SITE VALIDATION

MASTER PLAN
RELEASING ITS FULL POTENTIAL

ASQ DefinitionsAssurance: The act of giving confidence, the state of

being certain or the act of making certain.
Quality assurance: The planned and systematic
activities implemented in a quality system so that
quality requirements for a product or service will be
fulfilled.
FDA DefinitionValidation: Establishing documented evidence,
which provides a high degree of assurance that a
specific process will consistently produce a product
meeting its predetermined specifications.

Validation Master
Plan
The companys overall policy,
intentions and approach to
validation, including the
validation of production
processes, cleaning methods,
analytical test methods and
computerized systems,
should be established in the
Validation Master Plan.

Site Validation Master

Plan versus:
Project Master Plan
Cleaning Validation Master
Plan
Process Validation Master Plan
Computer System Validation
Master Plan

Site Validation Master

Plan
What
Where
Why
Who
How
Format
When
Sched.

Purpose
Scope
Policy & Rationale
Responsibilities
Doc. Content &
Prioritization &

Site Validation Master

Plan- Scope

Facilities
Lab Equipment
Laboratory
Methods
Water & Steam
HVAC
Gas Systems

Mfg. Equipment
Process
Cleaning
Computer
Systems

Equipment
Qualification

General
Pre-Qualification Activities
Qualification Activities
Protocol Preparation
Installation, Operational &
Performance Qualification
Acceptance Criteria
Summary Report
Re-qualification

Exclusions
Test instrumentation and simple equipment (pH
meters, viscometers, scales) will be qualified via
a procedure instead of a protocol. The
procedure approach is applicable to equipment
that:
Employs commonly used technology.
Is easily installed.
Is routinely (minimum daily) checked for
accuracy prior to use.
Does not require specialized operating
skills and expertise.

Re-qualification
The definition of what constitutes a change
to lab equipment that may require requalification includes the following:
Failure of test results
Relocation- equipment unplugged and moved
within a room, between rooms, between
buildings
Major component changes or modifications,
including software changes

Planning Step # 1:
Inventory Existing Work
Equipment List & Schedule:
ID

Equipment

Target
Qualification
Completion Date

Qualification
Status

1-01

Water HPLC

1Q-2008

--

1-02

Shimadzu
Spectrophotometer

3Q-2008

--

L 19

Temp. Recorder

N/A

Calibrated

L 19

Viscosimeter

Completed

Qualified

Product Contact List

Product Description:
ID

Equip.
Description

Alpha A Suspension.doc
Capacity

Location

MIXING TANKS
MT-1 Lee Tank

100 L

Rm. 21

MT-2 Lee Tank

400 L

Rm. 21

PORTABLE MIXERS
PM-1 Hobart

NA

Portable

FDA 483 Observations

Not all manufacturing ISO Class

[removed] rooms, Biological
Safety Cabinets and
manufacturing equipment have
documentation of cleaning
validations.
No validation studies were
conducted to support cleaning of
the [removed].

Product/Equipment
Matrix
Equip.
ID

3001

3002

Name

Tank-1

Tank-2

Prod.
Name

Prod.
Code

Batch
Size

Apha 1

DMEO

290L

Apha 2

DFEE

400L

Beta R

YHHJ

350L

Beta S

YHKP

700L

3003

3004

3005

Pump-1 Pump-2 Mixer-1

X
X

X
X

Planning Step # 2:
Prioritization
Priority 1 Products:
Product
Mfg.
Code
Name
on Site

Pkg.
Targeted
Lab.
on
Completion
Tests
Site
Date

Apha 1

DDGH

1,2

R/S

2Q 2008

Apha 2

GANN

1,2

R/S

3Q 2008

Beta R

KKLV

1,2

R/S

1Q 2009

Beta S

KKLC

1,2

R/S

4Q 2009

Planning Steps 3 & 4:

Establish a Timeline &
Estimate Resources
Category

Totals

No.
Req.
Val.

(A)
Pers.
Req.

