Behaviour and Practices in

Cleanrooms and Cleanzones

Tim Sandle
Microbiology solutions:
http://www.pharmamicroresources.com/
 Contents

 Part 1: all grades of cleanrooms

 Part 2: all grades cleanzones
 Part 3: Aseptic Filling Suite
 in addition to Parts 1 and 2
 A bench-mark...

Expected standard

GMP, audit and

inspection failure

Standards in cleanroom/zone behaviour and practices

will be assessed via specific micro audits
 Definitions:
 Cleanroom
 a room designed, maintained and controlled
to prevent particulate and microbiological
contamination of drug products
 Definitions:
 Cleanzone
 an area with a defined particulate and
microbiological cleanliness standard, usually
consisting of Laminar Air Flow protection.
 A cleanzone is designed to maintain asepsis or
sterility of the critical activity, product, test, or
material contained within it.
 Definitions:

 Critical activity
 an activity that involves close proximity or
manipulation of exposed product, raw materials
or sterile equipment and components
 Laminar Air Flow (LAF)
 Uni-Directional Air Flow (UDAF) at a velocity
sufficient to uniformly sweep particulates away
from the Cleanzone
Sterile Drug Products Produced by
Aseptic Processing [FDA]

 Aseptic processing:
where the drug product, container, and closure
are subject to sterilisation processes separately,
as appropriate, and then brought together

 ‘Any manual or mechanical manipulation of the

sterilised drug, components, containers and
closures prior to, or during, aseptic assembly
poses a risk of contamination and thus
necessitates careful control’
Sterile Drug Products Produced by
Aseptic Processing [FDA]
 ‘Poor cGMP conditions…can ultimately pose a
life threatening health risk to a patient’

 ‘Even successfully qualified systems can be

compromised by:
poor personnel activities
poor operational activities
poor maintenance activities’
 Sterile Drug Products Produced by
Aseptic Processing [FDA]

 ‘It is essential that operators involved in aseptic

manipulations adhere to the basic principles of aseptic
technique at all times…’
 Appropriate training should include:
 cleanroom behaviour
 aseptic technique
 microbiology
 gowning
 patient safety hazard posed by a non-sterile product
 Personnel training should be updated regularly
 Supervisors should routinely evaluate operators
 Scope of SOP...

All graded cleanzones (Grade A)

Microbiology sterility isolator (Grade A)
All graded cleanrooms (Grades B - D)

 Standards of behaviour and aseptic technique must be

transferable to all relevant situations
 this will be observed by an auditor/inspector
 if in doubt guidance must be sought
 SOP responsibilities
 Everyone entering cleanrooms/zones must:
 be trained and competent, or
 must be ‘closely’ supervised
 Everyone has a responsibility to:
 be familiar/compliant with expected standards
 report substandard behaviour (e.g. gowning)
 report damaged room fabric, equipment, gowns
Any persons who pose an unacceptable risk to the product,
process or facility must be excluded immediately and
retrained
Part 1: All cleanrooms
 All cleanrooms: Behaviour
 Good practice:
 gowns/PPE changed if damaged, wet or
used for long durations
 check yours and others regularly
 target max duration = 4 hours
Time 

 Avoid rapid movements

– creates particles
– disturbs air flows
 Avoid aerosol production
  personnel =  contamination
 All cleanrooms: Behaviour
 Aseptic technique must always be used wherever
applicable
 Fresh sterilised gloves must be worn immediately before
a critical activity and regularly sanitised
 but do not use disinfectant spray near product,
components, raw materials or env. mon. equipment
 All cleanrooms: Behaviour
Minimise spread of contamination
during critical activities:
 avoid touching your person or other people
 avoid touching human contact sites such as:
 pens bin handles
 keyboards paperwork
 keypads desks
 doors plugs/switches
 chairs any unclean equipment
 telephones containers (disinfectant cans?!)
if you do make contact - sanitise gloves
 All cleanrooms: Behaviour
 Sterile/sanitised implements
must be used for handling
product. If sterile their
50ml
sterility must be maintained syringe
throughout the activity
 Minimise particles when Tubing
opening autoclave bags Lid

