Master Validation Plan PDF

DOCUMENT NO.
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TITLE: Validation Master Plan (VMP) for the Pharma Co., EFFECTIVE DATE:
TRAINING DATE:
Inc. Springfield, NY Facility

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Glossary
2.0
PURPOSE AND INTRODUCTION......................................................................................................3

2.1 INTRODUCTION ......................................................................................................................... 3
2.2 PURPOSE ..................................................................................................................................... 3
3.0
SCOPE.....................................................................................................................................................4
4.0
RESPONSIBILITIES ..............................................................................................................................4
4.1 SITE QUALITY ASSURANCE VALIDATION ......................................................................... 5
4.2 SITE ENGINEERING VALIDATION ........................................................................................ 6
4.3 SITE MANUFACTURING TECHNICAL SUPPORT .............................................................. 6
4.4 SITE MANUFACTURING .......................................................................................................... 7
4.5 SITE ENGINEERING ................................................................................................................. 8
4.6 QUALITY CONTROL ................................................................................................................. 8
4.7 REGULATORY AFFAIRS ......................................................................................................... 9
5.0
DEFINITIONS, ABREVIATIONS AND REFERENCES ...................................................................9

5.1 DEFINITIONS LIST .................................................................................................................... 9
5.2 ABBREVIATION LIST .............................................................................................................. 12
5.3 REFERENCES .......................................................................................................................... 12
6.0
MATERIALS ..........................................................................................................................................12
7.0
PROCEDURE .......................................................................................................................................13
7.1 SPRINGFIELD, NY FACILITY OVERVIEW ......................................................................... 13
7.2 VALIDATION MASTER PLAN GOVERNANCE .................................................................. 13
7.3 VALIDATION APPROACH ...................................................................................................... 15
7.4 VALIDATION PROCEDURES ................................................................................................ 17
7.5 VALIDATION SUPPORT SYSTEMS..................................................................................... 18
7.6 KEY SOPs GOVERNING AND SUPPORTING THE ALLSTON LANDING VALIDATION
PROGRAM ................................................................................................................................ 21
7.7 IDENTIFICATION AND DESCRIPTION OF MANUFACTURING SYSTEMS AND
EQUIPMENT PRESENTLY IN USE AT THE SPRINGFIELD, NY FACILITY AND
ASSOCIATED COMPLETED VALIDATION ........................................................................ 21
7.8 VALIDATION MASTER PLAN REVIEW ............................................................................... 21
8.0
ATTACHMENTS...................................................................................................................................21
8.1 Attachment A: Process Flow Diagrams ................................................................................ 21
8.2 Attachment B: Key SOPs Governing and Supporting the Springfield, NY Facility
Validation Program .................................................................................................................... 21
8.3 Attachment C: Process Equipment List and Associated Validation Protocol Numbers
..................................................................................................................................................... 21
9.0
REVISION HISTORY...........................................................................................................................27
9.1 Revision History Table ............................................................................................................. 27
NOTICE
THIS DOCUMENT IS PROPRIETARY AND ITS CONTENTS ARE THE EXCLUSIVE PROPERTY OF PHARMA CO., INC.
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2.0
PURPOSE AND INTRODUCTION

2.1
INTRODUCTION
The validation program at the Springfield, NY Facility is intended to satisfy current domestic
and international regulations, guidelines and policies for drugs, biologics and APIs to verify
the equipment, systems, utilities, software and processes are properly designed, installed,
and function as intended in a consistent and controlled manner. The validation program
complies with Corporate Quality Standards and Polices (Ref. SOP-XXXX Validation
Program).
The revision of the Site Validation Master Plan (SVMP) comes from the validation
philosophy changes resulting from the implementation of the validation lifecycle approach
at Springfield, NY Facility. The changes made in this revision of the Springfield, NY Facility
SVMP bring the plan into alignment with the new lifecycle approach. The Springfield, NY
Facility has developed the site validation governance document SOP-XXXX, Validation
Project Life Cycle Approach at the Springfield, NY Facility, which defines the
validation philosophy to be used for validation at Springfield, NY Facility. SOP-XXXX uses
a risk-based approach with emphasis on verification and qualification that is focused on the
high risk attributes of facilities, utilities, equipment, and processes. This SVMP introduces
use of subordinate VMPs (sub-VMPs) that are categorized into eight areas and address the
full scope of Validation requirements applicable to the Springfield, NY Facility site in
support of SVMP.
2.2
PURPOSE
The purpose of validation is to assure that the facility, manufacturing process, and
supporting services are capable of supporting the manufacture of pharmaceutical product
that consistently meets its predetermined quality attributes. For this reason, each facet of
the Springfield, NY Facility site related to CGMP manufacture, monitoring, storage, and
testing will be validated. The Validation program is integral to design, construction /
fabrication, and CGMP Operation of the facility. Validation testing is intended to proactively
establish CGMP compliance prior to initiating manufacture of commercial product for
distribution. In addition, the sustenance operations at Springfield, NY Facility, such as
quality change control, calibration program, preventive maintenance, and periodic
requalification of critical equipment and processes ensure that manufacturing equipment
and processes stay under the validated state.
The purpose of this SVMP is to:
Define the requirements and validation approach for validation of systems,

