Applying Lean Six Sigma Methodology to a Pharmaceutical Manufacturing Facility: a Case Study

processes

Article Applying Lean Six Sigma Methodology to a Pharmaceutical Manufacturing Facility: A Case Study

Brian Byrne 1, Olivia McDermott 2,* and John Noonan 3

1 School of Engineering, University of Limerick, V94 T9PX Limerick, Ireland; [email protected] 2 College of Science and Engineering, National University of Ireland, H91 TK33 Galway, Ireland 3 Department of Mathematics and Statistics, University of Limerick, V94 T9PX Limerick, Ireland; [email protected] * Correspondence: [email protected]

Abstract: This research examines a case study on the implementation of an effective approach to advanced Lean Six Sigma problem-solving within a pharmaceutical manufacturing site which manufactures acetaminophen (paracetamol containing pain relief) tablets. Though this study was completed in a single manufacturing company, the implementation of this study delivers important application and results that can be deployed in other such manufacturing companies. The manufacturing site faced backlogs in customer orders due to increased demand. Increased demand is due to brand popularity and recognition, product efficacy and a COVID 19 pandemic that intensified the demand for pain relief tablets in an already very busy site. With increased demand, to ensure timely deliveries, customer satisfaction and minimize delays, sources of site productivity losses and wastes needed to be analyzed and reduced or eliminated. Manufacturing Packaging line downtime was identified as one area of concern. The goal of the research was to introduce a problem-solving technique to reduce downtime within a manufacturing site without affecting the production required to fulfil customer demand while increasing product quality. The research utilized an integrated LSS Citation: Byrne, B.; McDermott, O.; methodology which identifies, stratifies and effectively eliminates non-value adding (waste) activi- Noonan, J. Applying Lean Six Sigma ties, by following a 7-step customized problem-solving methodology which resulted in complete Methodology to a Pharmaceutical elimination of the issue under investigation and savings of just under half a million dollars. The Manufacturing Facility: A Case Study. learnings are being deployed and leveraged worldwide across the pharmaceutical organizations Processes 2021, 9, 550. https:// parent site and sister sites. The presented results demonstrated that Lean Six Sigma methodology doi.org/10.3390/pr9030550 and tools are effective for accurate root causing of problems and enablers of implementation of continuous improvement. Academic Editor: Lara Carvalho

Received: 3 March 2021 Keywords: Lean; Six Sigma; Lean Six Sigma; continuous improvement; pharmaceutical; prob- Accepted: 18 March 2021 lem solving Published: 20 March 2021

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in 1. Introduction published maps and institutional affil- The world is experiencing unprecedented times since the beginning of 2020. COVID iations. 19 has halted many manufacturing operations. The manufacturing facility where this case study was conducted continued to manufacture during the pandemic given its classification as an essential service and saw an unparalleled increase in volume demands. Paracetamol is used to treat mild cases of COVID 19 as it is effective in treating high temperatures. To Copyright: © 2021 by the authors. benefit from the increase in demand and avoid potential lost sales, it was critical for the Licensee MDPI, Basel, Switzerland. business to ensure a smooth, continuous supply of product to the customer. The researchers This article is an open access article needed to deliver results in an environment where there was an unprecedented spike in distributed under the terms and demand without any risk of disruption to supply. Lean Six Sigma methods were applied in conditions of the Creative Commons the manufacturing facility to root cause downtime issues and improve productivity and Attribution (CC BY) license (https:// met customer demand. creativecommons.org/licenses/by/ 4.0/).

Processes 2021, 9, 550. https://doi.org/10.3390/pr9030550 https://www.mdpi.com/journal/processes Processes 2021, 9, 550 2 of 24

Lean was derived from Taiichi Ohno’s post-war Japanese Production system, and its benefits are advocated by Womack and Jones in their 1990 and 1996 books “The Machine that Changed the World” and “Lean Thinking” [1,2]. The primary goal of Lean Thinking is to reduce or eliminate waste and waste is anything which adds no value in the eyes of customers. Lean thinking as “a way to do more with less and less human effort, less equipment, less time, and less space while coming closer to providing customers with what they want” [1]. Adding value, creating flow, and establishing pull in pursuit of continuous perfection or improvement aligns a philosophy of continuous improvement and putting the customer first [3,4]. Lean focusses on reducing or eliminating non-value-added waste including the seven wastes of Transport, Inventory, Motion, Waiting, Over-production, Over-processing, and Defects is particularly vital in helping add value and improving flow in an operation [4,5]. Lean is known for its five main principles that enhance production namely, Iden- tify Value; Value team Mapping; Create flow; establish pull and seek perfection. Steps within a process are then focused on to identify what is value adding for the customers perspective [4]. The Value Stream Map (VSM) is the products entire life cycle from raw materials to the customers use [6]. Value Steam mapping is utilized to eliminate waste and is important in designing processes for better flow [7,8]. To eliminate waste, there must be an accurate and complete understanding of the value stream [9,10]. Standard work is also a powerful Lean tool in the identifying waste and greatly assists in its removal [11]. Creating flow is another important principle of Lean and when the production line stops everyone is forced to solve the problem of flow and understanding flow is essential to the elimination of waste [12]. The Lean manufacturing principle of flow is about creating a value stream with no interruption, delays or bottle necks [2,6]. A pull system makes it easier to deliver products as needed, as in ‘just in time’ manufacturing or a customer demand driven system [13]. Enhancing product flow, the lean principle of pull makes sure that nothing is made in advance if there is not a customer order or requirement for the product [14]. Seeking perfection in Lean aims to ensure the perfect process happens step by step as continuous improvements and implementing preventative actions on root causes of quality problems and production waste [15]. Lean methods can not only reduce waste but reduce operational losses, namely, equipment failures, setup and changeovers, idling and minor stoppages, reduced speed operation, scrap and rework and startup losses [10]. Lean is a strategic approach to waste elimination and continuous improvement [6,16]. Motorola Inc. coined the term Six Sigma in the mid-1980s as a metric for measuring defects and improving quality. Six Sigma has evolved into a robust continuous and business process improvement initiative over the past thirty years [17,18]. The basic idea behind the Six Sigma philosophy is continuously to reduce product and process variation, for example, small variations in environmental conditions, operator performance, raw materials and machinery can cause cumulative quality problems [19]. Six Sigma methodology utilizes a structured DMAIC (Define-Measure-Analyze-Improve- Control) approach to tackle problems with unknown root causes and unknown solutions [20,21]. The DMAIC structure is aligned with the classic Plan–Do–Check–Act (PDCA) cycle, but Six Sigma specifies the quality management tools and techniques to use within each step [22]. The use of specific, challenging goals in Six Sigma projects can increase the size of improvements, reduce process variability and increase employees’ involvement in improvement efforts and their commitment to quality [23]. Six Sigma integrates business- level performance, process measures, and project metrics that managers can utilize to manage the organization quantitatively and achieve strategic aims and objectives [24]. When projects are aligned with a company’s scorecard or key performance indicators valuable results are achieved [25]. Six Sigma, as a statistical and non-statistical toolkit integrated within the DMAIC method gives a framework for process improvement [26]. Six Sigma uses a tiered set of trained improvement specialists, based on a martial arts “belt” system e.g., master black belts, black belts, green belts, yellow belts and a manager Processes 2021, 9, 550 3 of 24

