Radiopharmaceutical Production

Quality Manual

STOP
 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
• 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
 Purpose of the Quality
Radiopharmaceutical
Production
Manual
The organization should establish and maintain a quality manual
that includes
Quality Manual
Contents
a) the quality policy
Purpose of the Quality b) the scope of the quality management system, including
Manual details of and justification for any exclusions
Contents of the Quality c) the documented procedures established for the quality
Manual management system, or reference to them, and
Relationship of the
d) a description of the interaction between the processes of the
Quality Manual to the
quality management system.
Validation Master Plan
Examples of Quality
Manuals

STOP
 Contents of the Quality
Radiopharmaceutical
Production
Manual
• A quality manual is a document that a facility writes to explain
which regulations are applicable to the facility (i.e. which
Quality Manual
regulations will be followed by the facility.)
Contents
• The regulations that are to be followed are based on the
Purpose of the Quality
process(es) that are performed at the facility.
Manual
• The facility’s Quality Manual should outline which regulations
Contents of the Quality
are going to be followed, how they are going to be followed,
Manual
who is responsible for ensuring that the regulations are
Relationship of the
followed, and which of the companies approved procedures
Quality Manual to the
address the regulations to be followed. If all parts of a regulation
Validation Master Plan
are not going to be followed, a facility may want to include a
Examples of Quality
brief explanation as to why a part of a regulation is not
Manuals
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.
STOP
 Contents of the Quality
Radiopharmaceutical
Production
Manual
• The following are examples of sections that a Quality Manual
should contain:
Quality Manual
– Table of Contents
Contents
– Introduction
Purpose of the Quality
– Facility Background
Manual
– Purpose
Contents of the Quality
– Scope
Manual
– Quality Policies and Objectives
Relationship of the
– Organization and Structure of Documentation
Quality Manual to the
– Facility’s Products
Validation Master Plan
– References
Examples of Quality
– Quality Policies for Specific Regulation Elements
Manuals

• Table of Contents: A list of the sections contained within the

Quality Manuel and the page each section begins on.

• Introduction: A brief description of the facility, the facility’s

purpose for writing a Quality Manual, and a brief description of
STOP the scope of the Quality Manual.
 Contents of the Quality
Radiopharmaceutical
Production
Manual
• Background: List the name of the facility, where the facility is
located, what radiopharmaceutical products are produced at the
Quality Manual
facility, and how these will be distributed.
Contents
Purpose of the Quality
• Purpose: Provide general statements explaining why and how
Manual
the Quality Manual will be used.
Contents of the Quality
– Example: “This Quality Manual describes the quality management
Manual
system that has been established by facility X in order to meet
Relationship of the regulatory requirements for the production of PET
Quality Manual to the radiopharmaceuticals in the United State.”
Validation Master Plan
Examples of Quality • Scope: List the regulations that will be followed by the facility as
Manuals 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.”
STOP
 Contents of the Quality
Radiopharmaceutical
Production
Manual
• Quality Policies and Objectives: Include a brief statement about
the approach that the facility is taking in regards to quality, (i.e.
Quality Manual
a Quality Mission Statement) and list the quality objectives of
Contents
the facility. The quality objectives should not be numerous (five
Purpose of the Quality
to seven is a typical number) and should be briefly stated.
Manual
– Example: Customer issues are addressed in a timely, professional,
Contents of the Quality
and thorough manner.
Manual – Example: Personnel are adequately trained in the job they perform
Relationship of the – Example: Products and Services provided by our facility are
Quality Manual to the designed, manufactured, and delivered to our customers and meet
Validation Master Plan or exceed our customer requirements.
Examples of Quality
Manuals
• 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.
STOP
 Contents of the Quality
Radiopharmaceutical
Production
Manual
• Products: This section should include a brief description of the
products that are made and distributed by the facility including
Quality Manual
what the intended use of the products is to be. This description
Contents
should be similar to a marketing type summary in that it does
Purpose of the Quality
not list proprietary or explicit product information that would be
Manual
detrimental to the facility if persons outside the facility read the
Contents of the Quality
description. This section should provide enough detail to justify
Manual
the sections of the regulations that are and are not going to be
Relationship of the
followed.
Quality Manual to the
Validation Master Plan
• References: A list of all the different regulations that were sited
Examples of Quality
within the Quality Manual.
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),

STOP

Radiopharmaceutical
Production • Quality Policies for Specific Regulation Elements: This section will
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
Contents of the Quality Manual
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.
• CAPA Procedure SOP # XX. 01 Material Review Board SOP # XX. 01
Failure Investigation Procedure SOP # XX. 01 .......
 Contents of the Quality Manual
Radiopharmaceutical Topics that should be covered in the final section on
Production Quality Policies for Specific Regulation Elements

