M 133 Laboratory Master Plan

Master Plan
Laboratory Compliance
January 2014
This is an example of a Master Plan. It is a proposal and starting point only. The type
and extent of documentation depends on the process environment. The proposed
documentation should be adapted accordingly and should be based on individual risk
assessments. There is no guarantee that this document will pass a regulatory
inspection.
Publication from
www.labcompliance.com
Global on-line resource for validation and compliance
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for personal use. Users may not transmit or duplicate this document in whole or in part,
in any medium. Additional copies and licenses for department, site or corporate use can
be ordered from www.labcompliance.com/solutions.
While every effort has been made to ensure the accuracy of information contained in
this document, Labcompliance accepts no responsibility for errors or omissions. No
liability can be accepted in any way.
Labcompliance offers books, master plans, complete Quality Packages with validation
procedures, scripts and examples, SOPs, publications, training and presentation
material, user club membership with more than 300 downloads and audio/web
seminars. For more information and ordering, visit www.labcompliance.com/solutions.
Master Plan
Document Number: M-133 Ver. 1.xx
Page 2 of 53
Company Name:
Controls:
Superseded Document
N/A, new
Reason for Revision
N/A
Effective Date
January 1, 2014
Signatures:
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Reviewer
I indicate that I have authored or updated this Master Plan

according to applicable business requirements and our
company standards.
Name:
________________________________
Signature:
________________________________
Date:
________________________________
I indicate that I have reviewed this Master Plan, and find it

meets all applicable business requirements and that it reflects
the procedure described. I approve it for use.
Name:
________________________________
Signature:
________________________________
Date:
________________________________
I indicate that I have reviewed this Master Plan and find that it
meets all applicable quality requirements and company
standards. I approve it for use.
Name:
________________________________
Signature:
________________________________
Date:
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www.labcompliance.com (Replace with your companys name)

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Table of Contents
1. Introduction, Scope and Objectives of this Document...........................................6
1.1 Introduction..............................................................................................................6
1.2 The Laboratory........................................................................................................6
1.3 Scope of the Master Plan........................................................................................6
1.4 Objectives of the Master Plan.................................................................................6
2. Policy............................................................................................................................7
3. Structure of QMS Documentation.............................................................................8
3.1 Documentation Hierarchy........................................................................................8
3.2 Laboratory Compliance and Corporate Master Plans.............................................9
3.2.1 Risk Management Master Plan (19.1.1)..................................................................9
3.2.2 Equipment Qualification Master Plan (19.1.2).....................................................10
3.2.3 Computer System Validation Master Plan (19.1.3)................................................10
3.2.4 Network Qualification Master Plan (19.1.4).........................................................10
3.2.5 21 CFR Part 11 Compliance Master Plan (19.1.5)...............................................10
3.2.6 Training Master Plan (19.1.6)...............................................................................10
3.2.7 Calibration and Preventive Maintenance Master Plan (19.1.7)............................10
3.3 Processes..............................................................................................................11
3.4 Procedures and Work Instructions........................................................................11
3.5 Records..................................................................................................................11
3.6 Checklists, Forms, Templates, Examples.............................................................12
4. Organization and Responsibilities..........................................................................12
4.1 Management..........................................................................................................13
4.2 Quality Assurance..................................................................................................13
4.3 Department Manager and Supervisors.................................................................14
4.4 Analysts.................................................................................................................15
4.5 Safety Officer.........................................................................................................15
5. Facilities and Environmental Conditions...............................................................15
6. Document Control.....................................................................................................17
7. Internal Audits...........................................................................................................18
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8. Management Reviews...............................................................................................19
9. Staffing and People Qualification...........................................................................20
9.1 Procedure..............................................................................................................20
9.2 Training Courses and Tools for Pre- or Self-Study................................................21
9.3 Assessment Tools..................................................................................................21
10. Selection and Validation of Analytical Methods and Procedures........................22
10.1
Method Selection.............................................................................................22
10.2
Validation of Methods Developed by The Laboratory......................................22
10.3
Verification of Standard Methods.....................................................................23
10.4
Method Revalidation........................................................................................23
10.5
Using Alternative Methods...............................................................................23
10.6
Using Software for Automated Method Validation...........................................24
11. Equipment and Computers......................................................................................24

11.1
Equipment Identification...................................................................................24
11.2
Equipment Logs...............................................................................................25
11.3
Qualification of Equipment Hardware..............................................................25
11.4
Off-the-Shelf Computer System Validation......................................................26
11.5
Validation of Software Developed In-House....................................................27
11.6
Operation.........................................................................................................27
11.7
Maintenance.....................................................................................................28
11.8
Out of Service..................................................................................................28
11.9
Equipment Temporarily Leaving The Laboratory.............................................28
11.10 Decommissioning.............................................................................................28
12. Sampling....................................................................................................................29
13. Reagents and Calibration Standards......................................................................30
14. Traceability of Measurements.................................................................................31
15. Stability Testing.........................................................................................................31
16. Handling of Test Items..............................................................................................32
17. Testing........................................................................................................................33
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18. Quality of Test Results and Failure Investigations...............................................34
18.1
Ongoing Performance Control of the Analysis System....................................34
18.2
Out-of-Specification Results and Failure Investigations..................................34
18.3
Root Cause Analysis and Corrective and Preventive Action Plans.................35
18.4
Data Review and Validation.............................................................................36
18.5
Reporting Test Results.....................................................................................36
19. Identification and Management of Records...........................................................37

20. References.................................................................................................................38
20.1
Primers and Master Plans................................................................................39
20.2
Reference Publications....................................................................................39
20.3
Audio Seminars................................................................................................40
20.4
Standard Operating Procedures......................................................................41
20.5
FDA and International Regulations, Guidelines and Presentations.................43
20.6
Worksheets, Checklists, Forms, Templates, Examples...................................44
21. Attachments..............................................................................................................45
21.1
Laboratory Personnel.......................................................................................45
21.2
Document Master List......................................................................................45
21.3
Template and Example to Document Training Requirements.........................46
21.4
Template to Document Training.......................................................................47
21.5
Equipment List.................................................................................................48
21.6
List with Authorized Users of Equipment.........................................................49
21.7
Equipment Records.........................................................................................50
21.8
Recording Sampling Data................................................................................51
21.9
List of Records to be Archived.........................................................................51
21.10 Checklist for Testing.........................................................................................52

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Master Plan
1. Introduction, Scope and Objectives of this Document

Introduction
This Laboratory Compliance Master Plan documents The Laboratorys
approach and steps for compliance with FDA and equivalent international
regulations.
The Laboratory
The Laboratory performs analyses of raw material, intermediates and finished
products and performs stability tests at a pharmaceutical manufacturing site.
The site manufactures drugs for the United States and international markets.
Most of the processes are considered high risk because pharmaceutical
quality control laboratories are the last control step in drug manufacturing and
after the analysis result is released the drug products are shipped to the
market. As of the release date of this master plan (March 2006), The
Laboratory has 85 employees, 8 of them are employed part time.
Scope of the Master Plan
Analytical laboratories in (bio)pharmaceutical manufacturing.
US FDA and equivalent international GxP regulations.
This master plan has been developed for a pharmaceutical quality

control laboratory, however, the principles and approaches can be easily
customized and applied to other FDA regulated laboratories, e.g.,
regulated development laboratories and for clinical studies.
Objectives of the Master Plan
This laboratory master plan has several objectives:
It serves as a guideline for how cGMP requirements can be

implemented efficiently and consistently in The Laboratory.
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It answers the inspectors question about the companys

approaches for compliance in The Laboratory.
It demonstrates management commitment and support for

compliance in laboratories through its policy statement.
It helps personnel at all management levels understand how

compliance is approached and implemented in The Laboratory.
Assists in the preparation of project plans.
It helps to produce and maintain high quality analytical data.
2. Policy
The Laboratory produces high quality data and fully complies with US FDA and
equivalent international GxP regulations in a cost-effective manner. This is
achieved through:
Effective communication of the master plan to all employees and

assurance of correct understanding of the plan.
Following documented processes and procedures for cGMP and

quality relevant operations.
Clear definition of roles and responsibilities for management and

staff.
Ongoing monitoring of FDA and international guidelines and timely

adaptation of processes and procedures if necessary.
Risk-based processes and procedures.
Continuous evaluation and improvement of processes and

procedures.
Validation of critical processes, equipment hardware and computer

systems.
Adequate design and control of facilities and environmental

conditions.
GxP compliant recording and archiving of data.
Evaluation and investigation of deviations from expected results

with root cause analysis and corrective and preventive action plans.
Suitable handling of samples, chemicals and standards.
Regular system suitability tests or quality control checks before and

in between sample analyses.
Reviewing and validating analytical data.

