Radiopharmaceutical Production

Validation Master Plan

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 Validation Master Plan
• The Validation Master Plan (VMP) Contents
is an extremely important
• Validation in General
document because in constructing
it, many serious commitments and • Validation Policy
decisions have to be made. • Validation Master Plans
• The VMP is a document that
• Content of the VMP
documents the way the company
will operate, who has control over • Validation Plans
the various aspects of the • VMP Summary
validation activities, and how
• Literature and Example
production, quality control, and
personnel management will be
directed.

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 Validation in General
The process of validation starts with the construction (or renovation)
Radiopharmaceutical
Production
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:
Validation Master Plan • Water (generation, receipt, and distribution)
(VMP)
• Heating, ventilation, and air conditioning (HVAC)
Contents
• Terminal sterilization of product (either by autoclave or filter
Validation in General sterilization)
Validation Policy • Compressed air (generation and distribution)
Validation Master Plans • Premises (to be sure they meet all GMP practices – see the
Content of the VMP section on Facilities)
Validation Plans • QC laboratories (analytical and microbiological)
VMP Summary
• Production and control operations involved in the manufacture of
Literature and Example
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
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procedure or new or repaired equipment is used.
• A summary table is given on the next page
 Validation in General
Summary Table for Validation
Radiopharmaceutical
Production Elements Installation Operation Stage
Qualification Qualification
Validation Master Plan Develop a Project Design
(VMP) Validation
Contents Master Plan
Validation in General
Premises Engineering and Operational Construction
Validation Policy Construction Readiness Review
Validation Master Plans
Equipment Choose and install Perform validation Start-up
Content of the VMP
equipment protocols
Validation Plans
Validation Write validation Perform the Operation
VMP Summary
Plan protocols protocols
Literature and Example
Analytical Write SOPs for Test product and Operation
Methods GMP required tests refine analytical
methods
Process Test and Develop Optimize Operation
SOPs parameters
Analytical Revise SOPs for Refine analytical Revalidation
Methods GMP required tests methods
Process Revise SOPs Refine operational Revalidation
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 Validation Policy
Radiopharmaceutical
Production
 Qualification and validation should not be considered as once
in a lifetime exercises. An on-going programme should follow
Validation Master Plan their first implementation (continuous improvement) and
(VMP)
should be based on at least an annual review.
Contents
Validation in General
 The commitment to maintain continued validation status
should be stated in the relevant company documentation,
Validation Policy
such as the Validation Master Plan.
Validation Master Plans
 The responsibility of performing validation should be clearly
Content of the VMP
defined. A schedule of validation activities is an excellent way
Validation Plans
to be sure that all processes and equipment stays in
VMP Summary validation. This schedule should be signed off when the tasks
Literature and Example 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.

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Radiopharmaceutical
Validation master plans
Production
 The VMP should be a concise and easy-to-read document
which will serve as a guide to the personnel who are
Validation Master Plan responsible for performing validation.
(VMP)
Contents
According to the WHO
Validation in General
• The Validation Master Plan (VMP) complements the
Validation Policy producer’s site master file and should be the first document
Validation Master Plans to be reviewed during inspection by a regulatory authority.
Content of the VMP • To learn more about the site master file
More Site Master File
Validation Plans
VMP Summary • 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
• Introduction.
• Plan Origin and Approval.
Validation Master Plan • System Description.
(VMP) • Derivation.
• Validation Approach.
Contents • Scope of Validation Activities.
• Site Activities.
Validation in General • Validation Objectives.
Validation Policy • Documentation and Procedures.
• Validation Plan Review.
Validation Master Plans • Scope of Documentation.
• Roles and Responsibilities.
Content of the VMP • Validation Schedule of Activities.
• An Overview of Activities.
Validation Plans • Project Master Schedule.
• Division of Responsibilities.
VMP Summary • References
• System Description.
Literature and Example
• Glossary.
• Overview of System.
• Overview of Process.

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 Content of VMP
Radiopharmaceutical
Production • Manufacturing processes
Particular Attention should be
paid to the following areas • List of validation protocols,
Validation Master Plan within the VMP including format
(VMP)
• List of relevant SOPs
Contents • Production and QC premises,
Validation in General including controlled • Product specifications
including prospective (and
Validation Policy environments tentative) IPC acceptance
Validation Master Plans criteria
• Process and QC equipment,
Content of the VMP
including location • QC and IPC methods,
Validation Plans validation, if applicable
VMP Summary • Pharmaceutical air (HVAC) • Reasonable unexpected
Literature and Example and water systems events

• All potentially critical utilities

(such as compressed air,
steam and cooling liquids,
and so on)
• Computer control systems
Some Advice on the content
of the VMP from PIC/S can
be found by following the
arrow

More VMP Recommendations

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 Validation plan
Radiopharmaceutical
Production

• A validation plan describes the overall philosophy, intention

Validation Master Plan and approach to establishing that facility performance is
(VMP) adequate (validation policy).
Contents
• It should identify:
Validation in General
– the responsible persons
Validation Policy
– what should be validated,
Validation Master Plans
– where the validation should be done,
Content of the VMP
– when validation should be performed, and
Validation Plans
– why and how the validation should be performed.
VMP Summary
• It should include a breakdown of the process into separate
Literature and Example 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.

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 Types of Validation Plans
Radiopharmaceutical
Production
A new validation plan should be developed whenever these
situations arise:
Validation Master Plan
(VMP) • Construction of new premises
Contents • Major renovation or additions to existing premises
Validation in General • First time validation of previously unvalidated processes or unit
Validation Policy operations
Validation Master Plans • Automation or computerized implementations of processes
Content of the VMP • Installation of new equipment
Validation Plans
VMP Summary
Basic questions to be answered
Literature and Example
• 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?
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 VMP Summary
Radiopharmaceutical
Production
• Target all personnel involved in the validation when creating the
master plan.
Validation Master Plan
(VMP)
• Keep the VMP short, but provide enough information so that the
Contents
document is functional.
Validation in General
• Provide for flexibility to deal with changes, but do not avoid
making the required decisions early on in the project.
Validation Policy
• The life cycle mandates that the validation process becomes an
Validation Master Plans
ongoing project, which requires constant attention.
Content of the VMP
Validation Plans
VMP Summary
Literature and Example

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 Literature and Example
Radiopharmaceutical
Production
• An example Validation Master Plan can be found HERE
Validation Master Plan More Example VMP - long
(VMP)
Contents • Sample of a Simple Validation Master Plan
Validation in General
Validation Policy
More Example VMP - short
Validation Master Plans
• Literature on Validation Master plans and the Validation Process
Content of the VMP
can be found in the references to GMP. The major references
Validation Plans and some presentations on GMP are available by following the
VMP Summary MORE arrow.
Literature and Example
More General GMP Information

• More information specifically on Validation Master Plans can be

found by following this arrow
More VMP Recommendations

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