RESEARCH PROPOSAL

M04 EKM

EVALUATING THE EFFICACY OF cGMP-LEAN INTEGRATED TECHNOLOGIES IN

IMPROVING QUALITY AND COST IN PHARMACEUTICAL MANUFACTURING A
CASE STUDY

SYED SHAH AREEB HUSSAIN

0541198

TABLE OF CONTENTS

Abstract.........................................................................................................1
Aim of the Study..2
Objectives of the Study2
Project Deliverables..2
Significance of the Research3
Research Methodology....3
Data Sources..6
Draft Headings..7
Task Schedules..9
Gantt Chart12
References.13

EVALUATING THE EFFICACY OF cGMP-LEAN INTEGRATED TECHNOLOGIES IN

IMPROVING QUALITY AND COST IN PHARMACEUTICAL MANUFACTURING A
CASE STUDY

ABSTRACT
The purpose of this paper is to combine the lean manufacturing techniques with the current
good manufacturing practices (cGMP) and analyse its efficacy in a pharmaceutical
manufacturing setting. Implementing lean in the pharmaceutical sector has been met with
several complications due to stringent quality control requirements (Lanez et al. 2012).
Though cGMP principles are often are often viewed as contrary to those of lean
manufacturing, one can be used to support the other and therefore can complement each
other (O'Rourke & Greene, 2006). This study will analyse the current issues faced while
implementing lean into the pharmaceutical sector and attempt to address these problems by
associating it with cGMP principles. This will be done by implementing these principles within
a pharmaceutical company and assisting them in reducing their lead times, cycle times and
first yield quality pass rates. The results obtained in this study could be used as a standard for
efficient implementation of these technologies in the pharmaceutical sector.

AIM OF THE STUDY

The aim of the study is to relate cGMP to lean manufacturing techniques which can be
implemented in the production line of a pharmaceutical company, and to evaluate thee
efficacy of these principles in improving quality while reducing costs in the company.

OBJECTIVES

To identify and relate relevant cGMP and lean manufacturing principles that can be
effectively implemented in a pharmaceutical manufacturing sector
To analyse the current production process in the factory floor and identify key areas
of improvements
To develop and suggest improvements based on the cGMP-Lean combined principles
within the manufacturing process
To measure the variables governing quality, cost and time in the improved
manufacturing process
To evaluate the efficacy of the developed principles and techniques in improving
quality, cost and time analysing the results with respect to similar case studies
performed

PROJECT DELIVERABLES

Literature review highlighting the key concepts of cGMP and lean manufacturing and
their relation to pharmaceutical manufacturing
Enumeration of cGMP and Lean principles and techniques that can be applied in
relation to each other to the pharmaceutical manufacturing process
Current state map of the current process methods with yamazumi boards, pareto
chart and spaghetti diagrams providing details of the processes
Future state map of suggested techniques to be implemented with yamazumi boards,
standard op sheets and negare cell walk diagrams to provide details of improvements
Gantt chart and implementation plan for the integration of the techniques to the
current process flow
Table highlighting the changes in the variables defining quality, cost and time
measured before and after the implementation of strategies
Critical Analysis of cGMP-Lean principles in improving quality and cost while reducing
time in the pharmaceutical manufacturing process

SIGNIFICANCE OF THE RESEARCH

Stringent quality control regulations and growing complexity of diseases have led to the
increased costs in pharmaceutical manufacturing industries (DiMasi et al. 2003). While on one
hand, other technological sectors have greatly reduced their operating costs to provide the
best products at a reasonable price, the cost of production of medicines has only increased.
This is in part due to the lean manufacturing technology that is now implemented in almost
all other manufacturing industry. Previous studies have shown that lean manufacturing
principles can be modified and made concurrent with the pharmaceutical manufacturing
requirements to develop efficient manufacturing systems (Thomas 2005). However, often the
application of these techniques undermine the cGMP regulations (Dermot and Greene 2006).
Therefore there is a need to identify an integrated approach that combines the common
elements of lean manufacturing and cGMP guidelines.
The proposed research aims to develop a cGMP-Lean combined approach towards lean
manufacturing, which will then be applied in a production line of the selected pharmaceutical
company improve the cost and quality efficiencies. The results obtained from this study would
be applicable to any pharmaceutical organization and is expected to provide effective cost
reduction and improved quality.
As a biotechnology engineering graduate, the optimization of the pharmaceutical
manufacturing process is one of my key interests, which has strongly influenced my selection
of the research project.

