755101

8/3/2019 755101

http://slidepdf.com/reader/full/755101 1/15

12

Thomas Friedli1, Prabir Basu2, Thomas Gronauer1, and Juergen Werani3

1University o St. Gallen (Switzerland)2National Institute or Pharmaceutical Technology and Education (NIPTE),Purdue University, West Laayette (USA)

3

Schuh & Co. Complexity Management, St. Gallen (Switzerland)

Leading pharmaceutical companies all over the world are acing a “new reality“. Whereas, inthe past, value creation was mainly based on intellectual property and market exclusivity, theblockbuster business model was the major source o cash fow or most o these companies.Today’s “new reality” is characterized by shrinking R&D productivity, cost-reduction initia-tives rom payer organizations – mostly driven by governmental pressure, shiting globalgrowth, increased regulatory requirements and loss o market exclusivity or many o the late20th century blockbuster drugs. Despite this steadily increasing pressure we are still optimisticor the industry as a whole; however, new solutions to undamental strategic issues must beound. This is especially important when dealing with the role o manuacturing and sup-ply organizations and the way these organizations are managed and administrated. Pharmacompanies have now entered an era that other industries reached decades ago and, based onthese developments, Operational Excellence (OPEX) in pharmaceutical manuacturing musttake its place as the cornerstone o every sustainable operations strategy in this industry.

While in the past the pursuit o product and substance innovations was the key issue in thepharmaceutical sector, the manuacturing process remained mostly static. Those times aregone and now, both the need or and the speed and scope o continuous improvement withinmanuacturing will steadily increase in the uture. The key to excellence in this area is a o-

cus on people. They design, operate, improve and re-invent activities, processes, systems andstructures and we believe that it will be the ability to make each individual employee thinkin terms o change that will overcome the organization‘s internal inertia and separate thewinners rom the losers.

How to structure a book? For every publisher and editor this is one o the most challengingquestions! From our perspective, the pathway to OPEX in pharma today is really a journey into

I

The Pathway to Operational Excellence

in the Pharmaceutical Industry –Overcoming the Internal Inertia

I.1 The Structure of the Book

8/3/2019 755101


Section A – Introduction

13

new terrain or the whole industry. One o the important lessons learned over the last numbero years has been that the path is not as clear as it had been expected and that you cannotexplore this new terrain alone. Indeed, standardized implementation roadmaps rom externalconsultants, one-size-ts-all solutions and so-called ‘experts’ acting like mavericks have been

quite unsuccessul. The challenges o OPEX, as we see them, are characterized by uncertainty,a need or true teamwork, and or technical as well as behavioral leadership skills.

A more in-depth look brought us to the conclusion that this journey has much in commonwith the expeditions in the 18th century, when courageous sailors explored more o the un-charted territories o our world. Oten under a cloud o uncertainty, the captains could notaccomplish these eats alone; they had to rely on their crews, ships, and emerging navigationtechniques. Today‘s OPEX champions ace a similar situation; thereore, or inspiration welooked at one o the journeys o Captain James Cook.

When James Cook let Plymouth harbor (Great Britain) aboard the HMS Endeavour (a modi-ed three-masted sailing ship with a length o 30 meters and a width o only 9 meters!) onAugust 26, 1768, he was taking responsibility or a crew o 98 men as they sailed to ace anuncertain destiny. Their journey took almost three years, during which time Cook‘s crew o 75 seamen, 12 soldiers and 11 scientists, illustrators and service people was away rom theirhomes and their amilies. The combined mission given to him by the Royal Society and BritishAdmiralty required Cook to lead his men in adverse conditions. First he was to sail to Tahitito observe and to record the transit o the Venus as part o a scientic experiment and laterhe was to nd and conquer the mythical and unknown continent „Terra Australis Incognita“or the British Empire. However, it was not only his courage in the ace o uncertainty andhis natural leadership skills that allowed Cook to succeed; he also possessed special technicalskills. These skills would later revolutionize the navy in general and turn him into one o themost amous gures o his century.

With the hiring o James Cook as commander o a royal mission, the admiralty had made arather atypical decision. James Cook was born in 1728, son o a day laborer in North England.He started working on a coal reighter as a ‘ship‘s boy’ when he was 17 and joined the RoyalNavy in 1755. Obviously he was not one o the aristocratic ocers that had been so typicalin the Royal British Navy at that time; instead he was a talented man with experience and aconvincing track record.