equipment, and processes at Pharma Co., Inc. Corporations Springfield, NY Facility.
To list or reference the documentation supporting the current validated state of the
Springfield, NY Facility.
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This SVMP explains the governance structure in place that will achieve, demonstrate and
maintain acceptable standards of validation for systems, equipment, and processes used in
the manufacture of drug product at the Springfield, NY Facility. If the methodologies and
rationale presented herein are not followed, the rationale behind the alternate approach
must be documented appropriately.
This document is designed to accomplish the following objectives:
3.0
Identify the key Standard Operating Procedures governing and supporting the
validation program presented in SOP-XXXX.
Describe the manufacturing systems, equipment, and processes presently in use at
the Springfield, NY Facility.
Itemize the equipment and utilities used in the Springfield, NY Facility manufacturing
systems and link them to completed validation studies as evidence of a validated
state.
SCOPE
This Site Validation Master Plan applies to all verification, qualification, and validation
activities that support commercial manufacturing at Pharma Co., Inc. Corporations
Springfield, NY Facility. This VMP is a high-level document that refers to various
supporting documents. Validation program elements include:
Validation/qualification of facilities/utilities/equipment and corresponding

automation/controls
Validation of manufacturing processes
Cleaning validation
Sterilization and depyrogenation
Enterprise Computer systems
QC Laboratory equipment and methods
Interval based requalification
The commercial products that are currently manufactured, packaged, or stored at the
Springfield, NY Facility are listed in Table 7.1-1. The equipment within the scope of this
Validation Master Plan are listed in Attachment D, Process Equipment List and Associated
Validation.
4.0
RESPONSIBILITIES
This SVMP will be approved by the heads of the departments (or their designees) listed in
this section.
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The validation activities in Springfield, NY Facility are the responsibility of the Validation,
Engineering, Manufacturing, MTS, and Quality Assurance groups as shown in Figure 1.
The responsibilities outlined below align with the Validation Lifecycle Approach that is
presented in SOP-XXXX.
4.1
SITE QUALITY ASSURANCE VALIDATION
Generate, review, and maintain approve SVMP
Review and approve the sub-VMPs and Project VPs
Assist with the generation of User Requirements (URs) document
Review and approve the URS document
Assist with the performance of risk assessments
Review and approve Risk Assessments documents
Review and approve Critical Aspects (CAs) list and acceptance criteria, as
applicable
Review and approve the Process Control Strategy
Review and approve the Operational Control Strategy
Review and approve Commissioning and Qualification and Validation Plans
Review and approve Qualification Protocols and Reports for facilities, utilities,
equipment, and processes that have CAs
Review and approve Computerized Systems Protocols and Reports
Review and approve Performance Qualification (PQ) Protocols and Reports
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4.2
4.3
Review and approve Process Validation (PV) and Continued Verification

Protocols and Reports
Review and approve Qualification and Validation Protocol Deviations
Approve the use of vendor documentation to verify functionality of facility, utility,

and equipment
Reviewing and
documents
approving
the
Sites
Equipment
Requalification
related
SITE ENGINEERING VALIDATION
Review and approve SVMP
Generate, review, approve, and maintain sub-VMP for Facilities, Equipment

(including QC Lab storage and process equipment, such as refrigerators,
autoclaves and incubators) and Utilities, Cleaning Process, Sterilization and
Depyrogenation Process, and Computerized Systems
Lead/generate, review and approve Site Project VP for new products or projects
Maintain Validation Schedule per the Project Execution Plan (PEP) and Project
VP and CCR timelines
Assist with the generation of URS document
Review and approve URS document
Lead/perform risk assessments using CA list
Review and approve Risk Assessment document
Generate, review, and approve IQ, OQ, PQ Protocols and Reports for facilities,
utilities, equipment, and processes
Generate, review, and approve PQ Protocols and Reports
Generate, review, and approve Protocol Deviations
Review and approve Computer Systems Protocols and Reports
SITE MANUFACTURING TECHNICAL SUPPORT
Review and approve the SVMP, sub-VMPs, and Project VPs, as appropriate
Generate, review, approve, and maintain sub-VMP or PV
Review and approve URS of document
Review and approve Risk Assessment document, as applicable
Review and approve Validation Plans, as applicable
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4.4
Review approve and assist in updating the Process Control Strategy
Generate, review, and approve the Operational Control Strategy
Lead /perform Technical Transfer activities for product transfer
Lead/perform process development / engineering runs
Lead. generate, review, and approve PV and Continued Verification Protocols

and Reports
Execute PV Protocols
Generate, review, and approve PV Protocol Deviations
Create and update Manufacturing Process Descriptions and associated

