Qualification and Routine

Environmental Monitoring of
Critical Utility Systems
21th Annual Validation Week
Day Three, Session 10:30am 12:00 pm
Qualification and Routine
Environmental Monitoring of Critical
Utility Systems

1
CONTACT INFORMATION
for Course Leader

Ed Winnett/VP Operations
Validation Technologies, Inc.
San Diego, CA
Office: 800-930-9222
Fax: 858-676-3677
Email: edw@validation.org
Website: http://www.validation.org

2
PRESENTATION OVERVIEW
SUPPORT DOCUMENTATION
CONSTRUCTION QUALIFCATION
QUALIFICATION OF CRITICAL SYSTEMS
ESTABLISHING A ROUTINE
ENVIRONMENTAL PROGRAM
TRENDING AND DATA SUMMARY
PROBLEM AREAS - UTILITY SYSTEMS
REVALIDATION

3
 Part 1
Documents to Support
Equipment Qualification
DQ
PQ IQ

OQ
PV

IQ OQ
IQ/OQ Documentation
PQ VC

CQ

4
 Support Documents

The User Requirements Specification (URS)

Design Specifications
Functional Specifications
Purchases Requisitions
Turn-Over- Packages
Vendor Manuals
P&IDs
Manuals
Commissioning
FAT/SAT
Change Management
5
Part 2
Critical Utility Project
Strategy

Plan the Work and Work the Plan

6
PROGRAMS REQUIRED FOR FACILITY & CRITICAL
UTILITIES QUALIFICATIONS

PROJECT DESIGN SPECIFICATION

VALIDATION MASTER PLAN
PROJECT SCHEDULE
CONSTRUCTION QUALIFICATION PACKAGES
INSTALLATION QUALIFICATION PROTOCOLS
FACILITY STARTUP/COMMISSIONING
STANDARD OPERATING PROCEDURES
CALIBRATION PROGRAM
OPERATIONAL QUALIFICATION PROTOCOLS
ANALYTICAL METHODS VALIDATED
PERFORMANCE QUALIFICATION

7
PROJECT SCHEDULE
DEFINED CRITICAL PATHS
CONSTRUCTION ACTIVITIES
COLLECTION OF CONSTURCTION QUALIFCATION CQ
DATA
DEVELOPMENT OF PROTOCOL FORMAT
WRITE IQ & OQ PROTOCOLS
EQUIPMENT INSTALLATION ACTIVITIES
EXECUTION OF IQ PROTOCOLS
COMMISSION OF SYSTEM
EXECUTION OF OQ PROTOCOLS
ANALYTICAL METHODS VALIDATED
WRITE & EXECUTE PERFORMANCE QUALIFICATIONS

8
PROJECT SPECIFICATION

EQUIPMENT DATA SHEETS

SPARE PARTS LIST
VENDOR CERTIFICATION
FACTORY ACCEPTANCE TEST REPORT
MATERIALS OF CONSTRUCTION
ON SITE TESTS
CLEANING REQUIREMENTS
COMPONENTS SELECTION

9
VALIDATION MASTER PLAN

VALIDATION PROJECT ROAD MAP

FACILITY & PROCESS DESCRIPTION
VALIDATION PROGRAM
EQUIPMENT & UTILITY LIST
PROJECT RESPONSIBILITIES
VALIDATION PROJECT DESCRIPTION

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Part 3
Commissioning and
Construction
Program

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Good Engineering Practice (GEP)

Established Engineering methods and

standards that are applied throughout the
project lifecycle to deliver appropriate
cost-effective solutions

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Good Engineering Practice (GEP)
GEP project scope
Documentation
Organization and Communication
Requirements Phase
Design Phase
Construction Phase
Project Controls
Commissioning and Qualification
Project Closeout and Turnover

13
Commissioning Plan
Commissioning Plan should contain the following
deliverables: (Direct Impact Systems)
Commissioning Plan
Commissioning Schedule
Commissioning Budget
Overall Test Plan
Factory Acceptance Test/Report
Site Acceptance Test/Report
Inspection Plan/Report
Functional Test/Report
System Test Summary Reports
Commissioning Summary Reports