of champion belt level [27,28]. Each belt level represents a level of experience or training in Six Sigma tailored for that belt level and the knowledge and skillset associated with that level [22]. Six Sigma, when used alone or coupled with another methodology such as Lean, can improve profits and increase customer satisfaction [29,30]. George (2002) successfully integrated Lean and Six Sigma for business process improvement and claimed that the integrated approach is superior to using exploiting Lean or Six Sigma on its own. His view was that Lean is not well suited to resolving complex problems that require intensive data analysis and advanced statistical tools and techniques [31]. Lean and Six-Sigma aim at improving the productivity and efficiency of the business by removing waste and reducing variation, respectively [30,32]. The integration of Lean and Six Sigma is important as lean focuses on improving the flow of information and materials between the steps in the process steps and Six Sigma works strives to improve the value-adding transformations which occur within the process steps. Waste can also include rework or scrap, which are often the result of excess variability, so there is an obvious connection between Six Sigma and Lean [33]. The most appropriate blend of Lean and Six Sigma tools useful on applicable to any one given problem must therefore depends on the nature of the specific problem being solved [34]. The tools employed by lean and in Six Sigma were not all invented in these methodologies, but they were used in a structured approach to form each methodology. Thus, both can be thought of as toolboxes, where certain tools might be more suitable than others depending on the nature of problem or opportunity faced [33]. Successful implementation of Lean Six-Sigma is carried out using several process improvement tools (fishbone, flowcharting, check sheets, pareto charts, control charts, value stream mapping, quick changeover, waste analysis and scatter diagrams) and other statistical tools [20,35,36]. There are several critical success factors for the deployment and implementation of LSS, such as leadership alignment, proper selection of people and projects, training, motivation, accountability, information technology, marketing and supply chain management [37]. Lean thinking can form the basis for careful screening of the value stream current state to find the waste and eliminate it. Six Sigma based statistical improvement methodologies and problem-solving methods and tools can be deployed to eliminate the deviation and drive the business towards the future state and provide a competitive advantage to the business [18]. This research aims to apply Lean Six Sigma problem solving methodology and principles in a pharmaceutical manufacturing environment setting. The study demonstrates that an organization can improve productivity, reduce backlog, downtime, eliminate waste and ultimately improve customer delivery timelines through structured application of Lean Six Sigma problem solving methodology combined with selectively utilized resources.

2. Materials and Methods This project utilizes a customized LSS framework with a Six Sigma-based 7-step problem solving methodology (with DMAIC integrated) and Lean Six Sigma tools and techniques. This section (Section2) describes the first five steps of the pharmaceutical manufacturers seven-step problem solving structure as outlined in Figure1 and the Results, benefit realization and sharing are presented as part of Section3. Processes 2021, 9, 550 4 of 24 Processes 2021, 9, x FOR PEER REVIEW 4 of 25

FigureFigure 1.1. AA seven-stepseven-step in-company problem solving framework:framework: based on and integrated with the Six Sigma D,M,A,I, C methodology and utilizing Lean and Six Sigma tools. Six Sigma D,M,A,I, C methodology and utilizing Lean and Six Sigma tools.

2.1.2.1. LossLoss IdentificationIdentification StepStep oneone inin thethe problem-solvingproblem-solving frameworkframework identifiesidentifies the toptop losseslosses within an oper- ationsations productionproduction line.line. AA valuevalue streamstream mapmap waswas constructedconstructed toto revealreveal barriersbarriers blockingblocking continuouscontinuous flowsflows ofof materialsmaterials andand recognizerecognize availableavailable opportunitiesopportunities forfor preventingpreventing lossloss reduction.reduction. AA valuevalue streamstream mapmap (Figure(Figure2 2)) was was drawn drawn up up and and on on analysis analysis of of waste waste in in the the processprocess andand flowflow itit waswas demonstrateddemonstrated thatthat thethe packagingpackaging departmentdepartment waswas a a bottleneck. bottleneck. AA bottleneckbottleneck hashas resultedresulted inin 11.611.6 daysdays ofof ‘work‘work inin progress’progress’ (WIP)(WIP) accruing.accruing. This re- searchsearch willwill discussdiscuss identifyingidentifying thethe rootroot causescauses forfor waste within the packaging department. ItIt isis importantimportant toto notenote thatthat allall wasteswastes identifiedidentified werewere examinedexamined andand sub-projectssub-projects werewere deployeddeployed fromfrom thatthat analysis,analysis, thatthat willwill notnot bebe discusseddiscussed inin thisthis research.research. TheThe demonstrateddemonstrated averageaverage weeklyweekly run-rate run-rate in in the the packaging packaging department department was was 5.4 million5.4 million blisters blisters (tablets). (tablets). The customerThe customer requirement requirement was 6.5was million 6.5 million blisters. bliste Therefore,rs. Therefore, the run the rate run in rate the in “current” the “current” state wasstate 1.1 was million 1.1 million blisters blisters below below the customer the custom demand.er demand. Data Data were were then then reviewed reviewed from from the Packagingthe Packaging department department in relation in relation to Overall to Overall equipment equipment effectiveness effectiveness (OEE) (OEE) for produc-for pro- tionduction line line downtime downtime and and production production time time losses losses over over the the previous previous few few months months (Figure (Figure3 ). OEE3). OEE provides provides a quantitative a quantitative metric metric based base ond the on element’sthe element’s availability, availability, performance performance and qualityand quality for measuring for measuring the performancethe performance effectiveness effectiveness of individual of individual equipment equipment or entireor en- processestire processes [38]. [38]. Short Short stops stops are are simple simple problems, problems, including including trapping trapping of of a a piece piece in inupper upper transportationtransportation channel channel or or stopping stopping a defectivea defective product product by aby sensor, a sensor, cause cause them them [10]. A[10]. short A stopshort is stop effectively is effectively a breakdown a breakdown or tablet or feedtablet issue feed that issue can that be resolvedcan be resolved within 10within min or10 less.min Theor less. reason The it reason is classified it is classified as a chronic as a stop chronic is due stop to the is due high to frequency the high infrequency re-occurrence in re- andoccurrence contribution and contribution to downtime to on downtime the production on the line.production The stop line. is immediately The stop is immediately attended to, resolvedattended and to, resolved the packaging and the line packaging restarted line by the restarted operator, by butthe theoperator, root-cause but the of the root-cause issue is notof the understood. issue is not These understood. issues add These up due issues to theiradd highup due recurrences, to their high slow recurrences, production slow and contributeproduction to and a backlog contribute in the to packaginga backlog in area. the packaging area. The ‘short stop’ category will be the area of focus for this project. Various other The ‘short stop’ category will be the area of focus for this project. Various other Lean Lean tools were deployed to remove other major downtime losses, for example “Quick tools were deployed to remove other major downtime losses, for example “Quick Change- Changeover” or “Single Minute Exchange of Dies” (SMED) and Total Preventative Mainte- over” or “Single Minute Exchange of Dies” (SMED) and Total Preventative Maintenance nance (TPM) roll-out for breakdowns and deployment of “floating” staff to cover (TPM) roll-out for breakdowns and deployment of “floating” staff to cover labor unavail- labor unavailable. able.

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Figure 2.2. A Current Value SteamSteam MapMap withwith thethe packagingpackaging areaarea sectionsection highlightedhighlighted showed that there was aa backlogbacklog ofof inventoryinventory oror productproduct waitingwaiting toto gogo intointo packagingpackaging ofof 11.611.6 daysdays ofof workwork inin progressprogress (WIP).(WIP).

