Preparation of a Monitoring Plan for

Surface, Air and Personnel

European GMP Conference 2021 -Cleanrooms

Stephan Löw (B. Eng.) CSL Behring GmbH

Webex-Seminar
Agenda
 Contamination Control Stragtey
 Project phases during establishing a monitoringplan
• Planning phases
• Qualification phases
• Routine monitoring
 Personal monitoring
• Evaluation of monitoring points for routine monitoring
• Actions for recurring limit exceeding
First of all- define your Contamination Control Strategy

 Contamination Control Strategy (CCS)

• CCS as a prospective & proactive strategy

i. Appropriate design of facility & process

ii. Well designed procedures
iii. Apply monitoring concept to approve i. and ii.

• Environmental monitoring is part of the empirical evidence to approve

your contamination control strategy

Quelle: WDR 3
Measures for the establishment of monitoring plans

 Projekt phases

• Evaluation phase
• Risk assessment
• Planning phase
• Qualification phase
• Routine monitoring

Quelle: WDR 4
Evaluation phase
 Which clean room classes do we have or shall be reached ?

• Separation of clean room zones in regard to clean room class

e.g. class A-E, ISO 5-9

• Requirements out of guidelines in regard to limits

Pharmacopeias, ISO-Quidelines, Aseptic-Guide, EG-GMP-Annex 1 ect.

 Which room conditions in regard to installations are given?

• Establishment of installation plans

Room conditions, Aggregates / equipments

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Evaluation phase
 Which material flow into the clean room is given ?

• Evaluation of material routes

Material locks (Steam sterilizer, H2O2-lock, Airlocks ect.)
Condition of the materials (sterile, multiple-packaged, disinfectable ect.)

 Which personal flow into the clean room is given ?

• Evaluation of requirements in regard of numer of personal

Operators, Technicans, Service-personal

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Evaluation phase
 Visualisation of material flow in a clean room

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Evaluation phase
 Visualisation of personal flow in a clean room

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Risk assessment
 Evaluation of monitoring points during On-site-visit with QO

• Evaluation of the separation of clean room zones in regard to clean room

classes
e.g. class A-E, ISO 5-9

• Evaluation of critical work steps (workflow analysis)

e.g. critical intervention of operators into cleanroom class A

• Evaluation of frequently touched surfaces / plant components

e.g. Touchscreens, Tools, Door handles, Handrail of stairways, generall
surfaces

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Risk assessment
 Evaluation of monitoring points during On-site-visit with QO

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Risk assessment
 Evaluation of monitoring points during On-site-visit with QO

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Risk assessment
 Requirements in regard to staff / personal
• Evaluation in a risk assessment in regard to GMP-Risk
Use of men / women
- different microbiological spectrum on the body
- different behaviour in regard to sweating
- different gross / fine motor skills
Requirements in regrad to body size (Ergonomics study)
- thereby drawing conclusions about physical stress and risk areas on
the cleanroom garments
Requirements in regard to Health status
Training requirements / Training status

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Risk assessment
 Evaluation of sampling points

• Evaluation in a risk assessment in regard to GMP-Risk

Risk of contamination for the product
- Risik by additional interventions into critical zones for environmental
monitoring
Introduction of nutrient media into clean room areas
- Transfer procedure (prevention of carryover of microrganisms)
- Danger of nutrient media deposits (propagated growth)
Sequence of operation steps

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Planning phase
 Qualification plan

• Planning of the qualification efford

Qualification at rest
Qualification in operation

• Definition of limits
Physical (Particles / ft³ /m³)
Active microbiological sampling (Cfu / m³ or Cfu / x cm²)
Active microbiological sampling (Cfu / x cm² per x hours)

• Number of sampling points

As little as possible, as much as necessary

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Qualification phase
 Execution of Qualification
• Definition of qualification efforts by rational

• Execution of the qualifcation activities

Sampling at rest (e.g. three days morning / evening)
Sampling in operation(e.g. three days morning / evening)