Ater entering the Royal Navy he became interested in the art o military cartography and theprocess o navigation by a plane table, spacer, and goniometer, which ascinated him. Duringthe Seven Years‘ War he mapped the entrance to the Saint Lawrence River and acilitated theamous Royal Navy attack on the Plains o Abraham, a key moment or the British Empire anda deciding moment or Cook, as it demonstrated his skills to the admiralty.

Cook became more and more ascinated by the various methods o mapping and cartography,but he saw how dilettante most navigators and captains were with regard to these methods.He started to learn more about mathematics, astronomy, and navigation to perect thesetechniques. By continuously improving his approach, he dierentiated himsel rom othercaptains, who navigated mostly along visible coastlines, or by oten inaccurate observationso the stars. Through his endeavors Cook became a master in navigation techniques and astrong leader.

His combination o seamanship, superior surveying and cartographic skills orged him into anoutstanding man who ultimately received the rank o a Captain in the Royal British Navy. Hesailed into the unknown South Seas three times, navigated his ships through dangerous wa-

ters, even crossing the dangerous Great Barrier Ree with his, by comparison to other vessels,tiny, wooden ship and he was the rst man to sail the Antarctic Circle. Sometimes he seemedto be obsessed with exploring dangerous locations in order to conrm or reute commonly

8/3/2019 755101


Section A – Introduction

14

accepted “acts” but Cook was also well known or the act that his ships had seldom beenin great danger and the mortality rate o his crews was one o the lowest amongst all Royalmissions. One reason or this were Cook‘s activities relating to scurvy. More than other com-manders beore, he investigated this disease and took great care with diet plans or his crew.

Following his second journey James Cook was announced as a member o the Royal Societyin recognition o his studies o scurvy.

In many ways, James Cook and his journey are an excellent reerence point or what opera-tions leaders in pharma are acing today. On one hand, the pharma world is changing asterthan in the past, market structures are shiting, unknown terrain and market segments areemerging and courageous changes may be required. On the other hand, new paradigms o operational techniques and methods are going to revolutionize a system which, while goodor the „older times“, will not be a suitable t or the „new reality“ that we ace. We have cho-sen a „journey report“ as an analogy. To our understanding it refects quite well on the otenneglected points o uncertainty and sustainability. As with real expeditions, people rst needto know the starting position, beore dening the destination, setting the direction, gaining

awareness o the terrain that they will ace and looking or good maps, team members andequipment.

Thereore we have divided our journey report into our parts.

Beore you dene the destination and consider the best route to get there, an essential part

o navigation is to identiy your starting position. Whether you will nally reach your chosendestination, and achieve your long-term goals depends on how you are equipped or this journey, on your skills and capabilities. Let us look at the example set by Cook. His rst des-tination was Tahiti, a tiny island in the Pacic Ocean. As previously mentioned, the commonnavigation approaches at the time were „ollowing the coastline“ or making a rough calcula-tion based on the position o the stars. With these approaches it would have been pure luckto nd Tahiti. Consequently, Cook perceived that improved navigation skills were a key skillsetor the mission’s success.

Thereore our book begins with an overview o the actual state o the pharmaceutical sectortoday, the level o operational perormance and the biggest gaps. We continue by consideringwhich „methods and tools“ are available to us in our goal o achieving OPEX and what the

status o their actual implementation is.Gronauer and Friedli (University o St. Gallen) start by analyzing which trends, in (I) globalcustomer demand and healthcare systems, (II) product innovations and product portolios,(III) value chain, capacities, sourcing and cooperation, (IV) process innovations and technolo-gies, and (V) the regulatory ramework, may have signicant impact on manuacturing andsupply strategies. In summary, the industry‘s main challenges are loss o market exclusivity,an increasing number o ailing product candidates, unsecure product pipelines, uncertainassumptions about uture volumes and market growth outside o mature markets, and thesuccess o new cost-competitive players. Manuacturing will need to become more complexand agile to handle uncertainty, but it is not supportable to achieve this by paying the “price”o higher costs. To overcome this trade-o, existing paradigms have to be questioned.

