Radiopharmaceutical Production

Validation Master Plan

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Validation Master Plan

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

Elements

Summary Table for Validation

Installation
Operation
Qualification
Qualification

Stage

Contents

Develop a
Validation
Master Plan

Validation in General

Premises

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

Validation Master Plan

(VMP)

Validation Policy
Validation Master Plans
Content of the VMP
Validation Plans
VMP Summary
Literature and Example

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Project Design

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.

Radiopharmaceutical
Production

Validation master plans

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

The Validation Master Plan (VMP) complements the

producers site master file and should be the first document
to be reviewed during inspection by a regulatory authority.

To learn more about the site master file

More Site Master File

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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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

Components of a typical VMP

Introduction.
Plan Origin and Approval.

Derivation.

Scope of Validation Activities.

Validation Objectives.

Validation Plan Review.

Roles and Responsibilities.

An Overview of Activities.

Division of Responsibilities.

System Description.

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
Validation in General
Validation Policy
Validation Master Plans
Content of the VMP
Validation Plans
VMP Summary
Literature and Example

Particular Attention should be

paid to the following areas
within the VMP
Production and QC premises,
including controlled
environments
Process and QC equipment,
including location
Pharmaceutical air (HVAC)
and water systems
All potentially critical utilities
(such as compressed air,
steam and cooling liquids,
and so on)
Computer control systems

Manufacturing processes
List of validation protocols,
including format
List of relevant SOPs
Product specifications
including prospective (and
tentative) IPC acceptance
criteria
QC and IPC methods,
validation, if applicable
Reasonable unexpected
events

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

what should be validated,

where the validation should be done,

when validation should be performed, and

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

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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?

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

VMP Summary

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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Validation Master Plan

(VMP)

Contents
Validation in General

Content of the VMP

Validation Plans
VMP Summary

Example VMP - long

Sample of a Simple Validation Master Plan

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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

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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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