Radiopharmaceutical Production
Quality Manual
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Quality Manual
A Quality Manual documents the policies,
procedures, responsibilities, and
documentation, that must be in place
for the facility to comply with their
regulatory responsibilities.
Contents
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Purpose of the Quality
Manual
Contents of the Quality
Manual
Relationship of the Quality
Manual to the Validation
Master Plan
Examples of Quality Manuals
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Radiopharmaceutical
Production
Quality Manual
Contents
Purpose of the Quality
Manual
Contents of the Quality
Manual
Relationship of the
Quality Manual to the
Validation Master Plan
Examples of Quality
Manuals
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Purpose of the Quality
Manual
The organization should establish and maintain a quality manual
that includes
a)
the quality policy
b)
the scope of the quality management system, including
details of and justification for any exclusions
c)
the documented procedures established for the quality
management system, or reference to them, and
d)
a description of the interaction between the processes of the
quality management system.
Radiopharmaceutical
Production
Contents of the Quality
Manual
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Quality Manual
Contents
Purpose of the Quality
Manual
Contents of the Quality
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•
Manual
Relationship of the
Quality Manual to the
Validation Master Plan
Examples of Quality
Manuals
•
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A quality manual is a document that a facility writes to explain
which regulations are applicable to the facility (i.e. which
regulations will be followed by the facility.)
The regulations that are to be followed are based on the
process(es) that are performed at the facility.
The facility’s Quality Manual should outline which regulations
are going to be followed, how they are going to be followed,
who is responsible for ensuring that the regulations are
followed, and which of the companies approved procedures
address the regulations to be followed. If all parts of a regulation
are not going to be followed, a facility may want to include a
brief explanation as to why a part of a regulation is not
applicable to the facility and therefore will not be outlined in the
Quality Manual.
The Quality Manual should be written in general terms with
minimal specifics. The format of a Quality Manual is usually
different than the format used for the facility’s other approved
documents. The format should still include such things as a
facility’s name, version control, and approval signatures.
Radiopharmaceutical
Production
Contents of the Quality
Manual
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The following are examples of sections that a Quality Manual
should contain:
– Table of Contents
– Introduction
– Facility Background
– Purpose
– Scope
– Quality Policies and Objectives
– Organization and Structure of Documentation
– Facility’s Products
– References
– Quality Policies for Specific Regulation Elements
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Table of Contents: A list of the sections contained within the
Quality Manuel and the page each section begins on.
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Introduction: A brief description of the facility, the facility’s
purpose for writing a Quality Manual, and a brief description of
the scope of the Quality Manual.
Quality Manual
Contents
Purpose of the Quality
Manual
Contents of the Quality
Manual
Relationship of the
Quality Manual to the
Validation Master Plan
Examples of Quality
Manuals
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Radiopharmaceutical
Production
Contents of the Quality
Manual
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Background: List the name of the facility, where the facility is
located, what radiopharmaceutical products are produced at the
facility, and how these will be distributed.
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Purpose: Provide general statements explaining why and how
the Quality Manual will be used.
Quality Manual
Contents
Purpose of the Quality
Manual
Contents of the Quality
– Example: “This Quality Manual describes the quality management
system that has been established by facility X in order to meet
regulatory requirements for the production of PET
radiopharmaceuticals in the United State.”
Manual
Relationship of the
Quality Manual to the
Validation Master Plan
Examples of Quality
Manuals
•
Scope: List the regulations that will be followed by the facility as
well as any portions of the regulations that will not be followed.
Provide a justification for why those portions of the regulations
are not going to be followed.
– Example: “The system described in this manual is intended to meet
general requirements set forth in the United States Food and Drug
Administration (FDA) Regulation according to 21CFR Part 210,
21CFR Part 211 and 21CFR Part 212 as well as the relevant
section of 21CFR Part 823.”
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Radiopharmaceutical
Production
Contents of the Quality
Manual
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Quality Manual
Contents
Purpose of the Quality
Manual
– Example: Customer issues are addressed in a timely, professional,
and thorough manner.
– Example: Personnel are adequately trained in the job they perform
– Example: Products and Services provided by our facility are
designed, manufactured, and delivered to our customers and meet
or exceed our customer requirements.
