Validation master plan

1
Prepared by
P. Jagadeesh
M.Pharm I year
RIPER, Anantapur


Introduction
2
The design, construction, and commissioning of a new facility for
the pharmaceutical industry is a complex process. The approach that
can be used by the designer to ensure that the design, engineering
and construction process can meet the GMP requirements are
completely based on the plan of a Validation Strategy.

3
Defnition: A validation Master Plan (VMP) is a comprehensive
document describing the applicable validation requirements for the
facility, and providing a plan for the meeting those requirements.
Scope: VMP includes all relevant aspects relating to the production
of Pharmaceuticals in the production facility. The principle of
validation, the organization of qualification and equipment are also
described.
It covers all facilities used in various production areas, storage,
services and the rooms for staff.
Introductioncont..

4
•VMP is not a requirement of the FDA, but it has become almost an
industry standard.
•It is important to include such a document, as it sets the overall
goals and limits that will be followed during validation, and can be
referred to throughout the project.
•As a reference document, the plan permits the reviewer
immediately to understand the scope of the validation and so avoid
misconceptions.
•The validation plan is thus used to set the limits of the validation,
to define the scope of the project, the systems included and not
included in the qualifications, and what the project will attempt to
prove.
Importance of VMP

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Members:
•Validation manager, Quality Assurance dept.
•Member from production
•Member Engineering (utilities)
•Member from Calibration lab
•Member from QC lab
•Member from Maintenance
•Member from HVAC dept
•Member from Product development lab

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Organization chart:
Validation team
(review-team)
Validation
representative
Qualification
team
Process
Validation
team
Cleaning
Validation
team
Computer
Validation
team
External
Validation
service


8
Methodology:
This section should address the predetermined requirements by
identifying the standards that are to be applied to the facility. These are
then used in the development of the acceptance criteria that are used to
judge the validation.
It also involves planning and execution of documents such as,
protocols, records, reports, or other.
The standards will involve three elements:
•Regulatory and guidance documents
•National standards
•Company standards


9
Qualification:
This section encompasses all aspects of the design, procurement,
installation, and commissioning process.
The important issue is to ensure that definitions in the organization and
for a specific project are consistent and cover all aspects of the
validation process, and that the validation structure and organization is
clear to any inspection authority.
- Design qualification: providing documented evidence that the design
of the facility and equipment meet the requirements of the user
specification and GMP.


10
Change Control:
This section of VMP should lay down requirements for a set of
procedures for change control that cover:
-The project through design, construction, and commissioning
-The ongoing change that will inevitably occur in both the process and
the equipment and engineering aspects.
Procedures:
These cover engineering standards used in the project design, through
to commissioning phases, and the facilities standard procedures
(SOPs).


11
Documentation:
This section usually used to identify the documentation that should be
produced for the processing like;
•Engineering drawing
•Equipment supplier drawing and documents
•Factory acceptance documents
•IQ documents
•OQ documents
•PQ documents
Appendices:
The appendix is mostly used VMP to hold the information of type of
documents and formats that will be used in the execution stage.

Developing a Validation Master Plan: Documentation
•The document defines the validation approach, specifies the
responsibilities of each of the validation team member, and is a
important effort at the beginning of a project.
•The description of following systems are necessary to control
validation activities as well as the ongoing operation of the system,
process, or equipment:
- Protocol and documentation preparation
- Protocol execution
- Documentation control
- Change control 12
Preparation of VMP


 URS [User Requirement Spécifications]
 DQ [Design Qualification]
 IQ [Installation Qualification]
 OQ[Operation Qualification]
 PQ [Performance Qualification]
BASIC STEPS OF
QUALIFICTION


 Once the end user requirements specification or URS as it
is commonly called; is documented, agreed and approved
they form the basic URS Level-1 document. The engineers
(or vendor) can then commence the preliminary design to
establish exactly what functions are required for each of
the items specified in the user requirements specification,
the end user has listed. Once this functionality is
documented and approved it forms the URS Level-2
document. This is the final level of the URS unless
software is used.
USER REQUIREMENT
SPECIFICATION [URS]


 Design Qualification is used at the stage where a design
that has been developed from the URS, is reviewed and
documented by competent persons to ensure that the
designed equipment, if built, will satisfy all the detailed
specified requirements. The Design Qualification is the
only document that is going to confirm that the design will
work. It must be carried out by qualified people who can
challenge the design performance. If you have no such
persons on your staff you must contract them in, or
contract the DQ out
DESIGN
QUALIFICATION[DQ]