RESEARCH METHODOLOGY
The proposed research requires the use of both quantitative and qualitative research
methodologies. Qualitative research methodologies are concerned with individual
perspective and focus on drawing conclusions through discussions. On the other hand
quantitative research methods focus on absolute data and draw conclusions through
quantifiable data. The proposed research would require qualitative research methods in
order to obtain inputs from the factory operators on the applicability of the techniques. On
the other hand, quantifiable data related to cost, time and quality measurements will be used
to critically analyse the efficacy of the introduced techniques.
Literature Review Qualitative
A literature review highlighting the various cGMP and lean manufacturing techniques will be
produced. This will be done through qualitative analysis of the current advancement in these
technologies and will highlight the different advantages and challenges of said technologies.
A few case studies have been performed on the implementation of lean in the pharmaceutical
industry (Chowdary and George 2011, Carleysmith et al. 2009, Weller et al. 2006). These case
studies will be discussed in detail and will be used for reference for critical analysis with
respect to a cGMP-Lean combined approach.

Enumeration of cGMP-Lean techniques Qualitative

The literature review will be followed by the selection of appropriate lean and cGMP
techniques to be implemented in a selected production line at the designated pharmaceutical
manufacturing company. cGMP guidelines and lean manufacturing principles are often
viewed as opposed to each other because while the former focuses on increased quality
checks, the latter focuses on reduced wastes. However, the underlying concepts of these two
principles is the same that is to add value to the produce. Moreover, they share some
common ground as both are concerned with implementing standard operating procedures,
continuous improvement and flow within the process (Dermot and Greene 2006). Therefore
development of the techniques will require a qualitative analysis of these underlying
concepts, their relation and validity for application in pharmaceutical manufacturing.
Current State Map Quantitative
The Current state map is often the first tool used for implementing the lean principles. The
current state map provides a broad view of the current processes and the process stream
(Rother and Shook 2003). Developing the current state map will require quantitative
methodology in the form of data such as cycle times, inventory etc. that are obtained through
observation of measurement of variables at each of the processes within the selected
production line. The data collected will then be used to create a complete picture of the
process stream.
Future State Map Mixed
The next step in lean manufacturing is formation of the future state map, which defines what
the process should look like in the future after implementation of lean techniques. This will
require both qualitative and quantitative research methodologies.
Firstly, the cGMP-Lean principles need to be discussed with the factory floor workers to verify
their validity and applicability to the process. This will require discussions in focus group to
identify areas of improvement and implement strategies.
Secondly, optimizations in the process using the cGMP-Lean techniques will be measured to
produce quantifiable data, which will be used to calculate the different variables in the future
state map (Rother and Shook 2003).
Implementation Plant and Gantt Chart Mixed
The implementation plans will be produced based on the present data to ensure sufficient
time allowance. This will be done through discussions with the production line manager as
well as data collected in the initial stages.
Critical Analysis Qualitative
Mukhopadhyay et al. (1998) were the first to suggest implementation of lean manufacturing
techniques through an integrated approach to the pharmaceutical manufacturing. In recent
years several other case studies have been performed on implementation of lean within the
pharmaceutical industry (Weller et al. 2006, Carleysmith et al. 2009, Chowdary and George
2011). However, these case studies have not attempted to integrated cGMP practices to lean

manufacturing. The proposed research will explore the benefits of this integration as
compared to the previous work and critically analyse the various aspects of this approach.

Though the research methods to be employed are expected to produce the desired results,
several factors may hamper the effective analysis of data. Firstly, resistance to change can be
a key factor in reducing the involvement of factory workers and plant managers in focus
groups. This will greatly affect the ideas proposed and therefore reduce the effective
implementation. These problems can be overcome by efficiently communicating the need to
implement the change in the organization and the benefits the new system would provide.
Secondly, often sole quantitative analysis may not be sufficient in producing the current state
map as it may be necessary to discuss the variable related to machines being used for several
different products. In this case a discussion with the operator would be required to identify
cycle times and inventories for a specific product as these are not clearly visible.