Contents of the Quality
Manual
Relationship of the
Quality Manual to the
Validation Master Plan
Examples of Quality
Manuals
Quality Policies and Objectives: Include a brief statement about
the approach that the facility is taking in regards to quality, (i.e.
a Quality Mission Statement) and list the quality objectives of
the facility. The quality objectives should not be numerous (five
to seven is a typical number) and should be briefly stated.
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Organization and Structure of Documentation: Provide an
explanation as to how the documentation structure at your
facility is organized and managed in relation to the applicable
regulations.
– Example: Documents related to the quality system are organized in
a hierarchy structure, are maintained in accordance with applicable
regulatory requirements and our facility record retention policy, and
are managed through a document change control system.
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Radiopharmaceutical
Production
Contents of the Quality
Manual
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Products: This section should include a brief description of the
products that are made and distributed by the facility including
what the intended use of the products is to be. This description
should be similar to a marketing type summary in that it does
not list proprietary or explicit product information that would be
detrimental to the facility if persons outside the facility read the
description. This section should provide enough detail to justify
the sections of the regulations that are and are not going to be
followed.
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References: A list of all the different regulations that were sited
within the Quality Manual.
Quality Manual
Contents
Purpose of the Quality
Manual
Contents of the Quality
Manual
Relationship of the
Quality Manual to the
Validation Master Plan
Examples of Quality
Manuals
– Example: FDA Title 21, Code of Federal Regulations Part 210 &
211, Current Good Manufacturing Practice in Manufacturing,
Processing, Packing, or Holding of Drugs and Finished
Pharmaceuticals, FDA Title 21, Code of Federal Regulations Part
212 PET Drugs — Current Good Manufacturing Practice (cGMP),
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Contents of the Quality Manual
Radiopharmaceutical
Production
Quality Manual
Contents
Purpose of the Quality
Manual
Contents of the Quality
Manual
Relationship of the
Quality Manual to the
Validation Master Plan
Examples of Quality
Manuals
•
Quality Policies for Specific Regulation Elements: This section will
encompass the majority of the manual. It will include each
regulation that will be followed by the facility, a brief description of
how the facility intends to follow the regulation, and a list of the
approved documents (by document name and number) that the
facility has in place which specifically address/discuss the facility’s
policies and objectives as stated in this section of the Quality
Manual.
– Example: Purchasing Controls; Procedures are established and
maintained to ensure that materials, supplies, and services impacting
the Quality System and procured by facility X purchasing department,
conform to specified requirements.
• Receiving Procedure SOP # XX. 01 Vendor Qualification Procedure SOP #
XX. 01 Release of In-coming Goods Procedure SOP # XX. 01 ......
– Example: Corrective and Preventive Action; At facility X, Corrective
and Preventive Actions are integral in a variety of programs.
Whenever possible, these programs make an effort to determine the
root cause of the incident and to implement appropriate actions to
prevent the reoccurrence of the incident. Quality Assurance approves
all Corrective and Preventive plans and tracks their completion and
effectiveness.
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• CAPA Procedure SOP # XX. 01 Material Review Board SOP # XX. 01
Failure Investigation Procedure SOP # XX. 01 .......
Contents of the Quality Manual
Topics that should be covered in the final section on
Quality Policies for Specific Regulation Elements
Radiopharmaceutical
Production
Quality Manual
•
Contents
Purpose of the Quality
Manual
Contents of the Quality
•
Manual
Relationship of the
Quality Manual to the
Validation Master Plan
Examples of Quality
Manuals
•
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Deviations and Events
– Event Recording
– Reviews and
Investigations
– Remediation
Change Control
– Change Initiation and
Approval
– Change Execution and
Tracking
– Change Verification and
Closure
Audit Management
– Planning
– Execution
– Review and Remediation
•
Document Management
– Storing and
Classification
– Access and Viewing
– Creating New
Documents
– Lifecycle Managements
– Printing
• Training Management
– Employee Course
Management
– Training Request and
Approval
– Gap Management and
Records
• Equipment Management
– Inventory Management
– Preventative Maintenance
– Remedial Maintenance
Contents of the Quality Manual
Radiopharmaceutical
Production
Topics that should be covered in the final section on
Quality Policies for Specific Regulation Elements
Quality Manual
• General Requirements
Contents
Purpose of the Quality
Manual
Contents of the Quality
Manual
Relationship of the
Quality Manual to the
Validation Master Plan
Examples of Quality
Manuals
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– Security and Access Control
– Facility Management
– Corrective Action Preventive
Action (CAPA)
– CAPA Initiation
– Investigations and Action
Plan
– CAPA Closure
• Validation
– Documentation Structure
and Formats
– Change Control
– Planning and Scheduling
– Roles and Responsibilities
– Regulatory Requirements
for Testing
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A list of SOPs, Forms,
Validation Documentation
and other appendicies
Radiopharmaceutical
Production
Relationship of the Quality Manual
to the Validation Master Plan
•
Quality Manual: The quality manual is a document that a
facility writes to explain which portions of which regulations are
applicable to the facility and which documents the policies,
procedures, responsibilities, and documentation, that must be in
place for the facility to comply with these regulatory
responsibilities
•
Validation Master Plan: The Validation Master Plan is a
summary plan which communicates management’s
expectations and commitments to be followed for the sites
validation program including the responsibilities and is therefore
a key document at a site. It describes the program to be
conducted to get the items in question in a validated manner.