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Sufficient and appropriately qualified and trained personnel.
Auditing of actual processes for compliance with documented

processes and procedures.
Management support.
Annual review of processes and procedures.
3. Structure of QMS Documentation

This section of the master plan describes various types of documents and how they
interrelate with each other.
Documentation Hierarchy
There are different types of documentation as illustrated in the documentation
pyramid in Figure 1.
The master plan is the top tier of the document hierarchy. It describes the
approaches to achieve compliance and quality data. It also includes policy
statements describing the intent and goal of The Laboratory and key points on
how these goals can be achieved. The compliance master plan does not
include detailed processes or procedures on how to achieve compliance but it
does have a list of the processes and procedures.
A process describes how various compliance and quality requirements can be
achieved. For example, it describes how the requirement people should be
qualified for the assigned task can be implemented.
Procedures are step-by-step instructions on how to exactly perform a specific
task for a specific instrument. Depending on what the task is this can have the
form of an SOP or a test script. Examples are how to analyze sample X, how
to calibrate balance A from vendor B or how to test a specific chromatographic
data system.
Records are generated on a day-by-day basis. Examples are analytical results
from product tests or calibration records of a balance.

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Figure 1. Documentation Hierarchy

Laboratory Compliance and Corporate Master Plans
Master plans are documents that lay out a companys approach for specific
activities, e.g., how to achieve compliance for a laboratory. Approaches for
laboratories cannot be isolated from other activities and master plans in the
organization. For example, risk management strategies as defined in a
corporate risk management master plan should also apply to laboratory
system validation. Training for laboratory staff should be conducted and
documented following the companys training master plan.
Although this laboratory compliance master plan provides enough information
to implement a compliance program in The Laboratory, it does not give
enough details for supporting tasks. For example, it does not include detailed
information for validating computer systems, on preparing, conducting and
documenting trainings, or information on password conventions and risk
management strategies. However, these activities are also important for The
Laboratorys compliance strategies. Therefore there must be a tight link
between The Laboratory master plan and other master plans. For a better
understanding this chapter describes other master plans available in the
organization.
3.2.1
Risk Management Master Plan (20.1.1)
The risk management master plan describes the companys approach

for risk assessment and risk management, for example, to comply with
the FDAs Part 11 Guidance: Scope and Applications based on a
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justified and documented risk assessment. It is used as a source for
project specific individual risk management project plans.
An example master plan is included in the Laboratory Compliance
Package from Labcompliance.
3.2.2
Equipment Qualification Master Plan (20.1.2)
The equipment qualification master plan describes the companys

approach for qualifying equipment such as analytical instruments. It
also details steps for equipment qualification and owners and
deliverables for the qualification phase.
3.2.3
Computer System Validation Master Plan (20.1.3)
The computer system validation master plan describes the companys

approach for validation of software and computer systems. It is used as
a source for project specific individual validation plans.
3.2.4
Network Qualification Master Plan (20.1.4)
The network qualification master plan describes the companys

approach for qualifying IT infrastructure and networks. It is used as a
source for project specific individual qualification plans.
3.2.5
21 CFR Part 11 Compliance Master Plan (20.1.5)
The Part 11 compliance plan describes the companys approach and

steps for implementing compliant electronic records and electronic
signatures. An example master plan is included in the 21 CFR Part 11
Compliance Package from Labcompliance:
www.labcompliance.com/books/part11.
3.2.6
Training Master Plan (20.1.6)
The training master plan describes the companys approach on how to

identify training needs for employees, how to develop and implement a
training plan, how to conduct trainings and finally how to document the
trainings. Trainings for laboratory staff should follow the
recommendations in this master plan.
3.2.7
Calibration and Preventive Maintenance Master Plan (20.1.7)
The calibration and preventive maintenance master plan describes the

companys approach for calibration and maintenance of equipment.

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Processes
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Processes describe how various compliance and quality requirements can be

achieved. For example, it describes how the requirement people should be
qualified for the assigned task can be implemented. Another example is how
to make sure that equipment is suitable for its intended use. In this case the
processes on equipment qualification apply to instrument categories such as
analytical equipment hardware or more specific to an instrument family such
as UV-VIS Spectrophotometers, but processes are not like specific
instruments identified by a product number. For a better understanding
process flow charts should be included in a process description.
Processes typically are documented in standard operating procedures. A list
of SOPs for various processes is included in Reference 20.4.
Procedures and Work Instructions
Routine activities follow documented procedures. These are typically defined
as standard operating procedures and/or work instructions. While master
plans describe the tasks and approaches, procedures and work instructions
give step-by-step instructions on how to do the tasks. Examples for SOPs are
procedures for training, for qualification of equipment, for validation of
commercial off-the-shelf systems, for change control and for risk assessment.
An example for a work instruction would be how to execute a test script.
Records
FDA and equivalent international regulations require a specific type of
information to be retained for a specific amount of time.. For example, 21 CFR
211.194 defines which laboratory records should be retained and archived and
the duration. Examples are results of product tests and measurement
parameters, calibration results, sample descriptions and instruments used for
testing.
Besides the records explicitly mentioned in regulations, the FDA expects that
other records are available to demonstrate compliance with the CGMP
regulations. Examples are training records to demonstrate compliance with
people training and environmental monitoring records to comply with the
requirement to adequately control environments.
The Laboratory acquires and maintains all records as required by the FDA
and equivalent international regulations for at least the specific time as
defined in regulations. The exact retention period for each type of record is
defined by corporate policies.
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Checklists, Forms, Templates, Examples
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Checklists, forms, templates and examples help implement compliance

effectively and consistently. Examples are checklists and worksheets for
vendor qualification, handling out-of-specification results and for Part 11
compliance. Templates are available for system documentation, test protocols,
maintenance and change logs.
4. Organization and Responsibilities

Responsibilities of management and staff are defined and annually reviewed. While
the Quality Assurance department is responsible for setting up compliance
systems, implementation and maintenance of the system is the responsibility of
each manager, supervisor and employee. Copies of job descriptions, job
applications, resumes and annual reviews are kept on file in the Human Resources
department.
Figure 2. Org Chart

Attachment 21.1 lists laboratory personnel with names, positions, education level
and years of experience (total/current position).

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Management
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Management is responsible for reviewing, approving, supporting and

communicating the quality and compliance policy to employees.
Responsibilities and tasks include:
Management team is responsible for annually reviewing the

compliance and quality system.
The president has executive responsibility for compliance and shall

create an atmosphere where compliance and quality are the highest
priority.
The vice presidents are responsible for overseeing the

development, implementation and maintenance of compliance systems.
Each manager and supervisor is responsible for assuring that the

compliance systems are implemented in his/her area.
Quality Assurance
The Quality Assurance department sets up the compliance system and assists
The Laboratory in the development, implementation and maintenance of the
system. Tasks and responsibilities include:
Set compliance and quality goals and objectives for The Laboratory
and develop plans to meet those goals and objectives.
Manage and participate in periodic audits to assure that compliance

systems are implemented faithfully and effectively.
Train and advise management, supervisors and staff on quality

aspects and regulations and internal policies.
Recommend solutions to compliance problems and verify when any

problems have been resolved.
Report quality related issues to management.
Manage FDA and other external inspections and audits. Initiate

corrective and preventive actions if necessary.
Oversee initial and ongoing instrument calibration and qualification.
Oversee the annual maintenance service.
Oversee the documentation, archiving and distribution of laboratory

standard operating procedures.
Generate SOPs for non-analytical quality related operations.
Review all SOPs and other documents for completeness and

compliance with company standards and regulations.
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Review analytical data.
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Issue data summaries for annual product reviews.
Organize annual management review of the compliance system.
Manage vendor assessment and audits.
Manage complaints.
Department Manager and Supervisors