 The Installation Qualification (IQ) execution; verifies that the
equipment, and its ancillary systems or sub-systems have been
installed in accordance with installation drawings and or
specifications. It further details a list of all the
CGMPrequirements that are applicable to this particular
installation qualification. These requirements must all be
satisfied before the IQ can be completed and the qualification
process is allowed to progress to the execution of the
Operational Qualification (OQ).
INSTALLATION QUALIFICATION [IQ]


 This Operational Qualification (OQ)protocol comes with an
interactive SOP as a prefixed document. In the preparation of
the Operational Qualification validation protocols, it is
important to allow a degree of flexibility. Should the OQ remain
untouchable until the Installation-Qualification (IQ) is
completed and signed off. The Operational Qualification
includes a review of the Standard Operating Procedure (SOP's)
for startup, operation, maintenance, safety, and cleaning /
sanitization as applicable, must they be in fully approved
format? These flexibilities must be built into the qualification
process.
OPERATIONQUALIFICATION[OQ]


 The normal expectations for PQ are given as requiring,
documented verification that facilities, systems and
equipment, as connected together, can perform effectively
and reproducibly, based on the approved process method
and product specification. Onto that now should be grafted
The verification that the all the requirements specified in
theUser Requirements Specification (URS) have been
fully complied
PERFORMANCE QUALIFICATION[PQ]


User Requirements
Specification
 User Requirements Specification (URS), is the most
critical of documents and yet, the most often bungled.
Whether the system is purely mechanical, or a mix of
electro-mechanical, or solely a software program, the
successful compilation and execution of the Installation
Qualification (IQ) (for installation), Operational
Qualification (OQ) (for functionality) and the
Performance / Product Qualification (PQ) (for
operability), is dependent on an User Requirements
Specification (URS) containing clear, concise and
testable requirements.

1. Once the end user requirements specification is
documented, agreed and approved they form the basic URS
Level-1 document.
2. The engineers (or vendor) can then commence the
preliminary design to establish exactly what functions are
required for each of the items specified in the user
requirements specification, the end user has listed.
3. Once this functionality is documented and approved it
forms URS Level-2 document.
4. This is the final level of the URS unless software is used. If
software is to be used, the URS Level-2 document, is passed
to the code writers.
5. As the code is written, lines, or groups of lines, of code
must be attributed to the individual functions that
necessitate their presence. The completion of this task
results in the completion of the URS Level-3 document

Developing the URS to this level is unique in most
industries, but is, standard practice in strictly regulated
industries, as it is a major building block in the creation
of quality software. The URS Level-3 document,
contains all the traceability which is deemed mandatory
for software assessed to be critical to product quality, in
the pharmaceutical regulated industries.

Structure and content of the URS
The URS can contain a large number of requirements and should therefore be
structured in a way that will permit easy access to information. The
requirement specification must be formally reviewed and approved by the
pharmaceutical manufacturer.
The following guidelines should be followed during the production
of the URS :
1. Each requirement statement to be uniquely referenced,and no longer
than 250 words.
2. Requirement statements should not be duplicated nor contradicted.

3. The URS should express requirements and not design
solutions.
4. Each requirement should be testable.
5. The URS must be understood by both user and supplier;
ambiguity and jargon should be avoided.
6. The use of diagrams is often useful.
7. The scope for readers to make assumptions or misinterpret
should be minimized.
8. Wherever possible, the URS should distinguish between
mandatory/regulatory requirements and desirable features.

FORMATE
The URS for a GMP computer control system application will typically address the
following:
Scope of system supply
 Project objectives
 Regulatory requirements
 Process overview
 System boundaries
 Operational considerations
 Manufacturing design data
 Instrument application data
 Data records
 System functions
 System software
 System hardware and peripherals

System interfaces
 Environmental conditions
 Access security
 Diagnostics
 System availability
Safety
Test and calibration
 Quality procedures
Software development life cycle
Documentation requirements
Training
Engineering/installation standards
 Ongoing support
Warranty Delivery/commercial
requirements

Newly sanctioned systems will require compliance with regulations
for GMP electronic records and electronic signatures, and
definition of the functionality required will need to be included.
The structure of the URS be used as the basis for the presentation
format of the FDS and hardware and software design
specifications; this helps ensure design decisions are auditable
back to the source requirement.
Once reviewed and approved internally, the URS is issued to
prospective suppliers as part of the tender document set so that
detailed quotations for the system application can be obtained

URS provides the following key benefits for the validation program:
 Clarifies technical, quality, and documentation requirements to
the vendor( s).
 Enables the pharmaceutical manufacturer to assess the
technical, regulatory, and commercial compliance (or otherwise)
of submitted bids against a formal specification.
 Ensures the basis of a structured approach to the presentation
of information.
 Provides a basis for testing and test acceptance criteria.
 Provide a baseline for validation and verification..

