Annex 1 DRAFT

- Access and Transfer into Clean Areas -

Dr. Rainer Gnibl

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Rainer Gnibl, PhD
Government of Upper Bavaria
Department 53.2 Pharmacy
Maximilianstr. 39
80534 Munich
Germany

Phone +49 89 2176-2877

Fax +49 89 2176-402877
Mail [email protected]

This presentation states the personal view of the speaker and is therefore not
inevitably representative for the regulatory opinion. Rights and duties of third parties
cannot be derived from this presentation.

© Rainer Gnibl 2021

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Overview
1. Airlocks
2. Clothing
3. Personnel
4. Materials

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Overview
1. Airlocks
2. Clothing
3. Personnel
4. Materials

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1. Airlocks
 Physical separation … no direct connection/ air exchange between different grades
 Seperated airlocks required for
 Personnel
 Equipment & materials
If not practicable ► time-based separation
 Separate airlocks for entry & leaving grade-B „desirable“
 If not practicable: Time-based separation
 Personnel- & material flow between different grades
 Personnel
 Airlock-cascade: Clean Not Classified - CNC ► Grade-D ► grade-C ► grade-B
 Active filtered air-supply
 Hand washing facility only in 1-stage of change-room
 Material
 Airlock or pass-through hatch: No full cascade required

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1. Airlocks

 Active filtered air-supply

 Classification & qualification required

 Final airlock-stage: at-rest condition of adjacent higher grade room
 Viable & non-viable
 Differential pressure
 Ev. pressurization of airlocks
 Pos. pressure to keep hazardous material in higher grade
 Neg. pressure to protect higher grade against environment
 Ev. preesure-trap

 Interlocking system to grade-A/B

 Ev. time delay for „interlocked doors“
 Min. visual and/or audible alarm to grade-C & -D
 2-chamber-airlock allowed
 Covers 2 grades (e.g. direct from grade-D ► grade-B)

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1. Airlocks

 Miscellaneous
 Individual gowning-steps separated from each other in place
 Airlock separated in 2 areas by „sit-over bank“ non-clean - clean
 Two garment-cupboards/rags non-clean - clean
 Cupboards airrated or UV-lighted … desirable
 Pictogram gowing-procedure & mirror for self-check

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Overview
1. Airlocks
2. Clothing
3. Personnel
4. Materials

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2. Clothing
Clean room clothing minimum requirements
XXX
acc. Annex 1 DRAFT

GradeXXX
D: Hair, beards and moustaches should be covered. A general protective suit and appropriately
 XXX
disinfected shoes or overshoes should be worn. Appropriate measures should be taken to avoid
any ingress of contaminants from outside the clean area.
 XXX
Grade C: Hair, beards and moustaches should be covered. A single or two-piece trouser suit gathered at the
wrists and with high neck and appropriately disinfected shoes or overshoes should be worn. They
should minimize the shedding of fibres and particulate matter.
Grade C/D: Gloves should be worn when performing activities considered to be a contamination risk as
defined by the CCS.
Grade A/B: Dedicated garments to be worn under a sterilized suit. Sterile headgear should enclose all hair
(including facial hair) and where separate from the rest of the gown, it should be tucked into the
neck of the sterile suit. A sterile face mask and sterile eye coverings (e.g. goggles) should be worn
to cover and enclose all facial skin and prevent the shedding of droplets and particulates.
Appropriate sterilized, non-powdered, rubber or plastic gloves and sterilized footwear (such as
overboots) should be worn. Trouser-legs should be tucked inside the footwear and garment
sleeves into the gloves. The protective clothing should minimize shedding of fibres or particulate
matter and retain particulates shed by the body. Garments should be packed and folded in such a
way as to allow operators to gown without contacting the outer surface of the garment.

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2. Clothing

 SOP - Gowning Procedure

 Which type/quality in which area
 Gowning (entry) & de-gowing (leving) procedure
 Change-frequency
 Washing & sterilization
 Grade-B: Cycle-no., hold-time & traceability (acc. qualification study)
 Exchange frequency for re-usable garments & eye coverings
 Visual check of garments & eye coverings … for cleanliness & integrity
 … prior each gowning, entry & exit
 … post washing & pre sterilization
 … for packaging-integrity & sterilization-status
 ev. garment testing for non-visual damages … acc. qualification
 Washing
 Dedicated laundry facilities

