Number: VV-QUAL-139655 Version: 14.

0 Status: Effective Effective Date: 31 Aug 2021

SOP03657 Process Validation Greensboro PHC
Standard Operating Procedure (SOP)

GBO Organization:
Title: Process Validation
GBO-PHC Quality Assurance
Procedure #: SOP03657 Document Owner: Willis, Heather

1.0 SCOPE
1.1 This procedure applies to the Procter & Gamble (P&G) Greensboro Personal Health Care (PHC) site which
is required to validate production processes and monitor the performance of processes to ensure they
remain in a state of control.
1.2 This procedure provides a lifecycle for process validation of products, production processes, utility
systems, water systems, facilities, lab equipment, and computer systems, equipment, and
instrumentation systems supporting research and development, and manufacturing/distribution at P&G.
2.0 PURPOSE
2.1 This procedure provides uniform means for the P&G Greensboro requirements of product lifecycle for
process validation, and to ensure validation activities are performed and to confirm products,
production processes, utility systems, water systems, facilities, lab equipment, and computer systems,
equipment, and instrumentation systems are fit for use.
3.0 REFERENCES
3.1 EMA/CHMP/CVMP/QWP/BWP/70278/2012-Rev1, Corr.1, Guideline on process validation for finished
products - information and data to be provided in regulatory submissions, 21 November 2016
3.2 EQP-P-01, QA Requirements for Capital Projects and Initiatives
3.3 EU Guide to GMP Volume 4 – Chapter 1; Annex 1; Annex 15, sections 20-35; Annex 18, sections 12.4-12.5
3.4 FDA 21 CFR – Part 211 (Sections 211.63-67, 211.84, 211.110-113)
3.5 FDA Guidance for Industry, Process Validation: General Principles and Practices (January 2011)
3.6 Health Canada Validation Guidelines (2009)
3.7 ICH Q7, Good Manufacturing Practice for Active Pharmaceutical Ingredients
3.8 ICH Q8, Pharmaceutical Development
3.9 LAB-S-06, Periodic Audit Trail Review
3.10 LDR-P-04, Good Data Integrity Practices
3.11 OH-601, Process Validation
3.12 OH-802, Installation and Operation Qualification (IQ/OQ) of Analytical Instruments
3.13 QAS-S-04, Computer-System-Validation
3.14 QAS-S-16, Product Quality Reviews (PQR)
3.15 QAS-R-17, Control and Qualification of Spreadsheets
3.16 SOP02899, Numbering of Validation Documents
3.17 SOP02912, Experimental Orders
3.18 SOP02947, Change Control
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SOP03657 Process Validation
Standard Operating Procedure #: SOP03657
3.19 SOP02969, Equipment Usage and Maintenance Documentation
3.20 SOP03326, Site Equipment and Instrument Identification
3.21 SOP03347, Site Calibration System Management
3.22 SOP03570, Process Centerline Program
3.23 SOP03598, Product Quality Review
3.24 SOP03634, Process Controls
3.25 SOP03651, Statistical Process Control Analysis and Trending
3.26 SOP03751, Deviation and Non-Conformance Handling
3.27 SOP03878, Technical Documentation
4.0 DEFINITIONS
4.1 Acceptance Criteria – The pre-determined specifications or criteria included in a protocol or test plan to
verify that the equipment, facility, system, or process conforms to the pre-determined conditions.
4.2 Addendum Report- A document used to modify, clarify, or nullify a portion of the original report.

4.3 Batch/Run – A specific quantity of a material or finished product that is intended to have uniform
character and quality, within specified limits, and is produced according to a single manufacturing order
during the same cycle of manufacture. For continuous process, it is a specific identified amount produced
in a unit of time or quantity in a manner that assures it’s having uniform character and quality within
specified limits. For operations such as packaging, a run may be defined as one shift of operation
including start-up, shut-down, and a minimum of four hours run time.
4.4 Bracketing – The design of a qualification plan that includes running at the extremes of a certain design
factor such as package size (e.g. qualification runs include only the largest and smallest container size).
This approach may also include running at one or more intermediate sizes and assumes that the
qualification of any intermediate level is supported by validation of the extremes tested.
4.5 Change Control – A control and documentation system that evaluates proposed and actual changes to
ensure that the proper testing and documentation is planned and executed to maintain the facility,
utility, system, or equipment in its qualification or validated state.
4.6 Commissioning – A verification of equipment or processes that are not in direct product contact or in a
GMP area, such as chillers, cooling towers, non-GMP facility equipment. Commissioning can include
verification of equipment installation, operation, and performance.
4.7 Computer System - Includes hardware, software, peripheral devices, personnel, and documentation; e.g.,
manuals and Standard Operating Procedures. ANSI defines a computer system as a functional unit,
consisting of one or more computers and associated peripheral input and output devices, and associated
software, that uses common storage for all or part of a program and also for all or part of the data
necessary for the execution of the program; executes user-written or user-designated programs;
performs user-designated data manipulation, including arithmetic operations and logic operations; and
that can execute programs that modify themselves during their execution. A computer system may be a
stand-alone unit or may consist of several interconnected units.
4.8 Concurrent Validation – A type of validation in which a process is evaluated by a preplanned approved
protocol and predetermined acceptance criteria concurrently with manufacture of product for the
marketplace, therefore individual validation batches may be released to the market as they are produced
and may not be held until completion of all validation. Concurrent release might be appropriate for
processes used infrequently because of limited demand for the product, processes with necessarily low

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SOP03657 Process Validation
Standard Operating Procedure #: SOP03657
production volume per year and processes manufacturing medically necessary drugs to alleviate short
supply (which will be coordinated with the regulatory agency).
4.9 Continued Process Verification (CPV) - The activity that provides ongoing verification of the performance
of a manufacturing process. Guidance issued by FDA in 2011 emphasized the importance of
manufacturers undertaking CPV as an integral part of the process validation lifecycle.
4.10 Control Strategy (CS) – Documented plan that explains the strategy for controlling both material quality
and equipment monitoring related to each unit operation and overall process. Controls may consist of
material analysis and equipment monitoring at significant processing points.
4.11 Critical Process Parameters (CPPs) – A process parameter whose variability has an impact on a critical
quality attribute and therefore be monitored or controlled to ensure the process produces the desired
quality.
4.12 Critical Process Steps – A unit of operation within a process that contains a critical process parameter.
4.13 Critical Quality Attributes (CQAs) – Process measure or output that indicates product potency, product
characteristic, yields, and/or purity that is evaluated to determine whether or not a statistically significant
change occurs in any specific process. Critical quality attributes become the basis for routine product
release testing.
4.14 Design Specifications (DS) - Describe how a system performs the requirements outlined in the Functional
Requirements. Depending on the system, this can include instructions on testing specific requirements,
configuration settings, or review of functions or code.
4.15 Deviation – A variation that occurs during a validation, verification, or commissioning that violates the
overall objective of the protocol, leads to the direct failure of a test run versus acceptance criteria, and/or
impacts the defined critical parameters or criteria defined within the protocol per the associated Quality
Acceptance Criteria (QAC).
4.16 Discrepancy – A variation that occurs during a validation, verification, or commissioning that does not
violate the overall objective of the protocol or lead to the direct failure of a test run versus acceptance
criteria (i.e. typographical errors such as misspelled words, or an incorrect number, etc.).
4.17 E&I - Electrical and Instrumentation.
4.18 E&I Terminal Server – Terminal server located in the E&I Shop that houses the software and PLC
programs for the site. Managed by the electrical & instrumentation group.
4.19 Final Report - A document that summarizes and evaluates the results of an executed Qualification, Plan
or Protocol including a summary of discrepancies or deviations noted during the execution. The final
report must contain a conclusion statement.
4.20 Functional Design Specifications (FDS) – Documented evidence that a system has been designed to meet
requirement specifications derived by the user.
4.21 Good Data Integrity Practices – assures that data and records comply with regulation/guidances issued
by, but not limited to, United States Food and Drug Administration (FDA), World Health Organization
(WHO), Medicines and Health Products Agency (MHRA), and Health Canada.
4.22 Good Documentation Practices (GDP) - A term in the pharmaceutical and medical device industries to
describe standards by which documents are created and maintained
4.23 Good Manufacturing Practices (GMP) - The practices required to conform to the guidelines
recommended by agencies that control authorization and licensing for manufacture and sale of food,
drug products, and active pharmaceutical products
4.24 Installation Qualification (IQ) – Documented verification that all aspects of a piece of equipment, facility