Manufacturing Flow Diagrams (MFDs)
Generate process related sections of the Project VPs
Review and approve Project VPs that include PV
Lead/perform risk assessments for PV
Create and update Manufacturing History File (MHF)
SITE MANUFACTURING
Assist with the generation of the SVMP, sub-VMPs, and Project VPs, as
applicable
Review and approve the SVMP, sub-VMPs, and Project VPs, as applicable
Review and approve the Process Control Strategy
Assist Site Engineering with generation of project schedule
Generate manufacturing SOPs for use during validation
Review and approve IQ, OQ, PQ, PV, and Continued Verification Protocols and
Reports for facilities, utilities, equipment, and processes as applicable
Prepare schedule in support of IQ, OQ, PQ, PV, and Continued Verification
Protocols execution
Ensure equipment/facilities/materials/personnel availability and technical support

on the operation of the equipment during execution of qualification and validation
activities
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4.5
4.6
Ensure manufacturing procedures are developed for maintaining the validated

equipment in its validated state throughout its lifecycle
Review and approve Protocol Deviations affecting process equipment
Manage and execute the Sites Equipment Requalification program
SITE ENGINEERING
Lead the generation of URS document
Generate Functional Specifications based on URS
applicable
Review and approve the SVMP, sub-VMPs, and Project VPs, as applicable
Generate, review, approve, and maintain sub-VMP for Computer Systems
Generate, review, and approve Computer Systems Protocols and Reports
Review and approve Verification (including IQ and OQ) and PQ Protocols and
Reports for facilities, utilities, equipment, and processes as applicable
Participate in execution of Verification Protocols, as necessary
Review and approve Protocol Deviations affecting facilities, utilities, and

Computer Systems
Review and approve the Sites Equipment Requalification documents related to

facilities and utilities
QUALITY CONTROL
applicable
Review and approve the SVMP and sub-VMPs, as applicable
Generate, review, approve, manage execution of, and maintain sub-VMPs for
QC Laboratories
Review and approve Site Project VP for new products when QC testing is
required
Receive and use transferred validated methods
Review and approve method validation protocols and reports
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4.7
5.0
Generate, review and approve validation protocols and reports for laboratory test
instrumentation
Review and approve laboratory equipment validation protocols and reports

storage and process equipment, such as refrigerators, autoclaves and incubators
Review the PQ and PV protocols for analytical and microbiological testing

requirements, as applicable
Perform testing required for validation samples, as applicable
Review the PQ and PV Final Reports and verify the accuracy of testing data, as
applicable
Review and approve Protocol Deviations affecting QC test results and equipment
REGULATORY AFFAIRS
Assist with the review of SVMP, sub-VMPs, and validation requirements to

ensure compliance with regulatory filings
Update regulatory filings as necessary based on approved validation data
Assess the impact of validation activities on current approved product filings
Provide filing dates as part of validation activity scheduling
Incorporate pertinent validation data into annual reports
DEFINITIONS, ABREVIATIONS AND REFERENCES

5.1
DEFINITIONS LIST
Cleaning
Validation (CV)
Documented evidence that a cleaning process is consistently and

effectively reducing potential product and/or cleaning agent residues to
pre-determined acceptable limits.
Cleaning
Documented evidence that equipment is cleaned to pre-determined
Verification
specifications and may be released for use.
Clean in Place Introduction of cleaning solution and/or water rinses into equipment that
(CIP)
is fixed in place, for purposes of removing potential product and/or
cleaning agent residues.
Clean out of Cleaning of portable or disassembled equipment/parts involving the use
Place (COP)
of a cleaning station in a remote designated location.
Commissioning A well-planned, documented, and managed engineering approach to
the startup and turnover of facilities, systems, and equipment to the
System Owner that results in a safe and functional environment that
meets established design requirements and stakeholder expectations.
Concurrent
Validation of equipment, systems or processes while the equipment,
Validation
system or process is in current use for clinical or commercial production.
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Critical
Aspects (CA)
Critical Process
Parameter
(CPP)
Critical Quality
Attribute (CQA)
Elements of the systems or equipment, which are critical to the product

