Research Proposal (M04EKM)- Syed Shah Areeb Hussain - 0541198

8/10/2019 Research Proposal (M04EKM)- Syed Shah Areeb Hussain - 0541198

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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 HUSSAIN0541198


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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

..6Draft Headings ..7

Task Schedules ..9

Gantt Chart12

References .13


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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.


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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 timemeasured 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


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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 pharmaceuticalcompany 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 usedto 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.


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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 qualitychecks, 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 willrequire 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 George2011). However, these case studies have not attempted to integrated cGMP practices to lean


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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.


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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

2 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 cGMP2.1.4 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

3 Research Methodology

3.1 Types of Research Tools Employed

3.2 Data Collection Methods

3.3 Data Analysis Tools

4 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


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4.4 Current State Value Stream Map

4.5 Cell Design

4.6 Yamazumi Board

4.7 Future State Value Stream Map

5 Results

5.1 Lead Time reduction

5.2 First Yield Quality Pass Rate

5.3 Cost reduction analysis

6 Discussion

6.1 Improvements in the production line

6.2 Comparison with previous studies

6.3

Benefits of integration of cGMP with lean manufacturing principles6.4 Practical Validation

7 Conclusion

8 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 Re-

sources

Risks

1 Gather Literature 5 Library,

Computer

Library may

be closed

2 Read and Organize Literature 5 1, Com-

puter,

Books

Books may

be checked

out

3 Draft Section Headings 1 1, 2 Computer May Lose

data

4 Prepare Draft Literature Review 4 1, 2, 3 Computer May Lose

data5 Proof Read 1 1, 2, 3, 4 Computer May Lose

data

6 Apply corrections and prepare final version 1 1, 2, 3, 4, 5 Computer May Lose

data

Total 17

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

relation to each other to the pharmaceutical manufacturing process


sources

Risks


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1 Collect relevant literature(books and jour-

nals)

3 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

libraries4 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 cGMP-

Lean 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


sources

Risks

1 Select Production line for case study 1

2 Prepare draft overview of the process stream

by walking along the stream

1 1,

3 Note down the WIP at each process 2 1, 2 Calculator Too much

WIP may be

difficult to

count

4 Discuss other process variables like cycle

times, quality pass rate and availability with

operators

1 1, 2, 3 Inaccuracy in

measure-

ments

5 Using data collected, prepare a rough current

state map while walking along the process

stream

5 1, 2, 3, 4 A3 Sheet,

Calculator

6 Proof read CSM 1 1, 2, 3, 4, 5

7 Apply corrections if necessary and prepare fi-

nal version

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


sources

Risks

1 Prepare Yamazumi Board and relate to takt

time

1 Excel

Spread-

sheet

2 Analyze current state map with respect to 7

wastes

1 1, Literature

review


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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 implementa-

tion

1 1, 2, 3

5 Carry out focus groups to analyze the validity

of principles with respect to the current pro-

cess

2 1, 2, 3, 4 Recorder

6 Perform Future state calculations 1 1, 2, 3, 4, 5 Calculator

7 Using data calculated and techniques pro-

duced, develop a draft Future State Map

3 1, 2, 3, 4, 5, 6 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 cur-

rent process flow


sources

Risks

1 Discuss implementation timelines with plant

manager

2 Resistance to

change

2 Prepare draft implementation plan 5 1, Excel

Spread-

sheet

3 Discuss validity of plan with plant manager 1 1, 2

4 Prepare Gantt chart for implementation 3 1, 2, 3 ExcelSpread-

sheet

5 Take steps to introduce the plan in a smooth

and timely manner

5 1, 2, 3, 4 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


sources

Risks

1 Measure the cycle time, changeover times,lead time, quality pass rate etc. for each pro-

cess

3 Inaccuracy inmeasure-

ments

2 Prepare a table to contrast current variables

after implementation of strategy with those

in the current state map

1 1, Excel

Spread-

sheet

3 Calculate the first pass yield, lead time and

perform cost analysis before and after imple-

mentation

3 1, 2 Calculator

4 Contrast the obtained values in a detailed ta-

ble

3 1, 2, 3

Total 10


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Deliverable - Critical Analysis of cGMP-Lean principles in improving quality and cost while reducing

time in the pharmaceutical manufacturing process


sources

Risks

1 Compare data from tables produced in the

results sections

5

2 Identify benefits of implementing the princi-

ples 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 rele-

vant 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 3 1, 2, 3, 4, 5 Computer

7 Proof Read and perform corrections 1 1, 2, 3, 4, 5, 6 Computer

8 Prepare final version 3 1, 2, 3, 4, 5,

6, 7

Computer

Total 24

Total No. Of days = 107 days


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GANTT CHART


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Carleysmith, S.W., Dufton, A.M., and Altria, K.D. (2009) Implementing Lean Sigma in Pharmaceutical

Research and Development: A Review by Practitioners. R&D Management, 39 (1), 95106.

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

Pharmaceutical Company.Journal of Manufacturing Technology Management, 23 (1), 5675.

available from

Dermot, O. and Greene, A. (2006) Lean Manufacturing Practice in a cGMP Environment[online]

available from [29 December 2014]

DiMasi, J.A., Hansen, R.W., and Grabowski, H.G. (2003) The Price of Innovation: New Estimates of

Drug Development Costs.Journal of health economics, 22 (2), 15185.

Lanez, J.M., Schaefer, E., and Reklaitis, G.V. (2012) Challenges and Opportunities in Enterprise-

Wide Optimization in the Pharmaceutical Industry. Computers & Chemical Engineering, 47,

1928. available from

[13 December 2014]

Mukhopadhyay, S.K., Dwivedy, J., and Kumar, A. (1998) Design and Implementation of an

Integrated Production Planning System for a Pharmaceutical Manufacturing Concern in India.

Production Planning & Control, 9 (4), 391402.

Rother, M. and Shook, J. (2003) Learning to See: Value Stream Mapping to Add Value and Eliminate

Muda, Lean Enterprise Institute.

Thomas, H. (2005) Transforming the Pharma Industry: Lean Thinking Applied to the Pharmaceutical

Manufacturing. in World Congress of Chemical Engineering. held 2005

Weller, H.N., Nirschl, D.S., Petrillo, E.W., Poss, M.A., Andres, C.J., Cavallaro, C.L., Echols, M.M., Grant-

Young, K.A., Houston, J.G., Miller, A. V, and Swann, R.T. (2006) Application of Lean

Manufacturing Concepts to Drug Discovery: Rapid Analogue Library Synthesis.Journal of

combinatorial chemistry, 8 (5), 6649.

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Research Proposal (M04EKM)- Syed Shah Areeb Hussain - 0541198