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Six Sigma in Pharmaceutical industry and Regulatory Affairs: A Review

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Six Sigma in Pharmaceutical industry and Regulatory Affairs: A Review

Sharma O.P. *1, Gupta V. 2, Rathore G.S.3, Saini N.K.1, Sachdeva K.1
*1School of Pharmaceutical Sciences, Jaipur National University, Jagatpura, Jaipur- 302025
1
Faculty of Pharmaceutical Sciences, Jodhpur National University, Jodhpur
3
Faculty in L.B.S. College of Pharmacy, Jaipur

*Corresponding Author:
op.pradhan@gmail.com
______________________________________________________________________________
ABSTRACT
Six sigma is a statistical concept which helps us to define the problems systematically, provides
tools to measure and analyze the influential factors, identifies the improvements that can be
implemented easily and ensure that the changes which have been made, are kept alive through a
control process and maintains the gains over the time. It is a known fact that in a process with six
sigma capability, process variation is not reduces more than 3.4 defects per million opportunities.
There are two six-sigma sub methods namely DMAIC and DMADV. The pharmaceutical
industry is the most regulated of all industries. Regulatory affairs professionals are key players in
the product development and as communication link between the industry and agencies such as
FDA. Six sigma as a problem solving approach has been used in various fields to provide the
fundamentals of variation management and reduction in order to assist in transforming
established methodologies in to new and efficient techniques. Six sigma is becoming a
cornerstone philosophy among the worlds leading corporations because it has proven itself by
generating substantial business return. It is only fitting to the end that “we believed then and we
are convinced today… that there is an infinite capacity to improving everything” but there was
no methodology or discipline attached to that belief. There is now, it’s six sigma qualities, along
with a culture of learning, sharing and unending excitement.
____________________________________________________________________________