quality.
A process parameter whose variability has an impact on a critical quality
attribute and therefore should be monitored or controlled to ensure the
process produces the desired quality (ICH Q8 (R2)).
A physical, chemical, biological or microbiological property or
characteristic that should be within an appropriate limit, range, or
distribution to ensure the desired product quality (ICH Q8 (R2)).
Design Review A formal, documented, comprehensive and systematic examination of
the technical aspects of a product design or process. (21CFR Part
820.30)
Direct Impact Utility that is used for manufacturing of the product or critical processes
Utility
(CIP, SIP) such as Water for Injection, Clean Steam, and Process
Gases
Family
A Performance Qualification approach that allows for a reduced number
Approach
of validation studies when using equipment of equivalent design,
manufacture and operational functionality. This approach is typically
used for PQ for Bioreactors and Vessels
Functional
A prospective document that builds on the User Requirement
Requirement
Specification (URS) and provides a basic narrative on what functions
Specification
the process and its control system are expected to perform.
Installation
Establishing documented evidence that the equipment, system or
Qualification
software received is correct, is installed properly, in accordance with
(IQ)
Pharma Co., Inc.s and the manufacturers requirements, and has the
proper documentation and support information.
Matrix approach A validation approach that uses a philosophy which allows for the
testing of a subset of product batches or model / placebo products to
validate the entire range of a product /batch, in lieu of testing each
product / batch in the matrix. Typical examples of appropriate
applications of this approach include mixing validation and pooling
validation. The bracketing selection is based upon product / batch
attributes such as concentration, solubility, ingredient types, and batch
size.
Operational
Establishing documented evidence that the equipment, system or
Qualification
software installed, functions in accordance with Pharma Co., Inc.s and
(OQ)
the manufacturers requirements over the intended range of use, or for
the intended applications.
Performance
Establishing documented evidence that equipment or systems perform
Qualification
in a controlled and reproducible manner in accordance with Pharma
(PQ)
Co., Inc.s requirements under specific operational parameters, either at
the allowable upper and lower limits of the operation or using worse
case conditions compared to intended operating ranges.
Process
The collection and evaluation of data, from the process design stage
Validation (PV) through commercial production, which establishes scientific evidence
that a process is capable of consistently delivering quality products.
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(Guidance for Industry Process Validation: General Principles and
Practices, FDA, January 2011, Rev 1).
Project
A prospective document that defines the scope, requirements, rationale
Validation Plan and protocols necessary for the validation of a new project or process in
an existing site, which is under validated state.
Prospective
Validation of equipment, systems or processes prior to the
Validation
release/approval of the equipment, system or process for commercial
production or commercial distribution of product.
Protocol
A prospective or concurrent test plan with pre-established acceptance
criteria that when executed is intended to produce documented
evidence that a system or system component has been properly tested.
Quality Attribute A physical, chemical, or microbiological property of characteristic of a
material that directly or indirectly impacts quality.
Re-Qualification Establishing documented evidence that existing equipment and
(Periodic
processes continue to operate in a validated state, demonstrating
Qualification)
continued compliance, effective and reproducibility. This protocol type is
utilized for time based re-qualification activities, such as autoclaves,
SIP, ovens, SIP ovens, lyophilizers, environmental rooms, and cleaning
and is not applicable to Change Control Request driven validation.
Re-Validation
The validation of a previously validated process typically necessitated
by a change modification to the process.
Risk Based
An approach that allows basing the project related activities on risk
Approach
analysis and placing extra effort on activities that are assessed as
posing a higher risk to the processes and product quality.
User
A prospective document that describes what the equipment or system is
Requirement
supposed to do, thus containing at least a set of criteria or conditions
Specification
that have to be met. This can include regulatory, corporate, and process
(URS)
requirements.
Validation
Documented evidence, which provides a high degree of assurance that
a specific process will consistently meet its pre-determined
specifications and quality attributes.
Validation
A prospective document that defines the scope, requirements, rationale,
Master Plan
and protocols necessary for the validation of a new project or process.
Validation
A prospective document that provides a detailed test plan used to
Protocol
qualify/validate equipment, systems, utilities, software or processes.
Validation
A document that provides a detailed summary of the results from the
Protocol Final
execution of a Validation Protocol.
Report
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5.2
ABBREVIATION LIST
API
ASME
CFR
cGMP
CIP
CPP
CQA
CA
EMA
FDA
GAMP
ICH
IQ
ISO
ISPE
KPP
MFD
OQ
PEP
PQ
PV
QA
QC
RQ
SIP
SME
SOP
SVMP
UR
VMP
5.3
REFERENCES
6.0
Active Pharmaceutical Ingredient

American Society of Mechanical Engineers
Code of Federal Regulations
current Good Manufacturing Practices
Clean-In-Place
Critical Process Parameters
Critical Quality Attributes
Critical Aspects
European Medicines Agency
Food and Drug Administration
Good Automated Manufacturing Practices
International Conference on Harmonization
Installation Qualification
International Standards Organization
International Society of Pharmaceutical Engineers
Key Process Parameter
Manufacturing Flow Diagram
Operational Qualification
Project Execution Plan
Performance Qualification
Process Validation
Quality Assurance
Quality Control
Re-Qualification
Steam-In-Place
Subject Matter Expert
Standard Operating Procedure
Site Validation Master Plan
User Requirement
Validation Master Plan
See Attachment B for Key regulatory references and Corporate and site SOPs
Governing and Supporting the Springfield, NY Facility Validation Program.
MATERIALS
All materials needed to perform the functions referenced in this document will be found in
the individual referenced documents.
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7.0
PROCEDURE
7.1
SPRINGFIELD, NY FACILITY OVERVIEW

The Pharma Co., Inc., and is located at: 1 Main Street, Springfield, NY.
Pharma Co., Inc.s Springfield, NY facility is a multi-product manufacturing facility for
xxxx products. Manufacturing operations performed at the Springfield, NY facility
include bulk drug substance activities, testing, labeling, and packaging.
Drug substance manufacture for Product A is performed at this facility (see
Attachment A for Process Flow Diagram.)
Packaging and labeling operations are performed at this facility for Product A.
Quality Control (QC) testing for Product A may be performed in qualified laboratories
at Springfield, NY Facility, and approved vendor sites.
Table 7.1-1 outlines the manufacturing activities performed at the Springfield, NY
Facility for each product.
Table 7.1-1: Manufacturing Activities Performed at Springfield by Product
Product
Product A
7.2
Activities Performed at Springfield, NY Facility
Manufacturing, formulation, testing, labeling, and packaging
VALIDATION MASTER PLAN GOVERNANCE
The Validation Program incorporates evaluation and testing to establish:

