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’


‘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


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

Part 1: All cleanrooms

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


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


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


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


Items within cleanrooms must not obstruct HVAC/LAF vents


¨ 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


Part 2: All cleanzones

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


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


¨ 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

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


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


‘Buddy system’ recommended for some aseptic activities, e.g. Huber unloading


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


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

cleanroom sop slides

Health & Medicine

aseptic processing fda

aseptic manipulations

aseptic assembly

aseptic filling suite

grades of cleanrooms

sterile equipment

sterilised drug

substandard behaviour