HPE HPE 85 – Spring 2017 - Page 17

Meeting report Issue 85 | Spring 2017 Quality and safety More than 500 participants gathered in Hyères, France for the 19th European GERPAC conference. Topics included syringes for ready-to-administer injections, advanced therapy medicinal products and lean preparation of cytotoxics Christine Clark Editor, HPE Laurence A Goldberg Editorial consultant, HPE “How safe are syringes as the primary containers for ready-to-administer injections?” was the question posed in a workshop run by Irene Krämer (Director of Pharmacy, University Hospital Mainz, Germany) and Paul LeBrun (Head of Production, Central Hospital Pharmacy, The Hague, The Netherlands). There are good published data to support the use of syringes as primary containers from the microbiological safety standpoint. However, there is little information about substances that might be leached from syringes and end up in the injection solution, said Professor Krämer. Syringes can be two-piece or three- piece devices. In the two-piece syringe, both barrel and plunger are made of polypropylene. In the three-piece syringe the barrel and plunger are made of polypropylene but there is also a polyisoprene gasket and the inner side of the barrel is ‘siliconised’ to ensure that the plunger slides easily, explained Professor Krämer. In Europe, 50ml syringes are commonly used to administer drugs using a syringe pump, whereas small volume IV bags are more commonly used in the US. When drugs are prepared in syringes, it is important to bear in mind the possibility that there could be sorption of the drug on to the container or leaching of substances into the drug solution. In addition, drugs that are susceptible to photo-degradation will need protection from light and the container must be tightly sealed to avoid microbial contamination. One publication has described leachable and extractable components in pharmaceutical containers and showed that complex analytical techniques were required to identify them. 1 If leachable substances are found, then a toxicological assessment is needed. Leachable substances could be lubricants, anti-slip additives, anti- oxidants, stabilisers, metal ions and residues, for example, oligomers and unreacted monomers of the original plastic material. Leachables are usually reported as parts per million (ppm) and, Syringes were filled with sodium chloride and glucose and after one month no changes were evident in appearance, pH, weight, or particulate contamination. The only change was an increase in the concentration of leachables. The significance of this finding was not known. Working with a specialist laboratory (Toxicum, Belgium), they attempted to identify the leachable components. Twelve products were found but only four could be identified from the reference database. The general conclusion was that there “When drugs are prepared in syringes, there could be sorption of the drug on to the container or leaching of substances into the drug solution” although the concentrations may be low, they might influence stability or efficacy, said Professor Krämer. Both dose volume and contact time with the container can influence leaching and consequently there is wide variation in the risk of leaching. The topic has attracted considerable attention in recent years and it is covered in a monograph of the United States Pharmacopeia. There is no comparable monograph in the European Pharmacopeia. Dr LeBrun described a national study that was undertaken to examine the quality of 50ml syringes, which are widely used in intensive care in The Netherlands. The investigators found that the syringes (BD Plastipack) actually came from three different suppliers (in Ireland, Turkey and the US) and even underwent different sterilisation processes (ethylene oxide or gamma irradiation). was no toxicity, but this is not entirely satisfactory because several products were not identified, said Dr LeBrun. As a result of this study, the Dutch GMP guidance recommends investigation of every batch of syringes and a monograph has been compiled. “Alternatives to the single-use plastic syringe are necessary, said Dr LeBrun. One example is the ‘COC syringe’ in which both barrel and plunger are made from a cyclo-olefin copolymer (COC). COC syringes can be terminally sterilised after filling; potential drawbacks are that they are siliconised and are expensive. Another approach would be to use an alternative device, such as the Fleximed ® parenteral device, which is also sterilisable, added Professor Krämer. Advanced therapy Advanced therapy medicinal products (ATMPs) are a heterogeneous group of hospitalpharmacyeurope.com 15