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Figure 3. Packaging bar graphs of downtime issues/losses within the Packaging department with % OEE on the x-axis compared against Time (in weeks) on the y-axis. Breakdowns, Short Stops, Changeovers, Labor unavailable, Material Figure 3. Packaging bar graphs of downtime issues/losses within the Packaging department with % OEE on the x-axis Unavailable, Utilities/Overruns, Speed loss, Intrusive stops were all identified as sources of losses in downtime as compared against Time (in weeks) on the y-axis. Breakdowns, Short Stops, Changeovers, Labor unavailable, Material demonstrated in the bar graph. Unavailable, Utilities/Overruns, Speed loss, Intrusive stops were all identified as sources of losses in downtime as demonstrated in the bar graph. 2.2. Loss Stratification 2.2. LossThe Stratification purpose of this step (Loss Stratification) is to narrow the scope of the problem, as tryingThe purpose to solve of a ‘tabletthis step feed’ (Loss issue Stratificatio across alln) nine is to lines narrow is far the too scope wide of inthe scope. problem, The asobjective trying wasto solve to see a where‘tablet thefeed’ problem issue across is occurring all nine the lines most is and far dotoo a wide deep in dive scope. into thatThe objectivearea. As per was Figure to see4 ,where tablet the feed problem equates is to occurring 20,174 min the downtime most and across do a deep all nine dive packaging into that area.lines As between per Figure weeks 4, 2tablet to 18. feed This equates is, on average,to 20,174 20min h downtimedowntime acrossacross all linesnine packaging weekly. lines Frombetween further weeks analysis, 2 to 18. it This was is, ascertained on average, that 20 theh downtime tablet feed across issue all was lines not weekly. observed on three of the packaging lines. These lines had different equipment and production setups. The scope now shifted towards focusing on the six blister lines. Figure5 demonstrates the short stops related to tablet feed over six packaging blister lines and shows the spread of downtime across these lines. Based on the data collected in Figure5, it could be observed that tablet feed issues recorded were very high across all six blister lines. This informed the researchers of two key pieces of information: (1) There is a chronic problem across all lines, making it important to move fast, as product is being held up across all lines within the Packaging department for this issue (2) Lessons learned from correctly root causing the issue on one line will most probably resolve the issues on all lines where the corrective action is deployed.

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Figure 4. Breakdown of total downtime related to packaging Short Stops across nine packaging lines over a 16-week period.

the short stops related to tablet feed over six packaging blister lines and shows the spread Figure 4. BreakdownFigureof downtime 4. Breakdown of total across downtime of total these downtime related lines. to packagingrelated to Shortpackaging Stops Short across Stops nine across packaging nine lines packaging over a 16-week period. lines over a 16-week period.

From further analysis, it was ascertained that the tablet feed issue was not observed on three of the packaging lines. These lines had different equipment and production setups. The scope now shifted towards focusing on the six blister lines. Figure 5 demonstrates the short stops related to tablet feed over six packaging blister lines and shows the spread of downtime across these lines.

Figure 5. NumberFigure of 5. incidences Number of of incidences blister lines of short blister stops lines as short a result stops of tabletas a result feed of issues tablet measured feed issues across meas- six production lines (with quantityured across of short six production stop issues lines on the(with y-axis quantity and theof short line numberstop issues (line on type)the y-axis on the and x-axis) the line measured num- over a ber (line type) on the x-axis) measured over a 16-week period. 16-week period.

3. Project Selection Projects are prioritized in terms of beneﬁt (or impact) and the resources necessitated.

Figure 5. Number Identifyingof incidences appropriateof blister lines criteria short stops for as project a result selection of tablet feed is critical issues meas- to an effective Lean Six ured across six productionSigma project lines (with selection quantity process. of short The stop urgency issues on of th thee y-axis project and topic the line focusing num- on a small-scale ber (line type) on theproject x-axis) and me theasured chance over of a increasing16-week period. probability of success is important in Six Sigma project

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Based on the data collected in Figure 5, it could be observed that tablet feed issues recorded were very high across all six blister lines. This informed the researchers of two key pieces of information: (1) There is a chronic problem across all lines, making it important to move fast, as product is being held up across all lines within the Packaging department for this issue (2) Lessons learned from correctly root causing the issue on one line will most probably resolve the issues on all lines where the corrective action is deployed.

3. Project Selection Projects are prioritized in terms of benefit (or impact) and the resources necessitated. Identifying appropriate criteria for project selection is critical to an effective Lean Six Sigma project selection process. The urgency of the project topic focusing on a small-scale project and the chance of increasing probability of success is important in Six Sigma project selection [39]. Selection utilizing a matrix such as in Figure 6 is geared towards prioritizing ease of implementation against impact. Upon review of the problem under consideration in this research, this project aligns in the upper quadrants of high impact within Processes 2021, 9, 550 8 of 24 the categories of low effort and high effort. As a dedicated team of SMEs was required, some aspects had high effort tasks, such as understanding the full engineering and automation intricacies of a packaging line, but other aspects were low effort. Had it been a selection“Low effort”, [39]. it Selection would have utilizing been a fixed matrix previously. such as in Figure6 is geared towards prioritizing ease ofThe implementation problem statement against was impact. defined Upon and review measured of the in problem more detail. under consideration in this• research,Within the this packaging project aligns area in line the upperbeing quadrantsreviewed, of tablet high impactfeed issues within are the the categories highest of lowcause effort of and downtime high effort. within As the a dedicated short stop team category. of SMEs was required, some aspects had high• The effort impact tasks, is such 335 ash of understanding downtime over the a full 4-month engineering period and at an automation average 20 intricacies h per week of a packagingwith an line,upward but trend other aspectsobserved were in downtime low effort. for Had tablet it been feed aof “Low which effort”, one fifth it would (72 h) haveis been being ﬁxed contributed previously. by packaging line C80/2.

Figure 6. Project Selection Matrix with Impact on the y-axis and Effort on the x-axis. Tablet feed Figure 6. Project Selection Matrix with Impact on the y-axis and Effort on the x-axis. Tablet feed issues werewere deemeddeemed toto bebe aa highhigh impactimpact project project with with a a mix mix of of low low and and high high effort effort resources resources required. required. The problem statement was defined and measured in more detail. •3.1. TeamWithin Creation the packaging area line being reviewed, tablet feed issues are the highest cause ofTo downtimedefine and within assemble the shortthe team stop required category. to solve the problem, selection was based •on individuals’The impact knowledge, is 335 h of downtime skills and overtheir a ability 4-month to solve period the at anproblem. average The 20 typical h per week size of a withteam anfor upward a ‘Focused trend Improvement’ observed in downtime is 3 to 7 people. for tablet The feed team of which for this one project fifth (72 was h) agreedis beingat the contributed site leadership by packaging level and lineall team C80/2. members were informed prior to commencement. A weekly governance was established to ensure regular updates on actions 3.1. Team Creation and communicate progress to cross-functional members next steps. Engineering, process To define and assemble the team required to solve the problem, selection was based on individuals’ knowledge, skills and their ability to solve the problem. The typical size of a team for a ‘Focused Improvement’ is 3 to 7 people. The team for this project was agreed at

the site leadership level and all team members were informed prior to commencement. A weekly governance was established to ensure regular updates on actions and communicate progress to cross-functional members next steps. Engineering, process technicians and operators were included to provide a high level of understanding on how the production line equipment should work. Technical analysis will provide the team with an expert understanding on how the tablet performs throughout the tablet transportation system, and if there are issues relating to the product rather than to the equipment.

3.2. Problem Solving This section will detail the speciﬁcs of the manufacturing site’s problem-solving template. Step ﬁve ‘Problem Solving’ of the 7-step cycle utilized a problem-solving tool called the ‘6-step problem-solve’ or problem-solving template. This template is similar in structure to the DMAIC or A3 (utilizes an A3 size sheet/template) problem solving as shown in Figure7. Processes 2021, 9, x FOR PEER REVIEW 9 of 25

technicians and operators were included to provide a high level of understanding on how the production line equipment should work. Technical analysis will provide the team with an expert understanding on how the tablet performs throughout the tablet transportation system, and if there are issues relating to the product rather than to the equipment.

