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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.
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Master Plan Page 2 of 52
Document Number: M-133 Ver. 1.xx
Laboratory Compliance
Company Name:
Controls:
Signatures:
Author I indicate that I have authored or updated this Master Plan
according to applicable business requirements and our
company standards.
Name: ________________________________
Signature: ________________________________
Date: ________________________________
Approver 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: ________________________________
Reviewer 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: ________________________________
Table of Contents
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
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
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
17. Testing........................................................................................................................33
20. References.................................................................................................................38
Laboratory Compliance
1.1 Introduction
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:
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.
Master plans are documents that lay out a company’s 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 company’s training master plan.
3.5 Records
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.
Attachment 21.1 lists laboratory personnel with names, positions, education level
and years of experience (total/current position).
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.
Review analytical data.
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Laboratory Compliance
Issue data summaries for annual product reviews.
Organize annual management review of the compliance system.
Manage vendor assessment and audits.
Manage complaints.
4.4 Analysts
The safety officer manages activities required to ensure a safe and healthy
laboratory environment.
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.
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.
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.
The procedure for management includes but is not limited to the following
elements:
9.1 Procedure
Competence of people is based on education, experience, demonstrated skills and
training. People qualification is controlled through SOP S513 (Ref. 20.4).
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.
Performing pre-validation experiments.
Adjusting method parameters and/or acceptance criteria if
necessary.
Performing full internal (and external) validation experiments.
Defining criteria for revalidation.
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Laboratory Compliance
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.
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).
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 FDA’s
21 CFR Part 11 or equivalent international regulations.
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
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
qualification the vendor’s functional and performance specifications are
verified for compliance with The Laboratory’s 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).
11.6 Operation
11.10 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).
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
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.
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
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.
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Laboratory Compliance
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.
18.3 Root Cause Analysis and Corrective and Preventive Action Plans
20. References
This chapter lists the documents that are available to assist in implementing the
master plan.
SOPs indicated with (*) are included in the Laboratory Compliance Package
from Labcompliance:
www.labcompliance.com/books/lab-compliance.
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. (*)
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Laboratory Compliance
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, Follow-
up. (*)
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.
21. Attachments
Years of Experience
Name Position Education
total/current
Date of # Copies
Document ID Date of Issue
Description Location Last Distributed
(Number, Rev) or Revision
Review
S-233 SOP: Qualification QC Lab Jan 04, 2005 Dec 15, 6
Ver. 1.0 of Analytical 2005
Instruments
E-362 Requirement QC Lab Jul 23, 2005 N/A 7
Ver. 3.0 Specifications for
Excel Worksheet
#2534
Employee:
Supervisor:
Department:
Date:
Job Description:
Assigned Tasks:
Yes 0 No 0
Yes 0 No 0
Yes 0 No 0
Yes 0 No 0
Employee:
Supervisor:
Department:
Date:
Training Subject:
Training Objective:
Type of Training: E.g. classroom
Location:
Date:
Duration (Days):
Qualified Trainer:
Certificate Available:
Equipment ID:
Description:
Date Name of User Function Signature
Equipment ID:
Serial Number:
Description:
Location:
Installation Date:
Event Responsible Signature
Date
Activity Person
Sampling Location:
Sampling Equipment:
Sampling Procedure:
Date Environmental Conditions Observations Person