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SOP03657 Process Validation
Standard Operating Procedure #: SOP03657
or system that can affect product quality, has been constructed and installed as designed with the
expected capacity, and proper materials (static checks). Also, IQ documents that the equipment, facility
or system is properly connected, calibrated, and functions in accordance with all predetermined criteria
and that all cGMP (current Good Manufacturing Practices) requirements have been fulfilled.
4.25 Interim Report - A document that summarizes and evaluates the results of a partially executed
Qualification, Plan or Protocol including a summary of discrepancies or deviations noted during the
execution. An interim report can be written for product release for a concurrent validation.
4.26 Life Cycle – An approach to system development that begins with the identification of user requirements
and continues through design, integration, qualification, validation, change control and maintenance,
ending only when commercial use of the system is discontinued.
4.27 Manufacturing Area PLC’s - Located within a manufacturing area for the purpose of controlling the
manufacturing process.
4.28 Non-Validated Parameter or Routine/File - Any parameter or routine/file within a PLC program that has
no potential Quality impacts and has not been documented within a validation document.
4.29 Operational Qualification (OQ) – Documented verification that all aspects of a piece of equipment, facility
or system that can affect product quality, operates as intended throughout the anticipated operating
ranges and that all functional cGMP requirements have been fulfilled (dynamic checks). Operating ranges
should be shown capable of being held as long as would be necessary during routing production.
4.30 Performance Qualification (PQ) – Documented evidence that covers 2 phases: 1) the design of the facility
and qualification of the equipment, and utilities, and 2) process performance qualification.
4.31 PLC – Programmable Logic Controller.
4.32 Process – All key procedures and equipment used to produce a product and to assure its integrity and
quality. This may include measurement systems, cleaning and sanitizing procedures, and
manufacturing/packaging equipment, etc.
4.33 Process controls – Sampling and testing during commercial production of products to ensure that
processes remain controlled to validated conditions.
4.34 Process parameters – Numerical measures of the equipment operation (e.g. rpm (revolutions per
minute), psi (pounds per square inch), screen size).
4.35 Process Performance Qualification (PPQ) – Documented evidence of the effectiveness and reproducibility
of a process. The process performance combines the actual facility, utilities, equipment (previously
qualified in IQ, EO, OQ), and the trained personnel with the commercial manufacturing process, control
procedures, and components to produce commercial batches.
4.36 Process Validation – The collection and evaluation of data across the 3 stages 1) process design,
2) process qualification, and 3) continued process verification which establishes scientific evidence that a
process is capable of consistently delivering quality product. Process validation involves a series of
activities taking place over the lifecycle of the product and process.
4.37 Product Quality Review (PQR) - document summarizing the regular review of quality parameters affecting
a product or material’s specifications, manufacturing, or control procedures. The PQR is applicable to
types materials and products for which there is a Regulatory requirement in the region where marketed
for a periodic review.
4.38 Project Validation Master Plan (VMP) – A living document that describes the validation strategy for a
large initiative or project requiring multiple validations.
4.39 Programmer/Validation Executor – A person possessing skills and qualifications necessary to implement
program changes and write and/or execute validations that prove system capability and reliability.

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SOP03657 Process Validation
Standard Operating Procedure #: SOP03657
4.40 Prospective Validation – A type of validation in which a process is evaluated by a preplanned approved
protocol and predetermined acceptance criteria prior to distribution.
4.41 Protocol – A written plan stating how the qualification will be conducted, including product
characteristics, production equipment, test parameters and decision points on what constitutes
acceptable results.
4.42 Qualification - An action of providing that equipment or ancillary systems are properly installed, work
correctly, and lead to the expected results. Qualification is part of validation, but the individual
qualification steps alone do not constitute process validation.
4.43 Revalidation – Repetition of all or part of the validation process.
4.44 Routine/File - segmented portions within a PLC program that possess code that monitors and initiates
actions.
4.45 Simple Test Plan (STP) – A standalone validation document, which has a list of tests that provided
evidence that the control logic changes, and/or wiring changes are functioning properly and no other
logic has been adversely affected.

4.46 Single Batch Verification (SBV) – A one batch verification run that is used to verify product quality.
Circumstances under which SBV is acceptable can include sales samples runs in which only one
production run is conducted or to verify a product or process that is technically justified to be lower risk
due to similarities in formulation or equipment design but still requires verification to confirm product
quality.
4.47 Site Validation Master Plan (SVMP) – The document that defines the validation strategy and
requirements for overall management of the validation program.
4.48 User Requirements Specifications (URS) -The key document in the system development life cycle that is
required for both business (investment protection) and regulatory reasons (defining intended purpose).
4.49 Validated Parameter or Routine/File - any parameter or routine/file within a PLC program that has
potential Quality impacts and/or has been documented within a validation document.
4.50 Verification – a confirmation that products, processes, utilities systems, facilities, equipment, laboratory
systems, or control and information systems remain in validated state.
5.0 RESPONSIBILITIES
5.1 It is the responsibility of Procter & Gamble employees to follow this procedure.
5.2 All originators and approvers of process validation protocols and reports, Site and/or Project Validation
Master Plans must be properly trained according to site GMP (Good Manufacturing Practices)
training/documentation requirements.
• Follow Table 1 below for guidance on ownership of originating and approving protocols and reports.
• Protocol and report templates found in the attachments will be used for validation activities.
• Protocols and reports will be uploaded, edited, reviewed, and approved electronically in Veeva Vault
where the documents will be stored. When approvers are not trained and set up in Veeva Vault, hard
copy approval is acceptable for them. However, the document will then be uploaded to Veeva Vault
for the remainder of the approval electronic signatures.
• Protocol and report titles, and the Veeva Metadata Name must be structured in the following order:
Area/Line, Manufacturer, Equipment Type, or Formula, Protocol Type, and Protocol, Report, or
Assessment.
• Protocols and/or reports that receive 10 or more annotations during the review process will continue
to be reviewed until less than 10 annotations are obtained. Upon addressing these 9 or fewer
annotations, the document can then be sent for approval.
• Approvers may designate one qualified backup within their organization who may approve in

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SOP03657 Process Validation
Standard Operating Procedure #: SOP03657
their absence. If the backup is also unavailable, approval may be completed by a person in the same
function who is at the same level or higher.
• The approvers who approve a validation protocol must be the same approvers (or backup/designee)
• for the final report.
• External service providers, such as contractors and consultants, may assist in execution of
validation/qualification activities. However, documentation must be provided to support their
qualification, resume, and/or any training. Procter and Gamble employees that utilize external service
providers must ensure all documentation is in place prior to execution of validation/qualification
studies.
• Any individual accessing PLC code for the purpose of modifying it as part of a project and/or protocol
execution is responsible for ensuring that any identified validated parameter or routine/file is uniquely
identified with the descriptor “VALIDATED”. This identifier must be capitalized and in parenthesis.
5.2.1 Originator
5.2.1.1 Responsible for all technical content in the process validation protocol and report, the
executed protocol, or the Validation Master Plan where applicable. This includes
ensuring that all calculations and conclusions are technically accurate.
5.2.1.2 Identify critical processing parameters and acceptable ranges.
5.2.2 Project Leader
5.2.2.1 Responsible for communicating when to begin batch control requirements (i.e.
process order letter coding and memo details (reference SOP02869, Batch Assignment
Process) to all affected areas 3 ways: 1) electronically to operations leadership, 2)
placing an FYI at each affected area’s work station (i.e. PLQT/Admin desk), and 3)
placing an FYI in each affected area’s team room for discussion at shift transition prior
to the batch assignment.
Responsible for communicating when to stop batch control requirements to all
affected areas 3 ways: 1) electronically to operations leadership, 2) placing an FYI at
each affected area’s work station (i.e. PLQT/Admin desk), and 3) placing an FYI in each
affected area’s team room for discussion at shift transition prior to the further batch
assignments. If previous paperwork is available, remove it from the areas.
5.2.3 Approvers
5.2.3.1 Ensure that the Site Validation Master Plan clearly defines the validation strategy and
requirements for overall management of the validation program.

5.2.3.2 Ensure that the Project Master Plan describes the validation strategy appropriately for
the initiative or project.