Herlant (The Boston Consulting Group) discusses these challenges by ocusing on the linkbetween manuacturing strategy and business strategy. Indeed, or many pharmaceutical

I.2 Starting Point of Our Journey

8/3/2019 755101


94

Matthias Goetzried, Thomas Friedli, and Saskia Guetter

University o St. Gallen (Switzerland)

Many pharmaceutical companies claim to have achieved a remarkable level o OperationalExcellence (OPEX) similar to that o established “lean enterprises” in other industries. Theterm “Operational Excellence” has spread throughout the entire industry since several years.Companies are celebrating their successes in OPEX initiatives, telling impressive stories e. g.o 80 % lead time reductions. Some companies even describe their own transormation, orwhich Toyota needed decades, as „already nished“.

However, a broader look into the industry taken by the research project „Pharma OPEX Bench-marking“1 at the University o St.Gallen may be disillusioning. Based on the model presentedby Friedli and Goetzried2 the project shows a dierent reality across pharmaceutical com-panies. By pointing out the advancements and setbacks o the industry rom 2004 to 2009,this part o the book draws a balance rom hal a decade “Operational Excellence in the

Pharmaceutical Industry”.In the ollowing paragraphs the changes during ve years (2004 until 2009) are described indetail and substantiated by numbers o the ongoing research project “Pharma OPEX Bench-marking”. A comparison o the 2004 and 2009 results is presented with the ocus on the oursub-systems: Total Productive Maintenance, Total Quality Management, Just-in-Time, and theEective Management System. Key perormance indicators (“metrics or tracking progressand comparing with other companies”) and enablers (“methods and tools leading to top per-ormance”) are analyzed and interpreted or each o the categories. To give a comprehensiveinterpretation o the industry’s development, the ollowing analysis uses the median scoressurveyed by the benchmarking or each sub-system3.

1 See http://www.opexbenchmarking.com

2 See Friedli and Goetzried, In Retrospect: A Summary o Operational Excellence in the Pharmaceutical Industry in2006, Figure 7 (p. 33).

3 See questionnaire o the OPEX Benchmarking in 2010, p. 337.

Did Pharmaceutical Companies Establish an Efcient Management o Fixed Assets?

A boost in Overall Equipment Eectiveness (OEE) combined with an increase o unscheduledmaintenance due to direct stoppages show the inconsistency in Total Productive Maintenance

V.1 Total Productive Maintenance

V Operational Excellence Benchmarking –

Quantiying the Advancements rom 2004 to 2009

8/3/2019 755101


Section B – Starting Point

95

(TPM) perormance. The slight increase in „Preventive Maintenance“ (enabler) linked witha signicant increase o unplanned maintenance (perormance), leads to the diculties indeploying the TPM strategy in the industry. Also, companies were able to maintain the levelo practice implementation but did not improve remarkably. In act, an in-depth analysis o

preventive maintenance showed that companies are setting the ocus on technical aspects(e. g. checklists and documentation) rather than the empowerment o shop-foor employees(machine operators). Another point worth mentioning is the management o new technolo-gies in the production environment. The category “Technology Assessment and Usage” didnot reveal any improvements, i. e. it is not yet in the ocus o most production managers. Onecould argue that the industry is in a state o stagnation concerning TPM.

TPM represents a manuacturing strategy or the eective usage o process technology. TPMis designed to eciently manage xed assets such as machines, equipment, and propertythroughout their lie cycle. It does not only ocus on the technical aspects such as the reliabil-ity o existing equipment and a careul selection o new technologies, but also the engage-ment o all employees in the production environment, rom management level to shop-foor

employees in maintenance-related activities. In OPEX programs, TPM is the basis or stablerunning machines and therewith orms the basis or urther in-depth improvements in e-ciency4.

Due to high costs or maintenance (9 203 EUR per employee in 2009; employees include allpeople working ull-time at the site, e. g. production, QA/QC, EH&S, IT, etc.5), one could as-sume that pharmaceutical companies had set a ocus on this topic within the last ve years.Maintenance costs, whether or internal employees or external specialists, represent a majorpart o the total costs within production sites. However, the analysis o practices implemen-tation (enabler side) and corresponding key perormance indicators (perormance side) illus-trated in Figure 1 draws a dierent scenario.

On the perormance side, an increase in OEE or packaging o 15 % rom 2004 to 2009 couldbe observed. However, an OEE o 51 % (median) in 2009 is not really outstanding compared toother process industries and their packaging processes. Various cross-industry studies show anOEE o 60 % or an average production site in the ood and beverages sector. Pharmaceuticalmanuacturing still needs to catch up with regard to higher utilization in scheduled time,prevention o downtimes and avoidance o quality losses.

