PPMA Training - Validation Seminar Handout

Mario Carlo A.
Soliven Astoria Plaza

Pasig City
DIRECTOR 20 March 2015
QUALITY ASSURANCE AND PRODUCT DEVELOPMENT

Pascual Laboratories, Inc.
PIC/S GMP GLOSSARY
(Pharmaceutical Inspection Co-operation Scheme)
Action of proving, in accordance with the

principles of GMP, that any procedure ,
adddd
processd , equipment ,material , activity, or
system leads to the expected result
aaasas
Qualification/Validation VALIDATION
Cleaning Computer Facilities Equipment Process

FDA GUIDELINES
General Principles of Process Validation
Establishing documented evidence which

provides
d a high degree of assurance that
a specific process will consistently
produce a product meeting its
predetermined specifications

WHAT IS VALIDATION?
• Process validation IS NOT product

development
• Process validation IS an approach for

verifying process performance

WHAT IS VALIDATION?
• Process validation IS NOT process

development
• Process validation IS an approach for

demonstrating that the process is rugged,
reproducible and controlled

SCOPE OF VALIDATION
VALIDATION
Facilities Equipment Process Cleaning Computer
Utility Analytical
System Method

PRINCIPLE OF VALIDATION
PIC/S Annex 15.1:
“…Significant changes to the facilities, the
equipment and the processes, which may
affect the quality of the product, should be
validated. A risk assessment approach
should be used to determine the scope
and extent of validation.”

PRINCIPLE OF VALIDATION
PIC/S PI 006-3, 4.1.1
• Multidisciplinary approach: requires the
collaboration of experts (SMEs)
• Time constraints: rigorous time schedules;
always the last stage prior to routine
operation
• Costs: require time of highly specialised
personnel and expensive technology.

VALIDATION LIFE CYCLE
Risk Analysis VALIDATION MASTER PLAN
DESIGN Process Validation
QUALIFICATION
REVALIDATION
INSTALLATION Cleaning Validation

QUALIFICATION
OPERATIONAL Computer Validation MONITORING

QUALIFICATION MAINTENANCE
Analytical Method CHANGE CONTROL
PERFORMANCE
QUALIFICATION Validation
QUALIFICATION PROCESS VALIDATION VALIDATION

PHASE PHASE MAINTENANCE PHASE

VALIDATION LIFE CYCLE
Engineering Change Management
Impact Assessment Quality Change Control
Design
Process
Enhanced Design Commissioning PQ Validation
Review
IQ & OQ
Reference: ISPE Baseline ® Guide for Commissioning and Qualification

VALIDATION
DOCUMENTATION
• Validation Master Plan
• Validation Project Plan
• Risk Assessment
• Validation Protocol
• Validation Report
• Deviation Report
• Change Control

VALIDATION
MASTER PLAN
• High level document that summarizes the
firm’s overall philosophy, intentions and
approach to be used for establishing
performance adequacy. (PIC/S PI 006-3;
4.3.1)
• PIC/S Annex 15.2-5: Planning for

Validation

VALIDATION
MASTER PLAN
Should at least contain (PIC/S Annex 15.2):
a) validation policy
b) validation organisational structure
c) scope of validation
d) documentation format
e) planning and scheduling
f) change control
g) reference to existing documents

SCOPE OF VMP
PIC/S PI 006-3; 4.4:
• All validation activities relating to critical
technical operations, relevant to product and
process controls within a firm; includes
qualification of critical manufacturing and control
equipment
• PROspective, CONcurrent, RETROspective
Validations as well as Re-validations.
• For large projects, best approach is to create a
separate VMP. (PIC/S Annex 15-5)

VALIDATION PROTOCOL
• PIC/S Annex 15.6
• A Validation Protocol should be issued to
describe how qualification and validation
will be conducted.
• Should be reviewed and approved
• Should specify critical steps and
acceptance criteria
• Validation is complete when all
acceptance criteria are met

VALIDATION PROTOCOL
• Objective
• Scope
• Background/ summary
• Validation strategy
• Sampling plan
• Detailed test scripts
• Checklist: CPPs and acceptance criteria
• Deviation reporting and change control

VALIDATION REPORT
PIC/S Annex 15-7:
- cross-reference the qualification and/or
validation protocol
- summarise the results obtained
- comment on any deviations observed
- draw the necessary conclusions
- recommend changes necessary to correct
deficiencies.
- Any changes to the plan protocol should be
documented with appropriate justification.