5.2.3.3 Ensure that the process validation protocols are designed to achieve appropriate
technical objectives as pre-determined by the technical team.
5.2.3.4 Ensure that the protocol can be executed properly as written.
5.2.3.5 Ensure that all deviations from the approved protocol are documented and approved
before proceeding to the next stage of validation.
5.2.3.6 Ensure the protocols clearly describes the Product Disposition Intent. Product
Intended for “Testing Purposes Only” is deemed as “Intent to Scrap” and must be
scrapped after completion of testing. Product Intended for “Commercial Use” is
deemed as “Intent to Release” and will be dispositioned following normal work
processes [Standard Operating Procedure (SOP) SOP02981 Finished Product

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Disposition Procedures and SOP02925 Disposition and Destruction of Non-Performing
Inventory (as needed)].
• For PQR Reporting (Product Quality Report) and for FDA Metrics Reporting, the
FDA requires: Reporting of data should include all manufacturing operations,
including testing, which would be included in a Periodic Product Review (PPR)
(e.g., lots intended for commercial distribution, post-approval clinical trial lots
when the same manufacturing process and controls are used as for commercial
lots). Therefore, lots that are not intended for commercial distribution such as
those that are defined in a protocol as intended for scrap, are to be excluded from
FDA Metrics Reporting. Similarly, lots that are intended for commercial
distribution that are defined in a protocol as intended for release as saleable
product, need to follow not only the requirements of Protocol Deviation
Reporting (as required by applicable SOP), but also the requirements of
SOP03751, Deviation and Non-Conformance Handling.
• See Attachment VII – Guidance for Disposition and Deviation Reporting for
Production Intended for Scrap and Production Intended for Commercial
Distribution (PQR and FDA Metrics Requirements).
5.2.3.7 Ensure that the report clearly summarizes the protocol results and that the executed
protocol is completed in its entirety and as written.
5.2.3.8 Ensure all validation data/results support the conclusions and recommendations in
the process validation report.
5.2.3.9 Ensure that acceptance criteria are appropriate for the type of validation being
performed.
5.2.3.10 Ensure that bulk product involved in the validation efforts are clearly documented
within appropriate disposition (i.e. Release to Pack (REPA)).
5.2.3.11 Ensure no finished products involved in the validation efforts are released (Usage
Decision of “Accept” in SAP) to distribution until the validation is successfully achieved
and all appropriate validation documents (Interim Reports or Final Reports) are
reviewed and approved.
5.2.3.12 Ensure that the protocol and report follow all applicable Quality SOPs and policies.
5.2.4 Site Quality Assurance (QA) Validations Leader (additional responsibilities)
• Approve as site validation leader and after all other approvers for Final QA on all
validation and commissioning protocols and reports. Review the executed protocol to
ensure that it is completed in its entirety and as written.
• Ensure validation files exist and are kept current.
 For validations involving manufacturing site equipment and/or marketed product, the
original validation protocols & reports must be filed at the manufacturing site.
 For validations associated with R&D studies, the original validation protocols &
reports must be filed at the appropriate R&D facility (in Central Records) and
photocopies of the approved validation protocols & reports must be filed at the Swing
Road site.
 For Corporate validations of site systems, the original validation protocols & reports
should follow the procedure outlined in QAS-S-04, and copies may be retained at the
corporate site.
• Ensure that the protocols, reports, and other templates found in the attachments are
followed where applicable.

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SOP03657 Process Validation
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Note: The site QA Validations leader may act as the QA Project Leader in some
instances. In those cases, that individual may sign for both approvals.

5.2.5 Other Approvals

• Approvals may be added as necessary. The site QA Validations Leader should be consulted
during protocol generation to determine the appropriate approvals.
• Validation reports are reviewed by the same experts that approved the protocols to gain
concurrence that the testing has been performed correctly and that success criteria have
been met. Designated back-ups can sign reports if a protocol signatory is absent. The
executed protocol is reviewed to ensure that it is completed in its entirety and as written.
• Additionally, any technical justification proposed to explain and mitigate a failure is
approved by QA and the relevant operational leadership.

TABLE I - RESPONSIBLE ORIGINATOR AND REQUIRED APPROVERS (MINIMUM REQUIREMENTS)

Scope: Utility systems, facilities, equipment, formulation, designs, packages, making and packing
Planning processes
Existing (re-validation with no
New Changes
changes)
Originator Launch Leader Launch Leader Launch Leader
Mandatory Engineering Engineering Engineering
Approvers ITOT ITOT ITOT
(VMP) E&I E&I E&I
Operations Leader Operations Leader Operations Leader
QA Project Leader QA Project Leader QA Project Leader
Site QA Validations Leader Site QA Validations Leader Site QA Validations Leader
Optional E&I Leader E&I Leader E&I Leader
Approvers Analytical Leader Analytical Leader Analytical Leader
Micro Leader (clean/san scope) Micro Leader (clean/san scope) Micro Leader (clean/san scope)
Design Scope: Utility systems, facilities, equipment

Existing (re-validation with no

New Changes
changes)

Originator Engineering Engineering Engineering

Mandatory Operations Leader Operations Leader Operations Leader
Approvers Engineering (Control Strategy) Engineering (Control Strategy) Engineering (Control Strategy)
(EO/DOX, Safety Leader (EO/DOX) Safety Leader (EO/DOX) Safety Leader (EO/DOX)
Control Finance Leader (EO/DOX) Finance Leader (EO/DOX) Finance Leader (EO/DOX)
Strategy) QA Project Leader QA Project Leader QA Project Leader
Site QA Validations Leader Site QA Validations Leader Site QA Validations Leader
Optional ITOT ITOT ITOT
Approvers E&I Leader E&I Leader E&I Leader
Micro Leader Micro Leader Micro Leader
Analytical Leader Analytical Leader Analytical Leader

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Qualification Scope: Utility systems, facilities, equipment, formulation, designs, packages, making and packing
process
Existing (re-validation with no
New Changes
changes)
Originator Engineering/Initiative Leader Engineering/Initiative Leader Engineering/Initiative Leader
Mandatory Operations Leader Operations Leader Operations Leader
Approvers Engineering Engineering Engineering
(IQ, OQ) QA Project Leader QA Project Leader QA Project Leader
Site QA Validations Leader Site QA Validations Leader Site QA Validations Leader
Mandatory Operations Leader Operations Leader Operations Leader
Approvers E&I Leader E&I Leader E&I Leader
(STP) ITOT ITOT ITOT
QA Project Leader QA Project Leader QA Project Leader
Site QA Validations Leader Site QA Validations Leader Site QA Validations Leader
Mandatory Operations Leader Operations Leader Operations Leader
Approvers Site MPD Process / Packaging Site MPD Process / Packaging Site MPD Process / Packaging
(PPQ, Cleaning Central PD/MPD Section Head Central PD/MPD Section Head Central PD/MPD Section Head
and/or Category QA Manager Category QA Manager Category QA Manager
Sanitization) QA Project Leader QA Project Leader QA Project Leader
Site QA Validations Leader Site QA Validations Leader Site QA Validations Leader
Micro Leader (Clean/San) Micro Leader (Clean/San) Micro Leader (Clean/San)
Analytical Leader (Clean/San) Analytical Leader (Clean/San) Analytical Leader (Clean/San)
ITOT ITOT ITOT
Optional
E&I Leader E&I Leader E&I Leader
Approvers

Note: for Project Validation Master Plan Template approval requirements, reference the template.
Verification
SCOPE: UTILITY SYSTEMS, FACILITIES, EQUIPMENT, FORMULATION, DESIGNS, PACKAGES,
(SBV, Cleaning
MAKING AND PACKING PROCESSES
and/or Sanitization
Verification) Existing (re-validation with no
New Changes
changes)
Originator Operations/Site MPD Process Operations/Site MPD Process Operations/Site MPD Process
Mandatory Operations Leader Operations Leader Operations Leader
Approvers Site MPD Process Site MPD Process Site MPD Process
Central PD/MPD Director Central PD/MPD Director Central PD/MPD Director
Category QA Manager Category QA Manager Category QA Manager
QA Project Leader QA Project Leader QA Project Leader
Site QA Validations Leader Site QA Validations Leader Site QA Validations Leader
Micro Leader (Clean/San) Micro Leader (Clean/San) Micro Leader (Clean/San)
Analytical Leader (Clean/San) Analytical Leader (Clean/San) Analytical Leader (Clean/San)
Optional Approvers ITOT ITOT ITOT
E&I Leader E&I Leader E&I Leader
Engineering Engineering Engineering