Manufacturing & Laboratory Facility Installation
Direct Impact Utility Installation, Operation, & Performance
Manufacturing Equipment Installation, Operation, & Performance
Validation of Computer Systems & Software
Validation of Manufacturing Equipment Cleaning Processes and Cycles
Qualification of Laboratory Equipment and Instruments
Validation of Analytical, Physical, & Microbiological Test Methods
Transfer / Development of Manufacturing Processes
Qualification of Environmental Controls and Clean Rooms
Validation of Manufacturing Processes
Assessment and pre-determination of the longevity of CGMP equipment
It is not intended that the SVMP will describe the requirements in detail for execution of the
various Validation Program elements. The detailed requirement description may be found
in sub-VMPs, Standard Operating Procedures, Corporate Level Standards or Practices, or
relevant protocols.
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This SVMP will be revised at a minimum once per year to reflect the changes made to the
validated facilities, utilities, equipment, and processes at Springfield, NY Facility. In
addition, a periodic SVMP Summary Report (issued annually, at minimum) will document
the summary of changes to the validated systems and corresponding validation documents.
The Process Equipment List and associated document numbers will be updated with the
new document numbers and titles.
In order to address the full scope of Validation requirements applicable to the Springfield,
NY Facility site, validation activities have been categorized into eight areas, which will be
executed by corresponding sub-VMPs, to be created, and as listed below:
Sterilization and Depyrogenation Master Plan for Springfield, NY Facility

Cleaning Validation Master Plan for Springfield, NY Facility
Process Validation Master Plan for Springfield, NY Facility
Facility, Equipment, and Utility Validation Master Plan for Springfield, NY
Facility
Computer System Validation Master Plan for Springfield, NY Facility
Requalification Validation Master Plan for Springfield, NY Facility
QC Laboratory Equipment and Instrumentation Qualification Master Plan for
Springfield, NY Facility
Test Method Validation Master Plan for Springfield, NY Facility
The eight sub-VMPs will supplement the overarching SVMP, and will be governed by
corresponding Corporate Quality Operations Standards. The Sub-VMPs will present the
specific validation requirements and projects within each of these validation groupings,
along with the necessary details on the scope, validation approach, roles and
responsibilities, required deliverables (equipment, systems, processes to be validated and
corresponding protocols and documentation, URS, SOPs, test methods, etc.), and
acceptance criteria. The projected schedule and required resources will be covered by the
Project Execution Plan (PEP) and Project VP.
Standard content of the Sub-VMPs will include:
Policy statement and description of Validation Methodology to be followed.
Listing of applicable governance policy and procedures describing program
requirements.
Listing of current approved documentation supporting the validated state for the
program addressed.
Execution plan for the specific validation program addressed (based on calendar
year)
Upon approval of the Sub-VMP, annual updates will be issued to describe the current
years project plan status. Record of the annual review will be attached to the Sub-VMP.
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7.3
VALIDATION APPROACH
Validation of facilities, equipment, computer systems, and processes is performed at
the Springfield, NY Facility for production, monitoring, control, evaluation, and
storage of CGMP products. As indicated in the INTRODUCTION section, this site
VMP is based on the Validation Life Cycle approaches presented at the site level
through governing document SOP-XXXX. SOP-XXXX focuses extensively on the
early phases of a project (risk assessment, requirement specification, design,
construction, and engineering). The Validation Lifecycle Process Key Activities
shown in Figure 2 depicts the use of risk based approach that drives the verification
and qualification activities, which are within the scope of this VMP.
The Life Cycle Approach may be summarized as follows:
Facility Qualification will entail verifying that construction and utility installation is
according to design, and that the process requirements are met. Equipment &
Instrument Verification will verify and document that installation is according to
design (Installation Qualification), meets functional requirements (Operational
Qualification), and user requirements (Performance Qualification). All computer and
automated control systems employed in the facility will also be validated.
Process demonstration, or engineering runs, for new processes/products will be
executed utilizing the proposed manufacturing processes.
The process
demonstration phase will be based on documented process descriptions developed
for the product to be transferred to the Springfield, NY Facility site. To support
process demonstration, the test instruments will be qualified, and test methods will
be validated and / or formally transferred to the site Quality Control / Microbiology
Laboratories. During the demonstration phase, raw material supply, equipment
settings, process parameters, batch record, product storage, standard operating
procedures, and testing will be evaluated to assure satisfactory function. During the
demonstration phase, evaluations specific to processing and product quality may
also be undertaken.
After successful demonstration, confirmatory production performance qualification
and continued verification protocols will be executed to verify and document that the
manufacturing processes are capable of consistently yielding product that meets
predetermined quality attributes when run at prescribed operating settings and within
acceptable operating ranges. Stability testing will also be conducted to support
product expiration dating intervals.
Cleaning validation will be performed for process contact surfaces to assure that the
cleaning operation reduces product and cleaning agent to acceptable levels.
Subsequent to initial validation activities, the facilities, equipment, systems, and
processes are to be maintained in the validated state through implementation of site
procedures, including calibration, preventive maintenance, requalification, work
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order review, and change control. The validated manufacturing processes will be
assessed regularly to assure that it operates within specified critical parameter
ranges and the product produced continues to meet critical quality attribute
specifications. As necessary validation activities can and will be repeated for
facilities, equipment, instruments or processes that have been modified, replaced, or
otherwise altered to a state outside of the originally validated operating parameters.
The validated state of the critical processes, such as cleaning, sterilization, and
storage rooms, will be requalified periodically.
NOTES about the Validation Life Cycle Process:
The activities in this process are executed by a cross functional team, which
include Subject Matter Experts (SMEs) from the impacted stakeholder
departments. The responsibilities of SMEs from various functional areas are
listed in Section 4.0 of this VMP.
The order of activities in the Life Cycle Process follows the sequence shown in
Figure 2.
The requirement documents (user, functional, regulatory, etc) are generated by
contributions from stakeholder groups.
Risk assessment is conducted to identify Critical Aspects (CA) of the equipment
and processes.
Relevant documents are generated and executed per the Verification Plan, such
as FAT, SAT, commissioning, IQ, OQ, and approved prior to starting the next
activity.
Content of the verification protocols will depend upon the risk assessment as
delineated in the Verification Plan.
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The procedures that follow are part of the infrastructure for the validation process and are a
harmonization of these approaches supplemented by direction to specific Standards and SOPs,
when appropriate.
7.4
VALIDATION PROCEDURES
Validation activities occur for new or modified equipment, systems, utilities, software,
processes or routinely for the re-qualification of equipment, systems or processes
per VP-XXXX, Validation Program for Springfield Manufacturing Operations.
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Prospective validation is required for all new facilities, equipment, systems, utilities,
software, or processes that are necessary for the manufacture, testing, and
storage/distribution of commercial product and for clinical material. The steps
followed for a validation project are referred to as the Validation Life Cycle.
Concurrent validation can be used for PV if the manufactured product must be used
for commercial needs in which case, the PV test results must meet all of acceptance
criteria defined in the protocol as well as any other QA, corporate, and regulatory
requirements. For concurrent validation, the details of the conditions that have to be
met prior to the release of the batch for commercial use must be included in the PV
protocol.
The verification (commissioning, IQ, OQ, etc), PQ, and PV protocols are generated
and executed per the SOPs XXXX. The verification / qualification / validation results
are summarized in corresponding final reports.
The final reports are written in accordance with procedure SOP-XXXX and are
reviewed and approved by the same departments that reviewed and approved the
initial protocol.
7.5
VALIDATION SUPPORT SYSTEMS