Keywords :- Six Sigma, DMAIC, DMADV, FDA

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INTRODUCTION
The roots of Six Sigma as a measurement
standard can be traced back to Carl
Frederick Gauss (1777-1855) who
introduced the concept of the normal curve.
Six Sigma as a measurement standard in
product variation can be traced back to the
1920's when Walter Shewhart showed that
three sigma from the mean is the point
where a process requires correction. Many
measurement standards (Cpk, Zero Defects,
etc.) later came on the scene but credit for
coining the term "Six Sigma" goes to a
Motorola engineer named Bill Smith
(Incidentally, "Six Sigma" is a federally
registered trademark of Motorola).1
Sigma is a term use in statistics to represent
standard deviation, an indicator of the
degree of variation in a set of measurements
or a process or a product.
Six sigma is a statistical concept or a quality
management approach that measures a
process or a product in terms of defects at
the six sigma level and offers a way to focus
on developing and delivering perfect
products and services.2
In the early and mid-1980s with Chairman
Bob Galvin at the helm, Motorola engineers
decided that the traditional quality levels --
measuring defects in thousands of
opportunities -- didn't provide enough
granularities. Instead, they wanted to
measure the defects per million
opportunities. Motorola developed this new
standard and created the methodology and
needed cultural change associated with it.
Six Sigma helped Motorola realize powerful
Journal of Natura Conscientia, Vol.2, Issue 1, January 2011
bottom-line results in their organization - in
fact, they documented more than $16 Billion
in savings as a result of our Six Sigma
efforts. Six Sigma has evolved over time. It's
more than just a quality system like TQM or
ISO. It's a way of doing business. As Geoff
Tennant describes in his book Six Sigma:
SPC and TQM in Manufacturing and
Services: "Six Sigma is many things, and it
would perhaps be easier to list all the things
that Six Sigma quality is not. Six Sigma can
be seen as: a vision; a philosophy; a symbol;
a metric; a goal; a methodology." We
couldn't agree more.3
Six Sigma at many organizations simply
means a measure of quality that strives for
near perfection. Six Sigma is a disciplined,
data-driven approach and methodology for
eliminating defects (driving towards six
standard deviations between the mean and
the nearest specification limit) in any
process -- from manufacturing to
transactional and from product to service.4
OBJECTIVES
The key objective of the Six Sigma
methodology is the implementation of a
measurement-based strategy that focuses on
process improvement and variation
reduction through the application of various
Six Sigma methodologies including the key
processes like DMAIC and DMADV.
The other objectives of Six Sigma
methodology are as follows:
i. To increase customer satisfaction
i. To enhance competitiveness
i. To change organizational culture
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i. To make advancements toward
formal quality award application
i. To develop organizational
competencies
i. To improve organizational
performance.
Six Sigma is frequently perceived as a
statistics because of its definition and
measurement program, this is not the case.
The Six Sigma approach to management
uses statistics solely as tools for interpreting
and clarifying data. The ultimate goal is to
create Six Sigma companies, whose system
and processes are perfect as possible,
functioning at their best performance level.
To achieve such level of quality requires not
just statistics, but changes in culture of the
organization. The Six Sigma approach is
rigorous, requiring a deep commitment from
the highest level of management that
permeates through the entire organization, it
often requires proper training of key players
known as champions and black belts and
play vital roles in the success of Six Sigma
management.5
Although process improvement was
dominating the manufacturing industry, the
pharmaceutical and bio-pharmaceutical
companies have not recognized broadly, the
importance and potential of integrating
process improvement in clinical research
practice. There are no in depth studies that
Six Sigma can lead to breakthrough in
reducing cycle time, and error reduction in
clinical trials. However, due to increasing
competitive market pressure, more and more
pharmaceutical companies are beginning to
adopt process improvement strategies that
are established in other industries such as
Journal of Natura Conscientia, Vol.2, Issue 1, January 2011
Six Sigma, lean manufacturing. Issues
driving these needs include the necessity to
improve cycle time, marketing and
packaging efficiencies to monitor supply
chain and streamline manufacturing
processes to maintain profitability and
remain competitive in today’s global market.
Possible Areas for Implementation of Six
Sigma are-
RESEARCH AND DEVELOPMENT
The Research and Development process is
the most important process in
pharmaceutical industries and forms a major
part of costs. The Six Sigma concept is
desirable in this scenario to understand the
critical processes to new drug development,
and to research and streamline existing ones.
It is important to have these objectives to
reduce drug failures, effect maximum
utilization of resources, and increase
productivity and optimum utilization of staff
and other resources.
CYCLE TIMES
Increased cycle times are major factors
affecting the timely manufacture, supply and
launch new drugs. The earlier industries can
take advantage of this market situation
ultimately means the difference between
success and failure of the product.
Value stream mapping and process
modeling concepts of Lean Manufacturing
and Six Sigma can help in reducing cycle
times and operational costs, in addition to
increasing the efficiency of processes as
well as staff.
DEFECTS
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Any defects with respect to drugs would be
a big blow to any pharmaceutical industry.
Six Sigma concepts can help, as they utilize
tested scientific tools and statistical tools
that help reduce the cost of human errors.
Industries can use advanced tools to conduct
quality analysis, yield analysis, cost
comparison of jobs, risk assessment and
comparison of manufacturing processes at
different sites. Six Sigma is ideal for the
pharmaceutical industry. This position does
not exclude lean manufacturing or PAT
systems of management, but instead
recommends Six Sigma as the initial system
of practice. Why? For starters, Six Sigma
ideals are based on intense statistical
analysis and serious data collection, and the
pharmaceutical industry just happens to
have huge amounts of data and
documentation. This data and
documentation, with the appropriate amount
of time, could be analyzed according to Six
Sigma methods and then used to adjust less-
than-stellar aspects of the quality system.
The Six Sigma system also focuses on the
near obliteration of deviation or
nonconformance events, which for
pharmaceutical industries falls exactly into
line with regulatory standards and quality
management goals. Any reader may easily
hit that Six Sigma is difficult to implement
and that most pharmaceutical industries
don’t want to change anyways, however the
benefits of making the right changes within
the very wealthy pharmaceutical industry
are amazing. The online article states, that
“the potential worldwide cost savings from
efficiency improvement could be as high as
$90 billion.” This article still acknowledges
Journal of Natura Conscientia, Vol.2, Issue 1, January 2011
however that the reader is correct in saying
that Six Sigma is difficult to implement. Six
Sigma implementation requires know-how
and the appropriate instrumentation. That
know-how and instrumentation will vary
greatly since it is likely that a very small
percentage of Six Sigma black belts would
be even slightly qualified to cross the
pharmaceutical threshold (an intelligent in-
house manager might do well simply
studying up on Six Sigma principles).
A vast variety of software
solutions might be able to help provide the
needed Six Sigma success but should be
chosen carefully. For most pharmaceutical
industries it seems likely that management
tools/software for data collection (data and
document management software) and tools
for any type of deviations or
nonconformance management could be
valuable. Since small amounts of deviation
usually depend on the speed of information
distribution within a industry (although even
that assumption could be subjected to Six
Sigma analysis), an automated training
solution triggered by changes in SOPs, work
instructions, etc. might also be of great
value.
In a case study performed by one of the
Clinical Research Organizations (CRO), it
was studied that there was a breakthrough
reduction of greater than 70% in cycle time.
The existing Case Record Forms (CRF)
handling procedure and optical scanning
procedure were redesigned.
The pharmaceutical industry is the most
regulated of all industries. No drug would be
available without the teams of medical
researchers and other specialists who
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worked to make sure it received Food &
Drug Administration approval. Regulatory
affairs professionals are key players in the
product development and as communication
link between the industry and agencies such
as FDA, and they are responsible for
keeping up with the increasing scope and
complexity of regulations for the specific
country. In the pharmaceutical industry,
regulatory affairs professionals have
expertise in the legal and regulatory
environments, as well as in clinical research
protocols. They are the primary interpreters
of the laws and regulations for other
members of the industry’s R&D,
manufacturing, and compliance staff. As a
product goes through the review process,
regulatory affairs professionals are looking
at requirements for manufacturing,
packaging, and advertising. Manufacturing
further gets involved with quality assurance
and quality control, packaging and labeling.
Six sigma as a problem solving approach
has been used in various fields to provide
the fundamentals of variation management
and reduction in order to assist in
transforming established methodologies in
to new and efficient techniques.6
METHODOLOGIES
Six Sigma at many organizations simply
means a measure of quality that strives for
near perfection. Six Sigma is a disciplined,
data-driven approach and methodology for
eliminating defects (driving towards six
standard deviations between the mean and
the nearest specification limit) in any
process -- from manufacturing to
transactional and from product to service.
Journal of Natura Conscientia, Vol.2, Issue 1, January 2011
TYPES
Six Sigma methodologies include the key
processes like DMAIC and DMADV. The
Six Sigma DMAIC process (Define,
Measure, Analyze, Improve, Control) is an
improvement system for existing processes
falling below specification and looking for
incremental improvement. On the other
hand, the Six Sigma DMADV process
(Define, Measure, Analyze, Design, Verify)
is an improvement process used to develop
new processes or products at Six Sigma
quality levels. It can also be implemented if
a current process requires more than just
incremental improvement. In addition to
these processes, an increasing number of
manufacturers are using DMAICR (Define,
Measure, Analyze, Improve, Control,
Realise) process.
DMAIC
DMAIC refers to a data-driven quality
strategy for improving processes, and is an
integral part of the company's Six Sigma
Quality Initiative. DMAIC is an acronym for
five interconnected phases: Define,
Measure, Analyze, Improve, and Control.
Each step in the cyclical DMAIC Process is
required to ensure the best possible results.
The process steps are: --
Define the Customer, their Critical to
Quality (CTQ) issues, and the Core Business
Process involved.
1. Define who customers are, what their
requirements are for products and
services, and what their expectations
are.
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1. Define project boundaries the stop DMADV