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SOP03657 Process Validation
Standard Operating Procedure #: SOP03657
Commissioning
SCOPE: UTILITY SYSTEMS, FACILITIES, EQUIPMENT, FORMULATION, DESIGNS, PACKAGES,
(IV, OV)
MAKING AND PACKING PROCESSES
Existing (re-validation with no
New Changes
changes)
Originator Operations Operations Operations
Mandatory Operations Leader
Operations Leader Operations Leader
Approvers Engineering
Engineering Engineering
Site MPD Process
Site MPD Process Site MPD Process
QA Project Leader
QA Project Leader QA Project Leader
Site QA Validations Leader
Site QA Validations Leader Site QA Validations Leader
Optional Approvers ITOT ITOT ITOT
E&I Leader E&I Leader E&I Leader
Micro Leader Micro Leader Micro Leader
Analytical Leader Analytical Leader Analytical Leader
6.0 PROCEDURE
6.1 Templates attached to this SOP will be used for all validation activities.
6.2 Product Lifecycle Overview of Process Validation

TABLE II – PRODUCT LIFECYCLE OVERVIEW OF PROCESS VALIDATION

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6.2.1 Validation Planning activities shall be documented in two options:

• Project Validation Master Plan (VMP) – The project validation master plan will be used for
all large initiatives and/or projects requiring an overview change control and will be
assigned as a follow up to the associated overview change control. The plan will
document all validation requirements providing rationales for why validation is or is not
required, and all impacts related to product and associated facility and equipment
changes as well as any bracketing approaches to the validation plan. The plan will
establish requirements for all aspects of validation including, but not limited to, process
validation, computer system validation, cleaning and sanitization validation, and bulk hold
validation. Reference Attachment XII for the VMP template. Small projects not requiring
an overview change control will be managed solely through the change control process
where the appropriate validation documents will be assigned upon change control
approval.
6.2.2 Process validation activities include three stages throughout a product lifecycle:
• Stage 1 - Process Design - There are two steps to the design stage. The first step of
process, knowledge and understanding, is defined during this stage based on knowledge
gained through development and scale up activities. Activities conducted during this stage
can include Experimental Orders (reference SOP02912, Experimental Orders), R&D
development activities, and engineering development activities such as creation of User
Requirements Specifications (URS), Functional Design Specifications (FDS), Design
Specifications (DS), Engineering Instructions, etc. These engineering documents are stored
according to SOP03878, Technical Documentation and are referenced or attached to
associated validations. The second step, process control strategy, is defined by
establishing an approach to process control for each unit operation (equipment
monitoring) and material quality (sampling plans).
• Stage 2 - Process Qualification - The installation, operation and performance of the facility,
utilities, equipment, systems and processes designed are evaluated to determine if the
process is capable of reproducible commercial manufacture. Products manufactured
during the last step in this stage, if acceptable, can be released for distribution. These
activities include Factory Acceptance Testing (FAT), Site Acceptance Testing (SAT) (where
applicable), Installation Qualification (IQ), Engineering Study (EO), Operational
Qualification (OQ), Simple Test Plan (STP), and Process Performance Qualification (PPQ).
• Stage 3 - Continued Process Verification (CPV) - continual monitoring to assure that the
commercial manufacturing process remains in state of control and capable of consistently
producing product that meets all quality attributes and specifications.
Note: Running current business production outside the planned project schedule
while executing validation activities on the same equipment is not permitted without prior
QA Approval via an Authorized Planned Deviation. In the event business need dictates use
of this practice, an Authorized Planned Deviation will be created per CMP00761, Planned
Deviation, which outlines a thorough risk assessment.

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Table III. Product Lifecycle Overview of Process Validation

6.3 Process Design (Stage 1)

6.3.1 Process design activities must focus on producing a process suitable for routine commercial
manufacturing that can consistently deliver a product that meets its quality attributes.
• Process information available from product development activities must be leveraged in the
process design stage. The ability to design an efficient process with an effective process
control approach is dependent on the process knowledge and understanding obtained.
• It is essential that the product development activities and associated studies are documented.
Documentation must reflect the basis for decisions made about the process and support any
design changes. The documents produced during this stage are User Requirement
Specifications, Functional Design Specifications, and Design of Experiments.
6.3.2 Statistical process controls must be identified for each unit operation and the overall process.
Process controls must address variability to assure the quality of product by either reducing
the variation of inputs going into the process or by adjusting for this variation during the
manufacturing operation. A combination of both approaches maybe used as appropriate.
• Process controls must include information that specifies the critical process parameters and
rationale for determining Critical Process Parameters (CPPs), including those related to
materials and equipment.
• Critical Quality Attributes (CQAs) must be defined for process outcomes.
• Post regulatory submission documentation, if applicable, is to be provided containing
information to support initiation of PPQ.

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6.4 Process Impact Assessment, Commissioning/Qualification (Stage 2)

6.4.1 Impact Assessment is the process of evaluating impact of the operating, controlling, alarming
and failure conditions of a system.
• Direct Impact: A system, change or failure that has, or can have a direct effect on product
quality or patient safety and requires Process Commissioning.
• Indirect Impact: A system, change or failure that has or can have an indirect effect on product
quality or patient safety and requires Process Commissioning.
• No-Impact: A system, change or failure that has no effect on product quality or patient safety
that will not require Process Validation or any part thereof, or may include commissioning, at
the discretion of the system owner.
6.4.2 Process Qualification establishes evidence which provides a high degree of assurance that a
specific process or formulation will consistently produce a product meeting predetermined
specifications and attributes. It includes all the activities of performing Factory Acceptance
Tests, Site Acceptance Test (where applicable), Installation Qualification, Operational
Qualification, Experimental Orders / Engineering Studies (where applicable), and Process
Performance Qualification.
Factory Acceptance Tests (FAT) verify that the system meets requirements before leaving the
supplier factory. FAT should be conducted on all direct impact systems and equipment procured
for the making or packing of product. See the Site Validation Master Plan for direction.
Site Acceptance Tests (SAT) verify that the system meets the requirements when installed on site
and successful completion often symbolizes transfer of ownership from the supplier to the
facility.
Installation Qualification (IQ) verifies that the system is constructed and installed according to the
design. Installation Qualification should be conducted on all new equipment pertaining to GMP
processes, facilities, utilities, laboratories, and controls systems and information systems. The IQ
should verify at a minimum that equipment is installed as specified and operates per the
functional description. It should verify that utility systems and equipment are built and installed
in compliance with the design specifications (e.g., built as designed and properly connected and
calibrated). Reference Attachments I and II for IQ protocol and report templates. Note: IQ
covers qualification of all products, production processes, utility systems, water systems, and
facilities. Additional requirements for lab equipment and control systems and information
systems validation are covered below.
Operational Qualification (OQ) verifies that the system operates in accordance with the process
requirements in all anticipated operating ranges. This should include challenging the equipment
or system functions while under load comparable to that expected during routine production. It
should also include the performance of interventions, stoppage, and start-up as expected during
routine production. Operating ranges should be shown capable of being maintained as long as
would be necessary during routine production. Reference Attachment III and IV for OQ protocol
and report templates, and Attachments V and VI for IQ/OQ protocol and report templates.
Simple Test Plan (STP) provides evidence that simple Programmable Logic Controller (PLC)
changes function properly, and no other logic has been adversely affected. It may be used only as
a Control System & Information System validation with limited changes. Typically, simple
changes to a control system, such as a pressure alarm, indicator light or display, changing a
process set point, changing a timer setpoint, addition of a sensor for information/alarm only (not
control), addition, removal, or modification to logic limited to 5 – 10 rung, or addition, removal,

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or modification to wiring limited to 3 – 6 wires would require a Simple Test Plan. The Simple Test
Plan is to be approved prior to making changes and prior to execution. After execution, the
associated Test Plan Report must be approved and must include Logic Rungs and/or Comparison
Reports when applicable.
Process Performance Qualification (PPQ) provides evidence of the effectiveness and
reproducibility of the process combining the actual facility, utilities, equipment (qualified IQ, EO,
OQ) in producing product to specifications. All supporting documentation (cleaning assessments,
technical rationales, IQ and OQ Reports, etc.) must be approved prior to moving into PPQ
activities. A successful PPQ will confirm the process design and demonstrate that the commercial
manufacturing process performs as expected. A successful PPQ completion must be met before
commencing commercial distribution. See sections below for additional requirements of the
Process Performance Qualification. Reference Attachments VIII and IX for PPQ protocol and
report templates.