• Evaluation of results
Evaluation of detected particles / ft³ and m³
Evaluation of detected microorganisms / x cm² / h incl. species

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Qualification phase
 Evaluation of sampling results

• Evaluation of qualification activities

Sampling at rest
Sampling in operation

• Statistical evaluation of results

Sampling at rest
Sampling in operation

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Qualification phase
 Definition of sampling points for routine monitoring

• Surface sampling
Critical surfaces in general (e.g. class A)
Sampling points with statistical anomalies
Sampling points with limit excursions

• Air sampling
Critical areas in general (e.g. class A)
Sampling points with statistical anomalies
Sampling points with limit excursions

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Review Risk assessment
 Evaluated sampling points out of the risk assessment

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Routine monitoring surface and air
 Choosen sampling points out of the risk assessment

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Routine monitoring surface and air
 Choosen sampling points out of the risk assessment

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Routine monitoring surface and air
 Definition of sampling frequency for routine monitoring
• Sampling frequency for surface and air monitoring
Critical areas (e.g. class A)
- Active / passive air sampling several times a day / surfaces min. on a daily
basis
Critical areas (e.g. class B) after finishing of a working sequence
- Active / passive air sampling daily / surfaces min. on a daily basis
Controlled areas (e.g. surroung of isolators) weekly
Controlled areas (e.g. class D) monthly

• Which requirements shall be taken into consideration?

Passive air sampling outside class a becomes more and more significance

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Routine monitoring surface and air
 Definition of sampling frequency for routine monitoring of USP <1116>

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Routine monitoring surface and air
 Definition of sampling frequency for routine monitoring of USP <1116>

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Routine monitoring surface and air
 Passive air sampling becomes more and more significance
• Overview of recomended limits out of Eu-GMP-Annex

• Übersicht der empfohlenen Auftrittshäufigkeit aus der USP

Passive air sampling also required outside class A

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Routine monitoring surface and air
 Passive air sampling becomes more and more significance
• Suggested Initial Contamination Recovery Rates in Aseptic
Environments out of USP <1116>

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Personal monitoring
 Evaluation of sampling points for routine monitoring
• Which sampling points are representative?
Risk assessment of operator actions in regard to
- Working activities (physical körperliche stress)
- Product handling

Verification in a study (e.g. with fluorescent dye in desinfectant)

Determination of the most frequently touched positions on the
body/cleanroom garments
Qualification of operators in a gowning qualification with several sampling
points

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Personal monitoring
 Evaluation of sampling points for routine monitoring

• Surface sampling for operators

In critical areas (e.g. class A / B) both gloves and clean room garments
- After critical interventions
- At end of work / end of working shift
In controlled areas (e.g. class C surrounding for isolators) min. one glove and clean
room garments
External personnel (Technicans and Service-people) min. one glove

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Personal monitoring
 Evaluation of sampling points for routine monitoring
• Which sampling points are representative?

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Personal monitoring
 Evaluation of sampling points for routine monitoring
• Which sampling points are representative?

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Personal monitoring

 Evaluation of sampling points for routine monitoring

• Sampling frequency
Critical areas (e.g. class A) after finishing of the process step
Critical areas (e.g. class B) after finishing of the process sequence
Controlled areas (e.g. Isolatorin class C) batchwise / daily
Technicans and Service-people when they leave the cleanroom

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Personal monitoring
 Measures when limit exceedings apear multiple times

• Limit exceeding on glove-monitoring

Training of Hand -/ Glovedisinfection by standardized procedure
Review of disinfection sucssess with with fluorescent dye in desinfectant

• Limit exceeding on clean room garments-monitoring

Training of operator in regard to (clean room-) behaviour
Review of working steps and supervision of the operator during work steps
Requalification of gowning procedure

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 Thanks for your attention !!

Questions ???

Stephan Löw
CSL Behring GmbH
Emil-von-Behring-Strasse 76; 35041 Marburg
Tel. +49-(0)6421-39 2287
Email: stephan.loew@cslbehring.com

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