In act, the availability o equipment and machines seems to be a problem or the industry asa result o direct stoppages and breakdowns. In 2004, the proportion o unplanned mainte-nance work as a percentage o the overall time spent or maintenance work amounts to 25 %.Five years later it has increased by 8 % to 33 % (median) or unplanned maintenance. It can beargued that most pharmaceutical companies struggle with the establishment o stable run-

ning manuacturing processes, which is caused by a low implementation o TPM enablers.According to the OPEX model, three major principles o TPM on the enabler side can be dis-tinguished: “Preventive Maintenance”, “Technology Assessment and Usage“, and „Housekeep-ing”. Companies were able to slightly increase their level o „Preventive Maintenance“ rom2004 (industry median o 71 %) to 2009 (75 %). Further, companies have installed ormalprograms on operational levels or maintaining their equipment and machines. Nonetheless,pharmaceutical companies still reveal shortcomings in TPM which they have not addressed

4 See also Friedli and Goetzried, In Retrospect: A Summary o Operational Excellence in the Pharmaceutical Indus-try in 2006 or a detailed description o the sub-system TPM (p. 18).

5 Median numbers rom the 2009 benchmarking.

8/3/2019 755101


Section B – Starting Point

96

during these years. Especially practices pointing to autonomous maintenance by empoweringshop-foor employees are not very common. Most maintenance tasks are still perormed bymaintenance specialists rather than by machine operators. In sum, maintenance systems inpharmaceutical companies are still reactive rather than oresighted, e. g. planning mainte-nance programs based on ailure analyses.

The question remains i technology or equipment can be a source or strategic positioning.Other industries reveal that this can be the case, but to reach this some specic practicesconcerning assessment and selection at least have to be in place. For pharmaceutical com-panies this is still untypical. The 2004 analysis revealed that the pharmaceutical industry isvery restrictive when it comes to the implementation o new production technologies. Thismight be caused by the act that every change in the production process, including the us-age o new technologies, needs to be approved by regulatory bodies. This category points tothe screening o the market or new production technologies and the assessment o techni-cal and nancial benet. More, it includes the eective use o new technologies. With 58 %in 2009 compared to 57 % in 2004, this category did not undergo any essential change, i. e.the industry is still lacking behind other industries with regard to the assessment and actualimplementation o new production technologies.

A high score o 80 % in 2004 could be re-observed in 2009 or the category “Housekeeping”.The vast majority o pharmaceutical companies have beholden their employees to keep theirplant “neat and clean” and provide tools such as housekeeping checklists.

2009 75 %

2004 71 % +6%

Total Productive Maintenance (TPM)Comparison of the Benchmarking Results from 2004 and 2009 (medians)

2004 2009

Enablers

Preventive Maintenance

2009 51 %

2004 36 % +42%

Performance

Overall Equipment Effectiveness (OEE)

2009 33 %

2004 25 %

+32%Unplanned Maintenance

2009 58 %

2004 57 % +2%

Technology Assessment and Usage

2009 80 %

2004 80 % 0%

Housekeeping

Figure 1: Total Productive Maintenance (TPM) – Results 2004 and 2009.

8/3/2019 755101


135

Colleen M. Grifth, Nick Rondoletto, and Fadel Hamed

In 1973, over sandwiches at a local deli, biochemist Herb Boyer and geneticist Stanley Cohendrated the seminal experiment that lead to genetic engineering. By 1976, recombinant DNA

was responsible or the birth o biotechnology and the ounding o Genentech, Inc. By 2001,Genentech had developed one o the most sophisticated and advanced biotechnology manu-acturing operations in the world, and by 2004, had launched our new products in 16 monthsand was granted FDA approval or its drugs Avastin (bevacizumab) and Tarceva (erlotinib).

In order to meet the anticipated demand or Genentech’s products, the ever-growing pipe-line, and a 30 % increase in the manuacturing workorce, the decision was made in late 2004to launch Operational Excellence (OPEX) within Product Operations (PROP) at Genentech.The program’s charter was to support growth within manuacturing by strategically creat-ing continuous improvement capability and setting the stage or the Genentech ProductionSystem (GPS), which would leverage OPEX as an engine or ensuring planned, predictableperormance.