7.5.1 Re-Qualification Program
The Re-Qualification (RQ) process is governed by SOP-XXXX. The purpose of
this standard is to provide the mandatory compliance requirements for the
routine requalification practices to be utilized for equipment and processes
used in the manufacture of commercial and clinical material. The intent of
requalification is to ensure critical equipment and processes continue to
perform within defined limits and operate in a similar manner as originally
validated. This document is intended to provide direction to all applicable
Pharma Co., Inc. sites to ensure validation requalification programs comply
with current regulations and guidance documents authored by regulatory
agencies and industry organizations worldwide.
Detailed re-qualification requirements for equipment, systems and processes
at Pharma Co., Inc. facilities, which include the Springfield, NY Facility, are
governed by SOP-XXXX. This procedure is intended to define the time-based
re-qualification program for equipment, systems, and processes at Pharma
Co., Inc. facilities. Specifically, the procedure will identify the equipment,
systems and processes requiring routine re-qualification, the required
frequency and the type of testing and documentation required.
In addition, the Steam-in-Place requalification schedule at Pharma Co., Inc.s
Springfield, NY Facility is governed by SOP-XXXX. This requalification plan
identifies the equipment / systems group into families requiring Steam-in-Place
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sterilization procedures as part of a validated process. This requalification
plan also specifies and justifies the requalification frequency of the family
group and the family group members. The validated family groups then
require requalification according to SOP-XXXX.
The re-qualification program assures that critical equipment, systems, and
processes continue to perform within prescribed limits and are operating in a
similar manner as originally validated, thereby demonstrating a continued state
of control.
The re-qualification approach is to perform similar testing utilized during the
initial validation, however at an attenuated level deemed sufficient to evaluate
the performance of the equipment, system or process, and detect potential
adverse changes.
7.5.2 Metrology Program
Calibration policies and procedures are governed by SOP-XXXX, Metrology
Program. The Metrology Program covers the services provided by the
Pharma Co., Inc. Metrology Department to Pharma Co., Inc. Corporation. This
includes, but is not limited to, all Manufacturing and Quality Control operations
at Pharma Co., Inc.s Springfield, NY Facility. Services by the Pharma Co.,
Inc. Metrology Department may also be provided to Pharma Co., Inc.s
subsidiaries and to joint projects involving other companies having
partnerships with Pharma Co., Inc. and its subsidiaries.
In order for equipment to be included in this program, it must be used to
measure, gauge, test, inspect or otherwise examine a quantitative value to a
known degree of accuracy. If such equipment is used, it must be identified as
a Critical, Non-Critical, or Reference Use Only instrument.
Instrumentation requiring calibration must be current prior to and remain
current during protocol execution and throughout the Validation Program.
7.5.3 Change Control Program
The Corporate Quality Operations Standard for Change Control is documented
as SOP-XXXX. The Change Control Program to ensure that equipment within
the Springfield, NY Facility maintains its validated state is governed by SOPXXXX.
These program requirements apply to all Pharma Co., Inc. functional groups
involved in the manufacture and testing of products (both commercial and
clinical including material/ assays used to demonstrate product comparability)
at the Springfield, NY Facility.
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New equipment, both within Quality Control and Manufacturing intended to be
validated, is covered under this Change Control System.
7.5.4 Maintenance Program
The process used for developing and optimizing an effective asset
maintenance program is governed by SOP-XXXX, Springfield, NY Facility
Maintenance Management Program / Work Order System Procedure. The
procedure applies to new and in-service assets based on risks and operational
reliability while assuring employee safety. The process calls for utilizing
operational and maintenance experience relative to 21 CFR Part 210/211 and
quality management systems that must be compliant with CGMP regulations.
The process to determine / evaluate Part 11 compliance and security risks is
included.
The maintenance program targets critical production equipment, QC
Laboratory equipment and test instrumentation, plant utilities and
environmental areas with significant risk to product quality. Process steps for
developing / optimizing the maintenance program are described in the
program. Additionally, instructions for work order management and integration
with the Computerized Maintenance Management System (CMMS) are also
described.
7.5.5 Training Program
The general definitions, responsibilities, methodologies for assignments,
assessments, documentation of training, and integration with the LMS is
governed by SOP-XXXX Learning Management System. This document
outlines the activities required to document training in compliance with CGMPs
and other applicable regulatory requirements and ensures personnel
performing work affecting product quality will be competent on the basis of
appropriate education, training, and experience.
This document applies to the recording of training for full-time, part-time and
non-employees (temporary/contractors) and either concurrent or subsequent
entry of records into the LMS database, where applicable. If a Business Unit
has its own local training procedures, that procedure may take precedence.
Training is further defined in SOP-XXXX, to establish a set of initial, minimal
regulatory training requirements for personnel having the ability to impact
medical device or therapeutic product quality. This document applies to all
full-time, part-time, and temporary employees at all levels whose tasks affect
the design, production, testing, handling and distribution of products, or affect
the environment, process or systems in which products or data are produced,
controlled or managed.
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7.6
KEY SOPs GOVERNING