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Scope of the Commissioning and
Qualification Guide
Engineering Change Management
Impact Assessment
QA Change Control

Design
Development
Enhanced Design PQ
Process
commissioning
Review Validation

IQ & OQ

Design for Impact

Scope of Guide
GEP Contribution
Of Interest to the Regulatory
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System Impact and Component
Criticality
Indirect Impact or No Impact system are
comprised of non-critical components only
Direct Impact system have both critical and
non-critical components. (Components
deemed non-critical may be managed within
Good Engineering Practices (GEP) alone)
Design for Impact reduces the scope of the
system and components to Qualification
Practices allowing appropriate focus on the
components presenting a risk to product quality
Should an Indirect Impact or No Impact system
incorporate one or more critical components,
either the system has been mis-classified or
the component was wrongly assessed.
16
 Impact Assessment

Direct Impact Systems are expected to

have an impact on product quality

Indirect Impact systems are not expect to

have an impact on product.

Both types of systems will require

commissioning; however, the Direct Impact
system will be subject to qualification practices
to meet additional regulatory requirements of
the FDA and other regulatory authorities
System Impact Assessment Form Direct HVAC
System Template Part 1.doc 17
System Impact Assessment
Process Overview
Identify System

Develop System
Boundaries

Yes
Does the system have a direct
impact on product quality

No
Yes

Is the system linked to Indirect Impact Direct Impact

Direct Impact System
system system

No
Develop Supporting
No Impact System
Rationale
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 Qualification Risk Based
Assessment

Direct Impact Systems are expected to

have an impact on product quality
therefore the level of validation or
qualification must be determine by using
Qualification Risk Based Asessment
Qualification Level Analysis Form Direct
HVAC Template Part 2.doc
Qualification Level Analysis Results Form
Direct HVAC Template Part 3.doc

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Component Criticality
Assessment Process
The components within Direct Impact,
Indirect Impact and in some cases No
Impact systems should be assessed for
criticality.
Must have updated Piping and Instrument
Drawings (P&IDs)

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 Component Criticality
Assessment Process
Applicability of any of the following
criteria to a given component will
provide an indication that component
is critical:
1. The component is used to demonstrate compliance
with the registered process.
2. The normal operation or control of the component
has a direct effect on the product quality.
3. Failure or alarm of the component will have direct
effect on the product quality.

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 Component Criticality Assessment
Process (Continued)
Applicability of any of the following criteria to
a given component will provide an indication
that component is critical:
4. Information from the component is recorded as part of
the batch record, lot release data or other GXP related
documentation.
5. The component has direct contact with product or
product components
6. The component controls critical process elements that
may affect product quality, without independent
verification of the control system performance.
7. The component is used to create or preserve a critical
status of a system.

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System Impact and Component
Criticality
Indirect Impact or No Impact system are comprised
of non-critical components only
Direct Impact system have both critical and non-
critical components. (Components deemed non-
critical may be managed within Good Engineering
Practices (GEP) alone)
Design for Impact reduces the scope of the system
and components to Qualification Practices allowing
appropriate focus on the components presenting a
risk to product quality
Should an Indirect Impact or No Impact system
incorporate one or more critical components, either
the system has been misclassified or the component
was wrongly assessed.
Critical Component Analysis Form Direct HVAC
Template 4.doc 23
 Part 4
Qualification of
Critical Utilities
Systems

Design, Construct, Commission then

Qualify

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Critical Utility Qualification

Construction Qualification
During construction, document procurement and
verification of construction activities, are critical
components of a successful Installation Qualification
(IQ). Must have Engineering Turnover Packages (ETOP)
Design/Functional Specifications
Test Reports
Material Certifications
Purchase Specification & Orders
State and Local Code Compliance
ASME, ANSI and other Certifications
Pipe Specifications
Cleaning and Passivation Reports
Stainless Steel Weld Documentation
Vendor/Manufacturer's Submittals
Manufacturer's Mechanical Specifications
Instrumentation Specifications
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 Commissioning Phase: Leverage
Support Document
FAT/SAT can be leverage to support IQs and
OQs
Some of the test and information collected during
the commission phase can be used to support
I/OQ protocol execution
Most of the information contain in the FAT such
as material of construction can used to support
the IQ document.
Some of tests performed in the SAT are
duplicated during the execution of the OQ
therefore it only make sense to leverage of SAT
to support some of the tests in the OQ protocol
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Utility Qualifications