Lab managers and supervisors implement company policies and standards in their
laboratories.
Tasks and responsibilities include:
Assure compliance with FDA and equivalent international

regulations.
Responsible for the overall technical quality of the work performed

in The Laboratory.
Supervision of all personnel in The Laboratory.
Ensure management procedures, applicable standards and

specifications are followed.
Develop job descriptions for staff working in their departments.
Ensure that sufficiently qualified, skilled and trained personnel and

other resources are available to perform the assigned tasks.
Ensure that job descriptions, tasks lists and training records are
maintained to demonstrate staff competence for the assigned tasks.
Ensure that The Laboratory has appropriate equipment and

supplies.
Schedule analytical sample analysis and ensure completion of

analyses within required schedule.
Provide technical assistance to analysts regarding the selection of

appropriate analytical methods.
Review and approve analytical method validation protocols and

stability study protocols.
Review and validate all data before it is reported as final.
Generate and maintain Standard Operating Procedures (SOPs) for

laboratory operation within his/her own work area.
Schedule initial and ongoing equipment qualification and preventive

maintenance.
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Assist analysts with handling out-of-specification situations, failure

investigations, root cause analysis and corrective and preventive action
plans.
Identify and report any opportunities to improve efficiency,

compliance and quality.
Analysts
Analysts should perform their assigned tasks according to company
procedures in the most cost-effective way.
Responsible for the technical quality of work performed.
Follow SOPs and QA/QC requirements for routine tasks.
Perform sample analysis and document results.
Calibrate balances and other equipment on a day-by-day basis, if

required by SOPs.
Inform direct supervisors when analytical results are not in

specification.
Assist supervisor in data review if necessary.
Identify and report any opportunities to improve efficiency,

compliance and quality.
Safety Officer
The safety officer manages activities required to ensure a safe and healthy
laboratory environment.
Develop, implement and maintain laboratory safety plan and

material safety data sheets.
Train laboratory employees on the laboratory safety plan.
Manage hazardous waste storage and disposal.
Manage laboratory safety audits.

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5. Facilities and Environmental Conditions

Laboratory facilities ensure that environmental conditions do not adversely affect or
invalidate sample handling instrumentation, instrument calibration and qualification
and analytical testing. Procedures are described in SOP S151 (Ref. 20.4).
Following the SOP ensures that:
Laboratories are equipped with climate and ventilation control. Laboratory

facilities meet the required environmental conditions, e.g., temperature and
humidity, as specified by instrument manufacturers and as required for sample
processing.
Work areas are separated to ensure that analyses will not be adversely
affected within resources provided.
Floors in the laboratories are constructed from a material that is resistant

to most chemical spills and easily disinfected.
Workbenches are constructed of material that is easily disinfected and

impervious to most chemical spills.
The Laboratory is equipped with chemical hoods to capture hazardous

materials used or produced in the analysis and to protect employees from
hazardous concentrations of airborne toxic substances.
An auxiliary power generating system is in place to provide emergency

power for hazardous or sensitive operations.
Laboratory storage areas provide proper storage of samples, standards

and reagents.
Storage areas of sufficient size are present in The Laboratory to ensure

that glassware and portable instrumentation are properly stored.
Separate areas are maintained for incompatible activities, and measures

are taken to prevent cross-contamination.
The Laboratory areas are separated from other sections in the building
such as administration services, lunch room and conference rooms.
Any additional laboratory conditions for specified analysis conditions are

met, including hazardous biological and chemical material.
Laboratories are cleaned and maintained according to a schedule.
Supervisors implement environmental control programs in The Laboratory.
Supervisors recognize when environmental conditions are not met and

adversely affect tests being performed. Analysis is not performed if monitoring
reveals that required environmental conditions are not met.
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Laboratory employees plan and conduct laboratory operations in

designated areas.
Laboratory employees identify and suggest implementing any

environmental controls needed to complete sampling and analysis, and ensure
that these factors do not adversely affect the quality.
Laboratory employees properly handle and store hazardous waste as

defined in the Hazardous Waste plan.
Related SOP Reference 20.4

S151: Facilities and Environmental Conditions
6. Document Control
Development and maintenance of documentation is controlled through document
control and management procedures (SOPs S105 and S504) (Ref. 20.4) that are
part of the management system. Documents include internal and external
documents. Examples for internal documents are SOPs, master plans and training
plans. Examples for external procedures are regulations, standards, test methods
and instrument operating manuals.
The procedure for document control ensures that:
Official internal and external documents are created or acquired,

reviewed and approved prior to use.
Documents are uniquely identified with document and revision

number, date of revision and issuing authority.
A master list with all controlled documents is maintained by QA. The

list includes document and revision number, title, date of issue, date of last
review and locations. A template with examples is shown in Attachment
21.2.
Internal documents include page number and total number of pages

on each page.
Users of the documents are adequately trained before the

documents are released for use.
Current authorized versions are readily available at the users

workspace.
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Documents are reviewed according to a schedule and revised to

ensure suitability and ongoing conformance with regulations and internal
procedures.
Invalid and obsolete documents are promptly removed from all

points of issue or use, or marked as uncontrolled to assure that only
current authorized versions of appropriate documents are available for
active use at relevant locations.
Obsolete documents retained for either legal or knowledge

preservation are marked as Archived, dated and signed. The retention
period for the documents is in compliance with internal policies and
regulations.
Changes to a document are reviewed and approved.
The changes are recorded in a document change log. The log

information indicates the reason and the nature of the change.
When documents are created, signed and maintained in electronic

form, the computer system and records comply with the FDAs 21 CFR
Part 11 and equivalent international regulations. When paper documents
are scanned for electronic archiving, The Laboratory follows the procedure
in SOP S316 (Ref. 20.4).
Related SOPs Reference 20.4
S105: Document Control and Management
S137: 21 CFR Part 11 Scope and Controls
S315: Retention and Archiving of Electronic Records
S316: Scanning of Paper Records for GxP Compliant Archiving
S317: Data Back-up and Restore
S504: Generation and Maintenance of SOPs for Laboratories
7. Internal Audits
Internal audits verify conformance of actual work with documented procedures.
They are conducted according to SOP S511 (Ref. 20.4. The procedure includes an
audit schedule that ensures that all entities are audited over a certain time period.
For an audit checklist, see E184 (Ref. 20.6). The internal audit program addresses
all elements of the compliance and quality systems, including testing and people
qualification. QA is responsible for the coordination of internal audits and also
develops an audit schedule.
The procedure for internal audits ensures that:
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The audits are conducted by trained and qualified personnel.
Audits are objective through auditors coming from outside the

audited department.
Audits are conducted in a similar way to anticipated FDA or

equivalent international inspections.
Deviations from procedures are corrected through The Laboratorys

corrective action plan.
Each area of activity is audited and audit findings and corrective

action that arise from them are recorded.
Follow-up audit activities are conducted to verify and record the

implementation and effectiveness of the corrective action taken.
Follow-up activities are included in the annual management review

process.
S511: Auditing Laboratory Systems
S141: FDA Inspections - Preparation, Conduct, Follow-up
S142: Multinational GMP Inspections: Preparation, Conduct and Follow-up
8. Management Reviews
Management reviews verify continuous fitness for use and effectiveness of the
management system and initiate changes for improvements if needed. They are
conducted according to a procedure in SOP S510 (Ref. 20.4). The review serves
as a guide in making future determinations for the effectiveness and direction of the
quality and compliance system.
As a minimum, the review is performed annually. The review is conducted by The
Laboratorys executive management.
The procedure for management includes but is not limited to the following
elements:
Suitability of policies, processes and procedures.
Reports from managers and supervisors.
Outcome of recent internal audits.
Recalls, returned or salvaged drug products.

