Professional Documents
Culture Documents
Aide Memoire On Utilities
Aide Memoire On Utilities
PI 009-3
25 September 2007
AIDE-MEMOIRE
INSPECTION OF UTILITIES
Editor:
PIC/S Secretariat
e-mail:
web site:
info@picscheme.org
http://www.picscheme.org
PI 009-3
25 September 2007
TABLE OF CONTENTS
Page
1.
Document History............................................................................................ 1
2.
Introduction ..................................................................................................... 1
3.
Purpose........................................................................................................... 1
4.
Scope.............................................................................................................. 1
5.
6.
1.
DOCUMENT HISTORY
Adoption by Committee
24 April 2002
1 July 2002
2.
INTRODUCTION
2.1
2.2
PIC/S has paid due attention to these systems for the manufacture of medicinal
products. In 2001, the annual PIC/S Seminar was devoted to the inspection of
utilities used by the manufacturer of pharmaceuticals (Prague, Czech Republic).
3.
PURPOSE
3.1
The purpose of this document is to provide guidance for GMP inspectors to use
for training purposes and in preparation for inspections.
3.2
The Aide-Memoire is the direct result of the 2001 PIC/S Seminar and was
drafted with the aim of facilitating the effective planning and conduct of GMP
inspections of utilities. The Aide-Memoire should enable the inspector to make
both an optimal use of the inspection time and an optimal evaluation of GMP
compliance.
4.
SCOPE
4.1
4.2
At the time of issue, this document reflected the current state of the art. It is not
intended to be a barrier to technical innovation or the pursuit of excellence. The
advice in this Aide-Memoire is not mandatory for industry. However, industry
should consider PIC/S recommendations and aide-memoires as appropriate.
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25 September 2007
5.
Area of operation/Items
HVAC for medicinal
products
1.
1.1
AIDE MEMOIRE
Notes
Need for separate
systems
Level of filtration (Filter
specifications)
Crucial questions
Supporting documents
1.2
Qualification of HVAC
1
systems
DQ, IQ, OQ a PQ
Average speed and
uniformity of airflow
Pressure differentials
Air changes
Integrity and tightness
of terminal installed
final filters
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25 September 2007
1.
Area of operation/Items
HVAC for medicinal
products
Notes
Number of particles
Recovery tests
Air temperature
Smoke tests
Requalification
(parameters for
requalification)
Crucial questions
Supporting documents
Committee for
Standardisation CEN,
Brussels (May 1999).
EN ISO 14644-2:
Clean rooms and
associated controlled
environments
Part 2: Specifications for
testing and monitoring to
prove continued
compliance with ISO
14644-1.
International Organisation
for Standardisation ISO,
Geneva and European
Committee for
Standardisation
(September 2000).
Show me your
deviations and change
control reports for
HVAC?
Change control
1.3
Monitoring of HVAC
systems
Environmental
monitoring (particles,
micro organ, humidity,
temperature)
Guide 4.15,
Annex 1 4-6,
Chemical residue
testing
1.5
Maintenance and
calibration of HVAC
systems
Maintenance program
Calibration program
Guide 3.41
SOPs
Records
Breakdown/Emergency
including challenges of
alarm systems
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25 September 2007
1.
1.6
Area of operation/Items
HVAC for medicinal
products
Documentation for HVAC
systems
Notes
Crucial questions
Technical data
Supporting documents
Guide 4.1, 4.26, 4.28,
4.29
SOP, recordsmaintenance,
calibration, validation,
monitoring, deviations,
change control
Validation protocols
and reports
Asbuilt engine
drawing
2.
2.1
Area of operation/Items
Pharmaceutical water
system
Key design parameters
Notes
Crucial questions
WFI
Weld quality
Passivation of
pipeworks
Supporting documents
Guide 3.10
FDA- Guide to Inspection
of Highly Purified Water
Systems
Annex 1-35
Vent filters
Annex 15 9,10
All kinds of
pharmaceutical water
Suitability of
construction materials
Slope of pipeworks
Recirculation at
adequate velocity and
temperature
Sanitary joints
Capacity x daily
demand
Valves
Draining /flushing
Samplings ports
2.2
Qualification
All qualification
completed?
What do signatures
mean?
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25 September 2007
2.
