eXampleCG Enabling Excellence Forum

Tom Lacey, head of quality at the New Royal Infirmary in Edinburgh, explains how the hospital's sterilisation and decontamination unit significantly reduced clinical risk

Operating theatres all over the UK are being thrown into chaos and operations cancelled due to broken, missing or dirty surgical instruments. The Royal College of Surgeons is currently calling for a national audit of decontamination units, following a report in April's Clinical Services Journal on surgery being cancelled due to instruments being returned with visible blood and bone contamination. A report from the NHS decontamination programme has also revealed that 1,765 operations were called off at the last minute in 2005–06 because of instrument problems.


This is a high-profile problem for the NHS and it is taken very seriously, particularly since an audit eight years ago highlighted the need to upgrade and modernise decontamination facilities. Many hospitals have entered into contracts with commercial sterilisation services, while others, such as the New Royal Infirmary in Edinburgh, have an inhouse unit.




The HSDU at the New Royal Infirmary both before (left) and after (right) six sigma process improvement


The hospital sterilisation and disinfection unit (HSDU) at the New Royal Infirmary is one of the busiest in the UK, processing over 7m reusable instruments per annum. It employs over 100 staff operating 24 hours per day, 365 days per year and has been in operation since 2002.


The process is, in theory, straightforward. Surgical devices and instruments are returned from 30 sites across Lothian, stripped, washed, disinfected, reassembled in the clean room, sterilised and returned to the theatres.


'In 2005, the number of incidents of contaminated trays being returned to the HSDU reached chronic proportions'

However, even a small speck on an instrument may lead to rejection by a surgeon who is concerned about the risk it may pose to patients. In 2005, the number of incidents of contaminated trays being returned to the HSDU reached chronic proportions. The level of risk was measured using failure mode effects analysis and more advanced Bayesian analysis models and was assessed as high. Although the staff at the HSDU were working to improve the situation, they were essentially firefighting, working overtime and reworking trays as fast as possible. The problem just seemed to continue.


A proposal was put forward to resolve this problem using six sigma. There were many examples of where the same techniques had been successfully employed in industry and there was no reason to assume they would not work in the NHS. The advantage that six sigma had over other improvement tools was the emphasis on ensuring senior management commitment upfront, allowing maximum staff participation and statistical analysis where required. The plan was put forward to the director of operations, Jane Todd, and the HSDU manager, Alexa Pilch. Their response was immediate and positive, as although six sigma had never been used in the unit, events seemed to require a new approach to problem resolution.


Challenges


There were a number of factors to consider:



reducing the risk – how could we bring down the number of clinical risks?

demand pressure – typically the HSDU could han-dle 350 trays per day, but frequently there were in excess of 850 trays in the unit. How could the unit afford to deal with contamination issues when it was under such pressure for throughput?

conventional wisdom – management felt that there was little chance of taking time out to indulge in a new 'fad'. How could this mindset be changed?

budget – there were no funds available to tackle this problem. How could it be overcome utilising only the existing (overstretched) resources?


Six key success factors were identified up front:



senior management involvement from the start

get the right people on board

set clear achievable objectives

keep it simple

determination to achieve the objectives

to resolve the problem, be positive


Using six sigma


Six sigma is a management philosophy aimed at improving effectiveness and efficiency. Other quality initiatives focus on quality tools, but six sigma relies on the active involvement of all staff and especially management. This focus on staff involvement was the key factor in ensuring a successful outcome for the project.


A specific challenge with this project was how to achieve success using the key six sigma technique of DMAIC (define, measure, analyse, improve, control) in the HSDU, where no continuous improvement approaches had previously been used. The decision was taken early on to keep the project as simple as possible and key practical stages are outlined below.