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Failure investigations, corrective and preventive actions.
Assessments by external bodies, FDA inspection findings.
Changes in the volume and type of work.
Complaints and other feedback from users of the analytical test

results.
Quality control activities, resources and staff training.
The findings and the actions that arise from the review are recorded according to
The Laboratorys management review procedure. If needed, corrective actions are
initiated.
S510: Laboratory Management Review
9. Staffing and People Qualification

Laboratory management ensures that The Laboratory has sufficient resources and
personnel that have the education, expertise, training or a combination of these to
perform their assigned tasks.
Procedure
Competence of people is based on education, experience, demonstrated skills and
training. People qualification is controlled through SOP S513 (Ref. 20.4).
The procedure for training ensures that:
New hires complete an initial training module. Such trainings include

basics of the US FDA and equivalent international regulations, principles
of quality systems, safety, security and company procedures.
Training requirements are defined, outlined and documented on the
basis of job descriptions or duties, assigned tasks and responsibilities.
Personnel records contain the assigned tasks, requirements and
competence through education, experience, skills and training.
If the competence does not meet the requirements, a training plan is
developed. This includes training needs and a training schedule.
For in-house trainings a senior analyst serves as the trainer.

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For external trainings the competence of the trainer and/or the company
providing the training is documented.
Analysts are trained and must demonstrate competence before they
generate the first analytical results.
Laboratory managers identify personnel to perform testing and
calibration, to qualify equipment, to issue test reports and operate
particular types of instruments.
All personnel are qualified for the assigned task, this includes all levels of
management and both full time personnel and temporary hires. As the
first step, the supervisor documents the assigned task, required skills,
the persons qualification and whether additional training is required or
not. An example for a form is shown in Attachment 21.3.
The competency of the trainee is demonstrated and documented after
the training. An example for a form is included in Attachment 21.4.
Competence and requirements are reviewed between the individual and
supervisor in annual meetings.
Training not only includes technical competence but also knowledge on
the FDA and equivalent international regulations.
Training in The Laboratory includes all methods and techniques that
personnel are asked to perform.
When training records are created, signed and maintained in electronic
form, the computer system complies with the FDAs 21 CFR Part 11 and
equivalent international regulations.
Training Courses and Tools for Pre- or Self-Study
Human resources together with laboratory management search for and
recommend training courses. Trainers come from The Laboratory and also
from outside. Training tools are available from The Laboratory library for preor self-study and to assist trainers in developing and conducting training
courses. A list of training tools is included in Chapter 20. They include:
Primers and master plans

Reference publications
Audio seminars
FDA and international regulations and guidelines
Standard operating procedures
Assessment Tools
The effectiveness of trainings and competence is evaluated and documented
following the SOP S513 (Ref. 20.4). Assessment tools include:
Written evaluations, e.g., a test after a specific training.

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Interview by supervisor or trainer.
Observation of an employee performing a procedure.
Testing blind QC samples.
Testing of known samples.
Testing of previously analyzed samples.
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S125: Training for GxP, 21 CFR Part 11 and Computer Validation
S513: Training for Laboratory Personnel
10. Selection and Validation of Analytical Methods and Procedures

Analytical methods for product and stability testing are properly selected and
validated to ensure that they are suitable for their intended use.
Method Selection
When available, standard methods published by international, national or
regional standard committees are selected. Examples for standard methods
are those published by the United States Pharmacopoeia (USP) and
equivalent international Pharmacopeias, National Formulary (NF), Official
Methods of Analysis of the Association of Official Analytical Chemists (AOAC),
American Public Health Association (APHA) and some others.
If standard methods are not available methods published by reputable
technical organizations or private authors will be used. In this category also
fall validated methods supplied by reputable equipment manufacturers.
Validation of Methods Developed by The Laboratory
The Laboratory validates non-standard methods following the SOPs S612 and
S613 (Ref. 20.4). The procedures follow the validation life cycle approach and
include the following steps:
Definition of the application, purpose and scope of the method.
Specification of performance parameters and acceptance criteria.
Defining validation experiments.
Verification of relevant performance characteristics of equipment.
Qualification of materials, e.g. standards and reagents.

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Adjusting method parameters and/or acceptance criteria if

necessary.
Performing full internal (and external) validation experiments.
Defining criteria for revalidation.
Defining type and frequency of system suitability tests and/or

Analytical Quality Control (AQC) checks for the routine.
Documenting validation experiments and results in the validation

report.
The extent and type of validation and the acceptance criteria depend on the
application. Validation experiments can include:
accuracy
precision
specificity
limit of detection
limit of quantitation
linearity
range
ruggedness
robustness
Depending on the intended use and scope of the method, all or part of the
parameters will be tested.
Verification of Standard Methods
Standard methods generally follow the same life cycle principle. For standard
methods first define the scope and performance specifications of the method
as required by The Laboratory. If the scope of the standard method matches
the scope and specifications of The Laboratory method 100% only the
competence of The Laboratory and suitability of equipment to successfully run
the method will be verified. This typically includes repetition of two validation
experiments and running system suitability tests or quality control samples.
Any parameter outside The Laboratory specification is validated similarly to
methods developed in The Laboratory (10.2).

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Method Revalidation
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The method will be revalidated if it is out of the initial scope or specifications

after changing sample characteristics, instrument characteristics or method
parameters.
Using Alternative Methods
If standard methods exist but because of technical or business reasons The
Laboratory intends using alternative methods, The Laboratory demonstrates
equivalency of the alternative method to the standard method. To demonstrate
equivalency The Laboratory, at a minimum, analyzes four consecutive split
samples using the standard method and the alternative method. The
alternative method can be used if the results of the comparison meet preestablished acceptance criteria.
Using Software for Automated Method Validation
When software is used for automated method validation, the software itself is
validated. When validation documents are maintained and archived in
electronic form instead of paper the computer system complies with the FDAs
21 CFR Part 11 or equivalent international regulations.
S612: Validation of Analytical Methods
S613: Validation of Chromatographic Methods
S614: Transfer of Analytical Methods
11. Equipment and Computers

The Laboratory has equipment for sample preparation, testing and data
processing. Software is used for instrument control, data acquisition, data
evaluation and for archiving and retrieval of data. Procedures for proper selection,
qualification and maintenance of analytical instrument hardware and software
ensure that the equipment is suitable for its intended use. Equipment hardware is
purchased from vendors. Software is also purchased if available. For specific
projects The Laboratory develops software either as a standalone package or as
an add-on to commercial software. Equipment is adequately calibrated, qualified
and/or validated and maintained to ensure high system uptime, data accuracy,
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confidentiality and integrity. To ensure data integrity computer systems comply with
the FDAs regulation for electronic records and signatures: 21 CFR Part 11.
Equipment Identification
Each item of equipment hardware and each computer system used for testing
has an identification number that is unique to each instrument. Information on
the equipment is entered in the system inventory database. Initial and/or
updated information includes:
instrument description
manufacturers name
serial number or other unique identification
firmware or software revision
location of installation and use
date of installation
calibration/qualification/validation status
any damage, malfunction, modification and repair
An example of a form for the equipment documentation is shown in

Attachment 21.5.
Equipment Logs
Records are maintained for each item of equipment with information on
calibration and/or qualification, requalification, performance checks, damage,
malfunctions, modifications and updates. An example for a template is shown
in Attachment 21.7.
All documents necessary to support the above mentioned events or activities
are also maintained. Examples are results of performance checks, calibration
plots, calibration certificates and vendor declarations.
Qualification of Equipment Hardware
The Laboratory qualifies equipment following the SOP S240 (Ref. 20.4). The
procedure ensures that:
Qualification activities follow a documented qualification plan.
The instrument design meets The Laboratory requirements for the

intended use through a formal design qualification. During the design
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qualification the vendors functional and performance specifications are
verified for compliance with The Laboratorys specifications.
Instruments are developed and manufactured in a quality

environment. This is verified through a formal vendor assessment.
Instruments are installed according to vendor specifications. The

installation process is documented through formal installation qualification.
Larger systems are installed by vendor representatives while smaller
systems by laboratory staff. In both cases the laboratory supervisor signs
off the installation qualification documents.
Instruments are calibrated and/or qualified according to SOPs

specifically designed for instrument categories. For examples see SOP
S641 and SOP S644 (Ref. 20.4).
Ongoing performance is ensured through periodic testing of critical

parameters that may be impacted by the use of the system. An example is
a regular check of the intensity of HPLC UV detector lamps. This ensures
that specifications for the limit of detection and limit of quantitation are met
on a day-by-day basis.
Equipment hardware is fully revalidated or recalibrated at regular