VALIDATION REPORT
• Objective
• Scope
• Data and results
• Analysis
• Deficiencies/Deviations
• Conclusions
• Recommendations

VALIDATION TEAM

VALIDATION TEAM
MEMBERS
• Officer from Quality Assurance Department
• Member from Production
• Member from Engineering
• Member from QC Laboratory
• Member From Product Development Laboratory

PRODUCTION
- Review operability factors of the design
- Participate in performing the validation
steps during manufacturing and
packaging processes and equipment
qualification
- Develop the necessary SOPs for the new
process or equipment
- Assist in the collection of validation data.

PRODUCT DEVELOPMENT
- Define the process or product to be
validated: CPPs and CQAs;
specifications, limits, and manufacturing
methods
- Resolution of process related technical

issues during tech transfer and scale up

ENGINEERING
- Inspection or testing of equipment
against engineering specifications, and
analyzing and evaluating the test results
- Evaluate departures from engineering
specifications including potential impact
and responses
- Assistance with supplier assessments
- Collaborate with automation SMEs

ENGINEERING
- Define the necessary equipment
specifications, limitations, capacity,
calibration, and maintenance
requirements
- Provide the necessary training on the
proper operation and maintenance of
the equipment.

ENGINEERING
- Provides the necessary utilities and
equipment accessories.
- Provides engineering technical support
to ensure proper and efficient function
during the validation process.

QUALITY CONTROL
- Provides the necessary support for
sampling, testing, and reporting of test
results for validation
- Performs the microbiological testing and
environmental monitoring during the
validation process.

QUALITY ASSURANCE
- Review and approval of URS/PUR,
project plans, risk assessement,
verification reports, protocol including
deviations incurred

GMP PROCEDURES
AND PROGRAMS
• Change Control
• Calibration Program
• Preventive Maintenance Program
• Standard Operating Procedures
• Cleaning and Sanitization Program
• Environmental Monitoring Program
• GMP Training

COMMISSIONING
• Planned and documented series of
inspections, adjustments, and tests carried
out systematically to set the installation
into correct technical operation as
specified.
Reference : ISO/TC209 Working Groups at 2001-03-31 – Committee

Draft ISO/CD 14644-6 “Cleanrooms and associated
controlled environments” – Part 6: Terms and Definitions

STAKEHOLDERS
STAKEHOLDER System Impact
GROUP Direct Indirect None
Engineering X X X
Manufacturing X X X
Quality Assurance X
Validation X
Contractors X X X
Suppliers X X X

COMMISSIONING vs
QUALIFICATION
COMMISSIONING QUALIFICATION
- Direct, Indirect and No - Direct Impact System
Impact Systems Only
- Start-up; makes it meet - Checks that it is right
intentions
- GEP - GMP and GEP
- No participation from QA - QA and Validation
and Validation Participation
- Protocols for project - Protocols for auditors and
engineers other non-project
personnel

COMMISSIONING
User Requirement PERFORMANCE
What TESTING
Design Development
Setting-to-work
Functional Design Commissioning Plan Regulation and
How in concept
FAT/ SAT Adjustment Testing
Design Development
Detail Design Physical Completion

How to make and Inspection
PID
Impact Assessment
Implementation

QUALIFICATION
User Requirement
PQ Test Plan PQ
What
Design Development
Functional Design OQ Test Plan OQ

How in concept
Design Development
Detail Design IQ Test Plan IQ

How to make
Impact Assessment
Implementation

DIRECT IMPACT SYSTEM
Qualification Practice
User Requirement
What PQ PERFORMANCE
TESTING
Design Development
Functional Design Setting-to-work
How in concept OQ Regulation and
Adjustment Testing
Design Development
Detail Design
How to make IQ Physical Completion
and Inspection
Impact Assessment
Implementation

QUALIFICATION and VLC
Maintain Operational Retire
Use
Change
Control
Process
Validation
PQ Test Plan
User Requirement PQ
OQ Test Plan
Functional Specs OQ
IQ Test Plan
Technical Specs IQ
Implementation

QUALIFICATION
- The process to demonstrate the ability to

fulfill specified requirements
Reference: GAMP Good Practice Guide – Calibration Management