Note: Vendor validation documentation may be used but they must be included as an
attachment to a site validation protocol. Validation protocols provided by a vendor should be
audited by qualified site personnel to ensure that they have the appropriate acceptance criteria
and that design requirements are met. Upon execution, the vendor validation should be
reviewed for accuracy and correctness by a qualified P&G resource prior to completion of a site
validation report summarizing the results of the validation.
6.4.3 Process Performance Qualification (PPQ)
6.4.3.1 The performance of commercial manufacturing process must be qualified before it can
be used to supply material intended for commercial use (i.e. drug that is marketed,
distributed, and sold or intended to be sold). The process performance will demonstrate
that the commercial manufacturing process can consistently produce products that meet
established specifications and quality attributes at the line level.
6.4.3.2 It is expected that only the critical steps of a commercial manufacturing process that
have direct impact on critical quality attributes of a product will be qualified. Risk
assessment using process and product knowledge must be used to determine and
evaluate the critical steps of the commercial manufacturing process.
• Where the process is intended to be operated at different set points (feed rate,
agitation speed, batch size, etc.) the qualification must include data collection or
technical justification to support each of the different conditions.
• Product homogeneity will be performed by conducting quantitative testing of a
minimum of nine samples on all active ingredients and any other ingredients or
parameters that affect product efficacy throughout the qualification runs. If less than
nine samples are tested (i.e. beginning, middle and end of qualification), a technical
justification must be provided for the sampling plan.
6.4.3.3 The number of consecutive batches required for the PPQ is determined by all relevant
development data (including scale-up batches, experimental batches, etc.). The data
collected and analyzed during the performance qualification to demonstrate process
reproducibility may be used to establish a baseline for the continuous process
verification. Process verification execution and frequencies will be governed by the Site
Validation Master Plan.
• In a case where Sales Samples are needed for Procter & Gamble, a single batch
qualification may be performed in order to release the single production batch;
however, additional validation must occur in order to meet the requirement
determined by all relevant development data, typically 3 consecutive batches.

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6.4.3.4 Process Performance Qualification (PPQ) must be performed using approved protocols.
6.4.3.5 Prior to executing process performance qualification, the following related elements
must be in place:
• Facilities, utilities, systems, equipment, software etc. that have a direct impact
on product safety, identity, integrity; efficacy, quality, and/or purity must be qualified
and released for use.
• Qualified, validated, and/or suitable analytical methods must be documented and
approved.
• The process control and testing instrumentation required to ensure that the process
will perform as designed and to test product quality attributes must be calibrated or
qualified.
• Raw materials, in-process, and finished product testing methods and specifications
must be established, documented, and approved.
• Raw material suppliers must be approved.
• Personnel must be trained.
• Batch record(s) and procedures that encompass all activities required to perform the
process performance qualification must be approved.
6.4.3.6 After all the tests results and the executed batch records of the process performance
qualification have been reviewed a report must be prepared. The report must include
but not limited to the following:
• The data and records generated to meet the requirements of the protocol, or a
reference to such records.
• Summary of data collected and analyzed, as specified by the protocol.
• Control limits, calculated from a statistical analysis of results data, if required.
• Evaluation and discussion of any unexpected observations and additional data not
specified in the protocol.
• Evaluation and discussion including impact assessment of all manufacturing non-
conformances such as deviations, aberrant test results, or other information that
has bearing on the validity of the process.
• A replacement batch may be included for one of the PPQ batches if the original batch
needs to be replaced for a non-process cause (e.g. power failure).
• Evaluation and discussion of any corrective and preventive actions (CAPAs) and
changes that must be considered for continuous process improvements.
• Conclusion as to whether data analyzed indicates that the process and product met
the protocol criteria and whether the process is in state of control. If not, the report
must specify the corrective and preventive actions (CAPAs) or changes to the
process.
6.4.3.7 Concurrent PPQ may be allowed for products manufactured at a low frequency. Each
PPQ batch shall comply with the requirements of a prospective study but may be
released individually. Concurrent PPQ may also be conducted for validations of
equipment or processes requiring manufacturing runs over an extended period of time,
such as validations of site compressed air quality, purified water quality, or cleaning and
sanitization validation.
• This practice is permissible only if it is acceptable to the market regulatory authority,
justifiable and approved in advance by Quality Assurance.
• Concurrent validations of facilities and utilities systems including air quality, purified
water, compressed air, etc. should include monitoring of seasonal impacts on
product quality to ensure that acceptance criteria is maintained year round.

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• A PPQ report must be written at the conclusion of each batch or study followed by a
final summary report that shall be written, after the final PPQ batch is completed.
• Release of validated lots in a PPQ may be allowed with the approval of an interim
report provided that the PPQ batches pass all validation testing and meet finished
product release criteria.
6.4.4 Process Commissioning [Installation Verification/Operational Verification (IV/OV)]
6.4.4.1 If equipment or processes are part of a non-GMP area or are classified as non-product
contact, a commissioning approach may be executed to verify that the equipment or
process is installed, and functions as designed.
• Testing may be conducted to verify equipment but may require less stringent
acceptance criteria than a process qualification. For example, an IQ/OQ for an HVAC
that supplies air to a GMP space may include air quality testing to ensure product
quality is not compromised in addition to standard operability testing, but a
commissioning for an HVAC that supplies air to an office space (non-GMP) may only
require standard testing to verify operability. Reference Attachments X and XI for
IV/OV protocol and report templates.
6.4.5 System Specific Guidance for IQ/OQ/PPQ/Commissioning (As needed)
6.4.5.1 Validation of Product Changes in API Manufacturer, API site, or API Process
• API must be from an approved manufacturer.
• Evaluate Certificate of Analysis for 3 lots of new API compared to current API.
• Compare new API to site specifications.
• If new API is equivalent to current, then no PPQ batches are necessary, but
demonstration batches to support regulatory requirements must be considered.
• If new API is not equivalent, perform risk assessment. If the difference is not
significant, then no PPQ is necessary, but batches to support regulatory
requirements must be considered. If the difference is significant, a minimum of
one PPQ batch is required.
• Develop a sampling plan based on the risk assessment.
• Additional requirements for routine batch monitoring must be documented.
6.4.5.2 Lab Validations
• Lab Validations should follow the same qualification process and use the protocols
provided in the attachments.
• Compliance with electronic record and electronic signature regulation must be a
factor for computer operated instruments.
• The in-house qualification of the analytical instruments is composed of at least the
stages of IQ and OQ. Depending on the equipment, and its intended use, a PQ will be
added as a third stage. Where applicable, aspects of data security (e.g. backup, audit
trails, and restoration) must be included in the OQ.
• Any critical steps in the IQ/OQ must include screenshots, where applicable.
• Lab Instrument Categories and Validation Requirements
• Instruments are to be categorized according to their complexity into the following
groups:
 Group A: Instrument with no measurement capability. Simple
and mostly
mechanical instruments which are used in preparatory phases of the
analytical work, (e.g. evaporator, magnetic stirrer).

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Validation Requirements: Only visual inspection, usually documented activity
is not necessary (In some cases the availability of the calibration certificate is
needed).
 Group B: Simple analytical instruments providing measured
values that need
calibration and that are used in the actual analytical tests. (e.g., pH (Potential
Hydrogen) meter, titrator, viscometer, thermostat-controlled water bath).
Validation Requirements: Conformance of Group B instruments to the User
Requirements is performed according to the instruments’ procedures.
 Group C: Complex instruments that typically contain
mechanical, electric,
electronic, and computer-based components. (e.g., robotic sample
preparation devices, spectrophotometer, HPLC (High Pressure Liquid
Chromatography).
Validation Requirements: Conformance of Group C instruments to User
Requirements is highly specific, and the conformity bounds are determined by
their application. Installing these instruments can be a complicated
undertaking and may require the assistance of specialists. A full qualification
process applies to these instruments.