time intervals to ensure proper functioning. The schedule for the
requalification is defined for each instrument category.
Each piece of equipment is labeled with the calibration or

qualification status. Information includes dates of the last and next
scheduled calibration/qualification.
Qualification results are summarized in a qualification summary

report that mirrors the qualification plan.
Off-the-Shelf Computer System Validation
The Laboratory validates commercial off-the-shelf computer systems following
the SOP S656 (Ref. 20.4). The procedure ensures that:
Validation activities follow a documented qualification plan.
The computer system design meets The Laboratorys requirements

for the intended use through a formal design qualification. During the
design qualification the vendors functional specifications are verified for
compliance with The Laboratorys specifications.
Software and computer systems are designed, developed and

manufactured in a quality environment. The software is validated during all
development phases according to documented software development life
cycle procedures. Vendors are able to support the computer systems. This
is ensured through a vendor assessment program following SOPs S273
and S274 (Ref. 20.4).
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The computer systems are installed according to vendor

specifications. The installation process is documented through formal
installation qualification. During or after the installation the system is
documented with hardware items, firmware revision, operating and
application software and revisions and any accessories. For an example,
see E322 in Reference 20.6. Larger systems are installed and
documented by vendor representatives, smaller systems by laboratory
staff. In both cases the laboratory supervisor signs off the installation
qualification documents.
Software and computer systems are tested in the users

environment following the concept of risk-based validation. The procedure
is described in SOP S321 (Ref. 20.4). Tests are limited to key functions
and functions that are impacted by the environment. For configurable
systems the configurations as set by the users are tested in The
Laboratory. Security access is always tested because it is a critical function
and is typically configured for specific users.
Ongoing performance is ensured through periodic testing of the

complete system, when applicable, and through a rigorous change control
procedure. The change control procedure requires a risk assessment and
an evaluation of what and how much revalidation is required after the
change. All changes are recorded in the system logbook.
Validation results are summarized in a qualification summary report

that mirrors the validation plan.
An annual review of the computer system verifies that actual system

status and validation is in compliance with the documentation.
Validation of Software Developed In-House
The Laboratory validates software that is developed in-house following the
SOP S263 (Ref. 20.4). Examples for such software include standalone
software packages such as completely custom built statistical packages and
also add-on software, for example Macros for data systems. Also included in
this category are commercial spreadsheet applications such as MS Excel or
databases such as MS Access. The design, development and use follow the
SOP S266 (Ref. 20.4). The procedure ensures that:
Software is designed, developed and validated in a controlled

environment and the process is documented.
The software design meets The Laboratory requirements through

review of specifications by the users departments.
Every software installation is documented and entered in the

equipment inventory database.
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The software is tested in the users environment using the users

application. All functions are tested under normal, boundary and stress
conditions.
Changes to the software follow a documented change control

procedure. The procedure requires a risk assessment and an evaluation of
what and how much revalidation is required after the change. All changes
are recorded in the system logbook.
Operation
Authorized and well trained personnel operate the equipment. A list of
authorized users is maintained for each equipment. An example for a template
is included in Attachment 21.6. Up-to-date instructions on the operation and
maintenance are readily available for appropriate use by the appropriate
personnel.
Maintenance
Equipment hardware and computer systems are maintained to ensure correct
functioning and minimum downtime. Maintenance activities follow the SOP
S541 (Ref. 20.4). The procedure ensures that:
All parts are listed in the parts inventory database with criticality for
operation and anticipated usage.
Critical parts are stored in a storage room close to The Laboratory

to ensure fast availability when needed.
Critical parts are regularly exchanged. Schedule for exchange is

based on experience and vendor recommendations.
Time schedule for exchange is based on measured performance or

the part used if possible, if this is not possible, the schedule is based on
linear time.
Computer systems are regularly checked for viruses following the

procedure in SOP S321 (Ref. 20.4).
Out of Service
Equipment not meeting specifications, defective equipment and equipment
that cannot be used for other reasons, for example, equipment that has been
subject to overloading or mishandling, or equipment that gives suspect or outof-specification results is taken out of service. It is isolated and clearly labeled
as being Out of Service to prevent its use until it has been repaired and
verified to be suitable for its intended use through calibration or qualification.
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When equipment temporarily goes outside the direct control of The

Laboratory, The Laboratory ensures that the correct function and
calibration/qualification status is checked when the equipment is returned.
Decommissioning
When equipment is taken out of service, The Laboratory ensures that the
equipment is taken out of the equipment inventory database. When computer
systems are taken out of service The Laboratory ensures that data generated
on the computer system are migrated to the new system following the
procedure in SOP S261 (Ref. 20.4).
S240: Qualification of Equipment
S259: Configuration Management and Version Control of Software
S261: Retirement of Computer Systems
S262: Change Control of Software and Computer Systems
S263: Validation of Macro Programs and other Application Software
S266: Development and Use of Spreadsheets in Part 11 and GxP Environments
S273: Auditing Software Suppliers: Preparation, Conduct, Follow-up
S274: Quality Assessment of Software and Computer System Suppliers
S321: Virus Checks of IT Systems
S509: Change Control of Analytical Equipment
S519: Risk Assessment for Laboratory Systems
S541: Maintenance of Laboratory Equipment
S628: Development of User Requirement Specifications for Analytical Equipment
S641: Calibration of Analytical Balances
S644: Qualification of Refrigerators
S656: Validation of Laboratory Computer Systems
S662: Risk-Based Validation of Laboratory Computer Systems
12. Sampling
Samples are usually taken from production. Persons taking samples are either
laboratory or production staff. In either case, sampling of substances, materials or
products for subsequent testing follows the SOP S531 (Ref. 20.4). Procedures for
sampling specific materials are available at the location where sampling is
undertaken. The procedure ensures that samples are taken according to a
sampling plan to be representative based on scientifically sound sampling
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methods. The procedure also requires recording of sampling data such as
sampling procedure used, location, the identification of the person who took the
sample, the substance name or description, batch number, quantity, equipment
used for sampling and environmental conditions, if relevant. An example for a
template is shown in Attachment 21.8.
S531: Sampling for Analytical Testing
13. Reagents and Calibration Standards

Reagents and calibration standards are prepared or purchased following the SOP
S532 (Ref. 20.4). This ensures:
Reagents and calibration standards are purchased from qualified vendors

or are prepared from reagent grade materials.
When standards are purchased the date of the receipt is documented on

the certificate of analysis and certificates are filed for a minimum of five years.
Standards and reagents are prepared using Class A volumetric glassware

and calibrated dispersing devices.
All vendor supplied standards and reagents are recorded in an electronic

database. Recorded information includes as a minimum: vendor, date received,
lot number and expiration date.
The type of standards used in The Laboratory is defined.
Standards prepared in The Laboratory are recorded in an electronic

database. Information includes date of preparation, person who prepared it,
expiration date, quantity, storage conditions and the procedure used to prepare
the standard.
Standards and reagents are labeled with the standard or reagent name or
description, concentration, date of preparation and date of expiration.
Documented information is sufficient to allow traceability to the preparation
record that provides traceability of all ingredients.
Manufacturer specifies expiration dates for standards and reagents. If no

information is available from the manufacturer it is determined based on best
scientific judgment or through experiments, if necessary.
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When working standards are prepared from certified standards, the quality
of the working standard is determined through experiments. For the comparison
acceptance criteria are specified before the tests and test methods are
validated.
S532: Preparation of Calibration Standards
14. Traceability of Measurements

Measurement devices are traceable to national or international standards when a
traceable standard is available. Examples for measurement devices with
traceability to national standards are balances and thermometers. For an example
on determination of accuracy see SOP S533 (Ref. 20.4). Contracting companies
providing calibration or qualification services provide evidence of measurement
traceability of its own measurement standards and measurement equipment. This
is done by means of an unbroken chain of calibration or comparisons linking them
to primary standards.
Reference standards used in the lab or by equipment calibration or qualification
service providers are traceable to national or international standards, if such
standards are available. An example is caffeine to calibrate the wavelength
accuracy of HPLC UV detectors.
Contracting companies providing calibration or qualification services also provide
documentation demonstrating competence to perform these services.
Calibrations that cannot provide strict measurement traceability to national or
international standards are conducted such that the calibration results can generate
confidence in the measurements made in the course of the analyses.

