Qualification and Routine Environmental Monitoring of ... · PDF file1 Qualification and...

1

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

2

CONTACT INFORMATION

for Course Leader

Ed Winnett/VP Operations

Validation Technologies, Inc.

San Diego, CA

Office: 800-930-9222

Fax: 858-676-3677

Email: [email protected]

Website: http://www.validation.org

mailto:[email protected]

http://www.validation.org/

3

PRESENTATION OVERVIEW

SUPPORT DOCUMENTATION

CONSTRUCTION QUALIFCATION

QUALIFICATION OF CRITICAL SYSTEMS

ESTABLISHING A ROUTINE

ENVIRONMENTAL PROGRAM

TRENDING AND DATA SUMMARY

“PROBLEM AREAS” - UTILITY SYSTEMS

REVALIDATION

4

Part 1

Documents to Support

Equipment Qualification

IQ/OQ Documentation

IQPQ

OQ

DQ

OQ

CQ

VC

PV

PQ

IQ

5

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

6

Part 2

Critical Utility Project

Strategy

Plan the Work and Work the Plan

7

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

8

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

9

PROJECT SPECIFICATION

• EQUIPMENT DATA SHEETS

• SPARE PARTS LIST

• VENDOR CERTIFICATION

• FACTORY ACCEPTANCE TEST REPORT

• MATERIALS OF CONSTRUCTION

• ON SITE TESTS

• CLEANING REQUIREMENTS

• COMPONENTS SELECTION

10

VALIDATION MASTER PLAN

• VALIDATION PROJECT ROAD MAP

• FACILITY & PROCESS DESCRIPTION

• VALIDATION PROGRAM

• EQUIPMENT & UTILITY LIST

• PROJECT RESPONSIBILITIES

• VALIDATION PROJECT DESCRIPTION

11

Part 3

Commissioning and

Construction

Program

12

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

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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

15

Scope of the Commissioning and

Qualification Guide

Design

Development

Engineering Change Management

Enhanced Design

Review

Scope of Guide

Process

Validation

IQ & OQ

commissioning PQ

Design for Impact

Impact AssessmentQA Change Control

GEP Contribution

Of Interest to the Regulatory

16

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.

17

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

System Impact Assessment Form Direct HVAC System Template Part 1.doc

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System Impact Assessment

Process OverviewIdentify System

Develop System

Boundaries

Does the system have a direct

impact on product quality

Is the system linked to

Direct Impact System

“No Impact System”

“Indirect Impact”

system

“Direct Impact”

system

Develop Supporting

Rationale

Yes

YesNo

No

19

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

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)

21

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

Critical Component Analysis Form Direct HVAC Template 4.doc

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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

26

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

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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

• Operator’s 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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• 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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• 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

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• 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

32

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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• 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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• 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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• 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)

36

Part 5

Validation of Purified

Water Systems

Purified Water is used in Aspect of GMP

Manufacturing Operations

37

Water Usage in

Pharmaceutical Production

• Water Requirements

– Potable - EPA

– USP Purified

– USP Water For Injection

38

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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• 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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• 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.

41



– 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.

42



• 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.

43



• 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.

44



• 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.

45



• 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.

46



• 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.

47



• 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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• 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.

49



• 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.

50

Microbiological/Chemical Limits

Tests Potable

Water

Purified

Water

Water for Injection

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

51


• 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

52

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.

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.

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– 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.

55



Water Type Sample

Description

USP/EU

Conductivity/

TOC Tests

USP/EU

Microbial/

Endotoxin

USP/EU/CP

Chemistry

(Heavy

Metals/Nitrates)

/ Appearance

pH / Ion

Testing

Coliform Steam Quality

Testing

WFI Beginning of ,

Post Circulation

Pump and WFI

still outlet

Daily read/

Weekly data

collection

Weekly No Routine Sampling Not Required Monthly

(information

Only)

Quarterly

Point of Use Ports Weekly or Use

Data from inline

device

Monthly Weekly Not Required Not Required Not Required

End of Loop Sample

Daily/Compare to

inline device

Daily Daily Weekly Not Required Not Required

RO/DI RO Before EDI

(DI System)

Supply Inlet to

WFI Still

Weekly Weekly +

Coliform

No Routine Sampling Weekly Weekly Not Required

DI Supply Inlet to

WFI Still

Sample Weekly Weekly +

Coliform


Potable Water Infeed water to

RO/DI System2

Grab Sample

Weekly

Weekly +

Coliform


56

Part 5

Validation of Clean

System Systems

Clean Steam is used in certain aspects of

GMP Manufacturing Operations

57

Clean Steam Usage in


• Clean Steam Requirements

– Steam-In-Place (SIP)

– Sterilization Process

– SIP Water For Injection

58


• FDA Requirements: Phase 1& 3

• Same requirements as WFI system

Qualification.