and start of the process. DMADV (Define, Measure, Analyze,
1. Define the process to be improved by Design and Verify) is an improvement
mapping the process flow. system used to develop new processes or
Measure the performance of the Core products at six sigma quality levels.
Business Process involved.
4 Develop a data collection plan for SIMILARITIES OF DMAIC AND
the process. DMADV
1. Collect data from many sources to
determine types of defects and Let's first look at the DMAIC and DMADV
metrics. methodologies and talk about how they're
6 Compare to customer survey results alike. DMAIC and DMADV are both:
to determine shortfall. 1. Six Sigma methodologies used to
Analyze the data collected and process map drive defects to less than 3.4 per
to determine root causes of defects and million opportunities.
opportunities for improvement. 1. Data intensive solution approaches,
7 Identify gaps between current Intuition has no place in Six Sigma --
performance and goal performance only cold, hard facts.
1. Prioritize opportunities to improve. 1. Implemented by Green Belts, Black
9 Identify sources of variation. Belts and Master Black Belts.
Improve the target process by designing 1. Ways to help meet the
creative solutions to fix and prevent business/financial bottom-line
problems. numbers.
10 Create innovate solutions using 1. Implemented with the support of a
technology and discipline. champion and process owner.
11 Develop and deploy implementation
plan.
DIFFERENCES OF DMAIC AND
Control the improvements to keep the
DMADV
process on the new course.
12 Prevent reverting back to the "old DMAIC and DMADV sound very similar,
way". don't they? The acronyms even share the
13 Require the development, first
documentation and implementation three letters. But that's about where the
of an ongoing monitoring plan. similarities stop.
14 Institutionalize the improvements
through the modification of systems
DMAIC-
and structures (staffing, training,
incentives).
Define Define the project goals and

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customer (internal and needs

external) deliverables

Measure Measure the process to USE OF DMAIC & DMADV

determine current performance The DMAIC methodology, instead of the
DMADV methodology, should be used
Analyze Analyze and determine the when a product or process is in existence at
root cause(s) of the defects your company but is not meeting customer
specification or is not performing
Improve Improve the process by adequately.
The DMADV methodology, instead of the
eliminating defects
DMAIC methodology, should be used when:

Control Control future process 1. A product or process is not in

performance
DMADV-
Define Define the project goals and
customer (internal and
external) deliverables
Measure Measure and determine
customer needs and
specifications
Analyze Analyze the process options to
meet the customer needs
Design Design (detailed) the process
to meet the customer needs
Verify Verify the design performance
and ability to meet customer
existence at your company and one
needs to be developed
1. The existing product or process
exists and has been optimized (using
either DMAIC or not) and still
doesn't meet the level of customer
specification or six-sigma level.
"I Thought it was a DMAIC, But it
Turned Out to be a DMADV."
Occasionally a project is scoped as a
DMAIC for incremental process
improvement when it really required a
DMADV methodology improvement. And it
was a month into the project that you
realized this. Don't be discouraged about the
work you put into the DMAIC because –
1. It’s happened to more businesses
than just yours,
1. You understand the process at a
much greater detail than you did
initially, and
1. You were able to practice not just
DMAIC skills but also DMADV.