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S533: Measurement Traceability
15. Stability Testing

The Laboratory has a written testing program designed to assess the stability
characteristics of drug products. The results of such stability testing are used in
determining appropriate storage conditions and expiration dates. Stability testing
follows the SOP S551 (Ref. 20.4).
Following this procedure ensures:
Sample size and test intervals are based on statistical criteria for each
attribute examined to assure valid estimation of stability.
Reliable, meaningful, validated and specific test methods are used.
Storage of the drug product in the same container-closure system as that

in which the drug product is marketed.
Testing of drug products for reconstitution at the time of dispensing (as

directed in the labeling) as well as after they are reconstituted.
An adequate number of batches of each drug product are tested to

determine an appropriate expiration date and a record of this data is
maintained.
Accelerated studies, combined with basic stability information on the

components, drug products and container-closure system is used to support
tentative expiration dates provided full shelf life studies are not available and
are being conducted.
Where data from accelerated studies are used to project a tentative

expiration date that is beyond a date supported by actual shelf life studies,
stability studies are conducted, including drug product testing at appropriate
intervals, until the tentative expiration date is verified or the appropriate
expiration date is determined.

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S551: Stability Testing
16. Handling of Test Items

The Laboratory ensures proper identification and protection of samples from the
time the sample is taken until its disposal.
Receipt, protection, storage, processing, retention and disposal is

described in the SOP S534 (Ref. 20.4). The procedure includes provisions for
protection against deterioration, loss or damage during transportation, handling
and storage. When samples require special environmental conditions for
storage, environmental conditions are controlled and monitored.
The identification of samples follows the SOP S534 (Ref. 20.4). The
procedure ensures unique identification of samples through a sample number.
The sample number is used to track the sample from the time the sample is
collected until the analysis is completed. The sample number is also used to
provide traceability between the sample and test results.
When the sample arrives in The Laboratory it is physically inspected and

abnormalities or any other special observations are recorded. In case of
abnormalities the laboratory personnel consult the manager of the department
where the sample came from. After consultation it is decided whether to
proceed with the test or take a new sample.
Procedures for processing of samples are defined for each sample.
An appropriately identified reserve sample that is representative of each lot

in each shipment of each active ingredient is retained.
The reserve sample consists of at least twice the quantity necessary for all
tests to determine whether the product meets its established specifications.

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S534: Handling of Laboratory Test Items
17. Testing
Correct testing is most important to achieve accurate and reliable results. Analyst
use and follow a checklist to ensure that:
Each test follows a written procedure that is specific for the test.
Only validated methods are used for testing.
Only qualified equipment is used for testing.
Testing is performed by qualified people.
The system is calibrated before the first sample run and within a series of
runs sufficient calibrations are performed.
System suitability tests are performed before the first sample run and for
sequences within and at the end of the sequence.
Acceptance criteria are specified for each test.
Test results are documented according to a protocol.
Test procedures and parameters are documented with sufficient detail

such that sample runs including data evaluation can be repeated based on this
documentation
An example for a checklist is included in Attachment 21.10
18. Quality of Test Results and Failure Investigations

The Laboratory ensures high quality measurements and reporting of test results
through the implementation of multiple measures or mechanisms such as:
Ongoing control of system performance through system suitability tests or

analysis of quality control samples.
Procedures for handling out-of-specification results with root cause

analysis and corrective and preventive action plans.
Data review through the analysts supervisor and QA.

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Ongoing Performance Control of the Analysis System

The Laboratory follows SOP S621 (Ref. 20.4) to ensure ongoing performance of
the analysis system. Depending on the system, ongoing performance is controlled
through:
System suitability test before, in between and after sample runs.
Regular analysis of quality control samples and monitoring the data and
trends in quality control charts. Control criteria and corrective actions are
specified for quality control sample results. Discrepant results are documented
and The Laboratory supervisor is informed. The supervisor initiates follow-up
activities, e.g., flags test results.
Out-of-Specification Results and Failure Investigations
Deviations from expected test results are handled following the SOP S115
(Ref. 20.4). This procedure ensures that:
Analysts are aware of potential problems.
Analysts stop testing in case of an Out-of-Specification (OOS)

result.
Analysts inform the supervisor in case of an OOS result.
Samples are retained until data is reviewed and the investigation is

finished.
Analysts together with the supervisor document the OOS, each step
of The Laboratory failure investigation and investigation results.
The supervisor reviews and accepts or rejects the test results.
The supervisor goes through the details of failure investigations with

the analyst.
The supervisor informs the QA manager about the OOS.
The supervisor approves the failure investigation.
The supervisor together with the analyst identifies the root cause of
the failure.
The supervisor together with the analyst evaluates if the problem

could occur on other systems.
The supervisor together with the analyst develops and implements

a corrective and preventive action plan.
Failure investigations are completed within 20 working days.

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Root Cause Analysis and Corrective and Preventive Action Plans
The Laboratory continually revises and improves processes if necessary.
Failure investigations and evaluation of OOS results are one way to identify
problems. Other sources are customer complaints, internal and external
inspection findings and problems identified in management reviews. The
Laboratory has a formal CAPA program that follows the SOP S114 (Ref. 20.4).
Because of its close connection to testing, OOS results and RCA and CAPA
failure investigations are discussed in the chapter Quality of Test Results,
although RCA and CAPA may not only be initiated through OOS test results as
explained above.
Following the SOP S114 ensures:
Problems are clearly identified and described.
Problems are evaluated and the magnitude and impact is evaluated

through a formal risk assessment.
The investigation of the problem follows a documented plan.
The source of the problem is identified through a formal root cause

analysis.
An action plan is developed with a list of required tasks, time

schedule and owners.
A team is formed to implement the plan. The team may be crossfunctional if appropriate. For example, the local or corporate IT department
may get involved to find the root cause of a problem associated with a
computer system.
After implementation, the effectiveness of the actions is verified.
Data Review and Validation

Explained in SOP S671 (Ref. 20.4).
The analyst generating the analytical data has the primary

responsibility for data correctness and completeness. If critical data are
transcribed from a paper-based system into an electronic data
management system, a second analyst verifies accuracy of entries.
The primary analyst is responsible for assembling the data package

containing all relevant raw data needed for data interpretation and
validation for each batch of sample processed. A data package typically
includes: quantitative analysis reports, a list of instrument parameters,
chromatograms and log files.

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The Laboratory supervisor or his/her designee reviews and

approves all data for a given sample before it is released. This review
assures that results from different parameters for a given sample correlate.
As the last step the QA officer or his/her designee reviews the data,
releases the test result and the final report is issued.
The information to be reviewed depends on the test and for

chromatography typically includes:
Conformance of test results to written specifications.
Information on sampling and test method.
Information on compound identity and strength.
Completeness of the report header.
The initials or signature of the person who performed the test
and the date(s) the tests were performed.
Completeness of supporting material, e.g., chromatograms.
Criteria for calibration, retention and time windows.
Proper documentation of manual integration results.
Complete records of any modification of a method employed in
testing.
All calculations performed in connection with the test, including
units of measure, conversion factors and equivalency factors.
Quality control or system suitability data.
Documentation of irregularities.
Reporting Test Results
For reporting test results The Laboratory follows the procedure in SOP S672 (Ref.
20.4) to ensure consistent and compliant reporting. Results are reviewed to
address accuracy, clarity and objectivity.
Data in the test report include:
Reference to established test method and sample preparation procedure.
Deviations, additions to, or exclusions from the test method.
A statement of conformance or non-conformance with specifications.
Name of analyst.
Name of first and second reviewer.

If data on the final report needs to be revised after it has been released a
justification must be added.