• If more than one (1) instrument of the same is purchased, the validation effort in
consecutive installations can be reduced to an IQ and OQ.
• Instrument Installation, IQ, Maintenance, and Change Control
 All the activities related to installation, qualification,
maintenance, and
changes must be documented and must be under a change control procedure
where relevant.
• Qualification activities are required for groups B and C as these are the
instruments that affect the quality of the obtained analytical results.
• The frequency of qualification and ongoing maintenance activities must be
defined-in local instrument procedures. It must, whenever possible, be based on
the vendor and P&G corporate recommendations, where available, or practices
based on experience with the instruments.
• The in-house qualification of the analytical instruments is composed of at least the
stages of IQ and OQ. Depending on the equipment, and its intended use, a PQ will
be added as a third stage.
• Relevant parts of the IQ are required to be performed whenever the instrument
changes physical location within the facility or after a major change, (e.g.
replacement of sub-unit).
• The need for an OQ after the relocation of an instrument must be considered.
• Where applicable, aspects of data security (e.g. backup, audit trails, and
restoration) must be included in the OQ.
• The OQ will always include the functional testing as intended by the
manufacturer. The extent of the OQ is dependent on the complexity of the
instrument and intended use.
• The PPQ must be performed upon installation after major repairs, and changes.
• Alternatively, the PPQ may be performed as part of each analytical method by
running system suitability checks before the actual samples.

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• PPQ of Group C instruments must also include documented preventive
maintenance, and procedures for maintaining the qualified state of the
instrument.
• Where properly justified and documented, the PPQ may be performed instead of
the OQ. Alternatively, the OQ may cover the PPQ where the intended use is
exactly as defined by the manufacturer.
• Both the vendor and P&G corporate recommended maintenance and calibration
activities on the instrument must be included as part of the protocol.
• All preventative maintenance work orders that are established as part of the
installation must be included in the qualification documentation and must be part
of the qualification report approval.
• Both the vendor and P&G corporate recommended maintenance and calibration
activities on the instrument must be included as part of the qualification report.
The instrument procedure must be included as a part of the qualification report.
6.4.5.3 Control Systems and Information Systems Validation
Computer systems shall be validated in accordance with this procedure and QAS-S-04,
Computer System Validation (Worldwide Quality Assurance Standard Operating
Procedure). Systems can be validated on site or at the corporate level. If systems are
validated at a corporate level, the validation documentation should be stored and
maintained there. Category QA or another central resource will be contacted to obtain
validation reports generated above site level. However, if systems are validated at the
corporate level, a site-specific validation may be conducted to verify site specific scope
depending on system classification. The Validation Decision Tree below will be used to
identify the type of system and link it to the appropriate SOP, site SOP03657, Process
Validation, or corporate QAS-S-04, Computer System Validation.

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Validation Decision Tree

Computer System, Equipment, or Instrumentation Validation Activities/Documentation

Is this Standalone Equipment or Instrumentation Follow site's Standard Operating

(does not require a separate operating system's Yes Procedures for training, calibration, and use.
services to function)?
No
Is this Installed Equipment or Instrumentation Follow site's SOP for training, calibration,
Connected to a computer system/workstation? Yes and use.
Follow SOP03657, Process Validation for
qualification templates.
Follow procedures defined below in
System Access, Data Integrity, and Electronic
Signatures section.
No
Follow site's SOP for training, calibration,
Yes and use.
Follow SOP03657, Process Validation for
Is this Infrastructure Software Tools or Statistical
qualification templates.
Programming Tools?
Follow procedures defined below in
System Access, Data Integrity, and Electronic
Signatures section.
No
Is this a Spreadsheet? Yes Follow procedures defined below in
Spreadsheet section
No
Yes Follow procedures defined below in
Is this a Manufacturing Computer System (including
System Access, Data Integrity, and Electronic
but not limited to PLC, HMIs, etc.)?
Signatures section.
No
Maintain the validated state ongoing via
If, NO to all questions above, continue with QAS-S-04, site's change control, SOPs, Periodic Reviews,
Computer System Validations and/or Continued Process Verification
requirements.

6.4.5.3.1 System Access, Data Integrity, Electronic Signature

System access, data integrity, and electronic signature requirements must
be considered and included in qualifications when installing new and/or
making upgrades to existing validated Control System and Information
Systems.
• For system access, the following must be considered and qualified
where applicable:
 Personnel must have a unique user ID/Passcode for access.
 Historical records of computerized system users and associated
access privileges must be retrievable.
 Restricting security configuration settings for system

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administrators to independent personnel.
 The system must be able to verify the identification of input
devices when design requires the restriction of input to specific
devices or locations.

• For data integrity, the following must be considered and qualified

when equipment and/or computerized systems generate
data/records that support manufacturing, packaging, testing,
releasing, and distributing products for further processing or to
market.
 Audit trails must be included for the reconstruction of the course
of events relating to the electronic record.
 Creation of new electronic records must have an audit trail.
 Modification of an existing electronic record must have an audit
trail.
 Approval of an electronic record must have an audit trail.
 Deletion of an existing electronic record must have an audit trail.
 Audit trails should include the original data, data changes, user,
date/time stamp, and a reason for the change.
 Where proper operations require specific sequencing of steps, the
challenge test are executed as confirmation.

• For electronic signatures, the following must be considered and

qualified where applicable:
 The system must include a viewable or printed form of a record
The printed name of electronic approvers.
The time signings are executed.
 The system must be able to securely link electronic approvals with
respective electronic records.
 Signatures must use at least two different ID components, i.e.
name and password, one of which is known only to the user.
 The system administration assures uniqueness of signature
components combinations.
 The system administrator periodically verifies uniqueness of
signatures or periodically revises or recalls signatures to enforce
password changes.
 Validation deliverables with electronic signatures must be
printable on demand.
 Once an electronic signature is applied, no further changes are
allowed.

• Programmable Logic Controller (PLC) and Human Machine Interface

(HMI) Validated Parameters
 Programmer/ Validation Executor:
Identify validated parameters or routines/files (refer to
associated validation protocol and/or associated SOPs).
Create descriptions for each parameter or routine/file that
begin with the word “VALIDATED” for any that was or will be
validated.
• Individual Accessing PLC Program – Engineer/ Electrical &
Instrumentation Technician:

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 Gain access into the PLC program by use of the E&I terminal
server using individual security login credentials.
 When viewing the PLC code prior to any type of change to a
parameter or routine/file ensure it is non-validated by reviewing
the descriptor to ensure that it does not start with the word
“VALIDATED”. Any parameter or routine/file displaying the word
“VALIDATED” within its description will require a change control
(see SOP02947 – Change Control) to be created and reviewed
prior to any change taking place.
 Note: Manufacturing process PLC’s contain no non-validated
process or parameters. Any change within a process area PLC will
require a change control and associated validation plan if required
prior to the change. These PLC’s will not contain descriptors that
utilize the visible indicator “VALIDATED”.

• Validated:
 Any parameter that has been documented within the body of an
Executed protocol is considered validated. The “VALIDATED”
descriptor that has been added to its description should not be
deleted under any circumstances unless agreed upon as part of a
change control and subsequent protocol.
 Any routine or file that has been designated as validated within
the body of an executed protocol is considered validated. The
“VALIDATED” descriptor that has been added to its description
should not be deleted under any circumstances unless agreed
upon as part of a change control and subsequent protocol.

• Vendor and Equipment/Application Selection

 The selection process must be documented, and the decisions
Properly justified according to the relevant User Requirements
Specifications and local procedures.
 Equipment/application selection is to be based on the laboratory
needs in conjunction, where applicable, with market share and
service history in the pharmaceutical industry.
 The vendor evaluation shall include:
A review of the vendor’s procedures for the design of the
equipment/application and the relevant software.
A review of the vendor’s procedures of the handling of errors
and faults and how clients are kept updated.
A review of the vendor’s history of client support, including,
but not limited to, installation, configuration, and validation
services.
The equipment/application selection shall include a review of
the equipment/application features and expansion options
considering the production or laboratory needs, changes in
production or laboratory practices, and intended use.
Consideration is also to be given to the expected availability
of the application/equipment in the market (discontinuation
plan by vendor, etc.).

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6.4.5.3.2 Spreadsheets
Spreadsheets routinely used for data collection or text manipulations in
Regulated Computer Systems are required to be qualified and include
control measures such as passwords, locked cells, etc. Spreadsheets will
be qualified utilizing procedures defined in Worldwide Quality Assurance
Reference Document QAS-R-17, Control & Qualification of Spreadsheets.
The following control measures are required as a minimum: (They may be
achieved within the spreadsheet software or via a combination of
software systems that fulfill the requirement).