DATA SOURCES
The literature review will require mostly secondary data sources such as books, case studies
and journal articles. These will be obtained through the Lanchester library at Coventry
University.
The current state map will be developed through observations and discussions. Therefore it
would mostly involve primary data sources.
The Future state map will require both primary and secondary data sources. While previously
conducted research and case studies need to be used for developing ideas for improvement,
the feedback from operators in focus groups will also be needed to effectively implement
these techniques.
Gantt chart, implementation plans and the quality, cost and time measurement tables will
require the use of primary sources of data. This is because it will require going to the factory
floor and personally measuring the different variables in the process through observations
and discussions.
Finally both primary and secondary sources of data will be used for the critical analysis. The
primary sources used for this will be the different measurements of improvement that are to
be calculated. The secondary sources will be case studies and previous researches with which
the current case study needs to be compared.

Draft Headings
1

Introduction
1.1 Background
1.2 Aim
1.3 Research Objective
1.4 Scope and Benefit
1.5 Limitations of the Study

Literature Review
2.1 Current Good Manufacturing Practices
2.1.1 What is cGMP
2.1.2 Need for cGMP
2.1.3 Regulations based on cGMP
2.1.4 Other Good Practices (GLP, GCP, GRP)
2.2 Lean Manufacturing Principles
2.2.1 Value Stream Mapping
2.2.2 Pareto Analysis
2.2.3 Yamazumi Board
2.2.4 Spaghetti Diagram
2.2.5 Cell Design
2.2.6 Nagare cells and walk diagrams
2.2.7 Workload sharing
2.3 Pharmaceutical Manufacturing
2.3.1 Current Practices in Pharmaceutical Manufacturing
2.3.2 Challenges faced in drug development
2.3.3 cGMP in Pharmaceutical manufacturing
2.3.4 Lean in pharmaceutical manufacturing
2.3.5 Combining cGMP with Lean

Research Methodology
3.1 Types of Research Tools Employed
3.2 Data Collection Methods
3.3 Data Analysis Tools

Case Study
4.1 About The Company
4.1.1 Current Problems faced by Company
4.1.2 Selection of Production Line
4.2 Root Cause Analysis
4.3 Pareto Analysis

4.4
4.5
4.6
4.7

Current State Value Stream Map

Cell Design
Yamazumi Board
Future State Value Stream Map

Results
5.1 Lead Time reduction
5.2 First Yield Quality Pass Rate
5.3 Cost reduction analysis

Discussion
6.1 Improvements in the production line
6.2 Comparison with previous studies
6.3 Benefits of integration of cGMP with lean manufacturing principles
6.4 Practical Validation

Conclusion

References

TASK SCHEDULES
Deliverable - Literature review highlighting the key concepts of cGMP and lean manufacturing and
their relation to pharmaceutical manufacturing
No. Tasks
Days Dependency ReRisks
sources
1 Gather Literature
5
Library,
Library may
Computer be closed
2 Read and Organize Literature

5 1,

3 Draft Section Headings

1 1, 2

Computer,
Books
Computer

4 Prepare Draft Literature Review

4 1, 2, 3

Computer

5 Proof Read

1 1, 2, 3, 4

Computer

6 Apply corrections and prepare final version

1 1, 2, 3, 4, 5

Computer

Total

Books may
be checked
out
May Lose
data
May Lose
data
May Lose
data
May Lose
data

17

Deliverable - Enumeration of cGMP and Lean principles and techniques that can be applied in

relation to each other to the pharmaceutical manufacturing process

No.

Tasks

Days

Dependency

Resources

Risks

1 Collect relevant literature(books and journals)

Library,
Computer

Library may
be closed

2 Read and list all lean techniques

1 1,

Computer

May Lose
data

3 List all cGMP guidelines and regulations

1 1,2

ejournal
libraries

4 Compare and contrast lean principles to

cGMP guidelines

4 1, 2, 3,

5 Select and integrate suitable principles from

lean and cGMP to develop a list of cGMPLean techniques

4 1, 2, 3, 4

6 Discuss validity of techniques with plant

manager

1 1, 2, 3, 4, 5

7 Prepare final version of list

1
Total
15
Deliverable - Current state map of the current process methods with yamazumi boards, pareto chart
and spaghetti diagrams providing details of the processes
No.