Container
 All cleanrooms: Surfaces
 Items dropped on the floor
 floors are relatively dirty areas
 items must NOT be picked up during a critical activity
unless under exceptional circumstances
 if really needed the item must be thoroughly sanitised and
the operators gloves changed if they are completing the
activity
 All cleanrooms: Surfaces
 Touching floors must be avoided at all times
 if having to kneel, sit or lie on the floor, either
 disinfect the floor before and after
 place a sanitised/sterile sheet on the floor first
 Aseptic items must not be placed on the floor, or any
other unsterile/unsanitised surface
 place on a suitable surface, or
 place on a sterile, or disinfectant wipe
 All cleanrooms: Practices
 Items entering cleanrooms
 avoid material that cannot be effectively
sanitised
 avoid material that sheds excessive
particles
 All cleanrooms: Practices
 Work areas must be kept clean,
neat and tidy to reduce cross-
contamination/mix-ups
 All cleanrooms: Practices
 Items within cleanrooms must not
obstruct HVAC/LAF vents

 Standing water must be

cleaned up
 All cleanrooms: Practices

 Status labelling
 e.g. cleaned, sanitised, disinfected or sterilised
 soiled disposable equipment must be discarded
 soiled reusable equipment must be removed
Part 2: All cleanzones
 Cleanzones: Behaviour
To avoid contamination and disruption of air flow:
 Control movements within, and adjacent to, cleanzones
 Talking must be avoided within, or adjacent to,
cleanzones
 Interventions must be performed slowly and deliberately
 Covers, curtains and doors surrounding cleanzones must
be opened with minimal distance/force
 Aseptic technique must always be used regardless of any
other protection present
 Cleanzones: Behaviour
 ‘First Air’ principle:
 items being protected by air flow must receive clean ‘first
air’ - so all operator manipulations must be done
downstream of air flow
 Aseptic manipulations and operator gloves must
be restricted to within the protected zone during
a critical activity

Horizontal LAF
Vertical LAF



 Cleanzones: Behaviour
Operation of cleanzone:
 Workareas must be clean, neat and tidy.
 Items present within the cleanzone must be minimised
and located so as not to disrupt or reduce air flow
protection

 Cleanzone airflows must be

allowed to operate for at least
10 mins prior to use
 Cleanzone work areas must
be cleaned prior to use
Part 3: Aseptic Filling Suite
 Aseptic Filling Suite: Behaviour
Gloves must be sanitised at regular intervals, but
especially when related to a critical activity:
Before leaving the final change/SW5
Entering the filling room/critical zone
Before opening cleanzone screens/doors
Before handling container/closure bags
Before handling a sterilised implement/surface
After touching any part of ones self or others
After touching a human contact site
After touching microbiological media
 Aseptic Filling Suite: Behaviour
Use of disinfectant sprays
avoid excessive particles
spray away from env.mon. equipment including
particle counters (use Safe Zones in filling rms)
Use a jet spray for sanitising gloves
 deliver a pool into the palm of the hand
 spread across all surfaces
 allow to dry before commencing
 Aseptic Filling Suite: Behaviour
Filling rooms
must not be used as short cuts, even when not
in use
must not be used to store items not required
for filling activity in progress
must have personnel numbers minimised
 Long 24” outer gloves are mandatory at all times
 Goggles to be worn during critical activities
 Aseptic Filling Suite: Behaviour
 ‘Buddy system’ recommended for some aseptic
activities, e.g. Huber unloading

Grade A Grade B

N.B. The clean

‘CLEAN’ ‘DIRTY’
operator must NOT
operator operator touch anything that
is not sterile

Single wrap Double wrap

 Aseptic Filling Suite: Behaviour
 When working in cleanzones the operator must hold
gloved hands:
 at working height
 at/above waste height
 under protective air flow
 avoiding touching anything unsterile
 Aseptic technique must be demonstrated at all times,
regardless of any other protection
 NEW: microbiological audits
 Facilities, utilities and equipment
 Liquid, moisture Storage
 Fabric HVAC/UDAF
 Interlocks/airlocks Documentation
 Specific activities
 Gowning Aseptic Technique
 Working in UDAFs Cleaning/disinfection
 Aseptic Filling
 General items
 Cleanroom behaviour
 Process flows/Personnel Housekeeping
 For all areas covered by this SOP
 For Correction & PREVENTION
 Summary
 Increase in activity/personnel = increased chance of
contaminating product/facility
 Behaviour and practices required at BPL are industry
practice and regulatory expectations
 You may well be observed by an inspector and will need
to demonstrate good standards
 Standards of behaviour and aseptic technique should be a
transferable skill applied to different situations. If in
doubt - ask.
 From NOW you must comply with this SOP