Setting the objectives


This was a crucial first step to achieving success; projects so often fail because they are poorly defined, the scope is not manageable or the targets are too ambitious. Several weeks were allocated to this aspect, involving the 16 key operating theatres and senior management at each stage. Quality surveys were conducted using Likert scaling and project targets were discussed and agreed with senior management before the initiative began. These are outlined below:



clinical risk reports – decrease from six to zero per month within a year

contamination complaints – decrease from 118 to four per month within a year

rewash (rework) activity – decrease from 250 to 50 per month within a year

process sigma – achieve six sigma status within two years


Selecting the team


This was identified as the second critical step. First, a project coordinator was appointed, Chris Hodkinson. Chris had been working in the HSDU for several years and had first-hand knowledge of the problem and the processes. Although he had no experience of quality techniques, he possessed the skillset needed for the project. The next challenge was to allow Chris to stop working in the process department and focus solely on driving the project. Again, senior management commitment was crucial as there was a risk in taking people away from processing.


The remaining team members were carefully selected from each shift to ensure good coverage of the 24-hour operations. They then worked on the project as required.


Team training


Intensive training in the basics of DMAIC was undertaken over a period of two months. Again training was on a 'need-to-know' basis, as the intention was not to create a set of six-sigma experts. Basic quality tools covered how to define the problem: process mapping, data collection, survey techniques, fault tree, Pareto charting, simple control charting and sequential sampling.


Process mapping (see figure 1) was particularly critical to the success of the project. Detailed process maps were created and used to identify the potential sources of the contamination problems. It was also a superb method for getting maximum participation from the team members and focused problem identification.




Figure 1. Example of process mapping


Stakeholder analysis


A stakeholder was defined as anyone affected by the solutions arising as a result of the project. Stakeholder groups included operating theatres, senior management, HSDU management and staff were surveyed and each group's commitment to the project was assessed. The key results from this analysis allowed us to assess the level of senior management buy-in and identify where the main resistance would come from early on. This allowed us to greatly increase our chances of success.


The majority of the stakeholders were very much in favour of the project quality surveys. Likert scaling with non-parametric analysis to ensure statistically significant findings was conducted to confirm their commitment to its success.


One of the major concerns highlighted during the stakeholder analysis was valuable time and resources being taken away from the 'real' work of getting trays out of the HSDU. However, most staff were fully supportive of the project, which was confirmed by both formal and informal meetings. They were very receptive to any improvements that would make their life easier and reduce daily stress levels, but the importance of support from senior management simply cannot be overemphasised.


Results


The table in figure 2 demonstrates the results achieved in the unit. Not all of our targets were achieved within the timeframe specified.







The key target was the reduction of risk due to contaminated trays and this was achieved. With hindsight, secondary targets were too ambitious but even so were eventually achieved. Future projects will take account of the need to set realistic secondary targets in the unit, but the graph in figure 3 clearly indicates the positive gains that the unit achieved. The old 'chronic' level of contamination was overcome and, more importantly, maintained.




Figure 3. Number of contaminated trays per month


The future


Based on the success achieved in this project the director of operations, Jane Todd, has allowed further training and implementation of lean methodologies. The next areas to be addressed included missing equipment and devices requiring repair.


A kaizen approach initially involving 12 staff was used and training in February 2008 involving new staff members was well received and achieved positive results. A saving of 21 hours of staff time each day by process streamlining and removing redundant paperwork from the process was highlighted in the Edinburgh Evening News


Biography


Tom Lacey is head of quality at the New Royal Infirmary in Edinburgh. He is a chartered microbiologist and applied statistician with over 30 years' experience in the pharmaceutical and medical device industries. He is a member of the CQI.

Lean Six Sigma in Healthcare

Healthcare, as with any other service operation, requires systematic innovation efforts to remain competitive, cost efficient, and up-to-date. This article outlines a methodology and presents examples to illustrate how principles of Lean Thinking and Six Sigma can be combined to provide an effective framework for producing systematic innovation efforts in healthcare. Controlling healthcare cost increases, improving quality, and providing better healthcare are some of the benefits of this approach.

