An MD&DI December 1999 Column
Spurred by FDA's 1997 GMP changes, medical product manufacturers are bringing automation techniques to the forefront of the production process.
Over the past few years, customers in virtually all industries have been demanding higher quality from manufacturers. As end-user expectations have risen, manufacturers have responded by placing a higher emphasis on achieving consistent quality results.
Within this push toward quality, the medical and biomedical industries have led the way in many respects, partly in response to the more stringent regulatory requirements in these industries and partly because of the inherent business benefits of maintaining higher quality.
Adding to the medical industry's quality emphasis were the regulatory changes brought on by FDA's 1997 revised GMP guidelines.1 The practical advantages of lowered litigation risks and reduced return and rework costs also have made quality a core strategic imperative. Due in part to this increased pressure to deliver higher quality, manufacturers have increasingly turned to automation in their facilities. The expanded use of advanced automation techniques has given medical manufacturers a robust new set of capabilities for cost-effectively building repeatability, consistency, and quality directly into the production process.
DESIGN OVER INSPECTION
Leading up to its 1997 revisions to the GMP guidelines for medical manufacturing, FDA studied the causes of production defects and field failures in medical products. Exhaustive analysis indicated that the majority of product problems could be traced back to inherent flaws in either the product design or the manufacturing process design. For the most part, the studies also found that any attempts to inspect-in quality for such products merely led to high systemic costs because of the resultant need for massive inspection programs and the waste associated with lowered product yields.
As a result of the research findings, FDA's revised GMP guidelines focused on design procedures and production methods. Similar to ISO 9000 trends in other industries, the 1997 revisions expanded the scope of quality management to encompass the underlying process issues that ultimately lead to the desired quality results.
Spurred by the GMP changes, many manufacturers have selected advanced automation as an effective methodology for improving quality in the manufacturing process. Manufacturers are realizing that automation allows them to preserve flexibility, improve throughput, and reduce cost.
Manufacturing products of consistent quality requires the ability to perform detailed production tasks with high repeatability—the bedrock of process control. Unfortunately, human labor is inherently incapable of performing a given detailed task with near-perfect consistency and uniformity. Even a well-designed human-executed task will vary in results, thereby impacting the ability to control output quality. When many different detailed tasks are strung together—as is the case with most complex assembly processes—the per-task error potential is multiplied by the number of tasks, making overall quality control an even greater challenge. In addition, human-based assembly processes are subject to such random variations as periodic staff changes and other human-related factors that require close monitoring and continuous retraining.
Within any labor-intensive production model, significant costs must be allocated for ongoing training and product inspection to achieve even a suboptimal balance of throughput and quality. Exhaustive testing can generally sort product output to achieve required quality levels; however, this invariably reduces overall yields and greatly increases costs, while rarely achieving the high process uniformity that is required by both the new FDA guidelines and the competitive requirements of today's global market.
Automated techniques, on the other hand, are inherently well suited to achieving and maintaining process uniformity. Instead of constant tinkering with human process variables, an up-front investment in appropriately designed automation techniques can establish repeatable detailed-task methods and effectively integrate individual tasks into a well-balanced production line.
From a cost standpoint, the increasing use of automation techniques is validating FDA's finding that designing-in product and process quality can ultimately lower production costs. Even manufacturers in geographic areas with relatively low production costs, such as the Far East, are rapidly turning to automation techniques because of the combined benefits of quality improvement and cost reduction.
Figure 1. This modular automation system enabled the manufacturer to achieve improved product uniformity and a 96% yield from production.
For instance, a Singapore-based major manufacturer of disposable blood pressure monitors recently installed a modular automation system (see Figure 1). The system was developed and cleanroom tested in the United States in 1995. It was then shipped to Singapore, where it was retested and validated by the manufacturer, and started into three-shift production by early 1997. Since the changeover, the facility has achieved a substantially improved product uniformity, a 96% yield from production and a radical reduction in rework costs, a 96% reduction in labor hours, and a work-in-process inventory reduction of over 90%.
MEETING PRODUCT REQUIREMENTS
Of course, the effective use of automation in medical manufacturing depends on the specific product types and the required production volumes. A production system may be a single continuous automated process or a number of distinct and separate islands of automation. Individual automated processes may be linked via synchronous or asynchronous methods. Likewise, the indexing of individual tasks can be done in a broad-front parallel manner or sequentially, in either a linear or rotary fashion.
For example, some product lines require manufacturing in huge volumes at low cost and have the luxury of almost no product alterations over many years. In these instances, the automation methodology typically consists of highly integrated continuous-motion or broad-front indexing systems that produce high volumes per system. The downside of such systems is inflexibility—even modest product design changes can render an entire system obsolete. This type of automation has been used successfully for decades on products that experience long lifetimes and little change. But today's shrinking product life cycles make the monolithic automation approach less desirable for most applications.
Standard disposable syringes provide an example of a long-life product. Their basic product designs did not change substantially over a period of several decades. With the advent of safety syringes, however, the number of design variations multiplied, and, in turn, manufacturers began competing based on product differentiation. As a result, process flexibility and the ability to extend and alter the automation equipment quickly became more important.
Synchronous indexing equipment of rotary or linear design, or pallet-based flexible automation systems are often used for product lines manufactured in large volumes but with short life cycles. A pallet-based system can be partly synchronous and partly asynchronous, or it can use either one-up or multi-up configurations on individual operations. Such systems boost overall throughput by enabling each specific operation to run at its optimal speed.