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The following key strategies are suggested
to launch a Six Sigma effort within the
pharmaceutical industry –
1 Begin to change the traditional ways
of conducting clinical trials by
campaigning for the implementation
of needed integration initiatives
through the use of Six Sigma with a
commitment from top down
leadership.
2 Focus on the integration of
technology and workflow
improvement in meeting challenges
and extend new ventures not possible
using conventional isolated
implementation of technology or
homegrown process improvement
methodologies.
3 Provide tested research approaches
for the quantitative evaluation of
clinical development and process
improvement strategies, the
integration of which highly
correlates with strong financial
performance.7
TRAINING
Training is a vital part of making an
organizational culture favorable to Six
Sigma and arming the participants with the
skills and knowledge they need to
effectively contribute to the initiative.
The center of any Six Sigma training should
be the five-phased DMAIC methodology,
supplemented by the basics of champion and
Belt training.
CHAMPION TRAINING
Champion training typically ranges in
duration from one to four days. Champion
training should be long enough to provide an
overview of the Six Sigma problem-solving
processes and prepare champions for their
role as the Black and Green Belts guide,
mentor, and facilitator. Champion training
typically occurs before Black and Green
Belt training.
SIX SIGMA PRACTITIONERS
TRAINING
All Six Sigma practitioners—Master Black
Belts, Black Belts, and Green Belts—need
to receive training on quality tools and the
financial aspects of Six Sigma.
In general, a training program should focus
on helping the participants understand how
the tools fit into the overall methodology.
The training approach should consist of
training intervals followed by time for
practical application on actual projects.
GREEN BELT TRAINING
When designing Green Belt training, it is
best to include more of the day-to-day
process flow improvement issues and
overall process measures than the high-level
statistical tools that Black Belts need to
understand. Training time for Green Belts
varies, sometimes extending to three weeks.
BLACK BELT TRAINING
Black Belt training covers the topics that
Black Belts will need to master before
managing a Six Sigma project. Its basis is
the DMAIC approach and the Six Sigma
techniques and skills that support that
methodology. Additional training in project

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management skills, soft skills, the voice of
the customer, and lean management will
better prepare Black Belts for their
leadership role.
MASTER BLACK BELT TRAINING
Master Black Belts typically receive
additional training beyond the Black Belt
curriculum in order to improve their project
and coaching skills.8
SIX SIGMA CERTIFICATION
Six Sigma certification requirements vary
from organization to organization. It is good
idea to have documented processes for
certifying a Six Sigma practitioner as
competent in using Six Sigma and for
certifying projects. The certification
requirements typically involve successful
completion of training and one or more
projects.
For example, DuPont’s requires Black Belts
to complete training, demonstrate
competency, and complete a minimum of
two projects that return $350,000 hard
benefit per year.
In pharmaceutical industries, the Six
Sigma methodologies are used for reducing
the number of defects. The Six Sigma
methodology is primarily based on a data-
driven, systematic approach to problem
solving, with a focus on customer impact.
Statistical tools and analysis are often used
in the process. In addition, Six Sigma
identifies several key roles to employees for
its successful implementation. These
include:
Journal of Natura Conscientia, Vol.2, Issue 1, January 2011
1 Executive Leadership, which
includes CEO and other key top
management team members, is
mainly responsible for setting up a
vision for Six Sigma
implementation. They also provide
other role holders with the freedom
and resources to explore new ideas
for quality and efficiency
improvements.
2 Champions, who are generally
selected from the upper management
by the executive leadership, are
mainly responsible for the Six Sigma
implementation across the
organization in an integrated manner.
They also acts as mentors to Black
Belts (Six Sigma experts).
2. Master Black Belts identified by
champions, acts as in-house Six
Sigma experts for the company.
They devote 100% of their time to
Six Sigma and ensure integrated
deployment of Six Sigma across
various functions and departments.
4 Black Belts operate under Master
Black Belts to apply Six Sigma
methodology to specific projects.
While Black Belts focus on Six
Sigma project execution, Champions
and Master Black Belts focus on
identifying projects or functions for
Six Sigma.
5 Green Belts are the employees who
take up Six Sigma implementation
along with their routine job
responsibilities. They operate under
the guidance of Black Belts and
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support them in achieving the overall
results.
6 Yellow Belts are the employees who
have a basic knowledge of Six Sigma
techniques as part of a corporate-
wide initiative but do not lead
projects on their own, as does a
Green Belt or Black Belt. 5
DEPLOYMENT (OPERATION)
It is a known fact today that the success of
Six Sigma lays on the projects selected and
their link to the strategy of their
organization.
PROJECT SELECTION
Six Sigma projects are chosen based on their
potential to impact corporate objectives.
You should select ones based on core
processes that provide critical products to
external or internal customers. At the
beginning of your Six Sigma effort, choose
only a few, well-thought-out projects that
have a good chance of succeeding. If
projects do not deliver the expected bottom-
line results, then organizations will become
frustrated with the effort and as a result,
divert attention and resources to other
initiatives.
Characteristics of good Six Sigma projects
are as follows:
(a) The project should be linked
clearly to the business
priorities as reflected in the
annual operating plans.
(b) Addresses critical problems
that must be solved in order
for the organization to be
Journal of Natura Conscientia, Vol.2, Issue 1, January 2011
successful the following
year.
(c) Project should represent a
breakthrough in terms of
major improvement in both
process performance and
bottom-line results.
It is important that the project is doable and
can be completed in a short time (6-12
months) to keep the focus and interest in the
project. There should be clear quantitative
measures of success. Areas to be improved
should also affect directly customer
satisfaction. Six Sigma is aimed at the
problem in which the solution is not known.
Two important criteria in selecting a project
for Six Sigma are effort required and
profitability of success.
IDEA GENERATION
Six Sigma project idea can be come from
numerous sources: process assessments,
customer and employee surveys and
suggestions, benchmarking studies, and
extensions of current projects. Managers are
often instrumental in identifying areas for
improvement in the functions they oversee.
A documented process for generating,
capturing, and prioritizing ideas will help
steering committees or Six Sigma managers
identify viable projects. The process will
help them ensure that their projects align
with their organization’s strategic priorities.
For example, Raytheon’s project-idea-
generation process works like this. An
assessment team sponsored by management
performs a baseline analysis that determines
the project definition and goals. Detailed
data about the product or process is
identified and analyzed. The deliverable
from this process is a list of opportunities
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with calculated savings potential and