3.2. Problem Solving This section will detail the specifics of the manufacturing site’s problem-solving template. Step five ‘Problem Solving’ of the 7-step cycle utilized a problem-solving tool called the ‘6-step problem-solve’ or problem-solving template. This template is similar in struc- Processes 2021, 9, 550ture to the DMAIC or A3 (utilizes an A3 size sheet/template) problem solving as shown 9 of 24 in Figure 7.

Figure 7. Six-Step Problem Solving Template based on a mix of the Six Sigma DMAIC methodology and the A3 structured. Figure 7. Six-Step Problem Solving Template based on a mix of the Six Sigma DMAIC methodology and the A3 structured.3.3. Problem-Solving Approach The next phase of the problem solve was to develop the 5Ws and 1H: Who, What, 3.3. Problem-Solving Approach When, Where, Which and How. The simple question ‘Who found the problem’ can often Processes 2021, 9, x FOR PEER REVIEWThe next phaselead to of revealing the problem interesting solve detailswas to relatingdevelop to the problem-solving. 5Ws and 1H: Who, Figure What,8 demonstrates10 of 25 the

When, Where, breakdownWhich and How. of downtime The simple experienced question for ‘Who tablet found feed the issues problem’ in minutes can often by shift. lead to revealing interesting details relating to problem-solving. Figure 8 demonstrates the breakdown of downtime experienced for tablet feed issues in minutes by shift. Shift C has almost double the amount of downtime than Shift A and Shift B. How- ever, all shifts experience downtime relating to tab feed issues. On closer examination, it was established that shift C has more inexperienced operators and their reaction time to resolving the issue was not as quick as the other shifts.

Figure 8. StoppageFigure Time 8. BreakdownStoppage Time by Shift-comparisonBreakdown by Shift-comparison of the time lost of (in the seconds) time lost due (in to seconds) stoppages due per to shiftstop- demon- strated that Shiftpages A (233 per s) shift and shiftdemonstrated B (203 s) arethat practically Shift A (233 equal s) and but shift shift B C (203 (430 s) s) are is doublepractically the timeequal taken but shift for the C other (430 s) is double the time taken for the other two shifts combined. two shifts combined. Further analysis established that shift C had 71% of downtime relating to ‘tablet feed’ issues during night shifts. This was root caused to a lack of trainers available on that shift. Standard Work lays out the work sequence to develop standard operational proce- dures and it organizes the movements of the production operator [40]. A standard work instruction was developed to help operators understand the sequence of steps in resolving such issues within 60 s. Previous demonstrated standards took 120 s per stop. Table 1 on Standard work below illustrates this procedure.

Table 1. Standard work practice for line stops describing the exact work steps required to resolve a tablet feed line stop within 60 s. Until a root cause and corrective action for line feed stops are identified, standard work for clearing stops to minimize production disruption is required.

Process Step Work Performed Average Time Taken (s) 1 Operator removes broken half tablet from feed chute line using a spatula tool 20 2 Operator gets tablets from feed bowl to use to fill empty tablet pockets 10 3 Operator refills empty tablet pockets manually 20 4 Operator resets and restarts production line 10

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Shift C has almost double the amount of downtime than Shift A and Shift B. However, all shifts experience downtime relating to tab feed issues. On closer examination, it was established that shift C has more inexperienced operators and their reaction time to resolving the issue was not as quick as the other shifts. Further analysis established that shift C had 71% of downtime relating to ‘tablet feed’ issues during night shifts. This was root caused to a lack of trainers available on that shift. Standard Work lays out the work sequence to develop standard operational proce- dures and it organizes the movements of the production operator [40]. A standard work instruction was developed to help operators understand the sequence of steps in resolving such issues within 60 s. Previous demonstrated standards took 120 s per stop. Table1 on Standard work below illustrates this procedure.

Table 1. Standard work practice for line stops describing the exact work steps required to resolve a tablet feed line stop within 60 s. Until a root cause and corrective action for line feed stops are identiﬁed, standard work for clearing stops to minimize production disruption is required.

Process Step Work Performed Average Time Taken (s) Operator removes broken half 1 tablet from feed chute line 20 using a spatula tool Operator gets tablets from 2 feed bowl to use to ﬁll empty 10 tablet pockets Operator reﬁlls empty tablet 3 20 pockets manually Operator resets and restarts 4 10 production line

‘Tablet feed issues’ are the largest issues in scope. Getting an understanding of ‘What’ is happening is vital to gain clarity of the problem. A Gemba Walk was performed of the packaging area. Gemba is a technique used to observe and understand how work is being performed and is taken from the Japanese word “gembutsu” meaning “real thing” or “real place [41]. Going to the Gemba (and seeing what is happening and talking to the people working on the packaging line helped deepen the team’s understanding of the defect type. Figure9 was developed based on operator observations, i.e., the four types of defect that cause tablet feed issues were: broken half tablets, coating defect (ﬂaking on the tablet), split (horizontal) tablets, and thick tablets. Each time an operator observed a line stop, it was agreed to categorize each stoppage as per Figure9. This visual brought great clarity to the team in order that they could differentiate the different types of defect and granularity around the number of stops. This check sheet exercise was conducted on each shift whilst running product 10C821 on the C80/2 packaging line. Broken half tablets were observed and recorded as the highest cause of stoppages. The team observed what was transpiring: tablets in the feed-bowl system fall into one of twelve feed lanes and due to gravity fall down the tablet feed chute and into a PVC pocket and are sent off to be sealed and packaged into a ﬁnished box identifying the product. However, if a half tablet gets into the feed lane, it will turn 90 degrees and face lengthways causing a blockage in the feed chute. Figures 10 and 11 demonstrate a visual on what is happening in the feed system. With the feed chute blocked, no further tablets within that lane can continue along to the PVC pocket and then get packaged. When the vision system camera detects four consecutive empty pockets it stops the packaging line. The operator then re-starts the line as per the standard work (procedure) in Table1 on Standard Work. Most downtime was observed when loading or running product type 10C821 as per Figure 12. Processes 2021, 9, x FOR PEER REVIEW 11 of 25 Processes 2021, 9, 550 11 of 24

The research team wanted to understand when tablets break. The packaging department is the last process in the manufacturing process and an inspection was carried out before packaging to ensure product was conforming to speciﬁcation before going into packaging and was not broken. The team conducted a physical 100% inspection on four of the 80 kg drums to ensure the packaging operation received defect-free product in order to properly conduct the trial. Upon inspection, 751 defects (half tablets) were inspected out of the process prior to reaching the packaging department. The team deduced that these defects were created from the Processes 2021, 9, x FOR PEER REVIEW coating department or during transportation to warehouse, this can be11 said of 25 with conﬁdence

as the inside of the tablet is uncoated therefore, ruling out the compression department.

Figure 9. An example of a check sheet exercise run on one shift to breakdown occurrences of defect types. Every time an operator ha a broken tablet, coating defect, split table or thick tablet, they recorded the issue with a “tick”. Visually, it can be seen that most (or all) of the “checks” or “ticks” are under the broken tablet (half tablet) category.

