Superior productivity- in the laboratory and beyond

Analytical chemistry enjoyed a revolution in instrumental techniques during the 1960s and 1970s. This, in turn, stimulated new developments of simple laboratory automation led by improved analytical instruments, auto-samplers and chromatographic integratcs. During the 1980s, new generations of powerful laboratory automation emerged; primarily laboratory information systems and laboratory robotics for sample automation. In most applications, today's analytical techniques are capable of producing the required quality data. The next step is to maintain, and even raise, these standards while increasing analytical capacity. Trace analysis continues to demand greater sensitivity to measure ever-lower trace levels. Meeting this requires continuing technology improvements in sample preparation, separations techniques and analytical measurements. Superior productivity requires earning the greatest economic value from resources; people, time and capital. Improving productivity is valuable today, but will become critical to survival in the future and business will continue to demand more and more from their laboratory investment. Not only must today's laboratories improve internal productivity, they must stimulate productivity throughout their company by contributing quality, timely information for critical business decisions. In manufacturing, for example, errors in quality data might lead to shipping unacceptable products or rejecting acceptable products. Either condition initiates an ever more costly set of potential consequences, including: (a) Demotivating dedicated staff. (b) Sorting good from bad. (c) Rework. (d) Scrap. (e) Late customer deliveries. C/) Customer complaints.


Gaining strategic advantage
Analytical chemistry enjoyed a revolution in instrumental techniques during the 1960s and 1970s. This, in turn, stimulated new developments of simple laboratory automation led by improved analytical instruments, autosamplers and chromatographic integratcs. During the 1980s, new generations of powerful laboratory automation emerged; primarily laboratory information systems and laboratory robotics for sample automation.
In most applications, today's analytical techniques are capable of producing the required quality data. The next step is to maintain, and even raise, these standards while increasing analytical capacity. Trace analysis continues to demand greater sensitivity to measure ever-lower trace levels. Meeting this requires continuing technology improvements in sample preparation, separations techniques and analytical measurements.

Superior productivity
Superior productivity requires earning the greatest economic value from resources; people, time and capital. Improving productivity is valuable today, but will become critical to survival in the future and business will continue to demand more and more from their laboratory investment. Not only must today's laboratories improve internal productivity, they must stimulate productivity throughout their company by contributing quality, timely information for critical business decisions. In manufacturing, for example, errors in quality data might lead to shipping unacceptable products or rejecting acceptable products. Either condition initiates an ever more costly set of potential consequences, including: If the problems continue undiscovered or unresolved, the financial and emotional costs increase exponentially; in large companies, for example, lost customers, product recalls and law suits typically cost millions of dollars.
Whilst it would be desirable to have error-flee data to verify each critical step in manufacturing processes, it is too expensive to test every step thoughout the entire process. Instead, good data should be generated at key steps and introduce sufficient controls to quickly identify and solve potential problems. This leads to additional guiding principles: (i) For effective analytical support, introduce analysis and testing prior to high value-added steps.
(ii) Turn results around quickly. Since data is generated for critical business decisions, its value decreases rapidly over time.
Truly successful businesses require excellent technology, superior product quality and world-class customer service to achieve market leadership. This requires outstanding contributions by skilled, motivated people, thus high value-added people are essential to high valueadded organizations.
Experience clearly shows: (1) The value of good, timely data far exceeds the cost of determining it.
(2) The cost of bad data far exceeds any savings from inadequate analytical support.
(3) Problem resolution usually demands more data. This paper was read at the International Symposium on Laboratory Automation and Robotics (October 1992, Boston, USA).
For example, rnodern adhesives are used in high valueadded manufacturing such as the assembly of critical aircraft structures. It is vital to test the adhesive's characteristics prior to assembling valuable parts into a permanent structure.