III.1.1 The Three Phases of OPEX at GenentechThe OPEX program was to be rolled out in three phases; the “Foundational Phase” (2004), the“Stabilize Phase” (2007) and the “Transormational Phase” (2009). These three phases are il-lustrated in Figure 1.

In the Foundational Phase, the OPEX vision and strategy were developed. OPEX inrastruc-ture was targeted at leadership capability, project execution, OPEX methodology, measure-ment and communication. Process improvement initiatives and projects executed during theoundational phase were characterized by their ocus on building organizational capability,

increasing productivity, improving plant utilization, and maximizing plant capacity.

F. Homann-La Roche AG, Basel (Switzerland)

III.1 Genentech’s Journey to Operational Excellence(2004-2009)

III

The Best of Two Legacies: History, Present and

Vision of the Roche-Genentech OperationalExcellence Integration

8/3/2019 755101


Section C – Maps and Experiences

136

The Stabilize Phase o the OPEX program required a shit towards using the process improve-ment inrastructure to deliver planned, predictable perormance. It was during this phasethat the Class A journey, the GPS, and the Manage Operational Excellence (MOE) process weredeveloped and introduced to optimize operations and deliver signifcant business results.

Finally, in the Transormational Phase, OPEX was being used to enable PROP’s journey to

world-class perormance and the realization o its vision o being the most admired biotech-nology production operation, respected or world-class innovation, regulatory capabilities,people development and operational excellence. In early 2009, the Roche Group acquiredGenentech and, as a result, the Genentech Product Operations organization retired the PROPacronym and adopted the name Genentech Technical Operations (GT). During the transorma-tional phase o PROP (GT), OPEX continued to be instrumental in providing a ramework andnecessary capability or the successul execution and realization o transormational changeand successully delivering integration synergies.

III.1.2 The Foundational Phase

The OPEX methodology in PROP (GT) was launched using Lean Six Sigma as a core methodol-ogy to deliver business results. In addition to the classical Lean Six Sigma training and projectexecution, eective process improvement programs like Kaizen, 5S, Visual Factory, and TotalProductive Maintenance (TPM) were used to deliver signifcant business results. In addition toprocess improvement methodologies, PROP (GT) introduced change execution capability tosuccessully install and realize ormulated strategies.

As shown in Figure 2, the OPEX program in PROP (GT) began with Lean Six Sigma trainingto produce process improvement practitioners and uture leaders or the business. The train-ing was originally conducted by third party frms but later transitioned internally to deliverthe training. The internal training program developed and delivered a curriculum with ourequally important courses, each with a dierent purpose and objective:

OPEX or sponsors was an eight-hour course intended to teach project sponsors the char-acteristics o eective OPEX project sponsorship.

•

Figure 1: The three phases of OPEX at Genentech.

8/3/2019 755101


Section C – Maps and Experiences

137

OPEX or team leaders was a twenty two-day course designed to provide OPEX practitionersthe skills necessary to successully lead and execute the Lean Six Sigma methodology dur-ing a current project.

OPEX or team members was an eight-hour course designed to ensure that project team

members have a basic understanding o OPEX execution principles.OPEX or everyone was a our-hour course delivered on demand to the business with thepurpose o creating awareness or OPEX.

In just a ew years, the OPEX education curriculum delivered thousands o hours o targetedinstructions to thousands o Genentech employees across all unctions and sites. The OPEXeducation curriculum successully created OPEX capability and brand awareness and helpedpave the way or the introduction o additional OPEX programs like 5S, Visual Factory, Kaizenand TPM. The curriculum has since evolved to include on-line, sel-serve, short training mod-ules so that employees can also learn in a sel-paced environment.

III.1.3 The Stabilize PhaseThe stabilize phase addressed the next steps on the stairway to excellence by ocusing onplanned and predictable perormance. Class A, the GPS, and MOE process had been the keyconcepts o this phase.

Class A

As a critical frst step or achieving world-class perormance during the stabilize phase o theOPEX program rollout, the goal was established within the manuacturing sites to acquire

Oliver Wight’s Class A certifcation. To achieve and sustain Class A certifcation would showthat PROP was able to deliver planned, predictable perormance, proven through an objective,third-party benchmark that measured the sites’ journey towards world-class perormance.