This visual brought great clarity to the team in order that they could differentiate the different types of defect and granularity around the number of stops. This check sheet exercise was conducted on each shift whilst running product 10C821 on the C80/2 packaging line. Broken half tablets were observed and recorded as the highest cause of stoppages. The team observed what was transpiring: tablets in the feed-bowl system fall into one of twelve feed lanes and due to gravity fall down the tablet feed chute and into a PVC Figure 9. An examplepocket of aand check are sheet sent exercise off to be run sealed on one and shift packaged to breakdown into a occurrences finished box of de-identifying the prod- Figure 9. An example of a check sheet exercise run on one shift to breakdown occurrences of defect types. Every time an fect types. Every timeuct. However,an operator if ha a halfa broken tablet tabl getset, coatinginto the defect, feed lane,split table it will or turn thick 90 tablet, degrees they and face length- operator ha a broken tablet, coating defect, split table or thick tablet, they recorded the issue with a “tick”. Visually, it can be recorded the issueways with causinga “tick”. aVisually, blockage it can in the be seenfeed that chute. most Figures (or all) 10of theand “checks” 11 demonstrate or “ticks” a visual on what seen that mostare (orunder all) the of the broken “checks”is happening tablet or (half “ticks” in tablet) the are feed category. under system. the broken tablet (half tablet) category.

Average stop time 2 min

Figure 10. Tablet feed chute blockage (lateral view).

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Figure 11. Tablet feed chute blockage (Cross-sectional view).

With the feed chute blocked, no further tablets within that lane can continue along to the PVC pocket and then get packaged. When the vision system camera detects four consecutive empty pockets it stops the packaging line. The operator then re-starts the line as per the standard work (procedure) in Table 1 on Standard Work.

Most downtime was observed when loading or running product type 10C821 as per Figure 11. Tablet feed chute blockage (Cross-sectional view). FigureFigure 11. 12. Tablet feed chute blockage (Cross-sectional view).

Figure 12. Downtime by Tablet Type demonstrated that product type 10C821 had the highest Figure 12. Downtime by Tablet Type demonstrated that product type 10C821 had the highest downtime. downtime.

IfThe the research defect was team created wanted in the to compressionunderstand when process, tablets the half break. tablet The would packaging have coating depart- solutionment is onthe it,last as process the compression in the manufacturin departmentg process is the preceding and an inspection (upstream) was department carried out before packaging to ensure product was conforming to specification before going into from coating. This was not the case from the team’s observations. As shown in Figure 13, thepackaging trial proved and thatwas thenot tablet broken. breaks shown were in the packaging line and demonstrated Figure 12. Downtime by Tablet Type demonstrated that product type 10C821 had the highest whenThe specifically, team conducted most tablets a physical were breaking 100% inspection within the on line. four The of the team 80 needed kg drums to ascertain to ensure downtime. whythe tabletspackaging are breakingoperation in received Packaging defect-free and confirm product tablet robustness.in order to Fromproperly Figure conduct 13, when the tabletstrial. Upon break inspection, within the process,751 defec itts happens (half tablets) in a very were specific inspected area. out Feed-bowl of the process A is the prior entry to The research team wanted to understand when tablets break. The packaging depart- pointreaching to the the tablet packaging feed bowl department. system. In The total, team 114 breaksdeduced were that observed these defects at this were point. created Also ment is the last process in the manufacturing process and an inspection was carried out feedingfrom the into coating this area department is the top or hopper during which transporta sawtion 63 breaks. to warehouse, Of the 252 this breaks can be observed, said with before packaging to ensure product was conforming to specification before going into 70%confidence of them as were the in inside the feed of bowlthe tablet A and is topuncoated hopper therefore, areas. The ruling team rapidlyout the orientated compression to packaging and was not broken. concentratedepartment. in this area. The team conducted a physical 100% inspection on four of the 80 kg drums to ensure TheIf the team defect needed was created to ascertain in the ifcompression a step change process, in the the process half tablet was would contributing have coat- to the packaging operation received defect-free product in order to properly conduct the performanceing solution variability,on it, as the i.e., compression does the issue depart happenment straight is the preceding after a downstream (upstream) breakdown? department trial. Upon inspection, 751 defects (half tablets) were inspected out of the process prior to Doesfrom it coating. happen This on production was not the restart case afterfrom breaks? the team’s Does observations. it happen immediately As shown afterin Figure restart 13, reaching the packaging department. The team deduced that these defects were created ofthe a comprehensivetrial proved that clean? the tablet All breaks these questionsshown were need in the to be packaging considered line and and eliminated demonstrated to from the coating department or during transportation to warehouse, this can be said with provide a definitive root cause and corrective action (RCA). confidence as the inside of the tablet is uncoated therefore, ruling out the compression department.

If the defect was created in the compression process, the half tablet would have coating solution on it, as the compression department is the preceding (upstream) department from coating. This was not the case from the team’s observations. As shown in Figure 13, the trial proved that the tablet breaks shown were in the packaging line and demonstrated

Processes 2021, 9, x FOR PEER REVIEW 13 of 25

when specifically, most tablets were breaking within the line. The team needed to ascertain why tablets are breaking in Packaging and confirm tablet robustness. From Figure 13, when tablets break within the process, it happens in a very specific area. Feed-bowl A is the entry point to the tablet feed bowl system. In total, 114 breaks were observed at this Processes 2021, 9, 550 point. Also feeding into this area is the top hopper which saw 63 breaks. Of the 252 breaks 13 of 24 observed, 70% of them were in the feed bowl A and top hopper areas. The team rapidly orientated to concentrate in this area.

Figure 13. Pareto graph demonstrating the results of a trial to establish when tablets break within Figure 13. Pareto graph demonstrating the results of a trial to establish when tablets break within the Packaging process. It the Packaging process. It was demonstrated that 70% of breakages of tablet type C80/2 were in the was demonstrated that 70% of breakages of tablet type C80/2 were in the Feed Bowl and Top hopper areas. Feed Bowl and Top hopper areas.

The team3.4. needed Coating to Department ascertain if a step change in the process was contributing to performance variability,The firsti.e., characteristicdoes the issue tohappen consider straight was theafter hypothesis a downstream if the breakdown? upstream process, the Does it happenCoating on production department, restart was aafter contributory breaks? Does factor it tohappen breakage. immediately Typically, after the coating re- depart- start of a comprehensivement sprays tabletsclean? All for these 72 min. questions However, need a to process be considered change hadand movedeliminated some product to provide aportfolios definitive to root a ‘flash cause spray’ and corrective which means action it is(RCA). coated for 22 min. The temperature within the coating pan is 52 degrees, therefore the team needed to see if the shortened time for 3.4. Coating tabletsDepartment in the coating pan reduced the baking time effect. A normal spray with a 72-min spray time shows a typical tablet of 10 KP entering the The first characteristic to consider was the hypothesis if the upstream process, the coating process and raises to 13 KP minutes after the process. Coating department, was a contributory factor to breakage. Typically, the coating depart- Flash Spray tablets show the KP value as above 10 KP on entry to the process and ment sprays tablets for 72 min. However, a process change had moved some product port- 10KP minutes after the process—showing no increase in hardness. To see if this change in folios to a ‘flash spray’ which means it is coated for 22 min. The temperature within the spray time affected the performance of the tablet on the packaging line—the downtime coating pan is 52 degrees, therefore the team needed to see if the shortened time for tablets due to tablet issues was compared between normal and full spray process. in the coating pan reduced the baking time effect. As per Figure 14, there was no downtime difference due to tablet feed issues when A normal spray with a 72-min spray time shows a typical tablet of 10 KP entering the the C80/2 line ran on Flash spray vs. Normal spray and there was no difference in down- coating process and raises to 13 KP minutes after the process. time over the period of 4 weeks between the two spray types. The team then moved to Flash Spray tablets show the KP value as above 10 KP on entry to the process and understand whether there is a spike in downtime due to the restart of the packaging line 10KP minutes after the process—showing no increase in hardness. To see if this change in after a changeover and/or break. The potential root cause of spray type duration affecting spray time tabletaffected hardness the performance and resulting of the in breakagestablet on the was packaging rejected as line—the the tablet downtime feed issues remained due to tabletthe issues same was irrespective compared of between spray type normal used and in the full coating spray process. As per Figure 14, there was no downtime difference due to tablet feed issues when the C80/2 line3.5. ran Refined on Flash Problem spray Statement vs. Normal spray and there was no difference in downtime over the periodA refined of 4 problemweeks between statement the couldtwo spray now betypes. developed The team to reflect then moved the current to state and understandthe whether information there is the a spike team in understands downtime thusdue to far: the restart of the packaging line after a changeover and/or break. The potential root cause of spray type duration affecting tablet hardness- andBroken resulting (Half) in tablets breakages are getting was rejected caught in as the the feed tablet chute feed lanes issues (in remained randomized fashion), the same irrespectivewhich of is spray blocking type the used flow in ofthe tablets coating into process. the blister pockets, causing the feed system to stop. Based on the information obtained above, a deeper dive was conducted to see what is happening in the ‘Feed-bowl A’ area. This is where 70% of the breaks occurred. The team studied the entry of tablets to the feed hopper (Feed-bowl A) and broke down the sequence of the movement of tablets through this system and identified failure modes as per Figure 15. Processes 2021, 9, 550 14 of 24 Processes 2021, 9, x FOR PEER REVIEW 14 of 25