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2. Clothing

 Qualified laundry-process
 Visual check for damage after washing & before packing
 Quality
 No shedding due to excessive operator moving … when cold or sweating
 Clothing for operator-protection should not compromise product-
protection
 „No exteral clothing in airlock to grade-C & -B

 Long „facility-suits“ & „socks“ before entry of airlock to grade-C & -B

 Grade-A/B: „Max. duration of each garment use“ defined
 Incl. eye-covering & mask
 Regular glove-disinfection … during operations

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2. Clothing

Required: „Garment qualification program“

 Evaluates & determins overall „garment management process“

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Overview
1. Airlocks
2. Clothing
3. Personnel
4. Materials

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3. Personnel
General
 Min. amount present in cleanrooms
 Max.-number determined during qualification & validation … esp. for
aseptic processing
 Also definition of max.-no. in airlocks required
 Regular training
 Grade-A/-B operators:
 Basics in microbiology, hygiene, contamination control
 Aseptic gowning
 Aseptic practices

 Gowning (re-)qualification
 Unqualified staff no acces to grade-A/-B in-operation
 Procedure for exceptional cases (SOP)
 Supervision by qualified staff
 Access assessed & recorded

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3. Personnel
- (Re-)Qualification -

(Re-)Qualification
 Grade-A/-B operators: initial … prior unsupervised activities
 „Successful aseptic process simulation test“ (APS) & gowning-
qualification
 Grade-A/B operators: min. annual re-qualification
 Visual assessment
 Microbiological assessment
 Sample-locations s.a. hands, arms, chest & forehead
 Limits acc. chap. 9.30

 „Ongoing continuous monitoring programm“

 Incl. “some consideration of periodic monitoring under supervision of the
quality unit”
 Microbial monitoring immediate post „critical operations“ or
exiting grade-A/B
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3. Personnel
- Dis-qualification -

Dis-qualification
 In case of
 „Adverse trends“ from monitoring
 Failed re-qualification
 Failed APS
 Re-entry for operations after
 Retraining
 Re-qualification
 Succesfull APS … for grade-A/-B operators

 But also because of health status

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3. Personnel

Entry
 Procedure for hand-washing
 Not allowed
 Wristwatches, make-up, jewellery, personal items (e.g. mobile phones)
& non-essential items
 Electronic devices for production acceptable
 Designed to permit cleaning & disinfection
 Procedure required
 Human-/animal tissues or microbiol.-cultures … other than product
 Defined entry procedure
 Effective decontamination procedure before entry

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Overview
1. Airlocks
2. Clothing
3. Personnel
4. Materials

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4. Materials

 Goods- (materials, equipment) seperated from personnel-

transfer „… wherever possible“
 Materials & equipment for grade-A/-B ► Approved-list
 Developed during validation of transfer process
 Unapproved items: EXCEPTION & pre-approval
 Risk assessment
 Risk mitigating measures applied & recorded (acc. CCS)
 “Specific disinfection and monitoring programme” approved by QA
 Protection of grade-A-materials transiting grade-B zone

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4. Materials

 Materials & equipment for grade-D/-C

 “Cleaning and disinfection commensurate with the risk and in line with
the CCS”
 Conveyor belt grade-A to –B

 Aseptic process
 Uni-directional transfer … into grade-A/B
 Sterilization on transfer into grade-A/-B through double-ended sterilizers
… if possible
 e.g. Double-door autoclave or depyrogenation oven/tunnel sealed into wall
 If not possible: “Procedure with same objective should be validated and
implemented”
 e.g. effective transfer disinfection, rapid transfer systems for isolators, bacteria-retentive
filtration of gases or liquids

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4. Materials

 RABS- & isolators

 Entry via rapid transfer technologies or transfer-isolators „… preferably“

 Sterilization
 Possibly pre-sterilization … of material, equipment & components
 Multi-layer-wrapping (one layer per grade) … if pre-sterilization not possible
 incl. Disinfection
 Demonstration of transfer-effectiveness & disinfection conc. grade-A/B-contamination
 Filtration of gases & liquids
 Uni-directional transfer … in grade-A/B
 e.g. Double-door autoclave, depyrogenation oven/tunnel, airlocks, pass-through
hatches)

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4. Materials

 Post-sterilization: Storage under grade-A conditions

 Exception: „Multiple sterile packaging layers“
 Storage & packaging assures sterility
 Hold-Time studies … for sterile-packaging/ -container of materials, equipment &
components
 Max. hold-time before & expiry after sterilzation
 Inspection of each sterile item prior to use

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 That´s it from the
dark side !!!
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