Validation

Report
Radiopharmaceutical Production
Validation Master Plan
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Validation Master Plan
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The Validation Master Plan (VMP)
is an extremely important
document because in constructing
it, many serious commitments and
decisions have to be made.
The VMP is a document that
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.
Contents
• Validation in General
• Validation Policy
• Validation Master Plans
• Content of the VMP
• Validation Plans
• VMP Summary
• Literature and Example
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Validation in General
Radiopharmaceutical
Production
Validation Master Plan
(VMP)
Contents
Validation in General
Validation Policy
Validation Master Plans
Content of the VMP
Validation Plans
VMP Summary
Literature and Example
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The process of validation starts with the construction (or renovation)
of the facility to be in compliance with GMP guidelines. These
processes should be outlined in a Validation Master Plan (VMP).
The VMP should include:
• Water (generation, receipt, and distribution)
• Heating, ventilation, and air conditioning (HVAC)
• Terminal sterilization of product (either by autoclave or filter
sterilization)
• Compressed air (generation and distribution)
• Premises (to be sure they meet all GMP practices – see the
section on Facilities)
• QC laboratories (analytical and microbiological)
• Production and control operations involved in the manufacture of
radiopharmaceuticals.
Validation continues with validation plans for individual processes and
equipment. These include:
• The development of validation SOPs
• The development of process SOPs
• Testing of the production process
• Development of analytical methods
• Validation of the process
• Revalidation of the process whenever there is a change in the
procedure or new or repaired equipment is used.
• A summary table is given on the next page
Validation in General
Radiopharmaceutical
Production
Validation Master Plan
(VMP)
Contents
Validation in General
Elements
Develop a
Validation
Master Plan
VMP Summary
Project Design
Engineering and
Construction
Operational
Readiness Review
Construction
Equipment
Choose and install
equipment
Perform validation
protocols
Start-up
Validation
Plan
Write validation
protocols
Perform the
protocols
Operation
Analytical
Methods
Write SOPs for
GMP required tests
Test product and
refine analytical
methods
Operation
Process
Test and Develop
SOPs
Optimize
parameters
Operation
Analytical
Methods
Revise SOPs for
GMP required tests
Refine analytical
methods
Revalidation
Process
Revise SOPs
Refine operational
parameters
Revalidation
Content of the VMP
Validation Plans
Stage
Premises
Validation Policy
Validation Master Plans
Summary Table for Validation
Installation
Operation
Qualification
Qualification
Literature and Example
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Validation Policy
Radiopharmaceutical
Production

Validation Master Plan
(VMP)
Contents
Validation in General

Validation Policy
Validation Master Plans
Content of the VMP

Validation Plans
VMP Summary
Literature and Example

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Qualification and validation should not be considered as once
in a lifetime exercises. An on-going programme should follow
their first implementation (continuous improvement) and
should be based on at least an annual review.
The commitment to maintain continued validation status
should be stated in the relevant company documentation,
such as the Validation Master Plan.
The responsibility of performing validation should be clearly
defined. A schedule of validation activities is an excellent way
to be sure that all processes and equipment stays in
validation. This schedule should be signed off when the tasks
are completed and this document kept as a record of
completion.
If possible, all the validation procedures should be scheduled
for a specific time such as the first working Monday of the
quarter or year. This way all the continuing validation
procedures can be accomplished at the same time and it
makes it easier to remember to do them all.
Validation master plans
Radiopharmaceutical
Production