Tasks

Days

Dependency

1 Select Production line for case study

2 Prepare draft overview of the process stream
by walking along the stream

1
1 1,

3 Note down the WIP at each process

2 1, 2

4 Discuss other process variables like cycle

times, quality pass rate and availability with
operators

1 1, 2, 3

5 Using data collected, prepare a rough current

state map while walking along the process
stream

5 1, 2, 3, 4

6 Proof read CSM

7 Apply corrections if necessary and prepare final version

1 1, 2, 3, 4, 5
1 1, 2, 3, 4, 5, 6

Resources

Risks

Calculator

Too much
WIP may be
difficult to
count
Inaccuracy in
measurements

A3 Sheet,
Calculator

Microsoft
Visio

Total
12
Deliverable - Future state map of suggested techniques to be implemented with yamazumi boards,
standard op sheets and negare cell walk diagrams to provide details of improvements
No.

Tasks

Days

Dependency

1 Prepare Yamazumi Board and relate to takt

time

2 Analyze current state map with respect to 7

wastes

1 1,

Resources
Excel
Spreadsheet
Literature
review

Risks

3 Discuss the problems of the current state

map with factory operators and production
line manager

2 1, 2

Recorder

4 Introduce previously developed cGMP-Lean

principles and identify areas for implementation

1 1, 2, 3

5 Carry out focus groups to analyze the validity

of principles with respect to the current process

2 1, 2, 3, 4

Recorder

6 Perform Future state calculations

7 Using data calculated and techniques produced, develop a draft Future State Map

1 1, 2, 3, 4, 5
3 1, 2, 3, 4, 5, 6

Calculator
Microsoft
Visio

8 Proof Read and create final version

2 1, 2, 3, 4, 5,
6, 7
Total
13
Deliverable - Gantt chart and implementation plan for the integration of the techniques to the current process flow
No. Tasks
Days Dependency ReRisks
sources
1 Discuss implementation timelines with plant
2
Resistance to
manager
change
2 Prepare draft implementation plan

5 1,

3 Discuss validity of plan with plant manager

4 Prepare Gantt chart for implementation

1 1, 2
3 1, 2, 3

5 Take steps to introduce the plan in a smooth

and timely manner

5 1, 2, 3, 4

Excel
Spreadsheet
Excel
Spreadsheet
Resistance to
change

Total
16
Deliverable -Table highlighting the changes in the variables defining quality, cost and time measured
before and after the implementation of strategies
No.

Tasks

Days

Dependency

Resources

1 Measure the cycle time, changeover times,

lead time, quality pass rate etc. for each process

2 Prepare a table to contrast current variables

after implementation of strategy with those
in the current state map

1 1,

Excel
Spreadsheet

3 Calculate the first pass yield, lead time and

perform cost analysis before and after implementation

3 1, 2

Calculator

4 Contrast the obtained values in a detailed table

3 1, 2, 3

Total

10

Risks
Inaccuracy in
measurements

Deliverable - Critical Analysis of cGMP-Lean principles in improving quality and cost while reducing
time in the pharmaceutical manufacturing process
No. Tasks
Days Dependency ReRisks
sources
1 Compare data from tables produced in the
5
results sections
2 Identify benefits of implementing the principles as compared to the traditional approach

2 1,

3 Compare the results with those obtained in

previous studies

5 1, 2

4 Highlight benefits of cGMP-Lean over relevant literature

3 1, 2, 3

5 Identify the limitations of the research and

areas of further research

2 1, 2, 3, 4

6 Prepare draft Sections

7 Proof Read and perform corrections
8 Prepare final version
Total
Total No. Of days = 107 days

3 1, 2, 3, 4, 5
1 1, 2, 3, 4, 5, 6
3 1, 2, 3, 4, 5,
6, 7
24

Computer
Computer
Computer

GANTT CHART

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Chowdary, B. V. and George, D. (2011) Improvement of Manufacturing Operations at a
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available from
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