Ann M. Dufton

Lean Sigma is a systematic approach to redesigning business operations to minimize wastes (Lean) and variations (Sigma) that occur through process repetition. Lean Sigma has been widely employed in manufacturing activities; for example, Toyota developed "lean" concepts in the "Toyota Production System".

 Additionally, Motorola and General Electric developed Six Sigma concepts.

	Lean Sigma applications in the pharmaceutical industry have been focused on factory-based pharmaceutical manufacturing environments.

 The manufacture of hundreds of batches of product is repetitive and minimal variation in output is a key goal. Savings made from minimizing wastes and costs through a coordinated Lean Sigma programme across the manufacturing sites of a global pharmaceutical manufacturing company can be highly significant - GlaxoSmithKline (GSK) reported savings of £300 million (€333 million) in 2004.

	There has been widespread interest in employing Lean Sigma approaches to pharmaceutical development activities because of the opportunity to reduce waste, cost, cycle time and variability in outputs. There has been a number of conferences on the industrial application of Lean Sigma in pharmaceutical R&D, but there are few published descriptions of actual implementation activities and their outcomes. This paper describes the authors' experiences in implementing Lean Sigma in the pharmaceutical development department of GSK. Learnings and recommendations regarding both the application of Lean Sigma and change management approaches are drawn from their experiences.

	It has been reported that 50% of change programmes fail to deliver and/or sustain benefits, which is attributed to problems of implementation.

 Careful and controlled change management is considered vital to successfully implementing and sustaining improvement projects to reap benefits. In the authors' work, structured change management approaches were employed in conjunction with Lean Sigma methods.

	Broadly speaking, Lean Sigma involves assessing processes and operations to identify wastes (e.g., wasted time, money, material) and/or variations in the process employed or in the output (e.g., amount, quality, content). This assessment includes mapping and measuring cycle times, output quality and resource utilization for process activities. It is typically conducted by several process users at several locations to identify variations. Facts and data generated are used to identify potential benefits for each improvement project. The improvement project team members collect any additional data required, analyse it, and develop and implement the improved process. A key aspect of any Lean Sigma project is the delivery of a mechanism to sustain and build on the improvements for the long term.

	Essentially, this is a series of structured activities associated with the successful delivery of a change programme. Activities vary for a particular project, but typically involve analysis of stakeholder groups (i.e., all those affected by the change), identification of barriers to implementation, communications planning and risk management. A key aspect of change management that is often overlooked is active sponsorship with visible management support of change projects.

	Are other pharmaceutical R&D organizations employing Lean Sigma?

	A number of research-based pharmaceutical companies have embraced Lean Sigma. AstraZeneca, Johnson and Johnson and Pfizer representatives presented at recent conferences.

 Applications focused on reducing costs, variability and complexity of operations and processes. It is suggested that Lean Sigma can cut costs and bring products to market more quickly.

	Pfizer is employing Lean Sigma approaches successfully targeting the reduction in clinical manufacture lead times by 50%.

 Teva implemented lean manufacturing in 2001, and reported a 31% increase in commercial productivity, a 55% decline in manufacturing incidents, and a 41% decrease in deviations.

	The need to maintain cGMP compliance when optimizing processes has been highlighted.

 Lewis has detailed Lean Sigma principles and theoretical benefits when applied to solid-dose manufacture.

 A recent survey reported an increasing role of Lean Sigma within biopharma operations and considerable savings in the cost of materials and reduced failures.

	Lean Sigma has been well established within the global manufacturing and supply (GMS) factory organization of GSK for many years. The worldwide training, competency development, accreditation and knowledge management support for this programme has been coordinated in GMS 

 dedicated staff within individual sites and above-site in the central operational excellence department. Major cost savings on materials, reduced cycle times, improved yields and higher quality have been achieved.

	GSK R&D decided to leverage the experience and knowledge of GMS. However, there was an obvious question - would Lean Sigma reap similar benefits in an R&D environment where repetition is less common and risk is higher? The authors separately review the literature, which both supports and questions the use of Lean Sigma in R&D environments.

	GSK was formed in 2001 through the GlaxoWellcome/SmithKline Beecham merger. Each company had different operating systems and processes. Lean Sigma and application of change management procedures/processes appeared well suited to facilitate harmonization of processes and development of a joint culture.

	Regulatory pressures to build quality through process design and continuous improvement are also increasing.