Basic checklist is used for IQ -

Defined Direct/In-Direct/Non-Impact System
Manufacturer information: contact info., specs,
P.O., manuals, etc.
Equipment description (make, model, serial
number, etc.)
Instrumentation
Spare Parts
Control Panels
Safety
PM
Calibration
Support Utilities 27
IQ : IS IT INSTALLED CORRECTLY?

Full description of equipment capabilities, design features and

company's specific intended use in manufacture.
Vendor, equipment ID, serial number, etc.
Location of installation
Process Equipment Listing
Drawings or Flow Diagrams
Operators Manual
Maintenance Procedures and Schedule; Cleaning Schedule
Calibration Procedure and Schedule
Spare Parts List
Configuration of Components, Drawings
Materials of construction,
Interface with other equipment (peripherals); Interface with utilities,
facility
Safety
Appropriate Environmental Conditions
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Critical Utility Qualification

Installation Qualification - is a documented plan

for the performance of inspections and the
collection of documentation to verify static
attributes of a system.
System Location
System Description
Major Components Identification Summary
Field Inspection Report- Comparison of Actual to
Specified
Instrumentation List
Spare Parts List
Documentation/Drawings List

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Utility Qualifications

Operational Qualification - Does the

equipment function as intended?
Challenge the process (equipment)
parameters under worst case testing. This
is where you determine the degree of
robustness with the equipment.
Objective, Scope, Description, etc.
Operational testing
Acceptance criteria
Deviations (Excursions, etc.)
Approvals 30
Critical Utility Qualification

Operational Qualification (OQ) - is a documented plan for the

performance of inspections and tests to verify specified
dynamic attributes of a system.
SOP Review
Calibration Review
Test of Alarms
Test of Controls
Test of Interlocks
Start Up/Shutdown Sequence Verifications
Normal Run Mode Verification - Monitoring Applicable
Indications:
Pressure
Temperature
Time
Resistivity/Conductivity
Flow
pH

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PERFORMANCE QUALIFICATION
PROTOCOL FOR CRITICAL UTILITIES
OBJECTIVE
IDENTIFICATION
SYSTEM PERFORMANCE DESCRIPTION
REFERENCES
RESPONSIBILITIES
PROCEDURE
ACCEPTANCE CRITERIA
PERFORMANCE QUALIFICATION TEST
COMMENTS
DEVIATION/EXCEPTIONAL CONDITION
ATTACHMENTS

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Utility Qualifications

Performance Qualification -
Objective, scope, description, equipment
testing, approvals, etc.
Documented verification that the equipment
operates the way it is purported to do. This
operation must be reliable and reproducible
within a specified, predetermined set of
parameters under nominal or normal
production conditions.

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Critical Utility Qualification

Performance Qualification (PQ) - is a documented

plan for the execution of tests to demonstrate the
effectiveness and reproducibility of a
system/process as a fully integrated functional
entity.
All installed critical instruments shall be calibrated prior to
execution of the protocol.
All test instruments used to execute the protocol shall be
calibrated and certified prior to use.
Test methods, analytical procedures and sampling
techniques, when not defined in a protocol, shall be
written and approved as SOPs.
The system can consistently meet its predetermined
acceptance criteria.
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Critical Utility Qualification

Performance Qualification (PQ) - Standard Testing

Intervals
Water For Injection Systems - 30 to 45 Days (30
- 40 days Standard @ Shut Down Recover Test)
Purified Water Systems - 30 Days
Clean Steam Systems - 30 Days
Gases/Clean Dry Air Systems - 7 to 14 Days or
three lots
HVAC System (Controlled Environment)- 1
Baseline (Before cleaning), 3 Static States, 3
Dynamic (20 -30 days)

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 Part 5
Validation of Purified
Water Systems

Purified Water is used in Aspect of GMP

Manufacturing Operations

36
Water Usage in
Pharmaceutical Production
Water Requirements
Potable - EPA
USP Purified
USP Water For Injection

37
Validation of Critical Water Systems

FDA Requirements: Phase 1

All water systems should have
documentation containing a system
description and accurate drawing.