The cost of medical care is increasing at an alarming and unsustainable rate worldwide. Admittedly, a significant percentage of these cost increases can be attributed to an aging population and technological advances. These two factors, inevitable because of the technological and demographic developments of modern society, are largely beyond control. However, another significant source of healthcare cost increases can be broadly characterized as unnecessary operational inefficiency. Healthcare professionals have more control over this factor. Inefficiency can be measured and changes implemented to improve quality. These efforts provide more affordable and better healthcare for a large percentage of the population.

Some operational inefficiencies are associated with the direct medical service delivery process. Others are associated with the administrative, logistical, and operational side of the healthcare delivery system. Both areas can benefit from systematic process innovation activities.

Lean Six Sigma Healthcare

Lean Six Sigma has recently also been applied in the healthcare sector. George (2003), for example, describes pioneering work on Lean Six Sigma at Stanford Hospital and Clinics. In this section our own experience with Lean Six Sigma at the Red Cross Hospital in the Netherlands is discussed. Of course, as is often the case, elements of Lean Six Sigma were applied at the hospital years before the term itself was used (Van den Heuvel, Does, & Vermaat, 2004).

The Red Cross Hospital in Beverwijk is a 384-bed, medium-sized general hospital employing a staff of 966 with a yearly budget of 72.1 million. In addition to being a general healthcare provider, the Red Cross Hospital also houses a national burn care center with 25 beds that provides specialized services to all of the Netherlands. In 2004, the Red Cross Hospital had 12,669 admissions, performed 11,064 outpatient treatments, and received 198,591 visits to its outpatient units, of which 78,832 were first contacts.

The Red Cross Hospital began to use Six Sigma in 2002. However, the hospital management had already introduced a basic quality assurance system and obtained an International Organization for Standardization 9002 certification in 2000. Prior to the implementation of Six Sigma, management also deployed a number of teams to work on specific QI projects. At the time, management believed that these pre-Six Sigma projects worked well. Indeed, a number of the projects were completed with good results. However, over time, management discovered that an organizational framework and programs for project management, coordination, tracking, and support were necessary. Specifically, upper management identified the following problems:

Projects were not necessarily of strategic relevance.
Projects did not always have a significant business case.
A systematic project-tracking system was missing.
There was no uniform method for project management and control.
Too many projects were not completed.
At the end of 2001, the hospital management was introduced to Six Sigma and found that this methodology provided solutions to many of these problems. The initial implementation of Six Sigma at the Red Cross Hospital is described in the literature (Van den Heuvel, Does, & Bisgaard, 2005; Van den Heuvel, Does, & Verver, in press). In addition to outlining Six Sigma's management framework and lessons learned relevant to healthcare, these articles also describe selected examples of projects. A sampling will provide an impression of the range of problems tackled:

shortening the length of stay in chronic obstructive pulmonary disease patients
reducing errors in invoices received from temporary agencies
revising the terms of payment
allowing parents to room in with their children
reducing the number of patients requiring intravenous antibiotics
shortening the preparation time of intravenous medication
reducing the number of mistakes in invoices.
This list illustrates the important point that Six Sigma projects in healthcare typically include both medical and administrative problems. Indeed, some healthcare professionals think QI methods should address only defects, such as medication errors. Our experience is that significant gains can be made by widening the field of applications to all processes and all operational inefficiency and waste.

The list above also shows that several of the Six Sigma projects could just as well be characterized as Lean projects. For example, reducing the length of stay and shortening the preparation time for medication would be typical Lean objectives. On the other hand, the Lean approach would come up short in projects involving reducing errors in invoices received from temporary agencies, revising payment terms, and correcting the number of mistakes in invoices. The distinction between Lean and Six Sigma is artificial and often not helpful. An integration of the two approaches and a general focus on process innovation regardless of the origin of the tools and approaches would be more productive.
Introducing Six Sigma

Six Sigma was implemented in earnest at the Red Cross Hospital in September 2002 with the first wave of GB training. As is standard for Six Sigma, the training was provided in two separate periods of 3 days, 2 months apart. The GBs were required to complete a project in conjunction with their training. The financial threshold for initiating a project was an estimated minimum saving of 20,000. GBs typically worked 1 or 2 days a week on their projects. As part of the project-management system, teams were carefully monitored and allowed to proceed to the next phase of the DMAIC sequence only after presenting the Champion with a report providing evidence that the preceding phase had been completed. Teams were required to present their results twice in front of the entire class. The second presentation served as the GB graduation examination.