• Deviations and Events • Document Management

Quality Manual
Contents – Event Recording – Storing and
Classification
Purpose of the Quality – Reviews and
Manual Investigations – Access and Viewing
Contents of the Quality – Remediation – Creating New
Documents
Manual • Change Control
– Lifecycle Managements
Relationship of the
– Change Initiation and
Quality Manual to the Approval – Printing
Validation Master Plan
– Change Execution and • Training Management
Examples of Quality Tracking – Employee Course
Management
Manuals
– Change Verification and
– Training Request and
Closure Approval
• Audit Management – Gap Management and
– Planning Records
– Execution • Equipment Management
– Review and Remediation – Inventory Management
– Preventative Maintenance
STOP – 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
Contents
• General Requirements • Validation
Purpose of the Quality
– Security and Access Control – Documentation Structure
Manual
– Facility Management and Formats
Contents of the Quality
– Corrective Action Preventive – Change Control
Manual Action (CAPA) – Planning and Scheduling
Relationship of the – CAPA Initiation – Roles and Responsibilities
Quality Manual to the – Investigations and Action
Plan – Regulatory Requirements
Validation Master Plan
for Testing
Examples of Quality – CAPA Closure
Manuals
• A list of SOPs, Forms,
Validation Documentation
and other appendicies

STOP
 Relationship of the Quality Manual
Radiopharmaceutical to the Validation Master Plan
Production
• Quality Manual: The quality manual is a document that a
facility writes to explain which portions of which regulations are
Quality Manual
applicable to the facility and which documents the policies,
Contents
procedures, responsibilities, and documentation, that must be in
Purpose of the Quality
place for the facility to comply with these regulatory
Manual
responsibilities
Contents of the Quality
Manual
Relationship of the
• Validation Master Plan: The Validation Master Plan is a
Quality Manual to the
summary plan which communicates management’s
Validation Master Plan
expectations and commitments to be followed for the sites
Examples of Quality
validation program including the responsibilities and is therefore
Manuals
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,
STOP
utilities as well as analytical methods.
 Example of a Quality Manual
Radiopharmaceutical
Production
• One approach to the Quality Manual is to delineate the quality
policies for specific regulation elements by making a flow chart
Quality Manual
of every process and then assigning the SOP or other
Contents
document which addresses that process to ensure that
Purpose of the Quality
everything is covered with an SOP. An example of this is shown
Manual
on the next slide.
Contents of the Quality
Manual
• Note that each process or activity has an SOP number or
Relationship of the
document associated with it.
Quality Manual to the • The SOP numbers starting with A are the administrative SOPs
Validation Master Plan while those starting with Q are the quality assurance SOPs.
Examples of Quality
Manuals

STOP
Radiopharmaceutical
Example of a Quality Manual
Production
QS001 Quality Policy

Quality Manual A007 A008

Contents [11C] GMP

QA Unit Personnel Facility Control Process
Purpose of the Quality Production Framework
Process Control Diagram, D004
Manual Pre-Release Employee Job BNL Contracts
Training File
Q021, C020, Q005, Q038, Q004,
Preparation
Q002, Q010, Q013, Q027
Contents of the Quality Post-Release
Employee Job Security Q029
Training File Production Framework
Manual Document Control Q023
Diagram, D004
Production
Pest Control Q028
Training Matrix Red Hot Cell Diagram, D001 and
Relationship of the Master Document List
Red Hot Cell Process, D002

Quality Manual to the Annual Document Review

Equipment Q037
Specific Activity Q015
Control
Validation Master Plan Equipment Log Book Master Equipment List Pre-Release Pre- and Post-Release Testing
Review Testing Diagram, D004

Examples of Quality Reagent and Solvent Log Post-Release Pre- and Post-Release Testing
Book Review O_M Procedures Testing Diagram, D004
Manuals Q002, Q011, Q013, Q018, Q020,
Component Inventory Q034
Review Q021Q026, Q031, Q032, Q034,
Batch Record Q022
Q035, Q044,

Master Equipment List Anomalies/

Review CA001-CA005
Equipment Log Deviations
Books
Release Q033
Internal Review Internal Audit Form
Equipment Package and
Qualification Shipping A005
Name/Signature Form Name/Signature Form

Q025 Waste Disposal W001

Non-Conformance Report

Problem Reporting/CA CAPA Form

STOP
Radiopharmaceutical
Example of a Quality Manual
Production

• Another example of a Quality Manual with less detail but

Quality Manual
Contents
covering the major elements can be found by following the
Purpose of the Quality
arrow.
More Quality Manual Example
Manual
Contents of the Quality
Manual
Relationship of the
Quality Manual to the
Validation Master Plan
Examples of Quality
Manuals

STOP
Return to Main Menu