FigureFigure 14. 14.Analysis Analysis downtime downtime due due to to tablet tablet feed feed issues issues of of Flash Flash Spray Spray (a 22-min(a 22-min spray) spray) vs. vs. Full Full Spray Spray (a 72 min spray) showed no difference in downtime because of the two spray types over the (a 72 min spray) showed no difference in downtime because of the two spray types over the 4 weeks Processes 2021, 9, x FOR PEER REVIEW4 weeks of the analysis. Flash Spray type 2 used from 21 April to 27 April and 13 May15 toof 1625 May of the analysis. Flash Spray type 2 used from 21 April to 27 April and 13 May to 16 May and Normal and Normal Spray Type 1 utilized from 28 April to 12 May. Spray Type 1 utilized from 28 April to 12 May. 3.5. Refined Problem Statement A refined problem statement could now be developed to reflect the current state and the information the team understands thus far: - Broken (Half) tablets are getting caught in the feed chute lanes (in randomized fashion), which is blocking the flow of tablets into the blister pockets, causing the feed system to stop. Based on the information obtained above, a deeper dive was conducted to see what is happening in the ‘Feed-bowl A’ area. This is where 70% of the breaks occurred. The team studied the entry of tablets to the feed hopper (Feed-bowl A) and broke down the sequence of the movement of tablets through this system and identified failure modes as per Figure 15. From this risk analysis in Figure 15, the team next conducted a ‘Principal of Opera- tion Analysis’ (POA) (Figure 16) or functional analysis diagram in conjunction with brain- storming. The Principle of Operation Analysis Diagram identifies how the entire system operates correctly, analyzing that each movement works correctly by desirable sequences of movement [42]. The tool also identified the principles of movement and processing which shows how the specific components operate correctly and shows the relationship between the machine system and material system while processing. The POA is a very thorough analysis of angles, vibrations rates, oscillations and speed. Each step in the sequence is challenged as to why it happens. Each step in this condensed area of focus is broken down to a level that all aspects of ‘what is happening’ are completely understood.

Figure 15.FigureEntry 15. to Entry the to Feed the HopperFeed Hopper process process operation operation steps steps and and thethe associated failure failure modes modes that that can canoccur occur at each at step. each step.

In summary, the POA tool provided invaluable information for the team to proceed and develop the ‘5 Whys’ and start moving towards a solution. A 5 Whys analysis as demonstrated in Figure 17 shows the outcome of output from using the Principal of Op- eration tool. The principal of operation analysis resulted in an understanding that the upper hopper gravity feeds down onto the riddle plate. The shape of the hopper creates a vortex- type action creating pressure on the tablets within this stainless-steel unit—effectively, it resembles sand flowing through an egg timer. There is a window on the side of the hopper and upon observation shows that the tablets on the outside area of the hopper move last; the tablets in the center of the hopper get pulled down first thus creating pressure on the tablets.

Processes 2021, 9, 550 15 of 24

From this risk analysis in Figure 15, the team next conducted a ‘Principal of Operation Analysis’ (POA) (Figure 16) or functional analysis diagram in conjunction with brain- storming. The Principle of Operation Analysis Diagram identifies how the entire system operates correctly, analyzing that each movement works correctly by desirable sequences of movement [42]. The tool also identified the principles of movement and processing which shows how the specific components operate correctly and shows the relationship between the machine system and material system while processing. The POA is a very thorough analysis of angles, vibrations rates, oscillations and speed. Each step in the sequence is Processes 2021, 9, x FOR PEER REVIEWchallenged as to why it happens. Each step in this condensed area of focus is broken16 downof 25 to a level that all aspects of ‘what is happening’ are completely understood.

FigureFigure 16. 16. PrincipalPrincipal of of Operation Operation (POA) (POA) of ofthe the Feed Feed Hopper Hopper analysis analysis led ledto understanding to understanding of a series of a series of steps of stepswhich which contributed to the line stops. contributed to the line stops.

ProcessesProcesses2021 2021, 9, 550, 9, x FOR PEER REVIEW 17 of16 25 of 24

Figure 17. Five Whys analysis being conducted on the tablet feed issue led to root cause and corrective actions which Figure 17. Five Whys analysis being conducted on the tablet feed issue led to root cause and corrective actions which addressed the reason for feed issues and tables getting broken or stuck. addressed the reason for feed issues and tables getting broken or stuck. 3.6. Analysis of Robustness of the Tablets The principal of operation analysis resulted in an understanding that the upper hopperAn gravity obvious feeds solution down to onto preventing the riddle tablets plate. breaking The shape would of thebe to hopper increase creates their ahard- vortex- typeness action and this creating would pressurebe fixing the on the“true” tablets root withincause of this the stainless-steeltablets breaking unit—effectively, online and align it resembleswith the aim sand of flowing Six Sigma through methods an eggto find timer. the There“true” isroot a window cause. on the side of the hopper and uponHowever, observation increasing shows tablet that ha therdness tablets to fix on what theoutside is effectively area ofa process the hopper issue move on the last; themanufacturing tablets in the line center may ofnot the be the hopper best soluti get pulledon for both down the first customer thus creating and the company. pressure on theThe tablets. team looked at the effect of making tablets harder on the dissolution of the tablet (dissolving of the tablet in the body). Simply making tablets more robust (harder) will 3.6.increase Analysis theof chance Robustness of dissolution of the Tablets failure. In summary, if tablet hardness was to be increased: An obvious solution to preventing tablets breaking would be to increase their hardness and1. this It will would take be 2 fixingyears to the implement “true” root a change cause of as the a 2-year tablets stability breaking reference online andwill alignneed to with the aimbe of established Six Sigma for methods dissolution to find for theregulatory “true” rootauthorities. cause. 2. However, Increased increasinghardness affects tablet dissolution hardness to time fix. what As can is effectivelybe seen below a process in Figure issue 18, on an the increase of 1 KP to the product SKU 10C821 (currently at 10 KP) will mean the tablet manufacturing line may not be the best solution for both the customer and the company. product will fail on dissolution testing. An increase to 12 KP ensured over 50% sam- The team looked at the effect of making tablets harder on the dissolution of the tablet pled failed batch testing for dissolution of the tablet. (dissolving of the tablet in the body). Simply making tablets more robust (harder) will increaseTherefore, the chance the ofteam dissolution needs to mitigate failure. against broken tablets in the system rather than eliminateIn summary, the issue. if tabletEliminating hardness the wasissue to from be increased: happening, i.e., tablet breakages will not only be a costly and time-consuming regulatory submission but will affect the dissolution 1. It will take 2 years to implement a change as a 2-year stability reference will need to of the tablet in the body and hence the potential speed of efficacy of the product. It is highlybe establishedunlikely any for regulatory dissolution body for would regulatory accept authorities.a change in hardness that would have 2. Increased hardness affects dissolution time. As can be seen below in Figure 18, an increase of 1 KP to the product SKU 10C821 (currently at 10 KP) will mean the tablet

Processes 2021, 9, x FOR PEER REVIEW 18 of 25

Processes 2021, 9, 550 17 of 24

a negative effect on tablet efficacy and disintegration time in the body. After the PoO and 5 Whys exercise helped understand the root causes of the tablet feed and broken tablet issues, potential correctiveproduct actions will fail were on then dissolution brainstormed. testing. The An team increase then moved to 12 KPinto ensured the over 50% action implementationsampled stage and failed tracked batch testingresults. for dissolution of the tablet.

