HPE HPE 85 – Spring 2017 - Page 12

Symposium report Dr Jay Brown The National Institute for Occupational Safety and Health (NIOSH) (in the US) defi nes as CSTD as, “a drug transfer device that mechanically prohibits the transfer of environmental contaminants into the system and the escape of hazardous drug or vapor concentrations outside the system.” 4 This is a performance standard rather than a technical specifi cation, noted Dr Brown. 10 Evaluation of CSTDs Testing the effi cacy of a CSTD depends on the type of CSTD and its intended purpose – whether it is for use in injection preparation, administration or for waste disposal of cytotoxic drugs. One thing that is very important is that real drugs should be used in the testing process and not surrogate agents that could behave differently, said Dr Sessink. Another danger is that surrogates might damage the integrity of the CSTD and lead to false positive results, he warned. Testing should be undertaken initially under laboratory conditions but devices should also be evaluated in the ‘in use’ situation to refl ect normal practice. One way of assessing the performance of a CSTD is by measuring the amount of drug that is released into the environment. In practice this can involve wipe-sampling of surfaces, air sampling to check for release of particles and analysis of absorbent mats (if used). Sampling of gloves is important because they can be a route for skin contamination and absorption. Finally, urine analysis provides defi nite evidence of exposure, although not the route of exposure, said Dr Sessink. hospitalpharmacyeurope.com Pitfalls of testing “No CSTD system is 100% closed and much depends on the test process”, Alan Wilkinson (Managing Director, Biopharma Stability Testing Laboratory (BSTL) Ltd, Nottingham UK) told the audience. The challenge agent used in the test procedure should be chemically inert and in other respects behave in a “drug-like” way, he continued. Highly reactive chemicals, such as titanium tetrachloride are therefore not suitable. Isopropyl alcohol (IPA) was originally proposed by NIOSH as a challenge agent. It is inert but has a very high vapour pressure, unlike most injectable drugs. When used in vapour-containment tests, it can be shown that all CSTDs leak IPA, if a suitably sensitive detector is used. Fluorescent dye (fl uorescein) has previously been suggested as a way to assess leakage of liquid droplets but Dr Wilkinson questioned the scientifi c validity of the test methodology. In practice, it is almost impossible to distinguish between light emission from liquid on the surface of the container and liquid inside the CSTD-drug vial assembly. Other factors, such as the intensity and bandwidth of the light excitation source, can dramatically alter the results obtained. NIOSH protocol In 2015, NIOSH published a draft protocol for testing the vapour containment performance of physical barrier CSTDs (but not for the air cleaning/fi ltration type) in which the challenge agent was 70% IPA, Ian Pengelly (Principal Chemist, Analytical Chemistry Team at the Health and Safety Laboratory of the United Kingdom Health and Safety Executive) explained. The idea behind it was that pharmacists would build their own apparatus and carry out testing – a scenario that Dr Pengelly described as being “unlikely”. After consultation a new draft universal test protocol was published in 2016. This included nine potential surrogate compounds for use as challenge agents and used thermal desorption followed by gas chromatography and mass spectrometry (TD-GC-MS) for detection. This is a method that is capable of detecting parts per billion, in contrast to the infra-red detection method in the original protocol that can only detect parts per million. The new procedure is designed for use in accredited testing laboratories rather than pharmacies, noted Dr Pengelly. The principle of the new, universal protocol is that manipulation of, for example, a cytotoxic drug, is carried out in a sealed chamber so that leakages can be detected. Two air sampling devices containing a sorbent (Tenax) are positioned inside the chamber and used to collect air samples. Results are generated by a process of thermal desorption followed by gas chromatographic separation and mass spectrometry (TD-GC-MS). So far, more than 250 separate tests on three different CSTDs, using 2.5% solution of 2-phenoxyethanol (2-POE) as the challenge agent (following the universal protocol), have been carried out at an independent laboratory in the UK (BSTL). The popular perception is that physical barrier type CSTDs are superior to air cleaning/fi ltration types but the results show that both Tevadaptor (fi ltration type) and BD- PhaSeal (barrier type) release less than 0.71ppb (the limit of quantitation). In contrast, the Chemoclave released 2.7–7.3 ppb and the needle and syringe (open) method released more than 4.00 ppb. This difference can be attributed to the use of double-membrane connectors between vial and syringe adaptors the rather than Luer locks, said Dr Wilkinson. “The data presented clearly show the Luer lock connection provides a health worker with less protection than the open system using a needle and syringe”, he added. NIOSH has proposed nine potential surrogate compounds, including 2-POE, for use as challenge agents. Isopropyl