The first wave was followed by additional GB training waves scheduled every 6 months thereafter. The Six Sigma approach was well received. The GBs believed the Six Sigma training and project-management system supported them well throughout the process of a project. The data-driven approach was regarded as helpful in establishing support of the teams during the implementation of the results. The data-based analysis and decision making seemed to minimize resistance to change.

After completing the training of the fourth group of GBs, it was decided that the training process needed revision. The experience from the previous waves of GB training indicated that many healthcare problems involved various forms of wasted time. It was decided to experiment with combining Lean with the DMAIC methodology. Materials on time-value maps, value-stream maps, and the six standard forms of waste were added to the curriculum in the analysis phase. Furthermore, the curriculum for the improve phase was expanded to include complexity reduction, cellular production, pull systems, line balancing, and the 5S method to reduce inefficiencies due to clutter and poor organization. The total length of this revised training program was expanded to 8 days, divided into two periods of 3 days and an additional section of 2 days. The first Lean Six Sigma GB training program started in September 2004 with 18 participants distributed in teams of two or three GBs.

The Red Cross Hospital experience illustrates the key elements of the Lean Six Sigma approach. First, the hospital applied the organizational infrastructure typical of Six Sigma. Second, deployment of QI was project by project. Third, the Lean Six Sigma approach was based on developing organizational competency for innovation by training a dedicated force of Lean Six Sigma project leaders and GBs. Fourth, project selection had a strategic focus. In the present case the Dutch Ministry of Welfare and Health had imposed serious budget cuts on the Red Cross Hospital. This necessitated a strict focus on cost reductions while maintaining or possibly improving quality. Potential projects were suggested by Champions, all hospital department heads. The final word to proceed was given by the general manager, based on an evaluation of the project's strategic relevance.

Lean Six Sigma Project Cases

Complexity Reduction in Hiring Personnel
The Red Cross Hospital spends yearly more than 1 million on temporary personnel. Upper management suspected that the cost of hiring temporary personnel was unnecessarily high. A preliminary investigation indicated that errors on invoices was a problem resulting in significant non-value-added rework and unnecessary readministration. Thus, the project charter drafted by the GB and the project Champion stated that the objective of this project was to reduce the number of mistakes on invoices. The CTQ was the percentage of correct invoices received from the temporary agencies.

A baseline study performed in the measure phase showed that only 15% of the invoices were correct on first pass. The goal was set to improve the CTQ to 100%. If this ambitious goal was achieved, the financial saving was projected to be 36,000 per year. In the subsequent analysis phase, a number of influential factors and causes were identified. The most important were these:

The signature of the department head was missing.
A check on the hours worked was missing.
Breaks were not registered.
Mistakes occurred in the reported hours worked and time for travel.
There was no check on the number of the temporary worker's years of experience.
The hourly wage was incorrectly stated on the invoice.
Although a large number of mistakes were recorded, this initial analysis failed to unearth any single dominant type of mistake. However, further analysis showed that the errors were symptoms of a more significant problem. The root cause turned out to be that each of the temporary agencies used a different worksheet. Moreover, no single uniform standard for hiring and invoicing temporary workers was followed. Each department had its own forms and procedures. From a Lean perspective, having different worksheets for the same purpose is a non-value-added complexity that should be eliminated. This led to the following proposed improvements:

A standardized worksheet was introduced.
Requests for temporary personnel were centralized.
The number of temporary agencies was reduced.
A new administrative system for checking invoices was introduced.
In addition to these complexity-reduction measures, a visual management system to signal mistakes was introduced. A new procedure was introduced for hiring temporary personnel, requiring heads of departments to use a single standardized worksheet. This worksheet incorporated a "check invoice" feature designed to make it easy to compare invoices submitted by the temporary agency with internal documents, which made it easy to spot discrepancies. All of these incremental changes resulted in reduced rework and significant cost savings.