In research and product development, analytical errors often cause large opportunity costs. That is the lost time of valuable people and the delay in reaching conclusions, either successful or unsuccessful. These opportunity costs are never recovered and they continue to grow until the error is detected, replaced with valid data and a new direction is set. In the pharmaceutical industry, for example, a successful, new ethical drug should achieve annual sales of at least $250 M. In this example, misdirected development which delays product commercialization costs the profit contribution from $1 million revenue per day of delay. In the past, laboratory managers responded to daily demands for analytical support. Today's laboratory managers are proactive. They seek better ways to apply technology and resources to achieve business objectives.
The companies listed in figure 1, for example, have made major commitments to laboratory automation-including more powerful computers, new instrumentation and robotics and workstations for sample automation. Their experience demonstrates compelling business reasons for their investment and the significant benefits actually achieved.

Effective investing in laboratory automation
Many automation projects require significant resource investments. These investments must be justified in terms of business value and superiority over alternative investments. Typical accounting practices approach automation justification simply as a direct substitute for people performing the same task. Less quantitative benefits, such as more timely decisions, better quality, more effective people, are often excluded from the justification. Significantly reduce analysis cost in order to routinely gather all the data necessary to solve problems quickly rather than wait for more data. Just-in-time analysis 'Timeliness of results is our challenge for the 90s. All the return on investment justifications to purchase a robot cannot do justice to the need for timeliness Timeliness in the form of robotics has replaced cost as a competitive advantage to a food company' (Hershey Foods Corporation-Appendix A, reference 4).
Miles's goal is to achieve 'just-in-time release' ofproducts immediately following manufacture and packaging. To succeed, Miles needs more analytical data and faster sample turnaround than ever before (Miles, Inc., Consumer Healthcare Division Appendix A, reference 6).
The Glaxo, Inc., Research Institute reported that about two years ago, management wanted to accelerate clinical trials for an important new drug. Rather than subcontract these assays, Glaxo's bioanalytical staff requested the opportunity to demonstate even faster turnaround by performing the assays in-house with laboratory robotics. Using a fully automated system, these bioanalytical assays were completed in two weeks (see Appendix A, reference 3).
'Successful robotic automation of key elements of the analytical process will lead to more timely and high quality decision-making_ rather than a deferral of decision-making awaiting more data... Improved quality of regulatory submissions will lead to faster approvals of new products. Timely in-process information will shorten the development cycle' (Warner Lambert, Appendix A, reference 11).
Improved precision, documentation and defensible audit trails Improved data quality and documentation are some of the most widely reported benefits of laboratory automation. A dramatic drop in cost per assay enable Squibb to provide more data with improved quality and better documentation. This investment provides Bristol-Myers Squibb with a strategic advantage in the competitive drug development business (see Appendix A, reference 1).
Significantly reduce analysis cost In many quality control situations, the cost of analytical data limits the amount of routine analysis. Typically, laboratories must generate additonal data in order to determine the cause of specific problems. Using two, fully automated content uniformity systems, Miles staff routinely generates sufficient data, in virtual real time, to correct problems quickly and ensure quality production (see Appendix A, reference 6).
Transfer valid analytical methods to multiple sites Hershey uses laboratory robotic automation in their central analytical laboratories and has transferred the technology to the main plant laboratories and in-plant mini-labs (see Appendix A, reference 4).
These results triggered a new confidence in laboratory robotics technology. Today, it is the approach of choice. US laboratories are training Glaxo people, from around the world, on the effective use of the technology (see Appendix A, reference 3).
Improve motivation, reduce turnover and enhance effectiveness of people 'When a robot is used,, one can reasonably expect to see dramatic improvements in safety, productivity and precision. Even more important is the improvement in quality of life for employees, since robots do best those kinds ofjobs which are seldom interesting or challenging for humans' (Shell Development Company-Appendix A, reference 9).
'This dramatic success generated even greater commitment and additional strategic benefits, including... energizing existing staff and attracting new people as work became less routine and more challenging' (Glaxo, Inc.-Appendix A, reference 9). 'The purpose of robotics is to gain throughput, relieve staff of repetitive tasks, permit them to use their greatest tool, their brain, and most important of all, to yield routinely precise and accurate results in a timely manner' (Hershey Foods Corporation-Appendix A, reference 4). (1) It is expensive and must be added in large increments-people can be added incrementally, but space must be added in economical units. Even with sufficient land, the smallest practical new laboratory construction would be 30 000 to .50 000 square feet. This requires an investment of between $6 and $10 M. The relocation costs need to be added.