•

•

•

Figure 2: Building OPEX capabilities through the Manage Operational Excellence (MOE pro-cess.

8/3/2019 755101


220

Juergen Werani1, Giusal Bellando-Randone2, and Matthias Goetzried3

1Schuh & Co. Complexity Management, St. Gallen (Switzerland)2Pzer Inc, New York (USA)3University o St. Gallen (Switzerland)

Summary

Almost all pharmaceutical companies work on small-scale to large-scale operational improve-ment projects. Over the past 10 years, Lean, along with Six Sigma, has ranked among the mostprominent principles and methodologies supporting Operational Excellence (OPEX) strategies.However, according to our experience, many organizations have ailed to achieve predictedand expected savings, or bring about sustainable success. One aspect is that training andcoaching on how to oster behavioral change has not been properly addressed.

This chapter deals with the subject o training and coaching to avoid these pitalls. At thesame time it outlines the launch o an OPEX program in a global pharmaceutical companywith numerous plants worldwide. It describes the ideal ramework with regard to the deploy-ment o the program, training and coaching, roles and responsibilities and o the dierentkey players at dierent levels in the organization. It also emphasizes the importance o orga-nizational learning.

(1) Building the Organization (see II.1 or a detailed discussion)

Simultaneous or pilot launch?

One issue that oten arises is the question as to whether the program should be piloted orlaunched simultaneously. A pilot launch would give room or learning rom the unpredictedand prepare or the roll-out in a real-lie environment. For a simultaneous launch, it is cru-cial that everything is in place at the time o the launch so as not to lose credibility. Whencompanies tackle the simultaneous implementation o a program, they usually achievebetter and more sustainable results. However, substantial upront investments have to bemade, and unpredicted actors need to be anticipated.

Starting the initiative and maintaining the momentum with good communication prac-tices

A better understanding o the starting point enables companies to determine what to ocuson at the beginning o the program, and when to implement its various elements. This callsor a company-wide project management team with strong leaders1 and good communi-

•

•

1 See Crossman, Wyeth Pharmaceuticals – Transorming Culture, Delivering Results – Exploring the OperationalExcellence Productivity Frontier, p. 120.

IIMaking Operational Excellence Work – Training

and Coaching Supporting Behavioral Change

8/3/2019 755101


Section D – Exploring the Landscape

221

cation means. Communicating the initiative and its achievements is not only importantin terms o steadily leading the organization in one direction, but also in terms o sharingknowledge. For knowledge sharing, a powerul IT solution is required.

(2) Training and Coaching (see II.2 or a detailed discussion)

Proper sequencing o training across the organization

Training must be sequenced properly to avoid conusion among sta. Also, training needsto be adjusted to the organization‘s operational and hierarchical layers and their dierentrequirements. This is an absolutely essential item on the leader’s agenda. Broadly themed,company-wide training programs designed to instill a culture o new ways o working andthinking are vital or the success o any OPEX initiative. It is easier to train employees in thetechnical aspects o an OPEX program than conveying leadership skills, and it can be doneaster than making behavioral changes work. Technical solutions are objective, straightor-ward and visible, but behavioral changes can only be seen over time. I companies rush toimplement a toolkit without ensuring that their employees (including managers) are pre-

pared to understand its use and benets, change will not happen. Simulation and learningactories are good means to support new toolkits.

The design o a standardized training program

It is advisable to develop a common and standardized training program or dierent levelso skill sets. Only standardized programs can ensure that a common language is „spoken“ inthe long run. However, the training itsel should be provided in the local language whenev-er possible. This is particularly important or multinationally operating companies. For mul-tinational companies, cultural diversity should also be considered. Thereore, it is extremelyimportant to design a one-ts-all training program, execute the program and maintainstandardization over the years to nally speak one worldwide corporate language.

Involvement o senior leadershipIt is important to set up an appropriate organization supporting organizational learning, sothat human energy is mobilized and people become willing and able to adopt new behavior.Senior leaders oten delegate responsibilities to technical experts who may be well trainedin technical skills. However, many o them lack leadership skills and are thereore not in aposition to act as role models. Operational tools and approaches, the so-called „hard tools“need to be combined with „sot tools“ such as interpersonal skills, coaching, and confictmanagement.