The drawing needs to show all equipment in

the systems from water input to points of
use. It should also show all sampling points
and their designations.

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Validation of Critical Water Systems

FDA Requirements: Phase 1

After all the equipment and piping has
been verified as installed correctly and
working as specified, the initial phase of
the water system validation can begin.

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Validation of Critical Water Systems

FDA Requirements: Phase 1

During the initial phase the operational

parameters and cleaning/sanitation
procedures and frequencies will be
developed. Sampling should be daily after
each step in the purification process and at
each point of use for two to four weeks.

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Validation of Critical Water Systems

FDA Requirements: Phase 1

The sampling procedures for point of use should
reflect how they are taken, e.g. use of hose, and
time for flushing. At the end of the two (2) or
four (4) weeks the firm should have developed
its SOPs for operation and maintenance of the
water system.

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Validation of Critical Water Systems

FDA Requirements: Phase 2

The second phase of the water system
validation is to demonstrate that the system
will consistently produce the desired water
quality when operated in conformance with
SOPs.

42
Validation of Critical Water Systems

FDA Requirements: Phase 2

The sampling is performed as in the initial

phase and for the same period . At the end
of this phase the data should demonstrate
that the system will consistently produce the
desired quality of water.

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Validation of Critical Water Systems

FDA Requirements: Phase 3

The third phase of validation is designed to
demonstrate that when the water system is
operated, in accordance with the SOPs,
over a long period of time it will consistently
produce water of desired quality.

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Validation of Critical Water Systems

FDA Requirements: Phase 3

Any variations in quality of the feedwater,
that could affect the operation and ultimately
the water quality, will be noticed during this
phase of the validation.

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Validation of Critical Water Systems

FDA Requirements: Phase 3

Sampling is performed according to routine
procedures and frequencies.

For Water for Injection systems samples

should be taken daily from a minimum of
one point of use, with all points of use
tested weekly.

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Validation of Critical Water Systems

FDA Requirements: Phase 3

The validation of the water system is
completed when the firm has collected data
for a full year.

The FDA states that while the above

validation scheme is not the only way a
system can be validated, it contains the
necessary elements for validation of a water
system.

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Validation of Critical Water Systems

FDA Requirements: Phase 3

First, there must be data to support the
SOPs.

Second, there must be data demonstrating

that the SOPs are valid and that the system
is capable of consistently producing water
that meets the desired specifications.

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Validation of Critical Water Systems

FDA Requirements: Phase 3

Finally, there must be data to demonstrate
that seasonal variations in the feedwater do
not adversely affect the operation of the
system or the water quality. This last part of
the validation is the compilation of the data,
with any conclusions into the final report.

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Microbiological/Chemical Limits

Tests Potable Purified Water for Injection

Water Water
pH N/A 5.0 - 7.0 5.0 - 7.0
TOC N/A 500 ppb 500 ppb
Conductivity N/A 4.7 to 5.8 S/cm USP Specifications
Bacteria 500 cfu/mL 100 cfu/mL 10 cfu/100mL
Endotoxins N/A Not Specified 0.25 EU/mL
cfu = Colony Forming Units

50
Critical Utility Qualification

Performance Qualification (PQ) -

Standard Testing Intervals
Water For Injection Systems - 30 to 60 Days (20
- 40 days Standard @ Shut Down Recover Test)
Purified Water Systems - 30 Days

WFI PW Systems reduce sampling (3 Phases 1st

15 days, 2nd Phase 15 days, if results are acceptable
system be have interim release for GMP use)
3rd Phase 350 days (52 weeks or 1 yrs) systems
can be considered fully validated, historical data can
be trended to set true alert and action levels
51
ESTABLISHING ENVIRONMENTAL
MONITORING PROGRAM

When establishing a routine

environmental monitoring program, the
PQ study data should be the starting point
for determining the sampling sites and
testing frequencies.