(2) Long lead time: a decision to construct new laboratory space nust be made 18 to 24 months, or more, before it is needed.
(3) Requires extensive management time: successful laboratory expansions require management time to ensure that plans match strategic needs, plan layouts, redeploy people and instrumentation and negotiate conflict generated by the expansion.
If the average cost of laboratory space is $150 to $200 per square foot, the 'real' cost of usable bench space will be in the range of $750 to $1500 per linear foot.
Justifying laboratory automation: calculating direct cost savings The decision to invest in laboratory automation should be based meeting the stategy and financial needs of the business. Today's executives must place a value on intangibles and make them part of a business justification. Begin justification with the guidelines highlighted in figure 3.
Whether saving direct people cost is the prirnary justification or a side benefit, it's important to make valid calculations of the projected savings.
The first step is to determine average hours saved per unit of work. To do this, detc.rmine the actual effort currently expended, not the theoretical or ideal goal. Next, project 26 Determine the real business for automating this naethod or methods. Quantify the economic value of these benefits. Short-term labour savings are typically a reduction of investment-rather than the primary benefit.
If significantly lower 'cost of analysis is the primary benefit, calculate savings on the projected sample loads. Compare savings to actual experience not ideal models.
If this is new technology for you, consider a 'facilitating investment' by amortizing the learning and startup costs over potential projects. the effort required to perform the work using the proposed automated method. The difference becomes the manhours saved per unit of work. Finally, convert this to savings per week using the amount of work performed, or projected, each week.
Calculating direct cost savings: example Step l. Calculating real cost. Example: annual cost of senior Note: This is 70% of total time, which considered excellent.
Step 3. Summary Available hours to perform the job assignment is 180 days x 8 hours per day 1440 hours. The cost per hour actually performing the job assignment is $45 000 annual cost divided by 1440 hours available per year $31.00 per hour. The annual savings from saving hour per day performing the job assignment is 250 hours per year at $31.00 per hour $7500. Therefore, by saving hour per day: A $7500 investment will be recovered in year. A $15 000 investment will be recovered in 2 years.
In many organizations, the annual cost per person is much higher than this example and fewer days are available to perform the job assignment. Under these conditions, paybacks can be far faster than shown above.

Conclusion
The strategic challenges caused by world-wide competition and regulation continue to increase. People and time are our most .precious resources.
Modern laboratories must become a catalyst and role model stimulating greater productivity throughout their organizations. Laboratory managers must grow as business executives bridging the laboratory to strategy. Laboratory automation technology has demonstrated its ability to significantly enhance productivity in the laboratory and beyond. The added capacity provided by laboratory automation permitted internal running of the increased sample loadby existing staff. The initial robotic system generated these cost containment savings during 1990 and 1991.
Looking forward, MAP Scientific Operations plan to further increase capacity for even more bioanalytical assays; generated by expanded new product development regulatory requirements for more data and the routine assay of more standards made possible by automation. Their goal is to gain a 10-fold increase in assays per analyst by investing in laboratory instruments, computers and automation-supported by a highly skilled staff of automation siSentists. In addition, they expect to decrease the typical study turn-around time from six to eight weeks down to one to two weeks. By substantially reducing assay cost and study turn-around time, this centralized laboratory will attract bioanalytical work from About two years ago, management wanted to accelerate the clinical trials for an important new drug. Rather than subcontract these assays, Glaxo's bioanalytical assay staff requested the opportunity to demonstrate even faster turnaround by performing the assays in-house with laboratory robotics. Using a fully automated system, these bioanalytical assays were completed in two weeks.
These results triggered a new confidence in laboratory technology. Today, it is the approach of choice. Seven automated methods are performed routinely on four robotic systems. Only 30% of their bioanalytical assays are now subcontracted. And, the US laboratories are training Glaxo people, from around the world,, on the effective use of this technology.