VALIDATION PROGRAM
AND
SUPPORTING
THE
ALLSTON
LANDING
See Attachment B for a full list of key SOPs and standards used to support the
Springfield, NY Facility Validation Program. The site SOPs are written, revised, and
controlled per SOP-XXXX, Documentation System and Control.
7.7
IDENTIFICATION AND DESCRIPTION OF MANUFACTURING SYSTEMS AND

EQUIPMENT PRESENTLY IN USE AT THE SPRINGFIELD, NY FACILITY AND
ASSOCIATED COMPLETED VALIDATION
See Attachment C for a Process Equipment List and Associated Validation Protocol
Numbers.
7.8
VALIDATION MASTER PLAN REVIEW

This document must be reviewed, updated and approved on an annual basis to
reflect current philosophy, standards and Good Manufacturing Practices. A VMP
Review Schedule must be generated for the time of the year, when the Site VMP
and sub-VMPs will be reviewed and a VMP Review Summary Report generated.
8.0
ATTACHMENTS
8.1
8.2
8.3
Attachment A: Process Flow Diagrams

Attachment B: Key SOPs Governing and Supporting the Springfield, NY Facility
Validation Program
Attachment C: Process Equipment List and Associated Validation Protocol Numbers
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8.1
Attachment A: Product Process Flow Diagrams
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8.2
Attachment B: Key Documents Governing and Supporting the Springfield, NY Facility

Validation Program
Reference Documents
Food and Drug Administration (FDA) 21 CFR Parts 11, 210 & 211
European Medicines Agency (EMA) EudraLex Vol 4
International Committee on Harmonization (ICH) Q7, Q8, Q9 & Q10
International Standards Organization (ISO) - ISO 9001
FDA Guidance for Industry Quality Systems Approach to Pharmaceutical

cGMP Regulations
FDA Guidance for Industry Process Validation: General Principles and

Practices January 2011
ASTM International Designation E2500-07, Standard Guide for the

Specification, Design, and Verification of Pharmaceutical and
Biopharmaceutical Manufacturing Systems and Equipment
Corporate Standards:
SOP-XXXX: Change Control
SOP-XXXX: Quality Manual for the Pharma Co., Inc. Quality System
SOP-XXXX: Corporate Quality Operations Standard: Risk Management
SOP-XXXX: Corporate Quality Operations Standard for Equipment and

Process Requalification
SOP-XXXX: Method Development and Validation
SOP-XXXX: Validation Program
SOP-XXXX: Laboratory Equipment Qualification
SOP-XXXX: Cleaning Validation
SOP-XXXX: Process Validation
SOP-XXXX: Sterilization and Depyrogenation Validation
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General and Administrative SOPs:
SOP-XXXX: Documentation System and Control
SOP-XXXX: Generation of Protocols and Final Reports for Validation
SOP-XXXX: Change Control Procedure
SOP-XXXX: Metrology Program
SOP-XXXX: Records Retention
SOP-XXXX: Springfield, NY Facility Maintenance Management Program /

Work Order System Procedure
SOP-XXXX: Technology Transfer into TMD Manufacturing and Quality
SOP-XXXX: Guidance for 21 CFR Part 11 Compliance for

TMD Computer Systems
SOP-XXXX: Pharma Co., Inc. Corporate Quality Manual

Note: This manual also lists pertinent SOPs for validation
related topics
SOP-XXXX: Documentation of Employee Training
SOP-XXXX: Installation Qualification of Laboratory Instruments
SOP-XXXX: Learning Management System (LMS) Governance and

Documentation
SOP-XXXX: cGMP & Regulatory Training Requirements for Personnel
Engineering SOPs:
SOP-XXXX: Technical Project Management Process for Springfield, NY

