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ASEPTIC PROCESSING – CASE STUDY
Who: Andrew Barrow, Cherwell Laboratories What: Investigates media fill simulation failures
Case study
How: By identifying the root cause
Cherwell Laboratories outlines an investigation undertaken to identify the root cause of a series of media fill simulation failures not attributable to operator competency, while also identifying the appropriate corrective and preventative action (CAPA) measures to reduce risk to the aseptic compounding process.
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alidation of compounding is essential to demonstrate that appropriate controls are in place to ensure asepsis of the process and the sterility of filled products, and ultimately, guarantee patient safety. To monitor the aseptic liquid transfer technique of compounder operators, Great Ormond Street Hospital (GOSH) routinely undertakes aseptic process simulation validation (media fill simulations) using tryptic soy broth (TSB). STATUTORY REGULATIONS AND DISINFECTION MEASURES TO KILL SPORES Patient health can be seriously compromised by microbiological contamination of compounded medicines, particularly in the most vulnerable patients. Good Manufacturing Practice (GMP) regulation in the UK has been applied for many years following the introduction of the Medicines Act 1968, then the Human Medicines Regulations 2012.2,3 Compounding pharmacies have no exemption. Despite stringent disinfection procedures, Bacillus cereus contamination of intravenous total parenteral nutrition (TPN) caused 19 cases of septicaemia and three deaths on Bacillus subtilis endospores | Magnification: x7000
a neonatal unit in England 2014.6 An investigation by the Medicines and Healthcare products Regulatory Agency (MHRA) concluded that the contamination was introduced during manufacture and did not originate from any raw materials. This 2014 outbreak was considered an isolated incident, however, it highlighted the risk of contamination by resilient spores from the environment. Subsequent guidance from the MHRA included use of sporicides in a two-stage spray and wipe disinfection process during compounding.7 This guidance has been incorporated into a report by the NHS Pharmaceutical Micro Protocols Group which recommends a two-minute dwell time with sporicide.8 ASSESSMENT OF OPERATOR ASEPTIC TECHNIQUES DURING COMPOUNDING One of the standard procedures to maintain sterility during compounding is by assessing operators’ ability to transfer liquids aseptically in a simulation. Bacteriological medium, such as Tryptic Soy Broth (TSB), replaces compounding medicines and the flow through the compounder is examined for microbial growth. Any contamination events result in immediate cessation of compounding by the operator concerned, followed by retraining in aseptic liquid transfer. This is essential to uphold standards, provided the validation results are an accurate portrayal of competency. After a series of aseptic process simulation validation failures from multiple operators at GOSH, it was deemed unrelated to operator competence. This is because all operatives involved displayed excellent cleanroom techniques and practices. However, Bacillus species had been transferred to the Grade A environment in which compounding of parenteral nutrition is executed, despite adherence to new NHS guidelines regarding addressing sporicidal issues.8 This necessitated the investigation. IDENTIFYING ORIGIN OF MEDIA FILL SIMULATION FAILURES The study first confirmed GOSH’s media fill