This dramatic success generated even greater commitment and additional strategic benefits, including: (1) Effective methods transfer throughout Glaxo's worldwide laboratories.
(2) Energizing existing staff and attracting new people as work became less routine and more challenging.
(3) Improved analytical precision particularly through use of gravimetric techniques.
(4) Lower cost of analysis to meet the analytical demands of increasing regulation. 'Hershey uses laboratory robotic automation on their central analytical laboratories and have transferred the technology to the main plant laboratories and in-plant mini-labs. Their automation goal is not replacing people. Rather... The purpose of robotics is to gain throughput, relieve staff of repetitive tasks, permit them to use their greatest tool, their brain, and most important of all, to yield routinely precise and accurate results in a timely manner.
A major challenge to the food laboratory in the 1990s will be to incorporate the equivalent of just-in-time delivery of inventory and manufacture of finished goods. This is just-in-time results This is where robotics earns its keep; it frees staff to persue new technologies and react to one-off emergency situations to produce timely results.
Timeliness of results is our challenge for the 90s. All the return on investment justifications to purchase a robot cannot do justice to the need for timeliness TIMELINESS in the form of robotics has replaced COST as a competitive advantage to a food company'.
In a recent communication, Dr Martin summarized his thoughts: 'Laboratory robotics is not just a good idea, it is a necessary reality to address the demands placed on the laboratory of the 1990s'. They support formulation development, clinical study supplies, process development and process scaleup. The number ofdissolution sample batches remained relatively constant during the 1980s, but began increasing in 1990. The pharmaceutical development staff anticipated the increasing work demands and, in 1985, installed their initial laboratory robotics system to automate dissolution testing.
As they gained experience, a growing percentage of their dissolution testing was converted from manual to automated processing. By 1991, 90% of all dissolution testing was performed by three automated systems. During 1991, this saved 52% in man-days leading to financial savings over $500 000. From 1985 through 1991, the cumulative savings earned by automated dissolution testing exceeded $1 500 000.
Their three systems are virtually identical and are capable of running a wide range of dissolution assays. This automation not only increases assay capacity, but also automatically generates easily retrieved documentation for future reference.
j&j's approach to automated dissolution testing encouraged the rapid development and validation of automated methods and companion manual methods. The companion methods ensure a validated fall back alternative and also provide regulatory agencies with a valid method which can be performed by a non-automated laboratory.  1985 1986 1987 1988 1989 1990 1991 Cumulative Total Savings ($ 000)  1985 1986 1987 1988 1989 1990 1991 Figure 4.
its Alka-Seltzer family of antacid and cold-relief tablets. Miles produces over 10 M Alka-Seltzer tablets each day using seven formulations.
Miles' goal is to achieve 'just-in-time release' of products immediately following manufacture and packaging. To succeed, Miles ,needs more analytical data and faster sample turnaround than ever before. In essence, Miles is approaching traditional, final product quality-control at a process control challenge.
In many quality control situations, the cost of analytical data limits the amount of routine analysis. Typically, laboratories must generate additonal data in order to determine the cause of specific problems. Further in high volume production, the time delay in obtaining sufficient data leads to continuing production of large quantities of potentially unsatisfactory product.
Today, Miles has two fully automated content uniformity systems for Alka-Seltzer quality assurance. The dual capability ensures adequate testing capacity, rapid sample turnaround and back-up reliability. Miles's staff routinely generates sufficient data, in virtual real time, to correct problems quickly and ensure quality production. Their automation investment significantly reduced cost per analysis and, beyond this, they gained greater production productivity through lower scrap, reduced sorting of finished products and more rapid inventory turnover.
Alka Seltzer is a registered trademark of Miles Inc. They have applied robotic automation to tablet dissolution testing, tablet assays and dosed feed analysis. Senior management recognized the growing need for analytical support and the importance of relieving skilled scientists from routine work. They identified laboratory robotics as a new technology with the potential to meet these needs.
