Radiopharmaceutical Production
Quality Assurance and a Quality
Management System
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Quality Assurance
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The assurance of quality in products is
considered to be a prime responsibility
of facility management.
Radiopharmaceuticals are
pharmaceutical products and therefore,
must be manufactured according to the
guidelines of Good Manufacturing
Practices (GMP) which requires the
manufacturing and testing of products
in a specified and controlled manner
ensuring the application of validated
processes and procedures.
While the GMP guidelines are the basis
for manufacturing
radiopharmaceuticals, the management
of quality in the finished product and
integration of the internal policies and
procedures of the organization are
achieved through a well-defined and
executed quality management system
(QMS).
Contents
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Quality Assurance
Quality Management System
Validation and Monitoring
Documentation
See the IAEA publication
“Strategies for Clinical
Implementation and Quality
Management of PET Tracers”
To see an article about quality
management in commercial FDG
production GO HERE
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Quality Assurance
Radiopharmaceutical
Production
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Testing the product for quality is only one aspect of overall
quality management. More significant is the management of
quality which comprises of not only quality testing, but also the
overall quality assurance and GMP practiced at the production
facility. Detailed discussion on these subjects can be found in
published literature, including the IAEA publication in this series
[TRS 471 Radionuclide Production with a Cyclotron: Facility
Planning].
More TRS 471
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Quality assurance is a measure of overall performance of the
manufacturing facility, and hence, encompasses a much wider
scope and has greater implications. In this context, QA is a
sum-total of all activities that individually or collectively influence
the quality of the product. It is to be noted that the Good
Manufacturing Practices is an integral component of the QA.
Unlike the conventional pharmaceutical products,
radiopharmaceuticals necessitate special handling during their
manufacturing, owing mainly to the short half-lives of the
incorporated radionuclides, aseptic processing, parametric
release of the product batch, and the radiation protection
requirements. Therefore, attention in detail and adherence to
the GMP protocols is highly important in assurance of product
quality.
Quality Management
Contents
Quality Assurance
Quality Management
System
Validation and Monitoring
Documentation
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Quality Management
Radiopharmaceutical
Production
Quality Management
Contents
Quality Assurance
Quality Management
System
Validation and Monitoring
Documentation
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The basic elements of quality management according to the
WHO are:
• An appropriate infrastructure or “quality system”,
encompassing the organizational structure, procedures,
processes, and resources; and systematic actions
necessary to ensure adequate confidence that a product (or
service) will satisfy given requirements for quality.
• There is often confusion about what documents should be in
place to ensure that a working quality assurance program is
in place and that demonstrate to an inspector that all
aspects of quality assurance have been addressed.
• One approach to this documentation which has been used
successfully for the establishment of a program uses three
documents to delineate different aspects of the program.
The documents required are:
– Site Master File
– Quality Manual
– Validation Master Plan
Radiopharmaceutical
Production
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Quality Management
Contents
Quality Assurance
Quality Management
System
Validation and Monitoring
Documentation
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Quality Management
Each of these documents has a specific purpose and taken
together, give a clear picture of the facility purpose, the quality
plan for the facility and how the validation of this quality plan will
take place.
– The Site Master File (SMF) should contain specific
information about the quality management policies and
activities of the company, the production and/or quality
control of pharmaceutical manufacturing operations
– The facility’s Quality Manual (QM) 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.
– The Validation Master Plan (VMP) documents the way the
company will operate, who has control over the various
aspects of the validation activities, and how production,
quality control, and personnel management will be directed.
As can be seen, there is some overlap in the contents. As long
as all aspects are addressed, the exact division is up to the
facility management.
Quality Management
Radiopharmaceutical
Production
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Quality Management
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Contents
Quality Assurance
Quality Management
In the following slides, there is a description of the development
of a quality system starting with a quality manual and going
down to specific procedures and tests.
Information about the Site Master can be found by following the
arrow
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Site Master File
System
Validation and Monitoring
Documentation
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The Validation Master Plan is a separate document that covers
all aspects of validation for the facility. There is a entire section
on this document which can be found by following the arrow.
