Download - Cleanroom sop slides
Behaviour and Practices in
Cleanrooms and Cleanzones
Tim SandleMicrobiology solutions:
http://www.pharmamicroresources.com/
Part 1: all grades of cleanrooms Part 2: all grades cleanzones Part 3: Aseptic Filling Suite
in addition to Parts 1 and 2
Contents
A bench-mark...
Expected standard
GMP, audit and
inspection failure
Standards in cleanroom/zone behaviour and practices will be assessed via specific micro audits
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
Definitions:
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
Sterile Drug Products Produced by Aseptic Processing [FDA]
nAll graded cleanzones (Grade A)nMicrobiology sterility isolator (Grade
A)nAll 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...
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
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
Eff
icie
ncy
¨ Avoid rapid movements– creates particles– disturbs air flows
¨ Avoid aerosol production¨ personnel = contamination
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 sterility must be maintained throughout the activity
Minimise particles when opening autoclave bags
All cleanrooms: Behaviour
50ml syringe
Tubing
Lid
Container
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: Surfaces
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
All cleanrooms: Practices
¨ Standing water must be cleaned up
Status labelling e.g. cleaned, sanitised, disinfected or sterilised soiled disposable equipment must be
discarded soiled reusable equipment must be removed
All cleanrooms: Practices
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
Cleanzones: Behaviour
Vertical LAF
Hor
izon
tal L
AF
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
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
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
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
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
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