Balance between technical (hard) skills and leadership (sot) skills

Mastering sot skills means calling upon all employees to commit themselves to new wayso working and thinking. However, the technical skills required to embark on the new pathmust be mastered as well. Operations is the area that typically accounts or the largestnumber o employees with the greatest variety o skill levels.

(3) Sustaining Progress (see II.3 or a detailed discussion)

New perormance enhancing tools must replace existing perormance tools

The meaning o Lean and Six Sigma goes ar beyond simply applying the tools. These prin-ciples entail a dramatic change in our ways o working. The aim is to establish a culture inwhich employees see opportunities everywhere and continually improve their processes.This calls or sharing knowledge in a learning organization. Communities o Practice (CoPs)can help to share the knowledge and accelerate learning.

The development o internal subject matter experts, coaches and change agents

Project leadership is important or keeping on track. At the heart o any operational im-provement initiative, there are sucient resources, although internal resources typically

•

•

•

•

•

•

8/3/2019 755101


Section D – Exploring the Landscape

222

need to be built up rst with the help o external trainers. A well designed train-the-trainerprogram acilitates a quick start; however, experience should not be underestimated. Mas-ter Black Belts or Lean Masters should lead the program as subject matter experts andchange experts in the day-to-day business. They are responsible or spurring new ideas

and practices, and should act as champions or ostering the mindset o the continuousimprovement process. The advantage o such an approach is to relieve line managers andleaders rom the practical aspects o this task, while they still need to unction as sponsorsand process owners in the project execution. The responsibility or transormation initia-tives cannot be delegated or outsourced. External experts play a vital catalyst role as teach-ers, coaches and consultants, but they cannot serve as role models. They may convey thenew language, technical tools as well as interpersonal and leadership skills, but rarely stirthe desire to change behavior. Organizational capabilities need to be developed in order tobring about permanent change.

Leaders must become teachers

Leaders must become teachers because companies tend to rely too much on external spe-cialists. This may initially work when implementing, or instance, Lean. However, the re-sponsibility should be transerred to those who are in charge o operations as soon as pos-sible. For leaders this means adopting a new role and getting involved in coaching, trainingand supporting all activities which are part o the transormation including supervision,people management, technical and personal coaching. Managing perormance must be-come everybody‘s responsibility.

(4) Benchmark Reality (see II.4 or a detailed discussion)

A recent research study conducted by the Institute o Technology Management, University St.Gallen investigated the reality with respect to the above. A health assessment, conducted bya company which introduced CoPs in their global organization reveals the level o acceptance

o CoPs one year ater the launch. It is evident that innovative solutions o knowledge man-agement need time to become established.

•

The OPEX program was launched by the CEO and the president o global manuacturing at

the global leader’s annual meeting. This was the starting point or putting a global OPEXorganization in place. At its launch, the program was not designed as a cost cutting exercise,but was intended to increase quality by reducing process and product variation. AlthoughSix Sigma was introduced as the number one problem solving tool, the program was neitherlaunched as a Six Sigma, nor as a Lean program. Lean thinking became relevant much laterater the Six Sigma methodology was established. The organization comprised several leaders,each responsible or one specic geographical area o the enterprise, e. g. North and LatinAmerica, Asia and Arica and Europe. These leaders were organized as a group o peers withone inormal leader. The leaders reported to the leadership teams o their respective area o responsibility. An OPEX leader was nominated or each site who reported to the site leadershipteam o the respective site.

The role o the area OPEX leaders was to

implement plans to ensure a common understanding o OPEX undamentals;•

II.1 Building the Organization

8/3/2019 755101


324

Prabir K. Basu

The National Institute or Pharmaceutical Technology and Education (NIPTE)/Purdue University, West Laayette (USA)

There is now a recognition that i quality can be designed or built into the product then thatis to the benet o both the manuacturer and the regulator. The manuacturer receives quickapproval and operating fexibility within the approved “design space” and the regulator doesnot have to spend so much o its resources in reviewing and approving the documents andthey are instead able to spend their resources on more value-added activities.