Figure 1 shows the phased implementation process that commenced in 2003.

In 2002, senior managers within GSK R&D agreed to implement a Lean Sigma programme primarily to generate productivity gains and process harmonization. GMS experience and approaches were customized to align with GSK R&D needs. Greater focus was placed on Lean and change management, while reducing focus on implementing the statistical aspects of Six Sigma. The rationale for this was that there is insufficient process repetition in R&D to collect meaningful data sets for analysis (typically no more than three identical batches are processed). The Implementation of Lean Sigma within GSK R&D was called "Enhance".

	Six Sigma statistical tools are valuable and these were later incorporated into a Quality by Design programme undertaken separately within GSK.

	A network of senior managers was established with responsibility and accountability to implement Lean Sigma across R&D. Productivity targets were set as a yardstick for success.

	A 2-week intensive training programme delivered to senior managers and general staff was designed in collaboration with GMS Lean Sigma practitioners.

 Managers with significant local business knowledge and process improvement interest were trained in Lean Sigma and change management methodology during a 6-month period with mentorship from experienced GMS Lean Sigma practitioners. After training and successful completion of change projects, these managers were designated as "Enhance Experts" and accredited as Lean Sigma Green Belts (see details below).

	Six Green Belts (including the authors) were deployed as dedicated full-time Lean Sigma practitioners within pharmaceutical development.

	Standard templates, documents and training materials were devised to ensure consistency and to avoid duplication. Standard worksheets for calculating productivity gains were also generated together with a benefits-tracking database.

 Our green Belts initially led Lean Sigma projects involving global teams and/or complex process redesign activities. These projects (examples later) typically produced significant productivity gains, reduced wastes, lowered costs and/or improved quality. Implementation of the improved processes required careful use of change management tools and active sponsorship from senior managers.

	Benefits and successes were widely communicated to promote increased awareness and uptake of Lean Sigma.

	An accreditation scheme using Belts is standard within organizations adopting Lean Sigma. Black Belts and Master Black Belts are awarded to highly experienced trained practitioners who have delivered successful projects. Green and Yellow Belts are awarded to less experienced practitioners.

 Green Belts delivered 3 days of training in Lean Sigma and change management to selected staff from all levels (about one in 12 of the department, which equates to 120 staff). Following training, attendees were designated as 'Enhance Advocates'. All Directors within pharmaceutical development were trained as Advocates (primarily to support their roles as Sponsors, rather than to be practitioners).

	Enhance Advocates participated in large improvement projects to gain experience alongside their regular operational role. Advocates also typically led local improvement projects within their work areas where change management requirements were simpler and sponsorship from local management was available.

	Advocates were awarded Yellow Belts after completion of their 3-day training and successful application of Lean Sigma knowledge and skills to improvement projects.

	A Community of Practice for advocates was created, which provides on-going training 

 informal 'Lunch and Learn' events, personal mentoring, and an internal website containing training materials and examples of Lean Sigma tools in use.

	The Lean Sigma "Enhance" programme is sustained by mandatory sharing of good practices from individual projects; for example, by use of After Action Review events, shared knowledge repositories and learning forums.

 The Community of Practice and the Enhance Champions network support continuous improvement. For example, the advocate training resources are updated with relevant case studies from within the department to show the success and benefit of the Lean Sigma approach and build confidence in its application. Learnings from specific projects are documented and shared among Experts and Advocates. Templates for specific Lean Sigma tools and techniques are generated and improved based on best practices.

Table 1 lists some example projects. A specific case study on the 'Lean Lab' project then follows. Benefits (Table 1) include tangible (measurable) gains such as reduced costs/time, and less tangible benefits, such as improved quality and compliance.

	Projects focused on frequently conducted or high-impact activities and ranged from global complex projects, such as harmonization of batch records and associated process, to localized activities, such as a glassware cleaning and control system within a laboratory. Senior managers, typically Vice Presidents, sponsored large projects and Enhance Experts served as project leaders. Directors sponsored localized projects, which were led by an Enhance Advocate.

	Lean Sigma projects follow a set pattern of activities termed DMAIC (Define, Measure, Analyze, Implement, Control).

 This was used for Project Lean Lab to eliminate or reduce wastes within laboratories in the nine pharmaceutical development sites worldwide.

