surface wipe samples for antineoplastic drug contamination with repeated monitoring seems to be a beneficial tool to characterize the actual exposure situation and to assess surface contamination over time. Wipe sampling is a suitable control means to evaluate the work practices and the effectiveness of applied safety and hygiene measures and to identify the potential exposure risk for health care workers.

Background : Pediatric chemotherapy preparations are usually not analytically controlled, for several reasons. First, they are generally made in syringe, which does not allow to take a sample without changing the final volume. Secondly, the percentage of the dose consecrated to control is important and finally low concentrations can cause sensitivity problems. This lack of quality control, greatly reduces the security of the chemotherapy circuit. Objective : The main objective is to develop an analytical control to low volume pediatric preparations, made in syringes or in infusion bags with a final volume from 20 to 50 mL. Material and Method : The development of analytical control automatons, like QCPrep+ ® , allows a fast and reliable qualitative and quantitative analysis, using UV and Raman spectroscopy. Two protocols were tested. The protocol 1 was intended to test a small sample volume further diluted automatically by the QCPrep+ ® in order to obtain a sufficient volume for the analysis. The protocol 2 was aimed to test a one milliliter sample volume and several analysis volume without dilution. Results : Our protocol implies the overfilling with one milliliter of solvent followed by a sampling of one milliliter. The analysis is performed with 900 µL. Ten cytotoxic drugs commonly used in pediatric oncology have been validated according to ICH recommendations. The development of analytical control for low volume preparations allows young patients to benefit the same level of safety and quality than adult patients.