recommendations for project selection.

Six Sigma Cost And Savings By Company

Year Revenue Invested % Savings %

($B) ($B) Revenue ($B) Revenue
Invested Savings

Motorola

1986- 356.9(e) ND _ 16 1 4.5

2001

GE

1996 79.2 0.2 0.3 0.2 0.2

1997 90.8 0.4 0.4 1 1.1

1998 100.5 0.5 0.4 1.3 1.2

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1999 111.6 0.6
1996-
382.1 1.6
1999
POTENTIAL IMPACT OF A PROJECT
Before selecting a Six Sigma project, the Six
Sigma manager(s) or steering committee
needs to be sure that it will yield major
process improvements and significant
bottom-line results. The financial
representatives should work with the
practitioners and champion to determine the
potential impact for a given project.
For every project, the Black Belt determines
the appropriate baseline metrics. Any
relevant data can be used to determine the
baseline for a project; a lack of data should
not prevent a Six Sigma project from
moving forward, but it may impact the
organization’s ability to forecast the
project’s overall benefits.
Several key components of a project need to
be in place before it is initiated.
PROJECT TEAM
Each project team should consist of a Black
or Green Belt, the process owner, and team
members. The Six Sigma team leader must
hold a leadership position, be respected by
the organization, and be able to use the
methodology to improve the process, as well
as have the skills required to lead the team.
The project champion must be able to secure
the necessary resources, break down
barriers, and review the project regularly.
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0.5 2 1.8
0.4 4.4 1.2
The team members must have knowledge of
and experience with the process being
studied and be able to meet with the Belt as
required.
PROJECT DURATION
Six Sigma projects are best completed in
three to six months; this keeps the
organization and resources focused on the
project. If part-time resources are working
on the project, then completion will
obviously take more time than for full-time
ones. If part-time Black Belts are being
used, then Six Sigma managers should make
sure they have enough dedicated time set
aside weekly to work on the project so that it
can be completed in a reasonable time
frame. Champions and Master Black Belts
can help Black and Green Belts.
EXECUTION
Although every organization will have a
slightly different methodology for applying
Six Sigma to its projects, the basic Six
Sigma methodology-the DMAIC
methodology-provides the foundation. The
DMAIC methodology steps following:
Define- The project team identifies a
suitable project based on customer needs
and feedback and then identifies critical-
to-quality characteristics, which are
those characteristics that customers
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deem most vital to quality. The team
also sets the scope of the project and
documents its potential benefits.
Measure- The project team identifies
the key internal processes that influence
the process under investigation and
measures the associated defects. Once an
organization has specified the metric
data requirements, it can measure
process performance accurately. Process
owners can gather data on the
effectiveness of their efforts in meeting
all customer requirements. Then, using
Six Sigma tools, the team can compare
the performance of different processes
and identify major areas of deficiency.
Analyze- The project team uses Six
Sigma tools and techniques to discover
what the defects are and identify
solutions. It also assesses what can go
wrong, as well as the impact of those
mistakes.
Improve- The project team prioritizes
and implements improvement
opportunities. It uses Six Sigma tools
and techniques to confirm key variables
and quantify their effects, which may be
process improvement, addition of value,
reduction of costs, or integration of new
technologies and ideas.
Control- The project team sets in place
a control plan or system to sustain the
improvement and ensure that key
variables are kept within acceptable
ranges.
Each of these phases should consist of one
or more deliverables that must be approved
by Black Belts or Master Black Belts.
Journal of Natura Conscientia, Vol.2, Issue 1, January 2011
John Deere Health is on best practice
organization researched that has developed
its own Six Sigma methodology, based on
the DMAIC model, and called IMPACT.
I- Initiate the project (leadership hands off
the project to the team).
M- Map the current process to determine the
baseline and identify measures important to
the process.
P- Develop an improved process by
brainstorming ideas and potential solutions.
A- Achieve results (implementation, using
the new process).
C- Control the process.
T- Recognize the team. 6, 7, 9
PERFORMANCE LEVELS
Today, pharmaceutical manufacturers are
focused, as never before, on reducing
operational costs while ensuring
compliance. Cost pressures are increasingly
acute as many pharmaceutical manufacturers
see a dwindling product pipeline, as well as
greater competition from generics. To
ensure that their bottom lines remain solid,
pharmaceutical manufacturers are looking to
increase the efficiency of their operational
and manufacturing processes—optimizing
resources, improving efficiency, reducing
waste and controlling inventory. The
regulatory climate is, at last, conducive to
focusing on such changes, as the U.S. FDA
as well as other regulatory bodies now
support approaches that seek to reduce risk
by building quality into the manufacturing
process from the start, as opposed to relying
on end-process testing. In this climate,
pharma manufacturers are looking to Six
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Sigma principles—proven in other improving productivity, efficiency and