52
HIGH PURITY WATER SYSTEMS
ENVIRONMENTAL MONITORING PROGRAM

Sample Site and Frequencies Determination

For Water for Injection systems samples
should be taken daily from all point of use.
For Purified Water systems samples should
be taken daily from a minimum of one point
of use, with all points of use tested within a
week.

53
HIGH PURITY WATER SYSTEMS
ENVIRONMENTAL MONITORING PROGRAM

Sample Site and Frequencies Determination

For Water for Injection systems samples
should be taken daily from all point of use.
For Purified Water systems samples should
be taken daily from a minimum of one point
of use, with all points of use tested within a
week.

54
HIGH PURITY WATER SYSTEMS
ENVIRONMENTAL MONITORING PROGRAM
Water Type Sample USP/EU USP/EU USP/EU/CP pH / Ion Coliform Steam Quality
Description Conductivity/ Testing Testing
TOC Tests Microbial/ Chemistry
Endotoxin (Heavy
Metals/Nitrates)
/ Appearance

WFI Beginning of , Daily read/ Weekly No Routine Sampling Not Required Monthly Quarterly
Post Circulation Weekly data (information
Pump and WFI collection Only)
still outlet

Point of Use Ports Weekly or Use Monthly Weekly Not Required Not Required Not Required
Data from inline
device

End of Loop Sample Daily Daily Weekly Not Required Not Required
Daily/Compare to
inline device

RO/DI RO Before EDI Weekly Weekly + No Routine Sampling Weekly Weekly Not Required
(DI System) Coliform
Supply Inlet to
WFI Still

DI Supply Inlet to Sample Weekly Weekly + No Routine Sampling Weekly Weekly Not Required
WFI Still Coliform

Potable Water Infeed water to Grab Sample Weekly + No Routine Sampling Weekly Weekly Not Required
RO/DI System2 Weekly Coliform

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 Part 5
Validation of Clean
System Systems

Clean Steam is used in certain aspects of

GMP Manufacturing Operations

56
Clean Steam Usage in
Pharmaceutical Production
Clean Steam Requirements
Steam-In-Place (SIP)
Sterilization Process
SIP Water For Injection

57
Validation of Critical Water Systems

FDA Requirements: Phase 1& 3

Same requirements as WFI system
Qualification.

58
Validation of Critical Water Systems

FDA Requirements: Phase 3

The validation of the clean steam system is
completed when the firm has collected data
for a full year.

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 CLEAN STEAM SYSTEM ENVIRONMENTAL
MONITORING PROGRAM

Sample Site and Frequencies Determination

For Clean Steam systems samples should be
before manufacturing process i.e. SIP,
autoclave, etc. and from a minimum of one point
of use, with all points of use tested weekly.

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CLEAN STEAM SPECIFICATIONS

Table: Microbiological/Chemical Limits

Tests Clean Steam

pH 5.0 - 7.0
TOC 500 ppb
Conductivity Current USP Specifications/
method
Bacteria 10 cfu/100mL (Information Only
None Routine)
Endotoxins 0.25 EU/mL
cfu = Colony Forming Units

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 CLEAN STEAM SYSTEM MONITORING
PROGRAM
Type Sample USP/EU USP/EU USP/EU/CP pH / Ion Coliform Steam Quality
Description Conductivity/ Testing Testing
TOC Tests Microbial/ Chemistry
Endotoxin (Heavy
Metals/Nitrates)
/ Appearance

Pure (Clean) Steam Generator Endotoxin Weekly Not Required Not Quarterly
Steam Weekly
Required
Weekly

Point of Use Grab Sample Endotoxin Monthly Not Required Not Required Not Required
Monthly Monthly
(SIP)

Autoclave Monthly Monthly Quarterly No Routine No Routine Annually

Point of Sampling Sampling

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 Part 5
Validation of
Compress Gas
Systems

There are many different types of gases

used in a GMP manufacturing operation

63
Compress Gases Usage in
Pharmaceutical Production
Compress Gases Requirements
Preserve the Status of Product
Drying after Cleaning
Assist Cell Growth
Instrument Actuation
Move Fluid

