Six Sigma Project - Sugali Raveendra Naik
Six Sigma Project - Sugali Raveendra Naik
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Why Pharmaceutical
Industry?
• Deals with vital
Products
• Life Saving
• Perfection is
essential
• Generics Market is
progressing
rapidly
• Variability is the main
problem with Generics
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Pharma Product Life
Cycle
Patent Exclusivity ( 20 yrs )
5 yrs 5 yrs 2 yrs 8-10 yrs
Start Finish
Traditional Manufacturing
Earlier Later
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Dimensions of the FDA’s Initiative
on
Pharmaceutical Quality for the 21st Century
Strong
Public Health
Protecti
on Time
Integrated quality International
systems orientation cooperation
Science-base
d Risk-based orientation
policies and standards
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Dimensions of Pharmaceutical
Quality for the 21st
Century
• FDA initiatives
– cGMP
– Process Analytical Technology (PAT)
– ICH
• Quality tools
– TQM
– Six Sigma
– Fusion Management
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Pharmaceutical cGMP’s for
the 21
Century
st
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Product and Process Quality
Knowledge: Science-Risk
Based cGMP’s
Quality by Design GMP/CMC FOCUS
1st
Process Design Principl Design qualification
es
MECHANISTIC
UNDERSTANDIN
Yes, Limited to the G Focused; Critical
Experimental Process Control
CAUSAL LINKS
Design Space PREDICT Points (PAT)
PERFORMANCE
DECISIONS BASED ON Extensive;
Maybe, UNIVARIATE APPROACH Every
Difficult to Step
Assesses DATA DERIVED (CURRENT)
TRIAL-N-ERROR
FROM EXPERIMENTATION 11
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What is
PAT
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What is
PAT
Scientific principles and tools supporting innovation
• PAT Principles
– Process Understanding
– Risk-Based Approach
– Regulatory Strategy to accommodate innovation
– Real Time Release
• PAT Tools
– Multivariate Tools for Design, Data Acquisition and Analysis (Six Sigma)
– Process Analyzers (Six Sigma)
– Process Control Tools (Six Sigma)
– Continuous Improvement and Knowledge Management Tools (KAIZEN,
TQM, Lean Processing)
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PAT: Conceptual
Framework
Development/Optimization/Continuous Improvement
(DOE, Evolutionary optimization, Improved efficiency)
Incoming
LT Materials. Control of process critical
control points (PCCP). Multivariate
Specifications Systems
Process end point (PEPs’) range
Relevant to Approach
based on “performance” attributes.
“Process-ability”
PAC Risk
PAC PCCP PEP’s Classification
and
At-line Mitigation
In/On-Line Strategies
Process Analytical
Chemistry Tools CM Laboratory
PAC LT or other
IT
tests
Incoming material attributes
used to predict/adjust Chemometrics (CM)
optimal processing parameters and IT Tools Direct or inferential
within established bounds for “real time” assessment of quality
(more flexible bounds) control and decisions and performance
(at/on1-5line)
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International Conference on
Harmonization (ICH)
• The International Conference on Harmonization of
Technical Requirements for Registration of
Pharmaceuticals for Human Use (ICH) is a unique project
that brings together the regulatory authorities of Europe,
Japan and the United States and experts from the
pharmaceutical industry in the three regions to discuss
scientific and technical aspects of product registration.
• The purpose is to make recommendations on ways to
achieve greater harmonization in the interpretation and
application of technical guidelines and requirements for
product registration in order to reduce or obviate the need
to duplicate the testing carried out during the research
and development of new medicines.
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Continuous Improvement – Emerging
ICH
Q8 “Design Space” Concept
» Bioavailability
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Knowledge based decisions:
Improved Ability to
Generalize
Pharmaceutical Development
Knowledge
process
conditions
environmental
Robust process
Stable and Bioavailable product
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ICH cGMP
Q8 regulatory
oversight
C
o
m
p
a
n
y Risk
Process Post ’
Understanding approval s
change Q
u
a
l
CMC i
regulatory t
oversight y ICH
Q8&9
s
y
s 20
t
ICH Q8 +
Process Propose
Understanding Q9
d
ICH Q Process
Process 10 Understanding
CMC Understanding
regulatory
CMC
oversight
regulatory
oversight CMC
regulatory
cGMP oversight
Post
approval Continuous
change PAC to Improvement
Continuous
Risk
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Quality Programs Integration
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Evolution QC Six Sigma
Evolution
bles
a
en
Total Quality
T Control
PA Statistical
Inspection
Foreman
Operator
1900
1918
1937
1960
1980
"Real assurance of quality today requires far more than
good intentions, testing and inspection
A. V. Feigenbaum. activities,
Total Quality Control. 3rd Ed.,and a
McGraw-Hill,
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1983
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What is Six Sigma?
…
Methodology for achieving goals and
objectives
Quantitative technique for problem
solving
Comprehensive improvement
process
Tools For Driving Sustainable Change
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What is six
sigma?
You’ll be able to:
• Identify what % of revenue (approximate) is lost to poor quality at
3,4,5 & 6 sigma levels?
• Explain the Success/Change Formula.
• Identify the yield and DPMO at 4 sigma.
• Explain the differences between Six Sigma and TQM?
• Explain Customer Critical Criteria.
• Explain three different meanings used for Six Sigma?
• Explain the elements of the Scientific Method.
• Define SIPOC
– Explain each component
• Define DMAIC?
– Explain each component
• List and discuss the seven core competencies for Six
Sigma Plus.
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What Makes Six Sigma Different?
Adapted with permission from Hamadi Said, US Mint Philadelphia, PA
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but not Precise
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. . . So how does this principle ((ittiissi OOnnTTaarrggeet
thht eneteretrrereeisesidLdLaarrggeeVV
translate into the real world? )t,),bbB (uB(ugigi St Sgi i2gmm
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Six Sigma is… A
Quantitative
Methodology
Y= f(X1+X2+X3+…..Xn)
Today Customer
Target
Spec
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What “Six Sigma”
Means
308,540 ppm
66807 ppm
6210 ppm
233 ppm 3 .4 ppm
USL
Risk
sy t n
PAT
ge
35
ar
Fusion
ManagementTM
A tool for fusing PATand Six Sigma, TQM,
KAIZEN, Lean, Performance Excellence and
Management Systems to overcome
the existing constraints
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The Quality Systems Opportunity
A Historical Note on Quality: Milestones in Quality Journey or
Lurching from Fad to Fad?
• Six Sigma
– The Ultimate Six Sigma -
“The Big Q”
K. R. Bhote and A. K. Bhote. World Class Quality (2000) ISBN 0-8144-0427 37
Generics Pharmaceuticals
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Desired State
Product quality and performance achieved and assured
by design of effective and efficient manufacturing
processes
Product specifications based on mechanistic
understanding of how formulation and process factors
impact product performance
Continuous "real time" assurance of quality
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Desired State
Regulatory policies tailored to recognize the level
of scientific knowledge supporting product
applications, process validation, and process
capability
Risk based regulatory scrutiny relate to the:
level of scientific understanding of how formulation and
manufacturing process factors affect product quality and
performance, and
the capability of process control strategies to prevent or
mitigate risk of producing a poor quality product
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Finally
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THANK YOU
PRESENTED BY
SUGALI RAVEENDRA NAIK
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