 - a charter was approved by the sponsoring Vice President and contained the exact project scope, deliverables, team membership, roles and responsibilities. Deliverables described redefined standard ways of working, reorganized laboratory layouts, redefined responsibilities and resourcing of laboratory maintenance. Anticipated benefits included improved laboratory space utilization, reduced inventories and reduced time spent in wasteful activities, such as searching for equipment.

 - a baseline current state was measured to assess potential improvements. Typical Lean Sigma tools, such as process mapping and time/motion studies, were employed. Figure 2 shows a 'spaghetti map' for an individual analytical activity within a laboratory, which showed that 15% of time was wasted walking to access equipment, computers and materials. Other data measured included inventories of equipment and materials to identify excess or unused items.

 - baseline data were collated and assessed by the Lean Lab team. Specific improvement activities were identified from this analysis. These activities were then combined into an implementation plan that was approved and resourced by the sponsoring Vice President. Improvement activities included redesign of equipment layouts, re-assigning responsibilities and the removal of unused or underused equipment. 

 - A team was formed to drive the global implementation of recommended changes, including critical sponsor communications regarding the importance of Lean Lab. A network of Lean Lab Champions (approximately one per 12 laboratory-based scientists) was formed to ensure consistency of implementation in each laboratory worldwide.

		The Lean Sigma 5S activity of Sort, Store, Shine, Standardise, and Sustain. This entailed moving equipment and materials close to the point of use in an activity; cleaning and repair of all equipment that was regularly used; materials moved to storage in assigned labelled locations; and implementing local inventory management systems such as kanban for the replenishment of consumables. Benefits included significantly less time and effort moving around to locate or access equipment and materials, better use of expensive laboratory space, and reduced material costs because of improved stock control.

		A Lean Lab checklist was also developed for use during implementation, which contained a detailed series of questions designed to identify local targets for improvement.

Figure 3 shows a laboratory area, before and after, Lean Lab implementation.

Rarely used or defunct equipment was 'red tagged' by attaching a red label to indicate it would be sentenced unless claimed within a set period of time. Red-tagged equipment was then redeployed, removed to stores, given away to good causes or discarded. This red-tagging activity removed hundreds of items from laboratories, generating additional free space and reducing costs by stopping the service and calibration of unused equipment.

 - the Lean Lab Champions perform a weekly informal audit of the laboratories against the Lean Lab checklist. Results from the informal audits are shared, and actions agreed and undertaken. The sponsor and members of the Lean Lab team perform periodic walkthroughs of the laboratories to reinforce the need for lean practices.

		It is important to capture and display baseline facts and data before an improvement activity as this convinces sponsors and staff involved that there is a genuine and compelling need to improve.

		Sponsorship and senior management support throughout the organization is essential. Support from middle/lower management is also important as they generally assign work priorities on a daily/weekly basis and support individuals through the change projects.

		Communication of the overall Lean Sigma programme is vital to obtain support for the individual contributing activities and positively drive the culture towards that of continuous improvement. The language and culture of an organization is permanently changed when Lean Sigma is established as Lean Sigma tools, terminology and approaches become embedded in routine use.

		Sustain mechanisms are a necessary deliverable from any implementation programme. This ensures there is no regression to the old process and that continuous improvement is maintained.

		Lean Sigma approaches are particularly appropriate for optimization of bureaucratic activities in R&D, which are necessary, routine and frequent; for example, the checking and processing of analytical data.

		Experimentation in R&D deliberately generates variation as ideas and operating limits are explored. This is in apparent conflict with Lean Sigma thinking to drive down waste and variation. However, cost and time can be minimized through good design of experiments to increase the 'wanted variation' of experiments while decreasing unwanted variation.

		Sigma approaches can be useful in reducing the variability of inputs (e.g., better control of raw materials, such as excipients, standardization of equipment types and consumables), the processes (series of activities) and the outputs (e.g., templates to capture information).

		Assign full-time dedicated Champions to facilitate the implementation process.

		Obtain visible and active top-level management sponsorship.

		Introduce a Belt accreditation scheme to recognize and motivate practitioners.

		Coordinate rollout with consistent training, documentation and branding.

		Change the culture through the communication of successes, rewards and recognition.

		Generate an active community of practice and network of experts.

		Concentrate initially on bureaucratic repetitive activities such as documentation processes where there is scope for improvements, which resonates with scientists.

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Lean Sigma approaches can reduce waste, cost, cycle time and variability in outputs.