Reducing Operating Theater Starting Times
Operating theaters (OTs) are expensive and capacity-limiting facilities. Their optimal utilization is paramount to efficient hospital management. The general manager of the Red Cross Hospital suspected that the utilization of the OTs was far from optimal, so a GB team was assigned to increase the efficiency of the OTs. The GB team focused on the starting times of the OTs. The official starting time was 8 am. Baseline data collected in the measure phase showed that the average starting time was 8:35 am, which suggested a significant loss of capacity. As a realistic goal, it was decided to aim for an average starting time of 8:15 am.

During the analysis phase the GB team discovered several factors that affected the starting time:

Patients had not been administered the prescribed medication.
Patients were brought in late by the referring department.
The OT had insufficient manpower.
Specialists had to make rounds prior to performing procedures in the OT.
Anesthesiologists and other specialists were late.
While diagnosing these problems, the GB team found that the underlying problem was a poorly defined process. This made planning difficult. Tools were needed to manage this operational process. Designing a new admissions process based on the following simple principles was the solution:

Patients must be present at the OT facility no later than 7:35 am.
Before arriving at the OT, patients must receive preoperative preparation.
The referring department and the anesthesiologists must be informed about the planned OT treatment for the patient 1 day in advance of a procedure.
To control this new process, visual management was introduced. At the weekly staff meeting, a specially designed graph was reviewed, showing the OT start times for the previous week. The feedback from this control system was used to continually monitor the OT starting times and provide valuable input on how to improve processes even further.

Maintenance
The Red Cross Hospital has a system in place to manage mechanical breakdowns and irregularities. This system registers a problem and assigns a maintenance person a "blue coupon" with a description of the issue. After diagnosing the situation and solving the problem, the maintenance person reports that the problem has been solved. Although the system itself seemed efficient, the resolution of problems often took an excessive amount of time. A project team was chartered with the task of improving the process. The CTQs were the number of active, not yet resolved blue coupons and the lead time per blue coupon.

The first CTQ represents the overall cost in system downtime, whereas the second provides an indication of the quality of the service rendered. The following discussion will be limited to the first CTQ.

Analysis showed that the dominant problem was defective lights. It was further discovered that the maintenance department did not have standard operating procedures. Malfunctions were handled in an ad hoc fashion with no accounting for urgency or priority. A number of solutions were put into place to deal with this problem.

prevention: Lights were turned off at night to extend the life of light bulbs.
standard operating procedure: Guidelines were developed for dealing with breakdowns and failures.
work planning system: Problems were divided into urgency categories.
performance monitoring and visual management: Norms for fixing standard malfunctions were instituted and monitored.
The result of these simple systems changes was a significant decrease in the number of blue coupons. The related financial saving of this project was approximately 200,000.

These projects illustrate the benefits of combining Lean with Six Sigma. In all cases a thorough quantitative diagnosis was made before starting improvements. This is typical of Six Sigma. In all cases it was possible to use off-the-shelf solutions to solve the problems. The solutions were firmly anchored in the organizational infrastructure. Managers can keep track of the performance of CTQs using visual management systems and ensure that an organization does not revert to old habits and past performance standards. The gains are maintained.

Conclusions

Unless healthcare leaders deal with spiraling healthcare costs, a decreasing proportion of the citizens of industrialized societies will be able to afford high-quality healthcare. If healthcare services are inefficient, they cost more, and fewer can benefit from the technical advances of modern medicine. A persistence of traditional service practices will drain our economy. Continuous and relentless pursuits of innovations in the service delivery process are necessary. The industrialization of healthcare offers a viable alternative that can provide better economy, greater efficiency, and better service.

Industrializing healthcare does not mean that healthcare becomes less personal and that quality standards are compromised. For example, a modern car, objectively speaking, is far cheaper and of significantly higher quality than a handcrafted car manufactured 100 years ago. Prepackaged vacations typically offer better deals with higher levels of service than individually planned tours. Industrialization of services typically improves quality while making those services much more cost efficient.