More
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Validation Master Plan
Quality Management System
Radiopharmaceutical
Production
Quality Management
Contents
A quality management system can be thought of as a process
where we start with a philosophy of quality when then flows down
into specific steps and instructions which ensure that the product
being produced is always safe and effective. It involves the other
documents related to quality as well.
Quality Assurance
Quality Management
System
Validation and Monitoring
Documentation
Validation
Master Plan
Site Master
File
Quality
Manual
Job responsibilities
and authorities
Operating
Instructions
Reports
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Standard
Operating
Procedures
Completed Batch
Records
Tables
Quality Management System
Radiopharmaceutical
Production
Quality Management
Contents
Quality Assurance
Quality Management
System
Validation and Monitoring
Documentation
More Information can be obtained on each of these topics by
clicking on the appropriate box
The first step in the
development of a
management system is the
production of a quality
manual. This manual
comes before the Validation
Master Plan and other
Quality
documents
Manual
Job responsibilities
and authorities
Operating
Instructions
Reports
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Standard
Operating
Procedures
Completed Batch
Records
Tables
Quality Management System
Radiopharmaceutical
Production
More Information can be obtained on each of these topics by
clicking on the appropriate box
Quality Management
Contents
Quality Assurance
Quality Management
System
Validation and Monitoring
Documentation
The next step is to
apply the principles
stated in the quality
manual and assign
job responsibilities
and authorities
Quality
Manual
Job responsibilities
and authorities
Operating
Instructions
Reports
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Standard
Operating
Procedures
Completed Batch
Records
Tables
Quality Management System
Radiopharmaceutical
Production
More Information can be obtained on each of these topics by
clicking on the appropriate box
Quality Management
Contents
Quality Assurance
Quality Management
System
Validation and Monitoring
Documentation
The next step is to
have
knowledgeable
people develop
operating
instructions for all
the equipment
Quality
Manual
Job responsibilities
and authorities
Operating
Instructions
Reports
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Standard Operating
Procedures (SOPs)
must be developed
for every operation
related to the
manufacture of the
radiopharmaceutical
Standard
Operating
Procedures
Completed Batch
Records
Tables
Quality Management System
Radiopharmaceutical
Production
More Information can be obtained on each of these topics by
clicking on the appropriate box
It also includes the
completed batch
records for all the
product made at the
facility
Quality Management
Contents
Quality Assurance
Quality Management
System
Validation and Monitoring
Documentation
The operating
instructions and the
SOPs lead to the
documentation of all
the work that goes on
Quality
in the facility. This
Manual
includes the reports on
the equipment
Job responsibilities
validation and
and authorities
calibration
Operating
Instructions
Reports
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There are also
tables of results so
that trends may be
established and a
operational matrix
which ensures that
all the personnel
are currently
trained to perform
their assigned
functions
Standard
Operating
Procedures
Completed Batch
Records
Tables
Quality Management System
Radiopharmaceutical
Production
Quality Management
Contents
Quality Assurance
More Information can be obtained
on each of these topics by clicking
on the appropriate box
Quality Management
System
Validation and Monitoring
Quality
Manual
Documentation
Job responsibilities
and authorities
Operating
Instructions
Reports
STOP
Standard
Operating
Procedures
Completed Batch
Records
Tables
Validation and Monitoring
Radiopharmaceutical
Production
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Quality Management
Contents
Quality Assurance
Quality Management
System
Validation and Monitoring
Documentation
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Key features of the quality assurance program are that the tests
are performed with well-established protocols (the standard
operating procedures, SOPs), and the results are presented
with maximum confidence. All quality test procedures, therefore,
should be developed, tested, and fine-tuned (validation) prior to
putting into practice for testing FDG batches. Monitoring of the
test results ensures the continued suitability of the validated
processes.
More on Process Validation can be found by following the
MORE arrow
More Process Validation
More on Equipment Validation can be found by following the
MORE arrow
More Equipment Validation
Documentation
Radiopharmaceutical
Production
Quality Management
Contents
Quality Assurance
Quality Management
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Good documentation is one of the keys to a good quality
assurance program. Each piece of critical equipment must be
validated , each process must be clearly delineated and each
production run must be documented. These records must be
kept according to strict guidelines. Examples of these
guidelines can be found in the section on documentation by
following the arrows
System
Validation and Monitoring
Documentation
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Documentation
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