2.3
Area of operation/Items
Pharmaceutical water
system
Walk round inspection
Is water for injection
produced and used
according to
requirements of Note for
Guidance on Quality of
Water for Pharmaceutical
Purposes and Ph Eur?
Confront differences
between drawings and
reality, unplanned
maintenance and change
control.
Follow the system from
pre-treatment to user
points: in each part,
check leaks, sampling
points (access), who
does what, start up and
shutdown, cleaning /
disinfection / sterilisation),
quantities produced.
Notes
Crucial questions
Supporting documents
feed water
pre- treatment
distillation sight glass
storage tank-filter,
break valve, Q-spray
ball
Show me records of
alarms that have
occurred!
Annex 1 35
distribution loop-temp,
conductivity, TOC
heat exchangerintegrity
user points-number,
design and location
control system-alarms,
record of action, set
points and
demonstration
monitoring print outs
DISINFECTION? HOT
WATER? STEAM?
CONTINUOUS
RECIRCULATION?
2.4
PROGRAMME,
INCLUDING TEST
METHODS
SCHEDULE?
SAMPLING, WHO
TAKES SAMPLES,
TRAINING, VOLUME
SAMPLED, HANDLING
OF SAMPLES
Monitoring
Temperature
Speed
Guide 4.15
Annex 1 44
Vent filters
DI column regeneration
pH
UV light (PW)
Conductivity
Leakage
TOC
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25 September 2007
2.
2.6
Area of operation/Items
Pharmaceutical water
system
Maintenance and
calibration of water
systems
Notes
Crucial questions
Maintenance program
Calibration programme
Supporting documents
Guide 3.41
SOPs
Records
Breakdown/Emergency
including challenges of
alarm systems
2.7
Documentation
Drawing up to date
(SMF?)
Guide 5.38
Guide 4.1, 4.26, 4.28,
4.29
OOS evaluation
Deviation reports
Change control reports
Operation of the
system
Cleaning / sanitation /
sterilisation
Logbook monitoring
parameters- see 1.6,
incidents, filter
changes, shut down
periods,
cleaning/sanitation,
maintenance
3.
3.1
Area of operation/Items
Pharmaceutical steam
systems
Key design parameters
Notes
Crucial questions
Supporting documents
entrainment prevention
Guide 3.10
Annex 15 9-10
non condensable
gases reduction
slope of pipeworks
no dead legs
3.2
Qualification
3.3
All qualification
completed?
FEED WATER-TYPE,
LEVEL,
TEMPERATURE
Sample pointslocation, number,
access
System for removal of
air loop
Confront differences
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Page 6 of 9
25 September 2007
3.
Area of operation/Items
Pharmaceutical steam
systems
between drawings and
reality, unplanned
maintenance and change
control.
Notes
Crucial questions
Supporting documents
Monitoring
control of entrainment
Guide 4.15
limits
sampling
OOS results
Trending results
3.6
Maintenance and
calibration of the system
Maintenance program
Calibration programme
SOPs
Guide 3.41
Records
Breakdown/Emergency
including challenges of
alarm systems
3.7
Documentation
Drawing up to date
(SMF?)
OOS evaluation
Deviation reports
Change control reports
Operation of the
system
Cleaning / sanitation /
sterilisation
Logbook - monitoring
parameters - see 1.6,
incidents, filter
changes, shut down
periods, cleaning /
sanitation,
maintenance
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25 September 2007
4.
4.1.
Area of operation/Items
Pharmaceutical gases
Key design criteria
(compressed air)
Notes
Crucial questions
air inlet-source,
contamination risks
Supporting documents
Guide 3.10.
Annex 15- 9-10
Qualification
4.4.
4.5.
Leakage tests
Guide 4.15
Quality control
4.7.
Maintenance and
calibration of the system
Maintenance program
Calibration programme
Guide 3.41
SOPs
Records
Breakdown/Emergency
including challenges of
alarm systems
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25 September 2007
4.
4.8
Area of operation/Items
Pharmaceutical gases
Documentation
Notes
Crucial questions
Supporting documents
6.
REVISION HISTORY
Date
Version Number
1 July 2004
PI 009-2
25 September 2007
PI 009-3
PI 009-3
Page 9 of 9
25 September 2007