The industrialization of healthcare service will require a large number of innovations, especially pertaining to the delivery of services. The popular perception is that innovation, like artistic expression, is the product of genius. However, in today's competitive economic environment, this process must not remain a mystery. Indeed, it need not be. Pianists and painters attend conservatories and art schools to receive intensive training in their profession. Innovation, like artistic performance, can be learned. The combination of Six Sigma and Lean-with their tools, road maps, and management processes-is essentially a carefully managed process for systematically scheduling and carrying out innovation projects that can be taught, learned, and performed with a high degree of success.

The Role of Six Sigma in
Outsourced F&A Services

The positive spiral of cost and process productivity
—a look at how Six Sigma discipline can help
transform real-life buyers.
By Shantanu Ghosh & Monty Singh

Finance and accounting (F&A) outsourcing is one
of the fastest growing and largest segments in the
global sourcing space. Most Fortune 500 companies globally source at least a
couple if not more F&A processes. Corporations leveraging global sourcing
have reaped the traditional benefits of lower cost through labor arbitrage,
increased core competency focus, and access to talent.

But some companies go much further. They better cash management,
productivity, and controllership using Six Sigma to continuously improve
outsourced F&A processes and drive them to best-in-class.
Traditional outsourcing models transition F&A processes as is, thereby
transferring process defects too. Mature global sourcing vendors take a more
robust approach to F&A outsourcing. They use Six Sigma to identify defects
for remediation and totally re-engineer the process.

Read more .. at http://www.genpact.com/docs/resource-/3-32B5124B2E12B

Applying Lean Accounting Methods To The Accounts Payable Process

Prior to the introduction of lean thinking this company had taken the approach to centralize their accounting processes. The Accounts Payable department has 40 people and processes approximately 36,000 transactions each month. The company is in the process of implementing Lean Accounting but there has been little progress within the centralized service center because the people had not been included in any of the lean training or lean accounting workshops. As a first step, a kaizen event was organized within the shared services Accounts Payable department with the goal of eliminating waste, improving productivity, and reducing the processing lead time.

Read more at
http://www.maskell.com/lean_accounting/subpages/lean_accounting/field_stories/stories_from_the_field_10.html

Quality by Design (QbD)

Myth or Reality?

Girish Malhotra

In the United States, the FDA's initiative on nudging the pharmaceutical industry to invent, develop and commercialize products using technologies that will result in product quality by design (QbD) is a challenging task. It is also a noble task that will have major business process implications and ultimately high financial impact on healthcare costs.

Through presentations and pilot programs, the FDA is making its case to move the industry toward a win-win situation for all involved, especially consumers. These outlined items if submitted would assist in the approval process and allow continuous improvements. Since this is uncharted territory for drug developers and reviewers, it is necessary for the developers to present information that will convince the reviewers that the process will produce QbD "the desired state" rather than quality by inspection (QbI) "the present state". Because this is a change in process and mindset, there will naturally be apprehension on the part of industry as it has traditionally worked in a defined comfort zone and is not sure about the value of change.

With that said, processes are developed and commercialized by chemists and engineers with the involvement of regulatory personnel to comply with the FDA, EPA and OSHA rules and regulations. In this evolution, one has to optimize the impact of their actions when it comes to the total business process. The current QbI methodology creates business processes and inventories that need infrastructure to support quality pharmaceutical production. This costs money and the consumers pay for it. QbD can be equated to Just in time (JIT) as the industry will have total control of the manufacturing process. Volumes have been written about the value of JIT and we all know that it smoothes out the total business process.

The FDA in its expectation of process analytical technology (PAT) framework and QbD stipulate a complete understanding of the interaction of raw materials and intermediates and control of process parameters. In a commercial operation, this will result in a QbD rather than QbI product. This is easier said than done. It requires combined application of knowledge, common sense and stepping out of bounds to establish a new paradigm.

