Process Validation Master Planning DMAIC Fusion

Process Validation
Master Planning
Medical Device Lean Sigma
ARV Excellence is a consulting firm based in Galway Ireland.
ARV Excellence. Better results. Assured.

www.arvexcellence.com
Background
ARV Excellence: expertise in medical device, pharma and drug/device
combination product process improvement

Validation: Risk Management Verification
• Why Validate
– Patient Safety
– Regulatory Requirement
– Business Sense

Process Validation Planning
• Risk Management Plan
– ISO 14971 Section 3.4/ Annex F
– Contents
• Manage the risks
– Identify and control KIPV
• Verification of risk control measures
– By Validation (A.2.6.3)
• Document MVP and MVR
– Validation activities
– Verification activities

ISO 14971 Risk management plan
3.4 Risk management plan
This plan shall include ……….:
a) the scope – product, process realisation lifecycle
b) assignment of responsibilities and authorities…;
c) requirements for review of activities….;
d) criteria for risk acceptability….;
e) verification activities…….;
f) activities related to collection and review of relevant production and post-production
information.
EN ISO 14971:2007 (Detail in Annex F)

Validation Life Cycle
Product FMEA
IQ
OQ PQ
Change
Assessment
Revalidation
Design Development
Process Map Process
FMEA
Attribute
Test Method
Qualification
Variable Test
Method
Qualification
Master
Validation
Report
Master
Validation
Plan
Process
Monitoring
Process
Control
Development
Commercialisation

Validation
• Requirement:
“establish documented evidence which provides a high degree of assurance
that a specific process will consistently produce a product meeting its
predetermined specifications and quality attributes.” [1]QSR 820.3

Risk – both look the same
Risk

Validation - Document this:

Process Description:
Process MAP/ Process Flow Chart
• Process understanding and overview
• Description of the process
• Logical sequence of steps
Assemble
Xxxxx-00
Mould
xxxxx-01
Trim and Inspect
xxxxx-01
Pack & Blister
Seal
xxxxxx-01

Source of Information FMEA
Failure Mode and Effects Analysis
Product/
Process
Potential
Failure
Mode
Effect
from
Failure
Cause of
Failure
OCC SE
V
CI Det SOD Proposed
Corrective
Action
Pack No seal Non
sterile
Sealing
temperature
too low
2 -- -- --
Sealing
temperature
too high
Risk - CI = Severity x Occurrence;
Determines Criticality Index

Confidence and Reliability Example:
Quantify Risk
Data Type Confidence FMEA Risk Index
Level
Minimum Levels
Defective Reliability
Variable 95% II - FDA Mandated 0.1% 99.9%
II 0.3% 99.7%
I 5% 95%
0
Attribute 90% (10th
percentile)
II 1% 99%
I 3% 97%
0
Limit/
Challenge
90% (10th
percentile)
II 10% 90%
I 20% 80%
0

Goal: Target and Spread:
Confidence and Reliability
Accuracy = On target Precision = Spread
Specification
Reduce spread
Risk
Risk
Specification
Centre on target
Off centre and spread = process variation = risk.

Sources of Variation
Sources of
variation
> Curves in time > Eoin Barry
Methods
Measurement systems
Machines
Materials
Process Observed variation
performance
IQ
MSV
OQ
PQ

Business Case: Old Patterns
Assemble
Inspect
Weld
Inspect
Linish
Inspect
Polish
Scrap Inspect
Disassemble
Rework
Waste
Costly rework
and inspection
activities;
Documentation;
CAPA; MRB
Risk;

Business Benefits
Reliable processes
Assemble
Inspect
Weld
Inspect
Linish
Inspect
Polish
Waste
eliminated:
Resources
free to resolve
other issues;
Less risk
£ / € / $
Saving

Begin with the end in mind…

Blister Sealer
Assurance Consistently
95% confident that 99.9% of the blister seal pack are have a seal strength
between 1.5 and 2.5 lbs
X-bar +/- k s
Predetermined
BS ISO
16269-6
Determination of statistical tolerance
intervals

n: Sample Size
Planning
(Time and cost)
• Statistical validity
– minimum n to test Normality
• Wider Interval – Less likely to fit in specification
• Width of Tolerance Interval
– X-bar +/- ks
k = f(n, assurance, proportion)
– Lower n , wider interval
– Higher Risk Index, greater proportion, wider interval
BS 2846-7
Tests for departure from
normality

MVP Document

Validation Master Plan Document
• Defines the Scope of the validation effort
– Communication
– Planning tool
• Quality Document: Available for inspection
• Overview of the GMP compliant approach
• Living Document
– Process Improvement
– CAPA

MVP Table of Contents & Reference
Documents
Why validation is required.
TOC
• Responsibilities and Review
• Introduction
• Purpose
• Scope
• Revision History
• Reference Documents
• Process Description
• Master Validation Plan Matrix
• Product Performance Qualification
• Appendices
Reference Docs
• Validation Policy Document
• Process Validation SOP
• Product Specifications
• Process Flow Chart
• Component Specifications
• Control Plan
• Product Risk Analysis Workbook
• Process FMEA
• Training
Process & Products
covered: Phase
Contents and Ref Doc’s meet the requirements of ISO 14971 Section 3.4
& Annex F (Detail)