User Requirements Specification justifications URS
They must be comprehensive. Each and every
requirement relating to product safety, identity, strength,
purity, and quality must be identified. Hence, Quality
Assurance (QA) must have a significant role in reviewing
and approving the final set of requirements, and must be
an approver of changes to any requirement that can
affect the above product or process attributes (e.g.,
cGMP’s).

 Given a comprehensive User Requirements Specification that has
been approved by QA and is under project change management, the
Design Qualification(DQ) process then can be reduced to two key
objectives:
 Documented verification that the overall design appears to
address, by some means, each and every requirement affecting the
product and performance of the manufacturing process (or, in the
case of unknown product or multi-product manufacturing facility,
the required equipment/ system performance capabilities).
 Identification (and documentation) of the critical individual
physical components, attributes, and operational features that
directly support meeting each requirement.


DESIGN QUALIFICATION
 Design qualification (DQ) is the process of completing and
documentation design review to illustrate that all quality aspects have
been fully considered at the design stage .The purpose s to ensure that
all the requirements for the final systems have been clearly defined at
the start.
 Design qualification(DQ) defines the functional and operation
specification of the instrument and details the conscious decisions made
in the selection of the supplier. DQ should ensure that instruments have
all the necessary function and performance criteria that will enable them
to be successfully implemented for the intended application and to meet
user requirements.


The list below shows the recommended steps that should be considered for
inclusion in a Design Qualification.
 Description of the analysis problem.
 Description of the intended use for the equipment.
 Description of the intended environment.
 Preliminary selection of the functional and performance specification
(technical, environmental , safety)
 Preliminary selection of the supplier
 Final selection of the supplier and equipment.
 Development and documentation of final function and operational
specification


Vendor qualification as part of DQ
 As part of the design qualification process, the vendor should be
qualified .
 Is an established and documented quality system enough (e.g.ISO
9001), or should there be a direct audit?
 The answer is that there may be situations where a vendor audit is
recommended .
 For example, when complex computer systems are being developed for
a specific user.
 However ,this is rarely the case for balance and analytical instruments.


 If equipment does not include a computer system , a good reputation,
Ones own experience or god reference from other users –together with ISO
9001 certification can be sufficient.


Design Qualification(DQ)
 First step in the qualification of new HVAC system.
 It documents the design of the system and will include :
1. functional specification .
2. Technical /performance specification for equipment .
3. Detailed Air Flow Schematics.
4. Detailed layout drawing of the system.
 Compliance with GMPs and other regulatory requirements.


CONCEPT OF INSTALLATION
QUALIFICATION(IQ):


INSTALLATION QUALIFICATION(IQ):
Definition:
 It is defined by the FDA as ,establishing by objective
evidence that all key aspects of the process equipment and
ancillary system installation adhere to the manufacturer’ s
approved specification and that the recommendations of
the supplier of the equipment are suitably considered.
 IQ is an acronym for “Installation Qualification”
 The purpose is to ensure that all aspects(static attributes) of
the facility or equipment are installed correctly and comply
with the original design.


Before installation :
-Obtain manufacturer’s for installation site requirements.
-check the site for the fulfillment of the
manufacturer’s(utilities such as electricity, water and
gases plus environment conditions such as humidity,
temperature, vibrational level and dust).
-allow sufficient shelf space for the equipment itself, related
SOPs, operating manuals, logbooks and software.


Installation qualification scope(IQ):
The scope of the IQ testing/inspections will cover the under listed
subjects, but is not restricted to them alone:
• Verification that all component parts.
• Verify installation is as specified.
• Insert a brief description of what part of the validated product
process.
• Insert a brief description of the operational function.
• Identify and verify that serial numbers and model number of all.
• Confirm that. the issue level of software


Contents of IQ protocol
o Description
o History
o Fundamentals
o Purpose
o Attachment of IQ
• General
• Specific
o Documentation


 Specification
-Check completeness and current status of documentation.
-Check delivered equipment from manufacturer.
-Check if all parts of the plant are according to their
specification.
-Check the identity of all parts of the plant.
-Visual check of complete and craftsmanship installation of all
parts.
-Materials used are within specifications.