Facility Manufacturing Facility
SOP-XXXX:
Facility
SOP-XXXX: Commissioning Procedure for Start-Up of Systems and

Equipment at Springfield, NY Facility
SOP-XXXX: Engineering Document Management Procedure at the

SOP-XXXX: Administration of Drawings at Pharma Co., Inc. Springfield, NY

Facility
SOP-XXXX: Project Change Management Procedure at the Springfield, NY

Facility
Project Lifecycle Management Process - Springfield, NY
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Technical SOPs:
SOP-XXXX: Validation of Autoclaves
SOP-XXXX: Validation of Dry Heat Ovens used in Sterilization or

Depyrogenation Processes
SOP-XXXX: Validation of Filter Integrity Test Instruments
SOP-XXXX: Validation of Temperature/Relative Humidity Controlled Warm

Rooms/Chambers
Key Validation Department Operational SOPs:
SOP-XXXX: Master Validation Plan for the Pharma Co., Inc. Laboratory
Information Management System
SOP-XXXX: Standard Operating Procedure Guidelines for Determination of

Validation Requirements for Change Control Requests
SOP-XXXX: Guidelines for Computer Validation Protocols
SOP-XXXX: Guidelines for Generating, Approving, Amending and Closingout a Validation Plan at Pharma Co., Inc.
SOP-XXXX: Guidelines for the Performance of Airflow Pattern Testing for

Clean Rooms and Laminar Flow Hoods
SOP-XXXX: Protocol Execution Procedure at Springfield, NY Facility
SOP-XXXX: Routine Re-Qualification of Equipment, Systems and Processes
SOP-XXXX: Cleaning Validation and Changeover Verification
SOP-XXXX: Process Validation for Springfield, NY Facility
SOP-XXXX: Process Equipment Steam-in-Place (SIP) Requalification

Matrices and Scheduling Plan at Springfield, NY Facility
SOP-XXXX: Cleaning Master Plan for the Springfield, NY Facility

Manufacturing Facility
SOP-XXXX: Validation Project Execution Life Cycle Approach at the

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8.3
EQ #
Attachment C: Process Equipment List and Associated Validation Protocol

Numbers
Description
Size
Location
IQ
OQ
CIP
SIP
CQ
NOTICE
PQ/PV
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9.0
REVISION HISTORY
Revision History Table
9.1
Revision
Description of Changes
Initial Release
DCR
Number
Related
document
Date
xxxx
xxxx
mm/dd/yyyy
NOTICE

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DOCUMENT NO.

Inc. Springfield, NY Facility

PURPOSE AND INTRODUCTION......................................................................................................3

DEFINITIONS, ABREVIATIONS AND REFERENCES ...................................................................9

Inc. Springfield, NY Facility

PURPOSE AND INTRODUCTION

Define the requirements and validation approach for validation of systems,

Inc. Springfield, NY Facility

Validation/qualification of facilities/utilities/equipment and corresponding

Inc. Springfield, NY Facility

SITE QUALITY ASSURANCE VALIDATION

Generate, review, and maintain approve SVMP

Review and approve the sub-VMPs and Project VPs

Assist with the generation of User Requirements (URs) document

Review and approve the URS document

Assist with the performance of risk assessments

Review and approve Risk Assessments documents

Review and approve the Process Control Strategy

Review and approve the Operational Control Strategy

Review and approve Commissioning and Qualification and Validation Plans

Review and approve Computerized Systems Protocols and Reports

Review and approve Performance Qualification (PQ) Protocols and Reports

Inc. Springfield, NY Facility

Review and approve Process Validation (PV) and Continued Verification

Review and approve Qualification and Validation Protocol Deviations

Approve the use of vendor documentation to verify functionality of facility, utility,

SITE ENGINEERING VALIDATION

Review and approve SVMP

Generate, review, approve, and maintain sub-VMP for Facilities, Equipment

Assist with the generation of URS document

Review and approve URS document

Lead/perform risk assessments using CA list

Review and approve the Operational Control Strategy

Review and approve Risk Assessment document

Generate, review, and approve PQ Protocols and Reports

Generate, review, and approve Protocol Deviations

Review and approve Computer Systems Protocols and Reports

SITE MANUFACTURING TECHNICAL SUPPORT

Generate, review, approve, and maintain sub-VMP or PV

Assist with the generation of URS document

Review and approve URS of document

Review and approve Risk Assessment document, as applicable

Review and approve Validation Plans, as applicable

Inc. Springfield, NY Facility

Review approve and assist in updating the Process Control Strategy

Generate, review, and approve the Operational Control Strategy

Lead /perform Technical Transfer activities for product transfer

Lead/perform process development / engineering runs

Lead. generate, review, and approve PV and Continued Verification Protocols

Generate, review, and approve PV Protocol Deviations

Create and update Manufacturing Process Descriptions and associated

Generate process related sections of the Project VPs

Review and approve Project VPs that include PV

Lead/perform risk assessments for PV

Create and update Manufacturing History File (MHF)

Assist with the performance of risk assessments

Assist with the generation of URS document

Review and approve URS document

Review and approve the Process Control Strategy

Review and approve the Operational Control Strategy

Assist Site Engineering with generation of project schedule

Generate manufacturing SOPs for use during validation

Ensure equipment/facilities/materials/personnel availability and technical support