1. A password will be required to access the qualified, spreadsheet.

2. Modification of a qualified file either requires an additional password
(i.e., write-preservation password) or clear indicators that a file has
been modified or overwritten.
3. Access to locked cells requires a second password or clear indicators
that the file has been overwritten to prevent unauthorized or
accidental modification to the worksheets. All calculated cells must be
locked.
4. Only one version of the approved spreadsheet files must exist for use.
5. After qualification, data reviewers must periodically check that the
qualified spreadsheet file is the one in use. Currently, the Site
Validation Master Plan requires this to be performed annually.
6. All passwords associated with direct access to the spreadsheet must
be controlled, documented and stored in a secured location.

Qualification

1. Each type of protection must be tested and verified by a second

individual.
2. Math functions in common commercially available spreadsheet
software are generally regarded as validated. The spreadsheet’s
functionality is qualified by performing the following tasks:
comparing a test data-set vs. hand calculations, testing of
conditional statements, and verification of formulae.
a. For spreadsheets containing calculations without conditional
statements, a minimum of one set of data must be entered
into the worksheet and the calculations verified by a second
individual using a scientific hand-held calculator that does not
truncate data.
b. When conditional statements are built into any formula
contained in the spreadsheet, the overall intent of the
conditional logic must be briefly explained in the user
instructions. Each condition must be tested and documented.
When the same conditional statement is used in a range of
cells, it only needs to be tested once. In addition to testing of
the conditional statements, a minimum of one set of data

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must be entered into each worksheet; the calculations will be
verified by a second individual using a hand-held calculator.
c. A second individual will verify correct usage of all formulas
with the corresponding cell addresses for all worksheets.
3. “User Notes” that contain instructions for use, and/or
information about “boundary conditions” of the worksheet must
be included with or accessible from the worksheet file. “User
Notes” also reference any standards that rely upon their outputs.
This information must be protected.
4. Qualified worksheets must be under change-control. A worksheet
“History” that monitors and records changes must be included
with or accessible from the worksheet file. This will include, at a
minimum, three fields: Effective Date, Revision Number/unique
identifier and Comments to described changes made with each
revision. This information must be protected.
5. The final Qualified Protocol must contain documented evidence
such as print-outs, videos or screen shots to show the following:
a. Testing controls (including passwords)
b. Unique identification of the version of the spreadsheet that
was validated such as size, date time or other information so
that the spreadsheet can be confirmed to be the validated
version in the future
c. Each individual worksheet: spreadsheet with no data entered
d. Each individual spreadsheet with all formulas and
corresponding cell addresses
e. Each individual worksheet with the test data, signed by the
analyst and reviewer

Approval

1. Prior to implementation, the Qualification and supporting data

must be reviewed and approved.
2. All implemented passwords must be documented and stored in a
location that has restricted access.
Note: Individuals must not share their passwords (i.e., write-
preservation or file-open)

6.5 Continuous Process Verification (Stage 3)

6.5.1 A continuous process monitoring system must be in place to provide assurance that the
commercial manufacturing process remains in state of control considering where applicable
variation in materials, equipment and instrument, personnel, environmental conditions,
methods, production and process controls.
6.5.2 SOP03634, Process Controls, provides a uniform means for in-process monitoring, sampling, and
testing during commercial production of products to ensure that processes remain controlled to
validated conditions.

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SOP03657 Process Validation
Standard Operating Procedure #: SOP03657
6.5.3 A Site Validation Master Plan will be created and maintained by the Site QA Validation Leader.
This document should encompass the purpose and approach to validations at the site and define
a plan for revalidation of systems, processes, equipment, and products as required per analysis of
PQR data. It should address all facilities and utilities validations as well including critical systems
such as HVACs, purified water, and compressed air. The document should be approved by the
Site QA Leader and Plant Manager and be revised annually at a minimum.
6.5.4 SOP03651, Statistical Process Control Analysis and Trending must be used to analyze routine
production and/or product data to monitor trends, demonstrate that the process is in state of
control and can consistently produce product within desired quality attributes. The data collected
and analyzed must include but not limited to incoming materials or components, in-process
material and finished product quality attributes, and critical process parameters to:
• Understand the sources and extent of variation.
• Understand the impact of variation on the process and product quality attributes.
• Define continuous improvement actions to control the variation in a manner commensurate
with the risk it represents to the process and product.
6.5.5 Product Quality Reviews conducted per SOP03598, Product Quality Review, will maintain and
analyze the change controls conducted for all systems and processes by which product is
produced within the site. The Site QA Validation Leader should conduct annual analysis of this
PQR data for change controls and product data to determine whether revalidation of systems,
equipment, processes, or products is necessary. This analysis should be conducted within 3
months of PQR completion for a given product family. If revalidation is necessary, the Site
Validation Master Plan should be updated to reflect timing of revalidation.
Specifically, the Site QA Validation Leader shall complete the Process Validated State Assessment
Form (Attachment XIII) by reviewing product, process, and equipment changes, process
performance, and indicators of potential variation (such as defect complaints and out-of-
specification findings), to formally assess and document the validated state of a given process.
6.5.6 SOP02947, Change Control and SOP03751, Deviation and Non-Conformance Handling, requires
the assessment of all proposed changes and deviations for potential implications on validation
status, and in each case, must be evaluated to consider the need for process improvement
and/or additional process performance qualification.
7.0 ATTACHMENTS
7.1 Attachment I, Installation Qualification (IQ) Protocol Template
7.2 Attachment II, Installation Qualification (IQ) Report Template
7.3 Attachment III, Operational Qualification (OQ) Protocol Template
7.4 Attachment IV, Operational Qualification (OQ) Report Template
7.5 Attachment V, Installation and Operational Qualification (IQ/OQ) Protocol Template
7.6 Attachment VI, Installation and Operational Qualification (IQ/OQ) Report Template
7.7 Attachment VII, Guidance for Disposition and Deviation Reporting for Production Intended for Testing
Purposes Only (Scrap) and Production Intended for Commercial Distribution (Release)
7.8 Attachment VIII, Process Performance Qualification (PPQ) Protocol Template
7.9 Attachment IX, Process Performance Qualification (PPQ) Report Template
7.10 Attachment X, Installation Verification/Operational Verification (IV/OV) Protocol Template
7.11 Attachment XI, Installation Verification/Operational Verification (IV/OV) Report Template

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SOP03657 Process Validation
Standard Operating Procedure #: SOP03657
7.12 Attachment XII, Project Validation Master Plan Template
7.13 Attachment XIII, Process Validated State Assessment Form
7.14 Attachment XIV, Simple Test Plan Template
7.15 Attachment XV, Simple Test Report Template
7.16 Attachment XVI, Report Addendum Template
8.0 CHANGE HISTORY
Rev Summary of Revisions Reason(s) for Revision

14 Updated SOP owner. New system owner.

Added definition. Include Addendum Report definition.

Added section 7.16 Attachment XVI, Add standardized template.

Report Addendum Template
13 Added to the PPQ definition Add clarity to the process.
Added definition, and requirements for Improve Controls documentation requirements.
a Simple Test Plan to section 2.4.2, and
added Plan and Report Templates
Added requirements to keep To ensure all concerns are addressed.
protocols/reports in review until less
than 10 annotations are obtained
Added protocol and report title, and To continue to drive standardization as it was added to the
Veeva Metadata Name structure templates previously.
requirements to SOP
Added Operations Leader to the For awareness of the results of the annual reports associated
approval section of the Validated State with their areas.
Assessments
Updated definitions for “Deviation” and Add clarity to the process.
“Discrepancy”
Removed hard copy signature section Approvals performed electronically in Veeva.
from all related templates
Added approver requirements for Site Add clarity to the process.
and Project Validation Master Plans in
section 5.1.3
Removed all reference to Validation Process improvement, added all Validation Assessment
Assessment and associated template requirements to the Project Validation Master Plan.
Added expectation to assign the Project Add clarity to the process.
Validation Master Plan as a follow up to
change control for major initiatives
requiring an overview change control
12 Added title structure requirements to Standardized title structure.
each protocol and report template
Added the requirement to ensure that Ensure compliance with corporate SOP QAS-S-26.
all deviations from the approved
protocol are documented and approved
before proceeding to the next stage of
validation