Validation Master Plan
(VMP)
Contents
Validation in General
Validation Policy
Validation Master Plans
Content of the VMP
Validation Plans
VMP Summary
The VMP should be a concise and easy-to-read document
which will serve as a guide to the personnel who are
responsible for performing validation.
According to the WHO
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The Validation Master Plan (VMP) complements the
producer’s site master file and should be the first document
to be reviewed during inspection by a regulatory authority.
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To learn more about the site master file
More Site Master File
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The VMP reinforces the commitment of the facility to GMP.
Literature and Example
The Functions of the Master plan should be:
• Education of management
• Project monitoring and management
• Project training
• Audit of the validation program
• Update of regulatory agency requirements
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Components of a typical VMP
Radiopharmaceutical
Production
Validation Master Plan
(VMP)
Contents
Validation in General
Validation Policy
Validation Master Plans
Content of the VMP
Validation Plans
VMP Summary
Literature and Example
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Introduction.
Plan Origin and Approval.
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Derivation.
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Scope of Validation Activities.
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Validation Objectives.
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Validation Plan Review.
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Roles and Responsibilities.
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An Overview of Activities.
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Division of Responsibilities.
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System Description.
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Overview of System.
Overview of Process.
System Description.
Validation Approach.
Site Activities.
Documentation and Procedures.
Scope of Documentation.
Validation Schedule of Activities.
Project Master Schedule.
References
Glossary.
Content of VMP
Radiopharmaceutical
Production
Validation Master Plan
(VMP)
Contents
Particular Attention should be
paid to the following areas
within the VMP
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Production and QC premises,
including controlled
environments
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Process and QC equipment,
including location
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Pharmaceutical air (HVAC)
and water systems
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All potentially critical utilities
(such as compressed air,
steam and cooling liquids,
and so on)
Validation in General
Validation Policy
Validation Master Plans
Content of the VMP
Validation Plans
VMP Summary
Literature and Example
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Computer control systems
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Manufacturing processes
List of validation protocols,
including format
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List of relevant SOPs
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Product specifications
including prospective (and
tentative) IPC acceptance
criteria
QC and IPC methods,
validation, if applicable
Reasonable unexpected
events
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Some Advice on the content
of the VMP from PIC/S can
be found by following the
arrow
More
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VMP Recommendations
Validation plan
Radiopharmaceutical
Production
•
Validation Master Plan
(VMP)
•
Contents
Validation in General
Validation Policy
Validation Master Plans
Content of the VMP
Validation Plans
VMP Summary
•
Literature and Example
•
STOP
A validation plan describes the overall philosophy, intention
and approach to establishing that facility performance is
adequate (validation policy).
It should identify:
–
the responsible persons
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what should be validated,
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where the validation should be done,
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when validation should be performed, and
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why and how the validation should be performed.
It should include a breakdown of the process into separate
parts. It should also determine which processes are critical to
the quality of the product and therefore require validation.
For example, in a project to commission an FDG production
process, the operation of the synthesizer is critical and will
require IQ, OQ and PQ; and the operation of the laminar flow
hood is critical and will require IQ, OQ and PQ.
Types of Validation Plans
Radiopharmaceutical
Production
Validation Master Plan
(VMP)
Contents
Validation in General
Validation Policy
Validation Master Plans
Content of the VMP
A new validation plan should be developed whenever these
situations arise:
• Construction of new premises
• Major renovation or additions to existing premises
• First time validation of previously unvalidated processes or unit
operations
• Automation or computerized implementations of processes
• Installation of new equipment
Validation Plans
VMP Summary
Literature and Example
STOP
Basic questions to be answered
• What will be validated?
• Who is responsible for the validation tasks?
• How will the equipment be qualified and the processes
validated?
• How will the validation be documented?
• What are the criteria by which a successful validation will be
evaluated?
VMP Summary
Radiopharmaceutical
Production
Validation Master Plan
(VMP)
Contents
Validation in General
Validation Policy
Validation Master Plans
Content of the VMP
Validation Plans
VMP Summary
Literature and Example
STOP
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Target all personnel involved in the validation when creating the
master plan.
Keep the VMP short, but provide enough information so that the
document is functional.
Provide for flexibility to deal with changes, but do not avoid
making the required decisions early on in the project.
The life cycle mandates that the validation process becomes an
ongoing project, which requires constant attention.
Literature and Example
Radiopharmaceutical
Production
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More
Validation Master Plan
(VMP)
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Contents
Validation in General
Content of the VMP
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Validation Plans
VMP Summary
Example VMP - long
Sample of a Simple Validation Master Plan
More
Validation Policy
Validation Master Plans
An example Validation Master Plan can be found HERE
Example VMP - short
Literature on Validation Master plans and the Validation Process
can be found in the references to GMP. The major references
and some presentations on GMP are available by following the
MORE arrow.
Literature and Example
More
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More information specifically on Validation Master Plans can be
found by following this arrow
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General GMP Information
VMP Recommendations
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