59



• The validation of the clean steam system is

completed when the firm has collected data

for a full year.

60

CLEAN STEAM SYSTEM ENVIRONMENTAL

MONITORING PROGRAM


– 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.

61

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


62

CLEAN STEAM SYSTEM MONITORING

PROGRAM

Type Sample

Description

USP/EU

Conductivity/

TOC Tests

USP/EU

Microbial/

Endotoxin

USP/EU/CP

Chemistry

(Heavy

Metals/Nitrates)

/ Appearance

pH / Ion

Testing

Coliform Steam Quality

Testing

Pure (Clean)

Steam

Steam Generator

Weekly

Endotoxin

Weekly

Weekly Not Required Not

Required

Quarterly

Point of Use

(SIP)

Grab Sample

Monthly

Endotoxin

Monthly

Monthly Not Required Not Required Not Required

Autoclave

Point of

Monthly Monthly Quarterly No Routine

Sampling

No Routine

Sampling

Annually

63

Part 5

Validation of

Compress Gas

Systems

There are many different types of gases

used in a GMP manufacturing operation

64

Compress Gases Usage in


• Compress Gases Requirements

– Preserve the Status of Product

– Drying after Cleaning

– Assist Cell Growth

– Instrument Actuation

– Move Fluid

65

Compress Gases Usage in


• Types Of Gases

– Clean Dry Air

– Nitrogen

– Carbon Dioxide

– Helium

– Oxygen

– Argon

66

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)

67

COMPRESS GAS SYSTEMS ENVIRONMENTAL

MONITORING PROGRAM


– For compress gas systems samples should

be taken daily from all point of use for one

week.

68

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


69

COMPRESS GAS MONITORING PROGRAM

Type

Sample

Location

Dew Point Hydrocarbon

as Oil Mist

USP/EU

Gas

Content

Bacteria Non-Viable

Particulate

Clean

Compressed

Air

Source Monthly

Annually

Quarterly Monthly Monthly

Point of Use Grab Sample

Monthly

Not Required Not Required Weekly (day of

filling process)

Weekly (day of

filling process)

Carbon

Dioxide (CO2)

Source Monthly

Annually

With each new

lot

Monthly Monthly


Monthly

Not Required Not Required Weekly Weekly

Nitrogen

Source Monthly

Annually

With each new

lot or

Quarterly

Monthly Monthly


Monthly

Not Required Not Required Weekly Weekly

70

Part 6

Validation of HVAC

Systems

HVAC is used in Aspect of GMP

Manufacturing Operations

71

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.

72

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.

73

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

74

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

75

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?

76

Physical, Microbiological Testing Parameters

– 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.

•TABLE 1- Air Classification

77

SURFACE MONITORING

Table 2: USP’s 1116 microbial levels for Surface Monitoring

Classifications Zone Surface

CFU/ 2 in2

Personnel

CFU/ 2 in2

Frequency of

P Montoring

Critical Area

Class 100

(ISO 5)

M 3.5 3

(floor/except)

3 - gloves

(5-mask/gown)

Each Shift

Non-critical

Class 10,000

ISO 7

M 5.5 5

(10 floor)

5-gloves

(10-mask/gown)

Each Shift1

2x/week2

Support Areas

Class 100,000

ISP 8

M 6.5 20

(30-floor)

15-gloves

(30-masks/gown)

Weekly

1 Adjacent to Class 100

2 Support Areas - Product

78

CLEAN ROOM MONITORING PROGRAM

Classification Sample Method Minimum Sampling Frequency1

Grade A ( ISO Class 5)

Surface Viable

Viable Particulates

Total Airborne Particulates

Weekly or when Filling process is

being performed including during

each shift

Grade B

(ISO class ISO-5.5 Or 6)

Surface Viable

Viable Particulates


Weekly or when Filling process is

being performed including each shift

Grade C (ISO Class 7)

Surface Viable

Viable Particulates


Weekly or when entering into Grade

B and A area during filling operations.

Grade D ( ISO Class 8)Viable Particulates


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.

Restricted Areas With Monitoring Viable Particulates

Total Airborne ParticulatesMonthly

79

Part 7

Maintenance

Program for Critical

Utility Systems

Maintenance of Critical Utility Systems

insure the life cycle approach to validation

80

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.

81

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.

82

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

83


• 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

84


• 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

Thank You

Question and Answers

Validation Technologies Inc. 85

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