Contamination Control in Practice

1. Contamination Control in Practice Tim Sizer University of Leeds

2. Cleaning and Disinfection • Never separate • Cleaning always precedes disinfection • Effective cleaning and disinfection is essential to remove or reduce contamination • particulates • microorganisms • protective films • chemicals • static electricity • Necessary to satisfy regulatory requirements and written standards Products People / operators Air supply Packaging Paper Equipment

3. WHY WORRY ABOUT CONTAMINATION? • We have to comply with GMP “…cleaned thoroughly in accordance with a written programme” “Sanitation” The Quality Assurance of Aseptic Preparation Services Chapter 12. Cleaning: states: 12.1.2 “Clean areas must be regularly cleaned …. according to a written procedure. A log should be kept of the areas cleaned, indicating the agents used.”

4. Accidental drug spills contribute to surface contamination • Case 1 • Floor contamination with fluorouracil and ifosfamide after the renovation and cleaning of a pharmacy. • persistent contamination after two months of construction when the pharmacy area was not operationalConnor, Anderson, Sessink, & Spivey. (2002) • Case 2 • Clean, but used BSC installed in a new prep room. • Found contamination of cabinet and direct surroundingsafterinstallationVandenbroucke & Robays (2001)

5. Meningitis Due to Iatrogenic BCG Infection in Two Immunocompromised Children Stone, Vannier, et al N. England J. Med 1995; 333-561-563. • 2 children (ages 3 & 5) with leukemia  BCG-associated meningitis. • Neither was receiving BCG, neither had hx of BCG vaccination. • Infections may be due to accidental inoculation of BCG during admin of intrathecal methotrexate. • “The intrathecal chemotherapy … may have been accidentally contaminated during the preparation…..” • Failed to identify how contamination occurred • Surface samples failed to grow any mycobacteria

6. People cause contamination People are responsible for 80% of particulates in clean rooms A fully-clothed adult emits 9 x 106 particles in the size range 0.5 to 100 micron (µm) every minute Sitting quietly Moving Walking 100,000 1,000,000 5,000,000 particles shed per minute

7. Airborne Skin Squames 100 to 5,000 cfu every minute ! 14 μm … … … … … … 7 minutes 2 m

8. Normal Talking > 1-2 m/s 0.6 - 1.0 metres Coughing > 3 m/s 1.5 - 2.0 metres Sneezing>7 m/s (200 mph throat velocity!=100 m/s) 3 to 5 metres Coughing and sneezing can cause an alarming increase in contamination, because not only are particles being generated, but they are mixed with liquid droplets in aerosol as well. Opening your mouth causes contamination Normal Breathing >2 m/s

9. In pharmaceutical environments contamination is controlled: • partly by design & construction • partly by behaviour

10. Storage Areas Risk reduction is achieved through a continuum of tasks and activities Starts with goods receipt and continues through to administration • Items intended for aseptic preparation must be handled and stored appropriately • Dust free environments or protected • Minimal packaging • Appropriate handling e.g. trays / gloves / bags • Appropriate clothing and behaviour • Caution: Light Protection!

11. limits microbial growth increases viscosity slows degradation Problems Cleaning issues Unreliability Fluctuations in temperature Needs monitoring at all times Storage - refrigeration

12. Cleaning Materials & Equipment Nothing should be taken into the cleanroom that will increase the particulate level or add contamination to the environment. All cleaning equipment brought into the cleanroom must be spotlessly clean Appropriate clothing must be worn Make-up must notbe worn Paper of all types must be minimised

14. Optimum Techniques • Ensure thorough & complete wetting • Wiping essential to remove residues & biofilm • Using moist wipes • Dry wipes more likely to shed bits, generate static • Wet wipes likely to leave & spread residues • Damp wipes • minimise shedding • absorb liquids into fabric • lifting and removing soiling

15. Item Transfer - Spraying-In • Wear gloves for spraying • Gloves prevent hands contaminating items with microbes, chemicals and organic matter • They protect operators from the same things • Wear dedicated clothing for spraying • Work in spraying booths with fume extract or drip trays • Use correct technique

16. Item Transfer - Spraying-In • Aerosol is very important(droplet size) - 2 reasons • Wet all surfaces properly! • Labels are high risk – give particular attention • Wipe stage is very important • Attention to labels – high risk

17. Wipe stage is very important (QA of Aseptic Services - 4th Edn. 2005) • Wiping to remove spores • At least 2 decontamination stages (one to include wiping) • Spray WipeSpray • systematically wipe from the cleanest end to the dirtiest i.e. from top to bottom of a bottle • Use a fresh surface of the swab each time it comes into contact with item being disinfected • The swab should then be discarded

18. Contact Time • Surface drying time must be considered This will be related to the ventilation system • Disinfectant must stay in contact for sufficient time – to enable penetration • Disinfectant must be active during drying time • Varies according to disinfectant • alcohols - very rapid action • hypochlorites - fast • phenolics - slower • Varies according to nature of contaminants

19. Common Myths • “Disinfectants kill all known germs….dead!” • “Disinfectants will solve all our cleaning problems” • “We don’t worry about cleaning, we disinfect”

20. Cleaning validation is the determination of the efficacy of cleaning procedures used in production premises or on equipment Objective: to show that after cleaning, the production environment & equipment return to original state of microbiological and chemical cleanliness. Documented evidence that the cleaning procedure will reduce contamination to an acceptable level Validation enables routine monitoring to be reduced to a minimum

21. Conclusion • CLEANING IS IMPORTANT - it saves lives • It must be done well using • trained, competent staff (who are adequately supervised and undergo regular validations) • standardised, validated procedures • It must be documented • It must be monitored