MVP Matrix
Line # Process Name &
Number
Validation Scope
KEY: R – Required, L– Completed (historical data), NR – Not Required
Rationale for
Leveraging Historical
Validations (L)
or Elements Not
Required (NR)
Process IQ Process Verification Process Validation
Equipment
IQ/OQ
Software
IQ / OQ
Test
Method
Validation
Attribute
Test
Method
Validation
Cleaning
Validation OQ Limit
Performance
Qualification
(PQ)
1 Blister Seal
Xxxx-x1 R N/R L L L R R
Cleaning
validation
completed as
per doc
xxxxx-xxx
ATMV
completed as
per xxx-xxx
TMV
completed as
per xxx-xxx
P/T or
GR&R
completed
OQ
required
Sealer
already
installed

Planning for Success
DMAIC Phase DFSS
Define Measure Analyse Improve Control
Design x x x
600
500
400
300
200
Process Capability Analysis for Length
LSL Target USL
USL
602.000
Development 100
Target
600.000
x x x x x x
LSL
598.000
Mean
599.548
0
Sample N
100
Process Map x x
Risk (FMEA) x x x x
Process StDev process (Within)
3 process 4 process 2 process 1
StDev (Overall)
Potential (Within) Capability
Cp
CPU
CPL
Cpk
Cpm
0.576429
0.620865
1.16
1.42
0.90
0.90
0.87
trial
IQ Overall Capability Observed Performance Exp. "Within" Performance Exp. x "Overall" Performance
x x x
Pp
1.07
% < LSL
1.00
% < LSL
0.36
% < LSL
0.63
PPU
1.32
% > USL
0.00
% > USL
0.00
% > USL
0.00
PPL
0.83
OQ x x x x x
Postal applications are dealt
with too slowly when
returned to branch.
PQ x Surface Plot of Conversion
x x
Method
Validation
D New or
existing
e property
x
l i v e a r Control x x
b e
l Monitoring x x
Change x x x x x x
Revalidation x x x x x x RPN 186 155 127 106
Percent 32.4 27.0 22.1 18.5
Cum % 32.4 59.4 81.5 100.0
100
80
60
40
20
0
RPN
Percent
Example Pareto
598 599 600 601 602
% Total
% Total
% Total
Ppk
0.64
0.36
1.00
0.83
Process Data
Within
Overall
lab production
-42.55
-42.60
-42.65
-42.70
lab production
70
lab production
1
CMM
p o s it io n Y
2 3
123
Multi-Vari Chart for positionY by trial - part
Panel variable: part
Application
Time
Information
Requirements Method
69
Knowledge IT Systems
The time from when a customer first submits an
application to when all necessary information to
fully process the application is on the bank's
information system or relevant file
Customer does not
provide necessary
information on time
What
information is
required?
What method
is used to
supply it?
Application via internet
or via branch is faster
than postal application
Where and
when does it
originate?
How many applications are
received for each method?
What information must be
supplied manually?
Is there data
on speed of
application
for each
method?
Customer is not sure
what type of mortgage
he/she needs.
Bank staff
unable to
provide advise
due to lack of
knowledge
Internet site is too slow or down What is too slow?
How often is the site down?
Customer has difficulty
understanding
infromation
requirements.
10 +/- 5 days
Type of Mortgage
60
68
67
66
65
64
62
61 55
Time
160
63
165
50
Conversion
Temp 170
1 4 7 10 13 16 19 22 25 28
15.0
12.5
10.0
7.5
5.0
Obser v at ion
I ndividual Value
UCL= 14.36
_
X= 10.10
LCL= 5.83
1 4 7 10 13 16 19 22 25 28
8
6
4
2
0
Obser v at ion
Moving Range
UCL= 5.235
__
MR= 1.602
LCL= 0
1
1
1
I -MR Char t of Temp

Master Validation Report Matrix
Process
Name &
Number
Validation Scope
Process Verification Process Validation
Process IQ
Equip
ment
IQ/OQ
Software
IQ / OQ
Test Method
Validation
Attribute Test
Method
Validation
Cleaning
Validation OQ Limit
Performance
Qualification (PQ)
0x xxx-xx
Protocol
Prot Rept Prot Rept Prot Rept
Xxx-xx
Xxx-xx-
1
Prot Rept
0x
xxxx-2 Report
Document the protocol and report and
conclusion: Process is validated for its
intended use

Summary
• MVP Risk management plan ISO 14971
• Validation is verification of risk control measures
– Patient
– Regulatory
– Business
• Risk
– Variation
– Variation reduction strategy
• Business case
• Report
Help is available

Call us
www.MedicalDeviceLeanSigma.com
+353 (0)91 423 873
Eoin@arvexcellence.com

Process Validation Master Planning DMAIC Fusion

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