Figure 18. %Figure Acetaminophen 18. % Acetaminophen (APAP) tablet (APAP) disintegration tablet disintegrati target of 30on min target (on of the 30 y-axis)min (on vs. the Granulation y-axis) vs. time (in minutes) Granulation time (in minutes) on the x-axis. Granulation transforms the shape, size, surface, and on the x-axis. Granulation transforms the shape, size, surface, and density of powders to improve their physicochemical density of powders to improve their physicochemical properties and hardness. The higher the properties and hardness. The higher the granulation time (and KP), the more negative the effect on tablet disintegration. granulation time (and KP), the more negative the effect on tablet disintegration. For example, if For example,increased if increased to 12 to KP, 12 KP,50% 50% of the of sample the sample failed failed in dissolution in dissolution batch batch testing. testing. Therefore, the team needs to mitigate against broken tablets in the system rather than 3.7. Benefits Realization and Results eliminate the issue. Eliminating the issue from happening, i.e., tablet breakages will not Once the problem-solvingonly be a costly and stage time-consuming was complete, regulatorythe 6th stage submission of the problem-solving but will affect the dissolution seven-step processof the is tabletto measure in the the body benefits and hence and results. the potential Once the speed root of causing efficacy process of the product. It is was completed,highly the following unlikely actions any regulatory were taken body as would demonstrated accept a changein Table in 2. hardness that would have a negative effect on tablet efficacy and disintegration time in the body. After the PoO and Table 2.5 Key Whys corrective exercise and helped preventative understand actions. the root causes of the tablet feed and broken tablet Action issues, potential corrective actions wereWhy? then brainstormed. The team then moved into the action implementation stage and tracked results. Conduct diasorting Potential to remove 79% of broken tablets found on the packaging line Trial on riddle plate 3.7. Benefits Realization and Results Complete maintenance Once the problem-solving stage was complete, the 6th stage of the problem-solving check to get specific seven-stepIncorrect sized process plattens is to measure will not theremove benefits defects and (half results. tablets) Once effectively. the root causing process plattens in place and was completed,There the is followingno area to actionsstore plattens were taken to ease as demonstratedchangeover in Table2. allocate storage areas It was observed during the creation of the original POA that the riddle plate area Agree storage for plattens (located directly after the upper hopper (feed-bowl A—where 70% of the breaks happen) to enable changeover hasCurrent small holessystem to not remove working. excess Plattens dust from being the cross tablets. shared The between question lines. was posed, would it when running different be possible to increase the holeSets size being and mixed use the up riddle plate for two functions. That is, dust size tablets extraction and a dia-sorting function (remove broken tablets). If the riddle plate was tailor Create standard settings made for each product family to have specific sized holes in which broken/half tablets will No standard settings in place. Standard optimized settings will reduce to the packaging line fall through, it will effectively stop the broken tablets continuing through the process and variation output from setups to improve quality of production outputs transportation system into the tablet feed area, causing the production line to stop. A trial was conducted on the C80/2 line whilst running on 10C821 (the highest downtime was attributed to this product) with a product specific riddle plate as in Figure 19. It effectively removed all tablet feed It was observed during the creation of the original POA that the riddle plate area stops for the entire 48 h the trial lasted. (located directly after the upper hopper (feed-bowl A—where 70% of the breaks happen) Quantitative data on installation of the new riddle plates demonstrated an elimination has small holes to remove excess dust from the tablets. The question was posed, would it in short tops. There was consequently extra time afforded to the operators to complete be possible to increase the hole size and use the riddle plate for two functions. That is, value-adding steps (preparing for upcoming changeovers, getting carton leaflets rolls dust extraction and a dia-sorting function (remove broken tablets). If the riddle plate was ready for replacement etc.). The flow of the line improved and non-value additional stops reduced.

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Table 2. Key corrective and preventative actions.

Action Why? Conduct diasorting Potential to remove 79% of broken tablets found on the Trial on riddle plate packaging line Complete maintenance check to get speciﬁc Incorrect sized plattens will not remove defects (half tablets) plattens in place and effectively. There is no area to store plattens to ease changeover Processes 2021, 9, x FOR PEER REVIEWallocate storage areas 19 of 25

Agree storage for plattens to enable changeover Current system not working. Plattens being cross shared tailorwhen made running for different each product family to have specific sized betweenholes in lines.which Sets broken/half being mixed tab- up size tablets lets will fall through, it will effectively stop the broken tablets continuing through the processCreate standard and into settings the tablet feed area, causingNo the standard production settings line into place. stop. StandardA trial was optimized con- settings will ductedto the on packaging the C80/2 line line whilst running on 10C821reduce (the variation highest output downtime from was setups attributed to improve quality of totransportation this product) system with a product specific riddle plate as in Figure 19.production It effectively outputs removed all tablet feed stops for the entire 48 h the trial lasted.

Figure 19. POAFigure and pilot 19. POA on a and tailor-made pilot on a product-speciﬁc tailor-made product-specific riddle plate toriddle understand plate to understand how the plate how would the work. A new riddle plate wasplate trialed would on thework. C08/2 A new line riddle whilst plate running was triale 10C821d on tablet the C08/2 type. line whilst running 10C821 tablet type. Effectively, by dia-sorting tablets (removing broken tablets) at the riddle plate the line Quantitativerestart data procedure on installation (demonstrated of the new as riddle standard plates work demonstrated in Table1) wasan elimina- eliminated. This was tion in shortnonvalue tops. There additional was consequently work since extr operatorsa time afforded had to to conduct the operators standard to complete work multiple times an value-addinghour, steps depending (preparing on for the upcoming product (often changeovers, up to 20 getting times an carton hour). leaflets rolls ready for replacement etc.). The flow of the line improved and non-value additional stops reduced. Effectively, by dia-sorting tablets (removing broken tablets) at the riddle plate the line restart procedure (demonstrated as standard work in Table 1) was eliminated. This was nonvalue additional work since operators had to conduct standard work multiple times an hour, depending on the product (often up to 20 times an hour). The cost benefits of the project are presented in Table 3. The conservative savings of this case study in this one manufacturing plant are estimated at £388,426 (€446,460 or $541,000). The outlay in expenditure in providing all six blister lines is £26,400 equipment spend, plus capital project support cost of £3600 totaling £30,000 for the entire spend. The

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The cost benefits of the project are presented in Table3. The conservative savings of this case study in this one manufacturing plant are estimated at £388,426 (€446,460 or Processes 2021, 9, x FOR PEER REVIEW 20 of 25 $541,000). The outlay in expenditure in providing all six blister lines is £26,400 equipment spend, plus capital project support cost of £3600 totaling £30,000 for the entire spend. The net result will be £358,426 in recoveries to the OTC site but notwithstanding the benefits fromnet result a qualitative will be £358,426 point of in view. recoveries The trials to the conducted OTC site eliminated but notwithstanding the tablet feedthe benefits issues as shownfrom a inqualitative Figure 20 point. It is of important view. The to trials note conducted that the above eliminated figures the have tablet a 20% feed contingency issues as builtshown in forin Figure possible 20. variation It is important in performance to note that at the the above riddle figures plate area. have Therefore,a 20% contingency the figures presentedbuilt in for are possible understated variation and in performance the company at can the expectriddle plate a greater area. returnTherefore, than the the figures figures statedpresented above. are The understated learnings and from the this company project can are beingexpect deployeda greater return to multiple than sisterthe figures sites of thestated manufacturer above. The acrosslearnings the from world this and project the project are being savings deployed are expected to multiple to besister greater sites onceof thethe changes manufacturer are implemented across the world globally. and the project savings are expected to be greater once the changes are implemented globally.