QUALIFICATION
• Action of proving and documenting that
equipment or ancillary systems are
properly installed, work correctly, and
actually lead to the expected results.
• Qualification is part of validation, but the
individual qualification steps alone do not
constitute process validation.
Reference: ISPE Biopharmaceuticals Manufacturing Facilities
Baseline® Guide

QUALIFICATION
PRACTICES
• Impact Assessments
• Enhanced documentation, documentation
management and structured approval
process
• Should identify what should be checked ,
how, to what extent, why, and by whom
• Deciding on what to check and why

DESIGN QUALIFICATION
• To document that the design aspects have
been checked and approved.
• To show that the plant design agrees with
the design specifications
• To ensure that the important GMP aspects
are fulfilled and compliance with these
important GMP aspects is documented

RISK ANALYSIS
• To prove whether or not possible risks
are acceptable for the product quality
• To identify critical and non-critical
parts/aspects of processes and
equipment.
• To identify the activities necessary for
validation, maintenance, and calibration.

INSTALLATION
QUALIFICATION
- The documented verification that the
facilities, systems and equipment, as
installed or modified, comply with the
approved design and manufacturer’s
recommendations
Reference: PIC/S Annex 15 Glossary

PURPOSE OF IQ
- IQ establishes that critical components
are installed correctly and in
accordance with documentation
requirements

SCOPE OF IQ
PIC/S Annex 15-12:
• installation of equipment, piping, services
and instrumentation checked to current
engineering drawings and specifications;
• collection and collation of supplier
operating and working instructions and
maintenance requirements;
• calibration requirements;
• verification of materials of construction

IQ ACTIVITIES
Documents checked:
• URS/ PURS
• Functional Design Specifications
• Equipment Specifications
• P&I Diagrams
• Supplier Operating and Work Instructions
• Process Flow Diagrams
• Inventory Lists

IQ ACTIVITIES
CHECKS PERFORMED
1. Utility requirements
2. Major components specifications
3. Component material
4. Lubricant used
5. Safety features
6. Spare parts

IQ ACTIVITIES
CALIBRATION REQUIREMENTS
- calibrating equipment
- measuring devices used during OQ
- measuring devices related to the
installed equipment
- calibration requirements for measuring
devices for future use

OPERATIONAL
QUALIFICATION
facilities, systems, and equipment, as
installed or modified, perform as
intended throughout the anticipated
operating ranges
Reference: PIC/S Code of GMP Annex 15 Glossary

OPERATIONAL
QUALIFICATION
OQ should follow IQ (PIC/S Annex
15.13)
but depending on the complexity of the
equipment it may be performed as a
combined Installation/Operation
Qualification (IOQ).
Reference: EU-GMP Guide Part 1 Annex 15: Qualification and
Validation (draft, 06 Feb 2014)

PURPOSE OF OQ
- Documented evidence is given that all
parts of the plant and equipment work
within their specifications and process
parameters are within the acceptance
criteria.

SCOPE OF OQ
PIC/S Annex 15.14
• tests that have been developed from
knowledge of processes, systems and
equipment;
• tests to include a condition or a set of
conditions encompassing upper and lower
operating limits, sometimes referred to as
“worst case” conditions.

WORST-CASE CONDITIONS
MINIMUM/MAXIMUM MINIMUM/MAXIMUM
OPERATING RANGES LOAD EVALUATION
motor speed, time, -applies to mixers and
temperature, air pressure, blenders
vacuum, water pressure, - challenge testing should
steam pressure, flow go outside the limits
rates,
- if limits are exceeded or
weights, volumes
not met, good results will
not be achieved

SCOPE OF OQ
PIC/S Annex 15-15
• finalisation of calibration, operating and
cleaning procedures, operator training and
preventative maintenance requirements.
• formal "release“ of the facilities,
systems and equipment.

OQ ACTIVITIES
- Process controls that are part of the
equipment (e.g., PLCs) are qualified
- Simulation of normal production

conditions must be done to ensure that
the systems tested during OQ are doing
what they are believed to do

OQ ACTIVITIES
- Calibration of measuring and controlling
devices are checked
- Critical parameters and circumstances
identified in the risk analysis (RA) are
checked for conformity to the
acceptance criteria.

