Avoiding errors and risks in aseptic work

1. Avoiding errors and risks in aseptic work Mark Oldcorne

2. What errors can occur 1 • 1990: Johannesburg • Death of 15 babies Contaminated IV feeds • 2000: India • Death of 3 young mothers and 3 newborn babies Contaminated IV fluids • 2001: USA • FDA recall contaminated eye drops • containing Pseudomonas mendocina Klebsiella pneumoniae

3. What errors can occur 2 • 2004: South Africa • 6 premature babies died • Enterobacter cloacae • three containers • one infusion set A pharmacist's dirty hands the main reason • 2002: Brazil • 36 neonatal deaths in Brazil • contaminated intravenous fluids. Endotoxin contaminated IV medication

4. What errors can occur 3 • Evans Medical in Speke (not connected with present trading company) • Tue 6th April 1971 5% Sterile Dextrose Solution Lot D1192 • 29th Feb – 2nd Mar 1971 5 deaths at Devonport Hospital • 6th Mar 1972 - Investigation begins • 12th Jul 1972 - Clothier Report issued by Department of Health & Social Security Report of the Committee appointed to inquire into the circumstances, including the production, which led to the use of contaminated infusion fluids in the Devonport section of Plymouth General Hospital. (London: HMSO, 1972)

5. What errors can occur 4

6. What errors can occur 5

7. What errors can occur 6

8. Error Incident Rates • Bateman, R; 2003 • Pilot • n=198,000 items • 357 errors reported • 0.18% processes containing errors • 7 left department; 1 administered • UK • n=155,000 items • 1697 errors reported • 1.09% processes containing errors • 31 left department; 3 administered • Taxis and Barber; 2003 • 13% error rate for ward based preparation

9. Error Types Bateman, R; 2003

10. Severity of Errors

11. Additional Error Types • Aseptic preparation units vs Traditional Manufacturing Units • Microbiological Contamination • operator • transfer disinfection • environment • aseptic processing • Chemical • right drug • correct amounts of drug • right diluent • right salt \ hydration states

12. Factors Contributing to errors

13. Factors Influencing of Errors Red – Clothier Report 1972! • People • poor staff training (or not at all!) • staff capability - technical and management • inappropriate staffing levels – excessive workloads • inappropriately supervised staff • not following procedures • individual staff concentration • seeing what you want to see • Environment • air pressures – record but not acted on • poor transfer disinfection • cleanliness of work areas\equipment - inadequate cleaning • cleanliness of storage areas – high bioburdens • filtration • appropriate temperature and humidity

14. Factors Influencing of Errors • Records • transcription errors • actions not completed at time of action • calculation errors • incorrect dose & strength • incorrect diluent • incorrect final volume • Instruments \ Equipment • inadequate equipment • lack of calibration • lack of maintenance activity and logs • functioning correctly • use for appropriate use • validation

15. Factors Influencing of Errors • Procedures • lack of procedures • inadequate procedures (reflect practice – contemporary) • operators own interpretation of procedures • accessible • latest version • Ingredients • reconciliation checks • checks • selection errors – incorrect drug / diluent / container • Product • inspection and batch review • incorrect expiry • lack or failure of final product testing • chemical, particulates, microbiology, endotoxins • labelling errors

16. Sources of Errors • Human Errors • never deliberate • usually careless • system shortfalls • overwork • ignorance • Mechanical Malfunction • software malfunction • hardware malfunction • lack of calibration • inappropriate use (e.g. re-use of single use equipment) Combinations - Swiss Cheese Scenario

17. Minimising Errors Phil Crosby • Zero defects or Right First Time philosophy • emphasis on prevention • relies on measurement and data collection - eliminate errors (and waste) • Zero defect does not mean that people NEVER make mistakes • Rather – they are not assumed or expected to make mistakes Aim for perfection and miss it RATHER THAN Aim for imperfection and hit it

18. Minimising Errors “To err is human” “human error is caused by a lack of attention rather than a lack of knowledge” “lack of attention is created when we assume that error is inevitable” (or perhaps we think that the responsibility lies elsewhere) It means that accepting a 0.1% or even a 0.001% error rate is just not on, and that the only level worth striving for is 0%

19. Minimising Risks • Adoption of GxP systems • Rules and Guidance for Pharmaceutical Manufacturers and Distributors, 2007 • Quality Assurance of Aseptic Preparation Services Is that it? Unlimited Resources Integration with

20. Risk management • ICH 9 Quality Risk Management • Principles of Quality Risk Management • evaluation of risk to quality – based on scientific knowledge and ultimately link to patient safety • level of effort, formality and documentation of quality risk management process – commensurate with level of risk • Apply to • development, manufacturing, release, distribution, inspection, review processes • starting and final drug products • When • lifecycle of product

21. Risk Assessment • Risk Identification • What might go wrong? • Risk Analysis • What is the likelihood (probability) it will go wrong? • What are the consequences (severity)? • Risk Evaluation • Compares identified risk and analysed risk against given risk criteria • Risk score

22. Risk assessment • Objective • Elimination to reduction to acceptable levels • Outcomes • Patient safety • Regulatory compliance • Financial • Reputation

23. Risk Management

24. Minimising ErrorsRetrospective • Deviation Management\Change Control • Risk Management Tools • CAPA • RCA • Compare to Other Reporting Schemes

25. CAPA Corrective and Preventive Action • Closed loop process 1. Corrective Action • action taken to rectify the non-conformance/error 2. Preventive Action • action taken to avoid repetition of the same non-conformance. This could involve modification or enforcement of procedures, or implementation of further controls • Change Control

26. RCA Root Cause Analysis • Structured and objective method - Asking • What? How? Why? • Team approach – Facilitator • Analysing Errors - Human Error • timelines etc. • nominal group technique, brainstorming, brain-writing, fishbone, 5-whys, barrier analysis

27. Reporting Systems • Local Reporting Scheme • Hospital or Trust based • National Reporting Schemes • Regional • National • National Reporting and Learning System - NPSA • Pharmaceutical Aseptic Services Group / R. Bateman No Blame

28. Use of Quality Indicators • Trending environmental monitoring data • Deviation\Exception reports • Contamination rates • Trigger Tools • Safer Patient Initiative (SPI)

29. Minimising ErrorsProspective • Minimising errors by prospective analysis • Process mapping • Risk Management Tools • FMEA • HACCP

30. FMEA Failure Mode Effects Analysis • easy to use!! • evaluation of failure modes and likely outcomes • risk reduction • need in depth understanding of product and processes • methodically breaks analysis of complex processes into manageable steps • Used to • prioritize risks • monitor effectiveness of risk control activities • prioritize validation activities • Applied to equipment, facilities, products & processes

31. HACCP Hazard Analysis and Critical Control Points • Systematic, proactive and preventive tool • Quality, Reliability and Safety aspects • 7 steps • Conduct hazard analysis and ID preventive measures – each step • Determine critical control points • Establish critical limits • Establish – system to monitor the CCP • Establish corrective action when CCP not controlled • Establish system to prove HACCP system working • Establish record keeping system

32. Summary Gauge your risks! • Prospective • Retrospective • Use Risk Management Tools • Remember they are only tools