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Compress Gases Usage in
Pharmaceutical Production
Types Of Gases
Clean Dry Air
Nitrogen
Carbon Dioxide
Helium
Oxygen
Argon

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COMPRESSED GAS MAJOR COMPONENTS

Cylinders
Dryer
Manifold
Automatic/Manual Switchover System
Valves
Pressure Gauges
Filters
Control System (Low Gases, Low Oxygen)
Distribution System (SS or Type L copper)

66
COMPRESS GAS SYSTEMS ENVIRONMENTAL
MONITORING PROGRAM

Sample Site and Frequencies Determination

For compress gas systems samples should
be taken daily from all point of use for one
week.

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COMPRESS GAS SPECIFICATIONS

Table: Microbiological/Chemical Limits

Tests Compress Gas

Dew Point < -10 oC

Hydrocarbon as Oil Mist < 1 ppm
Gas Content Current USP
Specifications/
method for Purity
Bacteria < 0.1 CFU/ft3
Non-Viable Particulate: Room Classification
cfu = Colony Forming Units

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COMPRESS GAS MONITORING PROGRAM

Sample Dew Point Hydrocarbon USP/EU Bacteria Non-Viable

Location as Oil Mist Particulate
Type Gas
Content

Source Monthly Quarterly Monthly Monthly

Annually
Clean
Compressed
Point of Use Grab Sample Not Required Not Required Weekly (day of Weekly (day of
Air
Monthly filling process) filling process)

Source Monthly With each new Monthly Monthly

lot
Annually
Carbon Point of Use Grab Sample Not Required Not Required Weekly Weekly
Dioxide (CO2) Monthly

Source Monthly With each new Monthly Monthly

lot or
Annually Quarterly
Nitrogen
Point of Use Grab Sample Not Required Not Required Weekly Weekly
Monthly

69
 Part 6
Validation of HVAC
Systems

HVAC is used in Aspect of GMP

Manufacturing Operations

70
Clean Room Standards
This ISO committee will produce 10 new standards
documents that relate to cleanrooms or clean
zones (described below). The first two standards
have been published: ISO 14644-1 and -2.
The first document, ISO 14644-1, Cleanrooms
and associated controlled environments Part 1:
Classification of airborne particulates has been
released as a final document.
The second document, ISO 14644-2, Cleanrooms
and associated controlled environments Part 2:
Testing and monitoring to prove continued
compliance with ISO 14644-1; has been released
as a final document.

71
 Clean Room Standards
The cleanliness classification levels defined by FS209E
and ISO 14644-1 are approximately equal, except the new
ISO standard uses new class designations, a metric
measure of air volume and adds three additional classes
- two cleaner than Class 10 and one beyond than Class
100,000.

The second new ISO standard, ISO 14644-2, gives

requirements for monitoring a cleanroom or clean zone
to provide evidence of its continued compliance with
ISO 14644-1.

72
Clean Room Certification
Clean Room Certification Testing
Differential Air Flow
Humidity/Temperature
Supply Air Volume/Room Air Change Rate
Room Differential Pressures
DOP Test of HEPA Filters
Room Non-Viable Particulate Counts
Light Levels
Noise Levels
Recovery Time
Unidirectional and Parallelism
Enclosure Induction

73
Monitoring Program

Controls/Alarms reports verification

and review (procedure)
Weekly reports
Alert vs Action Limits
Failure investigations
Laboratory testing viable and non-
viable counts
Analysis of Trends (Quarterly)
Alert Limits
Refer to ISO-14644-2 and 14644-3 for
frequency guidelines and test
equipment recommendations

74
HVAC SYSTEMS ENVIRONMENTAL
MONITORING PROGRAM

Sample Site and Frequencies Determination

Would the act of sampling at a given site disturb the
environment sufficiently to cause erroneous data or
possibly cause the product to be contaminated?
At which site would the potential of microbial
contamination most likely affect product quality
adversely?
During the PQ study which sites were highest in
microbial contaminates.
What sites would be the most difficult to clean?
Should site selection involve statistical design or
should it be based on a grid profile?
How often is a particular area or process used?