OQ TESTING
- Specific Functional Tests
- Controls Verification (Mechanical and Electrical)
- Power Failure Verification
- Operational Testing of each equipment
mechanism at operating ranges
Alarms/Interlocks Verification Operational Run
Verification
- Standard Operating Procedure and Training
Verification
- Operation of Panels

PERFORMANCE
QUALIFICATION
facilities, systems and equipment, as
connected together, can perform
effectively and reproducibly, based on
the approved process, method and
product specification
Reference: PIC/S Code of GMP Annex 15 Glossary

PERFORMANCE
QUALIFICATION
• Although PQ is described as a
separate activity, it may in some
cases be appropriate to perform it in
conjunction with OQ or Process
Validation.
Reference: EU-GMP Guide Part 1 Annex 15: Qualification and

Validation (draft, 06 Feb 2014)

PERFORMANCE
QUALIFICATION
• Uses production materials, qualified
substitutes or simulated product
proven to have equivalent behaviour
under normal operating conditions
with worst case batch sizes.
• b) Tests should cover the operating
range of the intended process,

PURPOSE OF PQ
• PQ integrates procedures, personnel,
systems and materials to verify that the
pharmaceutical facility, environment,
equipment, or support system produces
the required output.

PQ ELEMENTS
• Material Compatibility Tests : Interaction
with contact surface areas or with product
• Capacity Test: Minimum & Max Batch Size
• Operational Consistency: Challenges
Equipment Capacity under load conditions
• Operational Accuracy: Challenges
Equipment Control of Variables
• Operational Ranges: Challenges
Equipment Min, Max and Target Loads

-END-

PPMA Training - Validation Seminar Handout

Uploaded by

Copyright:

Available Formats

PPMA Training - Validation Seminar Handout

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

PPMA Training - Validation Seminar Handout

Uploaded by

Copyright:

Available Formats

Mario Carlo A.

Soliven Astoria Plaza

QUALITY ASSURANCE AND PRODUCT DEVELOPMENT

Action of proving, in accordance with the

Cleaning Computer Facilities Equipment Process

Establishing documented evidence which

Cleaning Computer Facilities Equipment Process

• Process validation IS NOT product

• Process validation IS an approach for

Cleaning Computer Facilities Equipment Process

• Process validation IS NOT process

• Process validation IS an approach for

Cleaning Computer Facilities Equipment Process

Facilities Equipment Process Cleaning Computer

Cleaning Computer Facilities Equipment Process

Cleaning Computer Facilities Equipment Process

Cleaning Computer Facilities Equipment Process

INSTALLATION Cleaning Validation

OPERATIONAL Computer Validation MONITORING

QUALIFICATION PROCESS VALIDATION VALIDATION

Cleaning Computer Facilities Equipment Process

Impact Assessment Quality Change Control

Reference: ISPE Baseline ® Guide for Commissioning and Qualification

Cleaning Computer Facilities Equipment Process

Cleaning Computer Facilities Equipment Process

• PIC/S Annex 15.2-5: Planning for

Cleaning Computer Facilities Equipment Process

Cleaning Computer Facilities Equipment Process

Cleaning Computer Facilities Equipment Process

Cleaning Computer Facilities Equipment Process

Cleaning Computer Facilities Equipment Process

Cleaning Computer Facilities Equipment Process

Cleaning Computer Facilities Equipment Process

Cleaning Computer Facilities Equipment Process

Cleaning Computer Facilities Equipment Process

Cleaning Computer Facilities Equipment Process

- Resolution of process related technical

Cleaning Computer Facilities Equipment Process

Cleaning Computer Facilities Equipment Process

Cleaning Computer Facilities Equipment Process

Cleaning Computer Facilities Equipment Process

Cleaning Computer Facilities Equipment Process

Cleaning Computer Facilities Equipment Process

Cleaning Computer Facilities Equipment Process

Reference : ISO/TC209 Working Groups at 2001-03-31 – Committee

Cleaning Computer Facilities Equipment Process

Cleaning Computer Facilities Equipment Process

Cleaning Computer Facilities Equipment Process

Detail Design Physical Completion

Cleaning Computer Facilities Equipment Process

Functional Design OQ Test Plan OQ

Detail Design IQ Test Plan IQ

Cleaning Computer Facilities Equipment Process

Cleaning Computer Facilities Equipment Process

Cleaning Computer Facilities Equipment Process

- The process to demonstrate the ability to

Reference: GAMP Good Practice Guide – Calibration Management

Cleaning Computer Facilities Equipment Process

Cleaning Computer Facilities Equipment Process