In this paper, I am reviewing a chemistry outlined in a patent and sharing some of the opportunities to improve the manufacturing process. Process controls can be applied which will produce consistent quality product with no or minimal in-process testing. Similar methods and observations can be incorporated in the development of new chemistries so that we have a QbD process from the outset.

I have chosen production of an active ingredient rather than the formulation of the active pharmaceutical ingredient (API) with excipients. The reason for choosing reaction chemistry is its complexity and the length of time it takes to produce an API. In addition, much has been written about the formulation aspects and very little to none has been written about the manufacture of APIs. Thus, it needs proper consideration.

For the development of a process and chemistry of API's an alternate approach could be considered. This is "out the box" thinking but worth consideration. Instead of having a mindset that we are developing a "pharmaceutical", it might be easier to consider that we are developing a "specialty chemical" that might have pharmaceutical value. This should simplify many of the drug development processes.

In this alternate approach, once an optimum process has been developed for a specialty chemical where we know the interaction of each raw material and intermediates, the critical parameters and how to control them, every regulatory requirement can be included to meet the necessary standards. Since we have to apply regulatory requirements only on one process, the product and process development is simplified. Such an approach might also be a way to reduce the "time to market". I believe that if we are able meet quality and performance specifications all the time, we might have to contend with fewer regulations also.

By using the "right" process we will produce a "quality" product, which in turn will reduce waste, work in process inventories, regulatory oversight and bureaucracy i.e. simplify the business process. Doing it right the first time, by a repeatable process is the key and has to be the method of choice. If we are able to accomplish this from the outset, we would not have to live with 2.5 Sigma processes, and the process of continuous improvement would be less expensive compared to after the fact improvements.

The following considerations are necessary in the development, simplification and commercialization of the "right" process. Most of these are being used in the manufacture of chemicals. The understanding and application of these also allows the control of processes using commercially available process control technologies. The following are taught in chemical engineering curriculum, thus these are not new.

Total process feasibility. Each unit process step has to be reviewed individually and collectively.

Is the stoichiometry optimized?

Are the heat and mass balance optimized?

Are the reaction kinetics understood and applied to simplify the process?

Are proper unit operations being used?

Are the necessary steps in place to reduce the cycle time?

Can a single solvent be used for the whole process? This economizes solvent recovery and the related investment.

Can we eliminate isolation of intermediates?

Are the raw materials to be used easy to handle?

How can the phase separation be improved and simplified, if it is part of the process?

How can I improve the conversion of each process step? Lower conversion means that there is raw material loss, which has to be recovered and/or treated in the effluent system or disposed of as hazardous waste. Lower conversion also means that unless the unconverted raw materials or impurities are removed prior to the subsequent reaction steps, additional impurities will be created adding to the process complexity.

Are the safety requirements met and is the process safe?

If the developers were operating the process, what process modifications and/or additions would be included to have the simplest process?

Is the process meeting all of the environmental standards?

Is the rework eliminated and/or minimized?

Is the process economical? A thorough understanding of every interaction allows one to have a complete grasp of the impact of every process change and its influence on the product quality. If above considerations are followed all the time QbD becomes a natural part of the development process. In addition to the above considerations, each chemistry and process has its nuances and if recognized and implemented can simplify the manufacturing processes further. The incorporation also allows one to have complete control of the process. One can react to any unexpected changes and deliver quality. From my experiences, it also allows one to repeat the mistakes. If this can be done, developers will have done an excellent job. It would be like driving a car smoothly under every condition. Today's pharmaceutical manufacturing can be compared to an automobile driving us vs. us driving the automobile.

The application of the above considerations is part of the reviewed process. It is also possible that some of the process observations mentioned below if implemented can lead to a continuous process. It is well known that a continuous process is more economical than a batch process and produces consistent quality i.e. QbD.

Dr. Moheb Nasr, Director, CDER's Office of New Drug Quality Assessment, Dr, Janet Woodcock, Dr. Scott Gottlieb and others at the FDA have echoed the sentiment well know in the chemical industry that "the pharmaceutical industry can only realize the full benefit of QbD by developing and implementing continuous processing".

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