75
 Physical, Microbiological Testing Parameters

TABLE 1- Air Classification

a- All classifications based on data measured in the vicinity of exposed materials/articles during periods of
activity.
b- ISO 14644-1 designations provide uniform particle concentration values for cleanrooms in multiple
industries. An ISO 5 particle concentration is equal to Class 100 and approximately equals EU Grade A.
c- Values represent recommended levels of environmental quality. You may find it appropriate to establish
alternate microbiological action levels due to the nature of the operation or method of analysis.
d- The additional use of settling plates is optional.
e- Samples from Class 100 (ISO 5) environments should normally yield no microbiological contaminants.

76
SURFACE MONITORING
Table 2: USPs 1116 microbial levels for Surface Monitoring
Classifications Zone Surface Personnel Frequency of
CFU/ 2 in2 CFU/ 2 in2 P Montoring
Critical Area M 3.5 3 3 - gloves
Class 100 (floor/except) (5-mask/gown) Each Shift
(ISO 5)
Non-critical M 5.5 5 5-gloves Each Shift1
Class 10,000 (10 floor) (10-mask/gown) 2x/week2
ISO 7
Support Areas M 6.5 20 15-gloves Weekly
Class 100,000 (30-floor) (30-masks/gown)
ISP 8

1
Adjacent to Class 100
2
Support Areas - Product

77
CLEAN ROOM MONITORING PROGRAM
Classification
Grade A ( ISO Class 5)
Grade B
(ISO class ISO-5.5 Or 6)
Grade C (ISO Class 7)
Grade D ( ISO Class 8)
Restricted Areas With Monitoring
Sample Method
Surface Viable
Viable Particulates
Total Airborne Particulates
Surface Viable
Viable Particulates
Total Airborne Particulates
Surface Viable
Viable Particulates
Total Airborne Particulates
Viable Particulates
Total Airborne Particulates
Viable Particulates
Total Airborne Particulates
Minimum Sampling Frequency1
Weekly or when Filling process is
being performed including during
each shift
Weekly or when Filling process is
being performed including each shift
Weekly or when entering into Grade
B and A area during filling operations.
Monthly or when entering into Grade
C which leads into Grade B and A
area during filling operations.
Surface viable sampling should be
performed every quarter.
Monthly
78
 Part 7
Maintenance
Program for Critical
Utility Systems

Maintenance of Critical Utility Systems

insure the life cycle approach to validation

79
CHANGE CONTROL PROGRAM

Change Control Program (CCP) Maintains Utility

Systems Life Cycle Approach To Validations
Supports Revalidation Activities.
Should have established Change Control Program
which includes critical review process when
changes are made to any critical utility system.
CCP should include changes made and extent of
validation required.

80
REVALIDATION PROGRAM

Annual review of change control forms for each

critical utility system.

Annual review of the maintenance and cleaning

logs associated with each critical utility system.
Annual review of routine environmental monitoring
data.
Annual abbreviated PQ study may be required
under certain conditions.

81
VALIDATION MAINTENANCE PROGRAM
(CONT.)
Validation Maintenance Requirements:
1. System Specific Operation, Maintenance, Cleaning Procedures
2. System Specific Routine Monitoring Programs
3. Trend Analysis
4. Calibration Program
5. Preventive Maintenance Program
6. Change Control Program
7. QA Auditing
8. Deviation /Investigation Reporting
9. Revalidation Program

82
PROBLEM AREAS - UTILITY SYSTEMS

No diagrams provided, no narratives

Diagrams not detailed
Validation data summaries insufficient
monitoring too infrequent
sampling plan inadequate
monitoring not performed during production
inappropriate parameter tested
validation period too short
inadequate alert and action limits and specs

83
PROBLEM AREAS - UTILITY SYSTEMS

Validation data summaries insufficient

no SOP for corrective actions
no historical data base development
No discussion of system / equipment
maintenance or calibration
inadequate proposal for routine monitoring
program

84
Thank You

Question and Answers

Validation Technologies Inc. 85