Examples of product families that require a high level of production flexibility can be seen in the new biodiagnostic technologies, which have made great strides over the past decade. A stream of new and ever-better devices is constantly arriving on the market, with successor designs rapidly replacing existing products. These production environments demand high levels of modularity and flexibility. A flexible modular system can assemble, process, test, and package a complex biodiagnostic device by bringing together a number of readily replaceable and modifiable modules in what is essentially a plug-and-play format (see Figure 2). Ideally, the individual modules also consist of standardized components that enhance both the reconfiguration and the ongoing maintenance of each process operation.
Figure 2. By bringing together individual modifiable and replaceable modules, a flexible automation system like the one pictured here can assemble, process, test, and package successive designs of a complex biodiagnostic device.
The virtues of modularity include the ability to incrementally increase production without duplicating the entire production line. For instance, if a particular operation bottlenecks as production volumes increase, modular automation allows the manufacturer to institute parallel systems or multi-up processing for that process only, to cost-effectively bring it up to speed with the rest of the production line. In addition, the inherent flexibility of a modular production line permits extensive reuse of existing equipment as product designs change and evolve. The result is a combination of shorter time to market and lower overall production costs.
Cleanroom manufacturing techniques were pioneered in response to the demands of the medical and semiconductor industries. Increasingly, as product designs shrink and become more complex, the manufacturing process becomes more sensitive to the presence of contaminants and debris. For the most part, traditional cleanroom efforts have focused on creating a controlled environment that encompasses the entire production line, including equipment, human operators, and the surrounding air space. In these scenarios, large banks of HEPA filters are used in combination with elaborate facility designs to bring the whole production area up to the most stringent compliance level for airborne particulates required by any operation (e.g., Class 10,000, Class 1000, or Class 100).
In contrast, the new wave of advanced modular automation equipment provides a more cost-effective set of alternatives in which smaller HEPA filters are integrated directly into individual pieces of equipment, thereby targeting the particulate-management investment required by each operation (see Figure 3). Creating very clean conditions within specific machine envelopes can reduce by half the cost and size of filtering equipment. In addition, it enables manufacturers to avoid much of the expense associated with designing and maintaining an entire cleanroom environment to meet the requirements of an individual process operation.
Figure 3. HEPA filters are integrated directly into individual pieces of cleanroom equipment to target the particulate-management requirements of an operation.
Some medical applications require an aseptic environment within the manufacturing process to produce sterilized products without poststerilization. Implantable devices, for example, must often be manufactured in an aseptic environment, which adds significant cost and complexity beyond that required for cleanroom certification. The design of such an environment poses far more stringent requirements for the automation manufacturer. Once designed, however, the automated approach to aseptic production is generally more reliable and maintainable than attempts to control septic factors with human labor.
TRACEABILITY AND SUPERVISION
As manufacturers shift toward an emphasis on process over inspection, traceability mechanisms and integrated process control become ever more important. Accountability for all product components, whether in accepted assemblies or not, has been a critical feature of medical assembly for many years. Integrating automated assembly techniques with integrated bar code readers or laser markers, for example, provides tighter control over accountability tasks such as tracking component ID codes and lot codes, automating serial number assignments, and labeling assemblies.
Using built-in networking and communications capabilities, automated environments can also be effectively brought within the scope of overall process control and production monitoring systems. In response to pressure from the GMP guidelines, medical manufacturers are increasingly deploying advanced supervisory systems—which far exceed individual machine process control—to provide sophisticated quality analysis and management on a plantwide basis. The use of automation in conjunction with such comprehensive supervisory systems directly facilitates overall production flow while it simultaneously employs statistical process control techniques to guide product improvement programs. As with many innovations that began in the medical industry, the use of sophisticated supervisory controls as a valuable tool for managing quality is now spreading to other industries.
In today's manufacturing environments, automation techniques have provided a foundation for migrating and replicating standardized production methodologies within distributed manufacturing facilities around the world. In the past, with a heavy reliance on human labor processes, bringing a duplicate facility on-line in a different country would be fraught with difficulties, including training issues, the translation of procedures and assembly guidelines, and the differences in labor methods and skill levels, to name just a few. With the trend toward higher levels of automation and the incorporation of user-friendly, multilanguage operator interfaces, many of these redeployment challenges can be resolved simply by replicating the equipment layout within the new location. Automation equipment manufacturers are enhancing this global deployment capability through the incorporation of metric dimensions, easy conversion to different power parameters, and built-in compliance with multiple international safety specifications.
Given impetus from FDA's renewed focus on improving the level of process quality, the medical industry is responding with the increased use of advanced automation techniques. Not only has the deployment of automation helped to provide greater process consistency and repeatability, it has also lowered overall production costs while maintaining the flexibility to incorporate product design changes.
In addition, the example of the medical industry in the use of advanced automation techniques has become something of a beacon for other industries that, while often lacking the same stringent regulatory mandates, are nevertheless under heavy competitive pressures to improve quality levels. A wide range of industries, such as semiconductors, electronics, automotive, and even consumer products, are achieving significant gains by following the lead of the medical and biodiagnostic industries in adapting novel automation systems to enhance product quality.
1. Federal Register, 61 FR: 52654, October 7, 1996.
Charles Wyle is product manager in the medical division of Ismeca USA Inc. (Vista, CA), where he specializes in the automation requirements of high-volume medical device manufacturing. He designed his first automation equipment in 1949, and has concentrated on medical systems for more than 25 years. Ismeca develops and manufactures custom-designed assembly and processing automation for medical industries around the world.
Photos courtesy of Ismeca USA Inc.