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SOP03657 Process Validation
Standard Operating Procedure #: SOP03657
Updated approval section Moved some roles from optional to mandatory for better
clarity.
Changed requirement to verify annually Standardized the requirement.
vs. periodically, that the qualified
spreadsheet is being used after initial
qualification
Removed published date from the SOP Veeva tracks both.
and revision number from SOP and
related attachments
Added the requirement to pull in- Improvement to the Continued Process Verification process.
process data to the Validated State
Assessment Template
Added requirement for technical Typically, 9 samples are analyzed to validate homogeneity;
justification if less than 9 samples are therefore, less samples must be technically justified.
used to validate homogeneity to PPQ
section above
Added requirement to explain samples Any testing in addition to protocol scope must be within
needed by Mason Business Center to Formulation Part criteria.
PPQ Protocol Attachment
Removed “Change Control #” from the Validation Assessment is processed prior to change control;
header of the Validation Assessment therefore, not required.
Template
11 Added expectation to submit Validation To add clarity for when the assessment is utilized.
Assessments with the initial change
control for the change in section 6.2.1
Added a Sequence of Events section to To add clarity to project sequence of events.
Attachment XII, Validation Assessment
Template
Added expectation that all To ensure all documentation is approved as needed.
documentation supporting PPQ is
approved prior to PPQ activities 6.4.2
Added expectations for product control To ensure batch records for product impacted by qualification
to the Product Disposition and Release and validation activities are documented appropriately.
Criteria Sections of the attached
templates (also defined in section
5.2.2.1
Revised Section 1.0, and 2.0 To comply with QAS-S-04, Computer System Validations
Added reference to section 3.0 To comply with QAS-S-04, Computer System Validations
Added definitions to section 4.0 To comply with QAS-S-04, Computer System Validations
Added electronic signature To comply with QAS-S-04, Computer System Validations
requirements in section 5.0
Added reference to templates in section To comply with QAS-S-04, Computer System Validations
6.0
Added computer system decision tree to To add clarity around which procedure to follow, site or
section 6.4.5.3 corporate
Added System Access, Data Integrity, To comply with QAS-S-04, Computer System Validations
and Electronic Signature section
(6.4.5.3.1)

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SOP03657 Process Validation
Standard Operating Procedure #: SOP03657
Added Spreadsheet section (6.4.5.3.2) To comply with QAS-S-04, Computer System Validations
Minor grammar corrections throughout To correct imperfections
10 Formatting Improvements To better align documentation
Added SOP03634, Process Controls to To incorporate the process controls into this SOP as it is a tool
Section 3.0 and definition of process for ensuring that processes remain controlled to validated
controls to Section 4.0, and purpose to conditions
Section 6.4
Revised some of the definitions in To add clarity
Section 4.0, changed Validation
Inclusion to Validation Assessment,
Single Batch Qualification to Single
Batch Verification, and Functional
Specifications to Functional Design
Specifications
Revised most of Section 6.0 To include requirements defined in 21 CFR Part 11
Added referral to Table 1 in Section 5.0 To provide guidance for ownership of originating and
approving protocols and reports
Added Project Leader Responsibilities to To provide guidance for ownership of communicating batch
Section 5.2 code and memo requirements
Added IQ, OQ, and VMP templates To allow more options for templates in IQ and OQ, and
requirement for Project Validation Master Plans
Changed references to Validation To better document technical justifications
Inclusion to Validation Assessment, and
updated the definition and associated
requirements
Changed references to Performance To comply with 21 CFR Part 11
Qualification to Process Performance
Qualification
09 Added expectations to add screenshots To provide clear instructions for execution
for critical steps in lab protocols to
Section 6.3.9.2
Added expectations for clearly To provide clarity for reviewing executed protocols
summarizing protocol data in the report
and for ensuring that the protocol was
completed as written in Section 5.2.2.4,
5.2.3, and 5.2.4
08 6.3.9.3 Added details for computer To add reference to QAS-S-04, Computer System Validation
system classification and reference for
validation deliverables
CBA01017, Validation Inclusion was To link the Validation Inclusion to a SOP
converted to Attachment IX of this SOP
Section 3 Alphabetized and/or listed in Standard documentation principles
numerical order
Added details for Validation Inclusion in To link the document (currently CBA) to a SOP
sections 5.2.1, 5.2.3, 6.3.7.5, and Table
1. Also, added the Validation Inclusion
Template to Attachments (section 7.9)
07 Global: Formatting revisions To resolve numbering and spacing inconsistencies

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SOP03657 Process Validation
Standard Operating Procedure #: SOP03657
3.6 Updated reference to EMA Guideline To reflect the EMA guideline is now in effect.
on Process Validation
3.16 Removed “Annual” from title of To align with title from Rev 05 of SOP03598
reference SOP03598, Product Quality
Review as well as all internal references
(changed APQR to PQR)
3.25 QAS-S-16, Product Quality Reviews Adoption since last revision
(PQR) added to references
Some definitions were not included but the terminology was
4.7, 4.11, 4.17, 4.18, 4.19, 4.26, 4.30,
used in the document.
4.32, 4.37 Added definitions for GMP,
GDP, PPQ, Qualification, PQR, URS, FS, Revised definition for PQ to clarify PQ is for unit operation
DS, CPV and revised definition for PQ level

To allow for data-based determination of number of PPQs.

6.3.8.3 Added clarification for data-
based determination of number of PPQ
runs.
To formalize the validated state assessment process.
6.4.4 Added a requirement for
completion of Process Validated State
Assessment form.
To improve definition of PPQ and define alignment to the Site
Section 6 was rewritten to better align
Validation Master Plan
to Site Validation Master Plan and the
Lifecycle added as attachment IX
To provide form to document process validated state
7.8 Added attachment VIII
assessment

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SOP03657 Process Validation
Standard Operating Procedure #: SOP03657
9.0 QUIZ
1. A discrepancy is defined as a variation that occurs during a validation, verification, or commissioning that
violates the overall objective of the protocol, leads to the direct failure of a test run versus acceptance
criteria, and/or impacts the defined critical parameters or criteria defined within the protocol per the
associated Quality Acceptance Criteria (QAC).

True / False

2. When protocol samples are requested by Mason Business Center, an explanation of why samples are
needed, and the intent must be provided within the protocol. Additional testing must be within the
Formulation Part (FOP) criteria. If samples are requested for display only, they should not be included in
the protocol.

True / False

3. A Simple Test Plan (STP) provides evidence that simple Programmable Logic Controller (PLC) changes
function properly, and no other logic has been adversely affected. It may be used only as a Control System
& Information System validation with limited changes. Typically, simple changes to a control system, such
as a pressure alarm, indicator light or display, changing a process set point, changing a timer setpoint,
addition of a sensor for information/alarm only (not control), addition, removal, or modification to logic
limited to ______ rung, or addition, removal, or modification to wiring limited to 3 – 6 wires would require
a Simple Test Plan.

1. 5 – 10
2. 10 – 15
3. 15 – 20
4. 20 - 25

4. The project validation master plan will be used for all large initiatives and/or projects requiring an
overview change control and will be assigned as a follow up to the associated overview change control.
Small projects not requiring an overview change control will be managed solely through the change
control process where the appropriate validation documents will be assigned upon change control
approval.

True / False

5. All protocol and report titles must be structured in the following order: Area/Line, Manufacturer,
Equipment Type, or Formula, Protocol Type, and Protocol, Report, or Assessment. Which of the following
are correct?

True / False

6. Protocols and reports that receive 10 or more annotations during the review process will continue to be
reviewed until less than 10 annotations are obtained. Upon addressing these 9 or fewer annotations, the
document can then be sent for approval.

True / False

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SOP03657 Process Validation

Document Approvals
Approved Date: 31 Aug 2021

Owner's Approval Task Heather Willis, Site Validation Leader

Verdict: Approve ([email protected])
Owner
31-Aug-2021 14:09:05 GMT+0000

Approval Task Randy Graves,

Verdict: Approve ([email protected])
Document Control Approval
31-Aug-2021 14:12:00 GMT+0000

Approval Task Stephanie Ashe,

Verdict: Approve ([email protected])
Quality Approval
31-Aug-2021 14:19:18 GMT+0000

Final Approver(s) Approval Task Stephanie Ashe,

Verdict: Approve ([email protected])
Quality Assurance Approval
31-Aug-2021 14:45:49 GMT+0000

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