This document outlines standards of behavior and practices for cleanrooms and cleanzones. It defines key terms like cleanroom, cleanzone, critical activity, and aseptic processing. The document provides guidelines for behaviors in all cleanrooms and cleanzones, including proper gowning, minimizing contamination, and maintaining orderly work areas. It also outlines additional requirements for aseptic filling suites, such as proper glove sanitization procedures and using aseptic technique. The document states that compliance with these standards will be assessed through microbiological audits and is necessary to meet regulatory expectations for sterile drug production.

1. Behaviour and Practices in
Cleanrooms and Cleanzones
Tim Sandle
Microbiology solutions:
http://www.pharmamicroresources.com/

2.  Part 1: all grades of cleanrooms
 Part 2: all grades cleanzones
 Part 3: Aseptic Filling Suite
 in addition to Parts 1 and 2
Contents

3. A bench-mark...
Expected standard
GMP, audit and
inspection failure
Standards in cleanroom/zone behaviour and practices
will be assessed via specific micro audits

4.  Cleanroom
 a room designed, maintained and controlled
to prevent particulate and microbiological
contamination of drug products
Definitions:

5.  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:

6.  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
Definitions:

7.  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]

8.  ‘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]

9.  ‘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
Sterile Drug Products Produced by
Aseptic Processing [FDA]

10. 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
Scope of SOP...

11.  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
SOP responsibilities

12. Part 1: All cleanrooms

13.  Good practice:
 gowns/PPE changed if damaged, wet or
used for long durations
 check yours and others regularly
 target max duration = 4 hours
All cleanrooms: Behaviour
Time 
 Avoid rapid movements
– creates particles
– disturbs air flows
 Avoid aerosol production
  personnel =  contamination

14.  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

15. 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

16.  Sterile/sanitised implements
must be used for handling
product. If sterile their
sterility must be maintained
throughout the activity
 Minimise particles when
opening autoclave bags
All cleanrooms: Behaviour
50ml
syringe
Tubing
Lid
Container

17.  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

18.  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: Surfaces

19.  Items entering cleanrooms
 avoid material that cannot be effectively
sanitised
 avoid material that sheds excessive
particles
All cleanrooms: Practices

20.  Work areas must be kept clean,
neat and tidy to reduce cross-
contamination/mix-ups
All cleanrooms: Practices

21.  Items within cleanrooms must not
obstruct HVAC/LAF vents
All cleanrooms: Practices
 Standing water must be
cleaned up

22.  Status labelling
 e.g. cleaned, sanitised, disinfected or sterilised
 soiled disposable equipment must be discarded
 soiled reusable equipment must be removed
All cleanrooms: Practices

23. Part 2: All cleanzones

24. 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

25.  ‘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
Cleanzones: Behaviour
Vertical LAF

HorizontalLAF


26. 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
Cleanzones: Behaviour
 Cleanzone airflows must be
allowed to operate for at least
10 mins prior to use
 Cleanzone work areas must
be cleaned prior to use

27. Part 3: Aseptic Filling Suite

28. 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

29. 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

30. 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

31.  ‘Buddy system’ recommended for some aseptic
activities, e.g. Huber unloading
Aseptic Filling Suite: Behaviour
Grade A
‘CLEAN’
operator
Grade B
‘DIRTY’
operator
Single wrap Double wrap
N.B. The clean
operator must NOT
touch anything that
is not sterile

32.  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
Aseptic Filling Suite: Behaviour

33.  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
NEW: microbiological audits

34.  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
Summary