Oprerational Qualification


FDA
Establishing confidence that process equipement
and sub-systems are capable of consistenttly
operating within stated limits and tolerance.
WHO
Documented verification that the system or sub-
system performs as intended over all anticipated
operating ranges.
Definition

 The scope of the OQ testing/inspections must include but is not
limited to Verification that all loop installations, Insert a brief
description of what part of the validated product process.
 Insert a brief description of the operational OQ Scope.
 The scope of the OQ testing/ inspections must include but is not
limited to verification that all loop installations insert a brief
description of what part of the validated product process insert a
brief description of the operational function.
OQ Scope


 This Operational Qualification (OQ) protocol comes with an interactive
standard operating practice (SOP) document as a prefix introductory
document As you progress through this SOP you are auto populating the 00
This is a relay easy and straightforward document to use.
 In the preparation of Operational validation protocols, it is important to
allow a certain degree of flexibility.
 This must be debated and justified in the Validation Plan (VP) Should the
0Q remain untouchable, until the installation Qualification (10) is
completed and signed off? There are many Instances where this is not only
undesirable, but senseless and deleterious to project progress and costs
Shoued every function in a system or piece of equipment be qualified.
PROTOCOL


 If so, one must ask about validation progress and costings. It makes little
sense to fail something for not going to use.
 The Operational Qualification includes a review of the Standard
Operating Practice (SOPs) for startup operational maintenance, safety,
and cleaning sanitization.
 The modular process has been followed in constructing this Operational
Qualification in as much that where Tests / inspections are standard for
systems and or equipment, they are built into the basic protocol.
 Where they are not they are available as additional test protocols.
 Functional and software tests are authored in this stand alone test script
protocol format.


 This allows the generation of a standard 0Q that covers all the
many items the regulators are looking for, with the facility to have
integrated into it, the equipment specific testing tasks It also means
that these stand alone test scripts are available for tasks other than
validation, ie when system re-testing is required.
 I also saves unnecessary testing and re-testing For example, when a
room pressure regime has been commissioned by another party and
the completed report is in date and available, is it practical and legal
to use it.
 The IQ test script will be of standard format, the contractors tests
(containing the raw data) will be reviewed and data extracted from it
This data will be used to verify that the Operation Qualification test
script acceptance criteria has or has not Operational Qualification
Rationale been satisfied.


 Testing of database or data storage integrity
 Verification of the functionality of the equipment
 Challenge of software, where required;
 Review of system functionality to verify
 compliance with 21 CFR Part 11
 If system must be 21 CFR Part 11 compliant verification.
 Testing of security levels to prevent
 Recovery
 Testing for Electromagnetic interference and compatibility.
An integrated loop test verification


Full Life Cycle Documentation


Performance
qualification
 Performance qualification(PQ) also called process
qualification.
 Performance qualification comes under a process of
validation.
 The final section for equipment qualification protocols is
the Performance qualification(PQ)


Performance
qualification(PQ)
 Performance qualification is the process of
demonstrating that an instrument consistently
performs according to as specification
appropriate for its routine use.
 Performance qualification(PQ) implies that
factors such as loads,volumes and other
capacity and power-related issues are not
problematic throughout the specified
ranges.test methods shall be executed in the
order presented in the protocol.


Performance
qualification(PQ)
 The objective of Performance qualification is to provide
quality assurance that the system is capable of being
subsequently validated. GMP and other such guidelines
might not specify the frequency of performing PQ, so the
schedule or frequency you choose depends on a lot of
factors.


Performance
qualification(PQ)
 This will typically be one or more of the following:
 Everyday
 Each time the equipment or system is used.
 Before ,after, or even during, a system of operations
 Other periodic schedule, or as needed


Performance
qualification(PQ)
 Performance qualification should always be
performed under conditions that are similar to
routine sample analysis.
 Performance qualification should be performed on a
daily basis or whenever the equipment is being
used.
 In practice, Performance qualification can mean
system suitability testing,where critical key system
performance characteristics are measured and
compared with documented.


Performance
qualification(PQ)
 The test frequency depends not only on the stability of the
equipment but also on everything in the system that may
contribute to the analysis results.
 Control standards of similar values to the intended test
samples must be used for performance qualification.

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