Tablet dissolution testing was selected for automation because regulatory trends require dissolution rate specifications for tablets and capsules. Early testing was based upon the premise cited in the USP that a single-time point determination at 45 minutes would assure therapeutic acceptability if the product was 75% dissolved. As the technology has become more extensively used, dissolution rate testing has taken on an additional role of assuring that manufacturing processes remain in control. Today, dissolution rate testing is included in a series of tests that 'fingerprint' the quality of a dosage form. During drug development, comprehensive dissolution studies are preformed for multiple dosage formulations to profile dissolution rate and stability. For immediate release tablets, routine dissolution assays continue to be single point, but sample timing is selected to provide the most information about that specific drug formulation.
The more demanding uses for dissolution data, require even greater control over assay parameters such as media composition, temperature and dissolved gas. This, in turn, requries more powerful automation to measure and control these parameters as well as perform the actual test.
Pfizer has standardized their automated dissoluton approach such that their robotic systems become virtual workstations. Early attempts to have sample submitters directly interface with the systems were unsuccessful so Analytical Research provides skilled operators to set up and run samples.
Dosed feed assays for safety assessment and metabolism studies, are also successful laboratory robotics applications. Early in the development of a drug candidate, there may not be sufficient time to develop an automated analytical method to support safety studies. The goal, however, is to use a robotic system by the time the drug candidate is in long-term safety studies.
Tablet assay automation, however, has not met Pfizer's expectations. They desire a standardized, robust and compact automated workstation. Efficient laboratory space utilization has become a strategic factor in Pfizer's laboratory automation programmes. Sandoz Pharmaceuticals is a leading, multi-national developer and producer of pharmaceutical and healthcare producs. In his keynote presentation at the 1991 International Symposium on Laboratory Automation and Robotics, David Weinstein described how robotics accelerated their drug discovery research and stimulated a more creative scientific environment.
Dr Weinstein described a new environment in which laboratory robotics plays a key role: 'The role of the research director who is the product champion is to blend together the research personnel components with the creative environment provided by mangement in order to create the successful and stable integration of robotics into the early stages of drug discovery... At Sandoz Research Institute, we have created an opportunity for enterprising biologists to develop a drug discovery programme that is heavily based on robotic microplate management systems as analysis tools. This programme was accomplished with minimum amounts of funding and a staff of no more than two over a two-year period'.
Compounds Screened There are typically three stages in the rational drug discovery process: (1) Determine the biological site or mechanism of action to target.
(2) Develop in vitro and in vivo test models, which can discriminate between compounds with effectively alter the selected biological target.
(3) Assign large numbers of medical chemists to provide rational concepts toward design of complicated chemical molecules which may achieve the desired biological response.
Sandoz have realized a dramatic increase in screening assays from their manual assay capability in 1987 through installation of the firs't robotic system in 1988 and a second system in 1990. These assays are from complex in vivo screens which increased from 100 compounds tested in 1988 to well over 500 in 1992. More importantly, automation enabled them to increase the number of assays per compound from three in 1988 to 20 in 1992. The total number of assays, therefore, increased 35 fold from 300 in 1987 to over 11 000 in 1992.
At Sandoz, laboratory robotics provides a powerful tool to automate laboratory screening and, in doing so, frees up valuable time of skilled scientists. This is illustrated by the change in bench scientist activity at Sandoz between 1987 and 1991. In analytical chemistry, this translates to a need for more accurate, more rapid and more cost-effective analytical service'.
There are many forms of successful laboratory automation: 'Robots are probably the most complex of these approaches, and should be used only when the other forms of automation will not suffice. However, when a robot is used, one can reasonably expect to see dramatic improvements in safety, productivity and precision. Even more important is the improvement in quality of life for employees, since robots do best those kinds ofjobs which are seldom interesting or challenging for humans'.
Specifically, Shell reports: (1) The first robot at Shell has handled over 40 000 samples since 1984. It paid for itself within four months and requires no more than about one hour of setup and maintenance per day.
(2) Payback periods have been six months or less for several applications.
(3) Some environmental applications have been successfully duplicated at operating locations.
(4) Robotic applications have helped minimize worker exposure to hazardous chemicals and reagents.
