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:
“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 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,
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),

5. Meningitis Due to Iatrogenic BCG Infection in Two Immunocompromised Children Stone, Vannier, et al N. England J. Med 1995;
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, ,000,000
particles shed per minute

7. 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

8. Opening your mouth causes contamination
Normal Breathing
>2 m/s
Normal Talking > 1-2 m/s
metres
Coughing > 3 m/s
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

9. partly by design & construction partly by behaviour
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. Storage - refrigeration
limits microbial growth
increases viscosity
slows degradation
Problems
Cleaning issues
Unreliability
Fluctuations in temperature
Needs monitoring at all times

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 not be 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) 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

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

22. The End!
Any