industries—to help them boost operational
efficiency and improve quality, while
facilitating compliance.
The industry’s focus on maintaining the
status quo in its manufacturing environment
has produced inefficiency and waste. It is
estimated that the potential world-wide cost
savings from efficiency improvement could
be as high as US$ 90 billion. While
Research and Development (R&D) is
generally considered a major cost centre for
the pharmaceutical industry, manufacturing
quietly accounts for more than twice the
expense of R&D—representing, on average,
36 percent of a pharmaceutical
manufacturer’s costs. The true cost of
manufacturing becomes even more apparent
when one considers the amount attributed to
non-value-added activities and waste, which
is 80 percent and 50 percent, respectively.
quality. At the same time, the U.S. FDA and
other regulatory bodies are acknowledging
that the industry has fallen behind other
sectors in terms of efficiency and quality,
and have begun to endorse a “quality by
design model” that contrasts with the
industry’s historical “quality by test” results
approach. As part of this shift, the U.S. FDA
launched its Process Analytical Technology
(PAT) initiative, a risk-based guidance
model that seeks to direct pharmaceutical
manufacturers toward consistent and
predictable quality (higher sigmas). The
PAT approach is to build in quality
improvements on the factory floor through a
deep understanding of how variable process
attributes affect product quality at a
fundamental level.1, 8, 10, 11, 12

Several important factors have converged in

recent years to jumpstart substantial change
in how pharmaceutical manufacturers
approach and manage their manufacturing
operations. First, many manufacturers face a
declining development pipeline as well as
shrinking profit margins as they face
increased competition from generic drug
manufacturers. As such, they see a growing
need to abandon the status quo to focus on

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ISSN-2229-429 www.jonc.in

Sigma Performance Levels – One To

Six Sigma

Defects Per Million

Sigma Level
Opportunities (DPMO)

690,000
1

308,537
2

66,807
3

6,210
4

233
5

3.4
6

WHAT WOULD THIS LOOK LIKE IN THE REAL WORLD?

Its one thing to see the numbers and it's a whole other thing to see how it would apply to your
daily life.

Real-World Performance
Levels

Situation/Example In 6 Sigma
In 1 Sigma World In 3 Sigma World
World

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Pieces of your mail lost per

1,106 107 <1
year [1,600 per year]
Number of empty coffee
pots at work (who didn't fill
470 45 <1
the coffee pot again?) [680
per year]
Number of telephone
disconnections [7,000 talk 4,839 467 0.02
minutes]
Erroneous business orders
172,924 16,694 0.9
[250,000 per year]
1. Wrong excipient, so for each drug
product at least two defect
Process Calculation opportunities could be assigned.
How to Calculate Process Sigma? Apparently, some manufacturers
Consider a pharmaceutical industry example with large number of drug products
that measures their performance in uptime of prefer to [count two opportunities in
available command to their network. Here is this case]. My point is that this
the 5-step process to calculate your process approach dilutes Six Sigma metrics."
sigma. -Anonymous
Many Six Sigma professionals support the
Step 1: Define Your Opportunities counter point. I always like to think back to
An opportunity is the lowest defect the pioneer of Six Sigma, Motorola. They
noticeable by a customer. This definition, of built pagers that did not require testing prior
course, is debatable within the Six Sigma to shipment to the customer. Their process
community. Here's a useful clip from the sigma was around six, meaning that only
forum discussing this point: approximately 3.4 pagers out of a million
"Typically, most products (and services) shipped did not function properly when the
have more than one opportunity of going customer received it.
wrong. For example, it is estimated then in a Like that, the customer doesn't care if
drug product could have the following only approximately 3.4 drug products out
opportunities for error: of a million manufactured did not of
standard quality.
1. Wrong active principle and Returning to our pharmaceutical industry
example, an opportunity was defined as a
minute of uptime. That was the lowest