(B)
Time
Req.
(Yrs.)

(A) X (B) =
Total Time
Required
(Man-years)

Lab Equip.

111

89

2.5

Methods

124

60

9.0

9.0

Mfg. & Pkg.

Equip.

195

178

3.5

14.0

Process

65

65

2.25

8.0

18.0

Cleaning

65

65

7.25

7.25

Sub-Totals:

836

630

--

77.5

SITE VALIDATION MASTER PLAN

2Q
2008

2009

2010

2011

2012

2013

2014

2016

2015

2017

Gas
6 mo.
HVAC &
LFUs
2.0 yrs.
Lab Equip.
Qual.
1.5 yrs.
LOC Methods Validation
3.0 yrs.

All Other Methods

6.0 yrs.

Total Methods
Validation
9.0 yrs.

Cleaning Methods
yr.
LOC Equipment
1.5 yrs.

All Other Equipment

2.0 yrs.
LOC Process
Validation
3.0 yrs.

LOC Cleaning Validation

3.75 yrs.

Total Equipment
Qualification
3.5 yrs.
All Other Process Validation
5.0 yrs.
All Other Cleaning
Validation
4.25 yrs.

Total Process
Validation
8.0 yrs.
Total Cleaning
Validation
8.0 yrs.

LOC Transfer Project

All Other Validation
MENSZAK

Site Validation Master

Plan Value

The Site Validation Master

Plan provides clarity, and it
enables the validation
manager to communicate the
workload, capacity constraints
and justify the need for
resources. It facilitates
effective management and the
best performance.

Planning Step # 6:
Repeat Steps 1-5
FDA 483 Observation:

The firm has a protocol for the

qualification of solutions used in
Manufacturing. This protocol has been
effective since 21 Dec 2004. To date only
2 of the approximately 50 materials used
in either the manufacture of products or
for cleaning/disinfection have been
qualified.

Six Steps to Planning:

1.
2.
3.
4.
5.

6.

Inventory all existing and upcoming

work.
Prioritize.
Establish a timeline.
Estimate the resources needed.
Communicate to upper management
for involvement, commitment and
resources.
Repeat Steps 1-5 on a routine basis.

Process Optimization

How?
KIWI2.mpeg

1. Identify the Task

Document Changes
Protocol
Approval
(Signed)

Draft

Protocol
Execution
(Signed)

Revision

Summary
Report Approval
(Signed)

Amendment

Addendum

2. Concentrate the
Work

3. Form Partnerships

4. Define Performance
Responsibilities Matrix:
Activity
Planning
Define Priorities:
1) Analytical Methods
2) Laboratory Equipment
3) Facilities / Utilities
4) Production Equipment
5) Process

Val.

User /
Owner

QA

5. Training

The greatest benefit of

training comes not from
learning something new,
but from doing better
what we already know.

Five Steps to
Optimization
1.
2.
3.
4.
5.

Identify the tasks.

Concentrate the work.
Define performance.
Form partnerships.
Build continuous learning
and teaching.

Constraints vs.
Performance
Scope

Quality
Cost

Time

Look at the Big Picture

Periodic review applying an

holistic approach to quality
systems.

Process Optimization

Incorporate steps to optimize

individual processes (quality
system).
Look at the constraints.
Periodically review applying
an holistic approach to quality
systems.

Why?
Regulatory

Requirement
Assures Quality
Good Economics

References
1.

2.
3.

4.

5.

ASTM E 2500-07 Standard Guide for Specification,

Design, and Verification of Pharmaceutical and
Biopharmaceutical Manufacturing Systems and
Equipment
ICH Q9 Quality Risk Handbook
Pharmaceutical cGMPs for the 21st CenturyA RiskBased Approach
FDA Guide to Inspections of Quality Systems- August
1999
The Gold Sheet- January 2008: Quality Systems No
Longer Theoretical as Industry Begins Implementing
Concepts

Lee Menszak
Consulting, Inc.
leeminc@earthlink.ne
t
845-300-1730