The plan lists all of the validation activities to be completed, as
well as the schedule for their completion. The term validation is
used to demonstrate with written evidence that the item under
consideration, e.g. process does what it purports to do.
Validation includes but is not limited to: equipment, computer
systems, production processes, cleaning procedures, facilities,
utilities as well as analytical methods.
Quality Manual
Contents
Purpose of the Quality
Manual
Contents of the Quality
Manual
Relationship of the
Quality Manual to the
Validation Master Plan
Examples of Quality
Manuals
STOP
Example of a Quality Manual
Radiopharmaceutical
Production
•
Quality Manual
Contents
Purpose of the Quality
Manual
Contents of the Quality
Manual
•
Relationship of the
Quality Manual to the
Validation Master Plan
Examples of Quality
Manuals
STOP
•
One approach to the Quality Manual is to delineate the quality
policies for specific regulation elements by making a flow chart
of every process and then assigning the SOP or other
document which addresses that process to ensure that
everything is covered with an SOP. An example of this is shown
on the next slide.
Note that each process or activity has an SOP number or
document associated with it.
The SOP numbers starting with A are the administrative SOPs
while those starting with Q are the quality assurance SOPs.
Example of a Quality Manual
Radiopharmaceutical
Production
QS001
Quality Manual
A007
A008
QA Unit
Personnel
Manual
Pre-Release
Employee Job
Training File
Contents of the Quality
Post-Release
Contents
Purpose of the Quality
Manual
Document Control
Relationship of the
Quality Manual to the
Validation Master Plan
Examples of Quality
Manuals
Employee Job
Training File
Q023
Training Matrix
[11C] GMP
Process
Process Control
Production Framework
Diagram, D004
Preparation
Q021, C020, Q005, Q038, Q004,
Q002, Q010, Q013, Q027
BNL Contracts
Security
Q029
Pest Control
Q028
Equipment
Control
Q037
Production Framework
Diagram, D004
Production
Red Hot Cell Diagram, D001 and
Red Hot Cell Process, D002
Master Document List
Annual Document Review
Equipment Log Book
Review
Master Equipment List
Reagent and Solvent Log
Book Review
Component Inventory
Review
O_M Procedures
Q002, Q011, Q013, Q018, Q020,
Q021Q026, Q031, Q032, Q034,
Q035, Q044,
Q034
Master Equipment List
Review
Internal Review
Equipment Log
Books
Internal Audit Form
Name/Signature Form
Non-Conformance Report
Problem Reporting/CA
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Facility Control
Quality Policy
Name/Signature Form
Q025
CAPA Form
Equipment
Qualification
Specific Activity
Q015
Pre-Release
Testing
Pre- and Post-Release Testing
Diagram, D004
Post-Release
Testing
Pre- and Post-Release Testing
Diagram, D004
Batch Record
Anomalies/
Deviations
Q022
CA001-CA005
Release
Q033
Package and
Shipping
A005
Waste Disposal
W001
Example of a Quality Manual
Radiopharmaceutical
Production
Quality Manual
Contents
Purpose of the Quality
Manual
Contents of the Quality
Manual
Relationship of the
Quality Manual to the
Validation Master Plan
Examples of Quality
Manuals
STOP
•
Another example of a Quality Manual with less detail but
covering the major elements can be found by following the
arrow.
More Quality Manual Example
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