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(shortest) time period that was noticeable by Returning to our pharmaceutical industry
a customer. example, the yield would be calculated as:
Step 2: Define Your Defects Yield (%)= {(525,600 - 500) / 525,600} *
Defining what a defect is to your customer is 100 = 99.90%
not easy either. You need to first (Alternatively, the yield can be calculated
communicate with your customer through for you by using the iSixSigma Process
focus groups, surveys, or other voice of the Sigma Calculator - just input your process
customer tools. opportunities and defects).
To Motorola pager customers, a defect was Step 5: Look Up Process Sigma
defined as a pager that did not function The final step (if not using the iSixSigma
properly. Process Sigma Calculator) is to look up your
Returning to our pharmaceutical industry sigma on a sigma conversion table, using
example, a defect is defined by the customer your process yield calculated in Step 4.
as no product of standard quality. An
additional defect would be noticed that Sigma conversion table
elapsed where the customer didn't have YIELD (%) DPMO Sigma
product available.
6.68 933200 0
Step 3: Measure Your Opportunities and
Defects 8.455 915450 0.125
Now that you have clear definitions of what 10.56 894400 0.25
an opportunity and defect are, you can
13.03 869700 0.375
measure them. The pharmaceutical industry
example is relatively straight forward, but 15.87 841300 0.5
sometimes you may need to set up a formal 19.08 809200 0.625
data collection plan and organize the process
of data collection. Be sure to read 'Building 22.66 773400 0.75
a Sound Data Collection Plan' to ensure that 26.595 734050 0.875
you gather reliable and statistically valid
30.85 691500 1
data.
Returning to our pharmaceutical industry 35.435 645650 1.125
example, here is the data we collected: 40.13 598700 1.25
Opportunities (last year): 525,600 products
45.025 549750 1.375
Defects (last year): 500 products.
Step 4: Calculate Your Yield 50 500000 1.5
Subtracting the total number of defects from 54.975 450250 1.625
the total number of opportunities, dividing
59.87 401300 1.75
by the total number of opportunities, and
finally multiplying the result by 100 64.565 354350 1.875
calculate the process yield.

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69.15 308500 2 99.997 30 5.5

73.405 265950 2.125 99.99767 23.35 5.625
77.34 226600 2.25 99.99833 16.7 5.75
80.92 190800 2.375 99.999 10.05 5.875
84.13 158700 2.5 99.99966 3.4 6
86.97 130300 2.625
89.44 105600 2.75 Yield (%)= {(525,600 - 500) / 525,600} *
100 = 99.90% (from step 4), then
91.545 84550 2.875
Sigma = 4.625
93.32 66800 3
94.79 52100 3.125
ASSUMPTIONS
95.99 40100 3.25
No analysis would be complete without
96.96 30400 3.375 properly noting the assumptions that you
97.73 22700 3.5 have made. In the above analysis, we have
assumed that the standard sigma shift of 1.5
98.32 16800 3.625 is appropriate (the calculator allows you to
98.78 12200 3.75 specify another value), the data is normally
99.12 8800 3.875 distributed, and the process is stable. In
addition, the calculations are made with
99.38 6200 4 using one-tail values of the normal
99.565 4350 4.125 distribution.
99.7 3000 4.25
FORMULA FOR CALCULATION OF
99.795 2050 4.375 SIGMA
99.87 1300 4.5 1. Defects Per Million Opportunities
(DPMO) = (Total Defects / Total
99.91 900 4.625
Opportunities) * 1,000,000
99.94 600 4.75 1. Defects (%) = (Total Defects / Total

99.96 400 4.875 Opportunities)* 100%

1. Yield (%) = 100 - %Defects
99.977 230 5 1. Process Sigma (type this formula
99.982 180 5.125 into Excel) =NORMSINV (1-(total
defects / total opportunities))+1.5
99.987 130 5.25
Be sure to include the Equals (=) sign. This
99.992 80 5.375 will give you your process sigma (or sigma
capability) assuming the 1.5 sigma shift.