To understand Quality by Design (QbD), one needs to rst understand the evolution o qualityin general. There are three generations o management tools undamental to the evolutiono quality activities that are widely accepted in the literature (Fan et al . 2008). “Quality byInspection”, as is widely practiced in the pharmaceutical industry today, is viewed as the rstgeneration quality management tool. Inspectors remove deective products rom produc-tion lines, or send them or repair or correction. In the era o mass production, however,said method is considered to be inecient and cannot solve the problem rom the root. Thesecond generation tools, such as the Statistical Process Control (SPC) and Six Sigma, are char-acterized by the downstream approach to quality problems. They assist in achieving greaterimprovements in quality by preventing deects and reducing variations. However, they are stillreactive in nature and address ater-the-act problem solving; the eorts o quality improve-ment are made at a purely manuacturing level. Some methods – such as the Failure ModesEect Analysis (FMEA) that proactively approaches the quality problems – are generated andemployed by project teams within the Six Sigma tool box to anticipate the ailures, impacts,causes, and priorities, thereby minimizing the ailures through actions in the early stages o manuacturing.

The third-generation tools, on the other hand, are aimed at more actively detecting and solv-ing quality problems rom the earliest stages o product development and product planning.Typical examples o third-generation tools are Quality Function Deployment (QFD) and QbD.

I.1 Three Generations of Quality Management Tools

I

The Future of Pharmaceutical Manufacturing:

Quality by Design and Operational ExcellenceReinforcing One Another

8/3/2019 755101


Section E – Redening the Destination

325

The concept o building customers’ requirements in the nal product is not a new idea, butthe third-generation tools o quality activities enable a realization o this concept by usinga structured and methodical manner. Product objectives are achieved with improved quality,lower cost, and greater customer satisaction.

There is a potential advantage o implementing QbD in the early stages o product develop-ment rather than waiting or the product to be approved and marketed. QbD principles alsointegrate extremely well with the principles o achieving operational excellence. Figure 1 isa schematic o relative advantages o implementing QbD early in research and developmentand its overall impact to Operational Excellence (OPEX).

Process Understanding

QbD

Traditional

Product Life Cycle

Discovery

Potential of integratedQbD & OE Approach

Better results based on closer

contacts between

manufacturing &

R&D (cross-functional)

Better results based onEstablished continouusimprovement culture

Product Launch F o c u s

Q b D

F o c u s

O E

p r o g r a

m s t o d a

y

F o c u s

Q d b

Figure 1: QbD and its potential contribution to OPEX (OE = Operational Excellence).

Pharmaceutical companies are pushing ahead to evolve in quality (Figure 2). The FDA andindustry agree on the so-called “desired state” or pharmaceutical manuacturing. The deni-tion o “desired state” in pharmaceutical manuacturing is (Nally and Karaim 2007):

1. Product quality and perormance achieved and assured by design o eective and e-cient manuacturing processes.

2. Product specications based on mechanistic understanding o how ormulation and pro-cess actors impact product perormance.

3. An ability to eect continuous improvement and continuous “real time” assurance o quality.

It is suggested that one can get to the desired state by using QbD. As discussed earlier, QbD

is dierent rom traditional quality activities which ocus on improving existing productsand processes using statistical process control. QbD reers more to design o new products orredesign o existing products as i they were being looked at anew. QbD as dened by Hus-

I.2 Quality by Design

8/3/2019 755101


Section E – Redening the Destination

326

sain (2005) as “A systematic process o dening optimal design specications o a product,its manuacturing process and its quality control and assurance methods.” However, this canonly be achieved with the ollowing:

1. A high degree o process understanding.

2. High condence o low risk o releasing a poor quality product, and

3. Maintenance o high eciency through continuous learning and improvement.

QbD in pharmaceutical product development and manuacturing may be dened as design-ing and developing ormulations and manuacturing processes to ensure predened productquality (Yu 2006). It consists o our steps:

1. Dene a Quality Target Product Prole (QTPP) or dene product quality attributes.

2. Design and develop the product and manuacturing processes necessary to meet theQTPP.

3. Identiy and control critical raw material attributes, process parameters, and sources o variability.

4. Monitor and adapt these processes to produce consistent quality over time.

Conventional quality tools such as QFD can provide a means to determine Critical-to-Qual-ity (CtQ) criteria, which customers are most able to support. QFD tools such as the anitydiagram, shbone diagram, and the “house o quality” can be used to dene and prioritizethese CtQ’s.

The ultimate goal o QbD is to develop a robust process. Robust process is the ultimate “desiredstate”. The most appropriate denition o robustness, as described by quality guru Dr. Taguchi,

Figure 2: Pharma companies are pushing ahead to evolve in quality (QMT = Quality Manage-ment Tool).

755101

Documents