Shell expects the number of quantitative analyses in which robots are involved, one way or another, to increase from approximately 20% of the analyses in 1990 to over 50% by 1995. In conclusion, our experience at Shell with robotics has been a very positive one. In every case, we can identify benefits that were not foreseen in the original justification of the robotic equipment. The clinical testing industry is facing strategic opportunities and challenges.
(1) Clinical testing will increase due to our aging population.
(2) Government and third party reimbursements are decreasing.
(3) Large, efficient laboratories are likely to be the primary providerof sophisticated tests in the future.
(4) The supply of trained laboratory staff is rapidly falling behind industry needs while salaries and benefits are increasing.
(5) Regulatory requirements continue to increase.
SBCL believes that larger central laboratories can be more cost effective and afford the technology skills and automation investment necessary to meet these challenges. Their competitive strategy for the year 2000, includes: (a) Improve employee utilization. (b) Participate and assist in laboratory consolidation. (c) Invest in capital technology to improve quality and enhance service.
(d) Improve the entire testing process from specimen acquisition and ordering to results entry and filing.
A growing business segment for SBCL is drugs of abuse testing. Following initial screening, positive screens are confirmed by GC/MS. GC/MS confirmation testing requires extensive sample pre-treatment prior to analysis; and commercially available clinical analysers are unsuited to these pre-treatment procedures. To satisfy their needs, SBCL determined that automated sample prep was necessary and that it must meet NIDA In his keynote presentation at the 1990 International Symposium on Laboratory Automation and Robotics, Dr Fawzi described how laboratory automation is a strategic resource for meeting the regulatory and competitive demands of the pharmaceutical industry: 'The complexity of new drugs and delivery systems will increase, and the characterization required for pharmaceutical products of the future will be far greater than for conventional drugs and delivery systems. Recruitment and retention of pharmaceutical product development scientists requires enrichment of the job. In our industry, the first company to gain approval and market new products, usually captures the largest market share'.
At Warner Lambert: (1) The number of samples requiring analysis increased 20% per year from 1988 to 1990.
(2) The number of tests per stability sample more than doubled between 1985 and 1990.
(3) The cost for domestic stability testing of samples requiring HPLC analysis range from $400 000 to $600 000.
'Successful robotic automation of key elements of the analytical process will lead to more timely and higher quality decision-making rather than deferral of decisionmaking awaiting more data. Improved quality of information and prompt turnaround are expected to improve decision making... Improved quality of regulatory submissions will lead to faster approvals of new products. Timely in-process information will shorten the development cycle. Robotic automation has the necessary flexiblity to turn this vision into reality'. While many analytical laboratories operate as corporate cost centres, WMI-EML operates as a profit centre and must be competitive with independent testing laboratories in terms of price, service and quality. Waste Management created WMI-EML as a centralized groundwater testing laboratory supporting their landfills throughout the US and Canada. The large number of samples (nearly 200 000 in 1991), in similar matrices, laboratory automation.
As a business, WMI-EML evaluates capital investments by calculating the payback period required to recover the investment. For automation projects, the fixed cost includes system cost, set-up cost and applicable overhead. The variable cost per sample includes operator cost, overhead, chemicals and miscellaneous. The breakeven point is then the number of samples where the total fixed plus variable costs equal the revenue.
The initial laboratory robot installed at WMI-EML was applied to Chemical Oxygen Demand (COD) assays.
COD assays were selected as the first robotic application because of the rapid payback potential. For that application, the break-even point was determined to be about 4000 samples which represented about eight months work. During its four years of use, the total return on investment is approximately 600%. (1) Rapid financial payback (2) Equal or better data quality compared to manual procedures.
(4) Rapid sample turn-around-time. For example, the COD system can process 120 tests, operating unattended, during a 24-hour period.
(5) Improved staff utilization, including the transfer of human effort to innovation instead ofmundane tasks.
Dr Hockman concluded that: 'Laboratory robotics is a cost effective, automation tool as essential to the modern laboratory as a LMS or autosampler on an instrument'.