(a)

(b) Figure 20. (a) Before the project started and actions were implemented, tab feed stops or downtime associated with tab Figure 20. (a) Before the project started and actions were implemented, tab feed stops or downtime associated with tab feeds was the top downtime issue; (b) After the project implemented corrective actions, the tab fed issue was eliminated feeds was the top downtime issue; (b) After the project implemented corrective actions, the tab fed issue was eliminated as as a contributor to short stops or downtime. a contributor to short stops or downtime. Table 3. Benefits.

Minutes 20,888 Downtime

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Table 3. Beneﬁts.

Minutes 20,888 Downtime Projected Blisters 7,912,200 Lost per year Projected Blisters rejected on restart 180,000 Contingency of 20% 6,473,760 Recovery cost per Blister (£0.06) Total Savings of £388,426

As per Table3, there is a secondary beneﬁt to this project in relation to production startup rejects. These “hidden” losses occur when production starts immediately after commissioning, or the startup production does not meet the required quality and can grow in quantity [10]. On restart of the production line, six blisters automatically get rejected as the seal of the blister may be jeopardized as it sits above the sealing bar at 70 degrees for the duration of the stop (on average 2 min). Tablets or blisters rejected due to line restarts are now eliminated. No “good” tablets were rejected since the project actions were implemented and this failure mode is being removed from the manufacturing line downtime board and list. Table4 summarizes the elimination of the projected blister loss per year of 7.9 million which has been eliminated and demonstrates the downtime loss avoidance of 20,888 min downtime.

Table 4. The downtime in terms of minutes lost and blisters lost before the project was eliminated once the corrective actions were taken. This table demonstrates the amount of waste in the process prior to the project.

Total Blisters Line Minutes Lost Lost C80/2 4189 418,900 C80/6 3662 439,440 C95/5 3605 612,850 C65/1 3347 267,760 C95/4 3210 545,700 C95/3 2075 352,750

3.8. Future Value Stream Map A future-state VSM represents the ideal state of the manufacturing system [43]. A “future” value stream map was drawn up by the project team and stakeholders. Since the purpose of lean manufacturing is to reduce or eliminate waste, the Lean/Sigma team needed to deﬁne a future value-stream map that serves as a guide for all future lean projects. Once the project was completed, the team were able to gather data and measure the new performance and reﬂect that “new” or “after” process data in the future VSM. A comparison of the “before” vs. “after” process measures was utilized to populate the VSM. It can be observed from the visual Future Value stream map in Figure 21 and Table5 below that the project yielded 1. Product backlog into the packaging area reduced by 84% 2. The cycle per batch improved by 8.3%. 3. The line changeover time reduced by 25% 4. The line availability improved by 11%. The Packaging improvement (reduction of downtime) had an overall positive effect on the overall factory lead time (in days) and the overall factory value add time (in days) with improvement of 69% and 14%, respectively. Processes 2021, 9, x FOR PEER REVIEW 22 of 25

(Before) (After) Improvement Backlog into Packaging 11.6 1.8 84 (in days) Cycle Time per batch in Packaging 24 22 8.3 (in hours) Line changeover time in Packaging 120 90 25 (in minutes) Packaging Line availability 81,000 72,000 11 (in seconds) Overall Factory Lead Time 60.1 18.85 69 (in days) Processes 2021, 9, 550 21 of 24 Overall Factory Value Added 2.8 2.4 14 Activity (in days)

FigureFigure 21.21. “Future”“Future” ValueValue StreamStream Map.Map.

Table 5. Current VSM metrics vs. Future VSM metrics. Current VSM Future VSM % Measure (Waste) (Before) (After) Improvement Backlog into Packaging 11.6 1.8 84 (in days) Cycle Time per batch in Packaging 24 22 8.3 (in hours) Line changeover time in Packaging 120 90 25 (in minutes) Packaging Line availability 81,000 72,000 11 (in seconds) Overall Factory Lead Time 60.1 18.85 69 (in days) Overall Factory Value Added 2.8 2.4 14 Activity (in days) Processes 2021, 9, 550 22 of 24

3.9. Roll out and Share The ﬁnal step of the 7-step problem solving methodology is to roll out and deploy changes and share learnings. Internally within the manufacturing site, the actions implemented in this project are being investigated for deployment in the effervescent department as they have a similar process. On a global scale, the project was shared with all the organizations’ sister pharmaceutical sites globally and the parent site in the organization. At the time of writing, deployment of project learnings has already commenced in a European sister site. When the corrective actions described in this case study are implemented, the savings are expected to be increased ﬁve-fold.

4. Conclusions Operational Excellence methodologies such as Lean Six Sigma have the potential to address and enhance understanding of processes and provide a methodology and toolset to aid effective root causing and corrective action implementation. The two key findings from the study are: 1. The project demonstrated the benefits of implementing change through effective and structured problem solving by eliminating downtime, improving product flow, reducing backlog, eliminating product wastage, increasing productivity and ultimately enhancing customer experience by reducing the backlog for the product to leave the factory. 2. This project successfully utilized the Lean Six Sigma methodologies to determine root causes and implement corrective actions. This resulted in eliminating the problems under investigation without negatively impacting manufacturing cost, production time or product quality. On a global scale, the project was shared with all the pharmaceutical sites globally and the parent site in the organization. The learnings and corrective actions are being deployed to these sites as solutions to resolving broken tablets and other queries in relation to the methodology used as a problem-solving tool. Using Lean Six Sigma techniques, the site is moving incrementally towards improving flowing product through the value stream with the goal of pulling product at the rate of the customer demand. This study contributes to the body of knowledge in Lean Six Sigma methodology as the study demonstrates that, when successfully applied, the methods are very relevant in modern operations and in competitive environments.

Author Contributions: Conceptualization, B.B. and O.M.; methodology, J.N. and O.M.; software, B.B.; validation, O.M. and B.B.; formal analysis, B.B.; J.N.; O.M.; investigation, B.B.; resources, B.B. and O.M.; data curation, O.M.; J.N.; writing—original draft preparation, B.B.; J.N.; O.M.; writing— review and editing, O.M.; J.N.; visualization, B.B.; supervision, O.M.; J.N.; project administration, B.B. All authors have read and agreed to the published version of the manuscript. Funding: This research received no external funding. Institutional Review Board Statement: Not applicable. Informed Consent Statement: Not applicable. Data Availability Statement: All data are available upon request. Acknowledgments: The authors acknowledge the support of the company involved in the case study research. Conﬂicts of Interest: The authors declare no conﬂict of interest. Processes 2021, 9, 550 23 of 24

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