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S114: Corrective and Preventive Actions

S115: Handling Out-of-Specification Results
S512; Review and Approval of Analytical Test Results
S530: Laboratory Failure Investigations
S621: Ongoing Performance Control of Analytical Equipment
S672: Reporting of Analytical Test Results for FDA and ISO 17025 Compliance
19. Identification and Management of Records

Records are identified, maintained and archived following the SOPs S314 and
S315 (Ref. 20.4). Following the SOPs ensures:
Records are identifiable to the company, product, person or event to which

they pertain.
Records are dated and identify the person who established the records.
Entries on paper records are made in ink.
Corrections to paper records do not erase the original entry. Changes

include the correct information, the initials of the person who made the change
and the date.
When records are created, signed and/or maintained in electronic format,

the computer system and records created, evaluated, transmitted and archived
comply with the FDAs 21 CFR Part 11 and equivalent international regulations.
The definition of raw data follows the FDAs risk-based approach for Part
11. The Laboratory follows SOP S137 (Ref. 20.4).
Availability of electronic records in case of system problems or human

errors is ensured through a regular back-up. Back-up and restore of electronic
records follow SOP S317 (Ref. 20.4).
Records are kept confidential through limited and authorized access.
Records are stored in a dry and clean room.
Type of records to be archived and the archiving period is defined. A form

for identification is included in Attachment 21.9.
Records will be retained for at least as long as required by regulations.

Exact retention periods of records are defined by corporate policy for each
record type.
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All records required by the FDA and equivalent international regulations, or

copies of such records are readily available for authorized inspection during the
retention period at The Laboratory where the activities described have been
recorded. Records that are stored at another location can be immediately
retrieved from the other location by computer or other electronic means.
Records are retained either as original records or as true copies such as

photocopies, scanned to electronic files, microfilm, microfiche or other accurate
reproductions of the original records. Where reduction techniques, such as
microfilming are used, scanning or photocopying equipment and processes are
validated. When paper documents are scanned for electronic archiving, The
Laboratory follows the procedure in SOP S316 (Ref. 20.4).
For maintenance and archiving of electronic records, The Laboratory

follows the SOP S315 (Ref. 20.4).

S137: 21 CFR Part 11 Scope and Controls
S314: Record and Data Identification and Management
S315: Retention and Archiving of Electronic Records
S316: Scanning of Paper Records for GxP Compliant Archiving
S317: Data Back-up and Restore

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20. References
This chapter lists the documents that are available to assist in implementing the
master plan.
Primers and Master Plans
1. Risk Management Master Plan.
Example included in the Labcompliance Laboratory Compliance
Package: www.labcompliance.com/books/lab-compliance.
2. Equipment Qualification Master Plan.
3. Computer System Validation Master Plan.
Example included in the Labcompliance Computer System
Validation Package: www.labcompliance.com/books/computers.
4. Network Qualification Master Plan.
5. 21 CFR Part 11 Compliance Master Plan.
Example included in the Labcompliance Part 11 Compliance
Package: www.labcompliance.com/books/part11.
6. Training Master Plan.
7. Calibration and Preventive Maintenance Master Plan.
8. Good Automated Manufacturing Practice, Guide for Validation of
Automated Systems in Pharmaceutical Manufacture, Version 3,
March 1998, Version 4, December 2001 www.ispe.org.
9. Primer, FDA/EU Compliance in Analytical Laboratories.
10. Primer, Computer System Validation, Labcompliance, 2005, 40
pages.
Example included in the Labcompliance Computer System
Validation Package: www.labcompliance.com/books/computers.
Reference Publications
All are included in the Laboratory Compliance Package from Labcompliance:
www.labcompliance.com/books/lab-compliance.
1. A123: CAPA A Fundamental Quality Subsystem.
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2. A122: Preventing Out-of-Specification (OOS) Situations Caused by
Laboratory Errors.
3. A154: Definitions: Qualification vs. Verification, Calibration and
Validation.
4. A164: Qualification of Equipment and Computerized Systems.
5. A183: Implementing 21CFR Part 11 in Laboratories.
6. A188: 21 CFR Part 11 Compliance for Pharmaceutical Laboratories:
A Supplier's Perspective.
7. A194: Implementing 21CFR Part 11: Data Migration and Long Term
Archiving for Ready Retrieval.
8. A234: Equipment Qualification in Practice.
9. A239: Selecting Parameters and Limits for Equipment Operational
Qualification.
10. A273: Risk-Based Validation of Commercial Off-the-Shelf Computer
Systems.
11. A264: (Laboratory) Equipment Qualification and Computer System
Validation.
12. A553: Qualification of High-Performance Liquid Chromatography
Systems.
13. A603: Validation of Analytical Methods: Review and Strategy.
14. A605: Validation of HPLC Methods.
15. A607: Evaluation and Validation of Standard Methods.
16. A633: Preparation and Qualification of Certified Reference Material
and Working Standards.
17. M133: Laboratory Compliance Master Plan.
18. M610: 100 Most Frequently Asked Questions and Answers Related
to Laboratory Compliance.
Audio Seminars
1. FDA/EU Compliance in Analytical Laboratories (135).
Included in the Laboratory Compliance Package from
Labcompliance:
2. Validation of Software and Computer Systems in Analytical
Laboratories (112).
3. Validation of Computerized Laboratory Systems (106).
Implementing the new GAMP Laboratory Systems Guide.
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4. Laboratory Equipment Qualification (114).
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5. Writing Effective Test Scripts and Validation Protocols for the

Bio/Pharmaceutical Industry (115).
6. Electronic Raw Data in FDA Regulated Environments (128).
7. Analytical Instrument Qualification (AIQ) (132).
Understanding the New USP Draft Guidance <1058>.
8. FDA Compliant Electronic Records Management (134):
http://www.labcompliance.com/seminars/audio134/index.htm.
9. Audits of Computer Systems in Laboratories and Manufacturing
(116): http://www.labcompliance.com/seminars/audio116/index.htm.
10. Inspection of Pharmaceutical Quality Control Laboratories (139):
http://www.labcompliance.com/seminars/audio139/index.htm.
Standard Operating Procedures
SOPs indicated with (*) are included in the Laboratory Compliance Package
from Labcompliance:
1. S105: Document Control and Management.
2. S114: Corrective and Preventive Actions. (*)
3. S115: Handling Out-of-Specification Results. (*)
4. S125: Training for GxP, 21 CFR Part 11 and Computer Validation.
(*)
5. S137: 21 CFR Part 11 - Scope and Controls. (*)
6. S141: FDA Inspections - Preparation, Conduct, Follow-up. (*)
7. S142: Multinational GMP Inspections: Preparation, Conduct and
Follow-up (*)
8. S151: Facilities and Environmental Conditions.
9. S240: Qualification of Equipment. (*)
10. S259: Configuration Management and Version Control of Software.
(*)
11. S261: Retirement of Computer Systems. (*)
12. S262: Change Control of Software and Computer Systems. (*)
13. S263: Validation of Macro Programs and other Application Software.
(*)
14. S266: Development and Use of Spreadsheets in Part 11 and GxP
Environments. (*)
FOR INTERNAL
USE
Master Plan
Page 43 of 53
15. S267: Validation of Electronic Laboratory Notebooks. (*)
16. S268: Using Electronic Laboratory Notebooks in an FDA Regulated
Environment. (*)
17. S270: Validation of Electronic Document Management Systems. (*)
18. S271: Validation of Commercial Off-the-shelf (COTS) Computer
Systems (*).
19. S272: Auditing Computer Systems. (*)
20. S273: Auditing Software Suppliers: Preparation, Conduct, Followup. (*)
21. S274: Quality Assessment of Software and Computer System
Suppliers. (*)
22. S314: Record and Data Identification and Management.
23. S315: Retention and Archiving of Electronic Records. (*)
24. S316: Scanning of Paper Records for GxP Compliant Archiving. (*)
25. S317: Data Back-up and Restore. (*)
26. S321: Virus Checks of IT Systems.
27. S504: Generation and Maintenance of SOPs for Laboratories. (*)
28. S509: Change Control of Analytical Equipment. (*)
29. S510: Laboratory Management Review.
30. S511: Auditing Laboratory Systems.
31. S513: Training for Laboratory Personnel. (*)
32. S519: Risk Assessment for Laboratory Systems. (*)
33. S530: Laboratory Failure Investigations. (*)
34. S531: Sampling for Analytical Testing.
35. S532: Preparation of Calibration Standards.
36. S533: Measurement Traceability.
37. S534: Handling of Laboratory Test Items.
38. S541: Maintenance of Laboratory Equipment.
39. S551: Stability Testing.
40. S612: Validation of Analytical Methods.
41. S613: Validation of Chromatographic Methods. (*)
42. S614: Transfer of Analytical Methods.
43. S621: Ongoing Performance Control of Analytical Equipment.
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44. S628: Development of User Requirement Specifications for
Analytical Equipment. (*)
45. S641: Calibration of Analytical Balances. (*)
46. S644: Qualification of Refrigerators. (*)
47. S656: Validation of Laboratory Computer Systems. (*)
48. S662: Risk-Based Validation of Laboratory Computer Systems. (*)
49. S671: Analytical Data Review and Validation.
50. S672: Reporting of Analytical Test Results.
FDA and International Regulations, Guidelines and Presentations
Documents or links included in the Laboratory Compliance Master Plan:
1. Guidance for Inspectors and other FDA Personnel
Guide to Inspection of Microbiological Pharmaceutical Quality
Control Laboratories.
2. Guidance for Inspectors and other FDA Personnel
Guide to Inspection of Pharmaceutical Quality Control Laboratories.
3. PIC/S Aide Memoire: Inspection of Pharmaceutical Quality Control
Laboratories.
4. FDA 21 CFR 211
Current Good Manufacturing Practice for Finished Pharmaceuticals.
5. Guidance for Inspectors
Drug Manufacturing Inspections.
6. 21 CFR 11
Electronic Records Electronic Signatures.
7. Guidance for Industry
21 CFR Part 11; Electronic Records; Electronic
Signatures, Scope and Applications.
8. Guidance for Industry (draft)
Mass Spectrometry for Confirmation of the Identity of Animal Drug
Residues.
9. Guidance for Industry (draft)
Analytical Procedures and Methods Validation.
Bioanalytical Method Validation.