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Review Article Available online through
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For example if you type this into Excel,
=NORMSINV(1-100/1000000)+1.5
you will get 5.22 for your Process Sigma. 9,
10, 11, 12, 13
BENEFITS AND APPLICATIONS
The pharmaceutical industry is the most
regulated of all industries. Regulatory affairs
professionals are key players in the product
development and as communication link
between the industry and agencies such as
FDA. Six sigma as a problem solving
approach has been used in various fields to
provide the fundamentals of variation
management and reduction in order to assist
in transforming established methodologies
in to new and efficient techniques.
Six Sigma is becoming a cornerstone
philosophy among the worlds leading
corporations because it has proven itself by
generating substantial business return. It is
only fitting to the end that “we believed then
and we are convinced today… that there is
an infinite capacity to improving
everything” but there was no methodology
or discipline attached to that belief. There is
now, it’s six sigma qualities, along with a
culture of learning, sharing and unending
excitement.
The division of Motorola that oversees their
Six Sigma services is known as Motorola
University. Motorola University claims that
the return on investment for properly
implemented Six Sigma projects ranges
between 10:1 and 50:1.
Few industries would not be interested in
learning more about a process that can offer
that level of return on investment. The
Journal of Natura Conscientia, Vol.2, Issue 1, January 2011
popular literature is filled with the benefits
that Six Sigma can provide industry in
which its principles are incorporated. Many
of these benefits can be associated with how
an industry must be aligned towards
continuous improvement in everything it
does.
Teambuilding: Teambuilding is an essential
element of Six Sigma. Many industries wish
that their workforce would communicate
effectively across functional areas.
However, they have no idea how to initiate
this communication. The Six Sigma process
requires just this kind of cross-functional
communication in order to succeed.
Constant improvement: One of the most
basic views of Six Sigma is constant
improvement.
Six Sigma supporters state that while 3.4
defects per million attempts may be
unattainable for the vast majority of
industries; this goal serves as a constant
reminder that there is no such thing as good
enough. The only constant is the need for
improvement.
Mandated training: Many organizations
never seem to have time for training. Either
these organizations do not properly
prioritize training or they see it as an
unnecessary expenditure of capital with no
obvious correlation to revenue. The Six
Sigma Quality Control Program mandates
training in all aspects of organizational
processes. Any business process that
incorporates Six Sigma must be refined and
this refining process requires training.
Return on investment: One of the greatest
advantages that the Six Sigma Quality
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Control Program offers organizations is the
reported return on investment. According to
its 1997 annual report, AlliedSignal reported
a $1.5 billion savings due to Six Sigma. GE
chairman Jack Welch has been credited with
claiming savings in the billions of dollars
that directly correlated to Six Sigma
implementation. Yet, in order to achieve
these levels of return on investment,
organizations must be willing to commit
significant time, energy, and resources to the
process. There is no such thing as partially
committing to Six Sigma as it is an all or
nothing proposition.
Increased aptitude for organizational
change: Finally, Six Sigma can introduce an
increased aptitude for change. Six Sigma is
dedicated to constant improvement and
repeated change in all business processes.
All members of the organization are
continually asked for examples of processes
that can be improved and recommendations
of solutions to these inefficiencies. This
constant solicitation of input creates a
corporate culture in which change is
required after and implemented with relative
ease.
Customer satisfaction: Today, most of the
packaging manufacturers are focusing on
introducing innovative packaging solutions
that cater to the ever-changing customer
requirements. Six Sigma processes can help
packaging manufacturers to analyse which
packaging solution offers the most
customer-friendly features as well as meet
their expectations regarding price and
quality.
Cost reduction: Six Sigma processes enable
packaging manufacturers to minimize
Journal of Natura Conscientia, Vol.2, Issue 1, January 2011
operational costs by focusing on defect
reduction, and identifying and eliminating
costs that provide no value to customers
(costs incurred due to waste). Besides, Six
Sigma techniques also allow for the
significant cost avoidance as some parts of
the previous processes simply disappear
with the streamlining of production
processes under Six Sigma methodologies.
This further results into increase in output,
improved capacity utilization and reduction
in labour costs, etc.
Cycle time reduction: The Six Sigma
methodologies also allow manufacturers to
reduce manufacturing lead-time! Cycle time
(i.e. delay from the moment the order is
ready for set up to completion) by
optimizing the throughput of individual
manufacturing processes through
improvement in tool capability, consumable
material reliability, etc. The cycle time
reduction further allows for increased
flexibility, i.e. customer orders can enter the
manufacturing processes at the earliest
without having to wait for planned lot. Also
materials progress through the production
process faster without waiting in lengthy
queues at each workstation. 2, 10, 14
References
1. B. Greg, Six Sigma for
Managers. McGraw-Hill, New
York, 2002.
2. M. Palkar, P. Rajadhyaksha, M.
Shah, A. Shedge, G. Goyal,
“Application of six sigma in
292
 Sharma O.P. et al. / Journal of Natura Conscientia 2011, 2(1), 273-293
Review Article Available online through
ISSN-2229-429 www.jonc.in

pharmaceutical industries”, in Publishing Company Limited,

59th IPC, BHU, Varanasi, New Delhi, 2005.
December 2007, 500. 10. P. Pande, L. Holpp, What is Six
3. http://healthcare.isixsigma.com/li Sigma ?. Tata McGraw-Hill
brary/content. Publishing Company Limited,
4. M. Goel, A. Raj, D.K. Yadav, New Delhi, 2002.
“Six sigma the road map to 11. http://www.articlesbase.com/man
th
customer impact”, in 59 IPC, agement-articles/six-sigma-and-
BHU, Varanasi, December 2007, lean-for-the-pharmaceutical-
480. industry-539845.html.
5. http://healthcare.isixsigma.com/li 12. http://www.pharmafocusasia.com
brary/bio/ksimon.asp. /manufacturing/lean_sixsigma_m
6. G. Kaur, S. Khanna, A. Nasa, anufacturing.html.
“Six sigma in pharmaceutical 13. http://www.articlesbase.com/man
regulatory affairs”, in 59th IPC, agement-articles/why-a-six-
BHU, Varanasi, December 2007, sigma-based-quality-system-
501. may-be-the-answer-for-
7. http://www.isixsigma.com/sixsig pharmaceutical-companies-
ma/six_sigma_calculator.asp. 337277.html.
8. M.J. Harry, Resolving the 14. http://mastercontrol.com/solution
Mysteries of Six Sigma: s/quality_management_fb.html.
Statistical Constructs and
Engineering Rationale. Palladyne
Publishing Phoenix, Arizona,
2003.
9. S.E. Blashka, J. Crager, D.
Lemons, W. Vestal, Six Sigma
Management: A Guide for Your
Journey to Best-Practice
Processes. Tata McGraw-Hill

Journal of Natura Conscientia, Vol.2, Issue 1, January 2011 293

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