Contamination Control in Practice Tim Sizer University of Leeds

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

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.”

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 operational Connor, Anderson, Sessink, & Spivey. (2002) Case 2 Clean, but used BSC installed in a new prep room. Found contamination of cabinet and direct surroundings after installation Vandenbroucke & Robays (2001) Connor, T.H., Anderson, R.W., Sessink, P.J., & Spivey, S.M. (2002). Effectiveness of a closed-system device in containing surface contamination with cyclophosphamide and ifosfamide in an i.v. admixture area. American Journal of Health System Pharmacy, 59, 68-72. Vandenbroucke, J., & Robays, H. (2001). How to protect environment and employees against cytotoxic agents, the UZ Ghent experience. Journal of Oncology Pharmacy Practice, 6(4),146-152.

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

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

Airborne Skin Squames 100 to 5,000 cfu every minute ! 2 m 14 μm … … … … … … These pictures are taken from work done by myself and Dr Owen Lidwell at the Central Public Health Laboratory, Colindale in the late 70’s. (In fact this is probably Dr L that you are looking at here) In terms of size, skin scales lie between Flugge droplets and droplet nuclei. On average they settle at approximately 30cm per minute But N.B. the scales fragment easily and can result in particles as small as 5u in diameter - less likely to carry organisms but likely to persist longer in the airborne state 2 m 7 minutes

Opening your mouth causes contamination Normal Breathing >2 m/s Normal Talking > 1-2 m/s 0.6 - 1.0 metres Coughing > 3 m/s 1.5 - 2.0 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. Sneezing > 7 m/s (200 mph throat velocity! = 100 m/s) 3 to 5 metres

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

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!

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

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 not be worn Paper of all types must be minimised

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

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

Item Transfer - Spraying-In Aerosol is very important (droplet size) - 2 reasons Wetting - coalescence of droplets Health and Safety – OEL’s Occupational Exposure Limits Wet all surfaces properly! Labels are high risk – give particular attention Wipe stage is very important Attention to labels – high risk

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

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

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

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

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

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