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FOR INTERNAL
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11. FDA Guidance
Requesting Methods Validation for Abbreviated New Drug
Applications (ANDAs).
12. FDA Industry Guidance
Investigating Out-of-Specification (OOS) Test Results for
Pharmaceutical Production.
General Principles of Software Validation.
14. Annex 11 of EU GMP
Computerized Systems.
Worksheets, Checklists, Forms, Templates, Examples
All included in the Laboratory Compliance Package from Labcompliance:
1. E184: Worksheet: Laboratory Audit.
2. E116: Checklist Out-of-Specification Situations (OOS).
3. E255: Requirement Specifications for Chromatographic Data
Systems.
4. E269: Requirement Specifications for Excel Applications.
5. E308: User Requirement Specifications - 20 Good/Bad Examples.
6. E131: Template/Examples: Test Protocol for Excel Spreadsheet
Application (with traceability matrix).
7. E322: Template/Examples: Computer System Identification.

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FOR INTERNAL
Master Plan
Page 46 of 53
21. Attachments
Laboratory Personnel
This is a template to document laboratory personnel with name, position/title,
education level and years of experience.
Name
Position
Education
Years of Experience
total/current
Document Master List

This is a template to list controlled documents with document id, description,
owner and status.
Document ID
(Number, Rev)
Date of
Last
Review
# Copies
Distributed
Jan 04, 2005
Dec 15,
2005
Jul 23, 2005
N/A
Description
Location
Date of Issue
or Revision
S-233
Ver. 1.0
SOP: Qualification
of Analytical
Instruments
QC Lab
E-362
Ver. 3.0
Requirement
Specifications for
Excel Worksheet
#2534
QC Lab

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Template and Example to Document Training Requirements
Employee:
Supervisor:
Department:
Date:
Job Description:
Assigned Tasks:
Required
Qualification
Understands
requirements of
21 CFR Part 11.
Education, Previous
Experience or Training
Courses
Attended 3 day training
course on 21 CFR Part 11.
Certificate available.

USE
(Additional)
Training Required
Yes 0
No 0
Yes 0
No 0
Yes 0
No 0
Yes 0
No 0
Yes 0
No 0
FOR INTERNAL
Master Plan
Page 48 of 53
Template to Document Training
Employee:
Supervisor:
Department:
Date:
Training Subject:
Training Objective:
Type of Training:
E.g. classroom
Location:
Date:
Duration (Days):
Qualified Trainer:
Certificate Available:
Training Objective Met:
Yes 0
No 0
Judged By:
E.g. certificate or through personal

examination by the supervisor.
If Objective Not Met Explain Why:

Approval by Supervisor:
__________ ______ _____________

Name

USE
Date
Signature
FOR INTERNAL
Master Plan
Page 49 of 53
Equipment List
This is a template to document the available equipment in the lab.
Equipment
ID
Description
Manufacturer
Location

USE
Date of
Installation
Qualification
Status
FOR INTERNAL
Master Plan
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List with Authorized Users of Equipment
Equipment ID:
Description:
Date
Name of User
Function

USE
Signature
FOR INTERNAL
Master Plan
Page 51 of 53
Equipment Records
This is a template to record equipment events such as calibrations,
(re)qualification, performance checks, modifications, updates, damages,
malfunctions and repairs.
Equipment ID:
Serial Number:
Description:
Location:
Installation Date:
Date
Event
Activity

USE
Responsible
Person
Signature
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Recording Sampling Data
Sampling Location:
Sampling Equipment:
Sampling Procedure:
Date
Environmental Conditions
Observations
Person
List of Records to be Archived

Record
Identifier
Description
Storage
Media

USE
Storage
Location
Archiving
Period
FOR INTERNAL
Master Plan
Checklist for Testing
Item
Page 53 of 53
Description
Check
Test follows SOP

Method validated
Equipment qualified
Reference material qualified
People trained
System calibrated
System suitability tests
performed
Acceptance criteria specified
Results documented according
to protocol
Test procedures documented

USE
FOR INTERNAL

M 133 Laboratory Master Plan

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Validation of Methods Developed by The Laboratory......................................22

Verification of Standard Methods.....................................................................23

Using Alternative Methods...............................................................................23

Using Software for Automated Method Validation...........................................24

11. Equipment and Computers......................................................................................24

Qualification of Equipment Hardware..............................................................25

Off-the-Shelf Computer System Validation......................................................26

Validation of Software Developed In-House....................................................27

Equipment Temporarily Leaving The Laboratory.............................................28

Ongoing Performance Control of the Analysis System....................................34

Out-of-Specification Results and Failure Investigations..................................34

Root Cause Analysis and Corrective and Preventive Action Plans.................35

Data Review and Validation.............................................................................36

Reporting Test Results.....................................................................................36

19. Identification and Management of Records...........................................................37

Primers and Master Plans................................................................................39

Standard Operating Procedures......................................................................41

FDA and International Regulations, Guidelines and Presentations.................43

Worksheets, Checklists, Forms, Templates, Examples...................................44

Document Master List......................................................................................45

Template and Example to Document Training Requirements.........................46

Template to Document Training.......................................................................47

List with Authorized Users of Equipment.........................................................49

Recording Sampling Data................................................................................51

List of Records to be Archived.........................................................................51

21.10 Checklist for Testing.........................................................................................52

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1. Introduction, Scope and Objectives of this Document

Analytical laboratories in (bio)pharmaceutical manufacturing.

US FDA and equivalent international GxP regulations.

This master plan has been developed for a pharmaceutical quality

It serves as a guideline for how cGMP requirements can be

It answers the inspectors question about the companys

It demonstrates management commitment and support for

It helps personnel at all management levels understand how

Assists in the preparation of project plans.

It helps to produce and maintain high quality analytical data.

Effective communication of the master plan to all employees and

Following documented processes and procedures for cGMP and

Clear definition of roles and responsibilities for management and

Ongoing monitoring of FDA and international guidelines and timely

Risk-based processes and procedures.

Continuous evaluation and improvement of processes and

Validation of critical processes, equipment hardware and computer

Adequate design and control of facilities and environmental

GxP compliant recording and archiving of data.

Evaluation and investigation of deviations from expected results

Suitable handling of samples, chemicals and standards.

Regular system suitability tests or quality control checks before and

Reviewing and validating analytical data.

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Sufficient and appropriately qualified and trained personnel.

Auditing of actual processes for compliance with documented

Annual review of processes and procedures.

3. Structure of QMS Documentation

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Figure 1. Documentation Hierarchy

Risk Management Master Plan (20.1.1)