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Originally Published IVD Technology June 2005

Processing Technologies

The Advantages of Modular Automation for Productivity and Compliance

A commonsense approach to developing IVD manufacturing processes and systems pays off for the manufacturer and equipment supplier alike.

David A. Zier and James H. Parshall

Figure 1. A modularized bioreactor process cell schematized (click to enlarge).

The rising demand for lowering the cost of healthcare is prompting changes in the IVD industry that include, significantly, improving manufacturing productivity without sacrificing quality standards or regulatory compliance. Failure to employ appropriate tools and methods to implement new manufacturing processes can have a negative effect on productivity. Overbudget projects, late deliveries, higher operational or maintenance costs than desired, delay in reaching full capacity, and gaps between actual performance and project requirements or compliance goals are possible outcomes.

It is not uncommon for medical device and IVD manufacturers to have a fractured approach to equipment acquisition and maintenance. Often, automation requirements, including design and testing, are regarded separately from their discrete-equipment equivalents. In the current cool economic climate, as technology to control and monitor manufacturing processes becomes more capable—and also more complex—manufacturers have been nevertheless finding it easier to think of automation and computer system validation as bolt-on components that mainly increase the time and costs necessary to procure and maintain a production line.

Today’s requirements for precise control and monitoring of equipment do necessitate the use of automation, however. Manufacturing equipment has limited functionality without a governing computer system, and a computer system adds no value to manufacturing without equipment to control and monitor. Therefore, automation should be considered an integral part of the manufacturing equipment and treated accordingly in engineering methodology.

Many opportunities are available to improve both the value of automated equipment deliverables and the operational productivity of the automated line that is put together. The focus in this article is on a modular design and delivery approach that takes special account of purchasing solutions from original equipment manufacturers (OEMs). OEMs, used extensively in the device industry, play no small part in a modular strategy. The automation approach proposed here involves:

• Leveraging industry standards.
• Focusing on modularity.
• Practicing active and structured vendor management.
• Establishing a robust delivery process that incorporates standards, modularity, and vendor management.

Leveraging Industry Standards

Heeding industry standards has become practically common sense for today’s manufacturers. Regulations aside, many business advantages derive from doing so. The reality in today’s competitive landscape is that, especially for smaller companies, making the most of what standards offer can spell the difference between profit and loss.

Official standards bodies are made up of talented people who represent many companies and industries. The development and release of a new standard can be a slow process; however, once the standard is issued, it is generally very robust. Leveraging standards allows a manufacturer to increase productivity by minimizing original work. Effort that has to be invested in an expensive go-it-alone strategy—a product-differentiation luxury that smaller IVD manufacturers and OEMs cannot afford—has already largely been expended through the standards-setting process. Issues and challenges have already been discovered and addressed.

Furthermore, standards promote common terminology and practices within an industry. This helps with developing user requirements, setting vendor expectations, and fostering communication between the IVD company and any OEM.

A wide variety of standards for IVD manufacturing exist, many developed by the Instrumentation, Systems, and Automation Society (ISA; Research Triangle Park, NC). ISA is an affiliate of the American National Standards Institute (ANSI) and has produced standards that relate to modular manufacturing, device-level networks, and drawing and symbols.^1-3 Standards for work processes include the good automated manufacturing practice (GAMP), which provides guidelines for the regulation and use of automated systems in healthcare industries.⁴

A Modular Approach

Figure 2. The module hierarchy of the material charging module in Figure 1 (click to enlarge).

The concept of modularity has proven itself in information technology for decades with techniques such as object-oriented programming. A similar modular approach in medical device and IVD manufacturing can be driven by leveraging industry manufacturing standards such as the one known as S88 (ANSI/ISA-88).⁵ Like taking advantage of standards, applying a modular approach to process-system design may help give many companies a competitive edge.

A module is a standardized independent component that provides process functionality and can be used to build other, more-complex components or systems. Modules are composed of physical equipment, the equipment control (often implemented in software), and requisite documentation.
For example, an IVD manufacturer may employ a bioreactor process wherein solutions are prepared, vessels are filled, reactions are managed, and finished material is discharged. This process might be visualized in a simplified schematic fashion, where the equipment is recursively modularized down to specific equipment or process functions (see Figure 1). Each module in the system may have several inputs, several outputs, and managing logic; however, from the point of view of control, the module is treated as a single entity.

The modular hierarchy of the material charging module as a component of the bioreactor process might itself be analyzed (see Figure 2). The material charging module incorporates seven device modules, each of which manages a particular physical device. There are five valves, one variable-frequency drive, and one totalizer. While there may be five instances of the valve module in this system, the valve module class was created and tested only once. The five standard valve modules were configured separately to act on the specific valves as needed.

The material selection module within the material charging module manages the coordinated action of the four valves in the valve header. It takes a command (what material to select) and translates that into an action (which valve to open), resulting in a new state for the four valves.

Figure 3. The typical equipment procurement process (click to enlarge).

The modular approach can also be applied to the environmental controls and to the device assembly operations, including molding, forming, bonding, welding, and testing. The point is that the availability of modular production line components enables IVD manufacturers to avoid the missteps in equipment delivery or in new product launch that they can no longer afford. Pricing and time-to-market pressures will drive weaker companies out of business, or at least force them into merging with stronger rivals. But modular manufacturing technology can improve the competitiveness of IVD manufacturers by conferring several important benefits in the areas of efficiency and economy (the last three affecting OEM suppliers more directly):

• A more-robust testing process improves quality and lowers development costs.
• Replication improves quality, lowers implementation costs, and speeds delivery.
• Maintenance and troubleshooting can be performed more easily and quickly.
• Process flexibility and optimization are facilitated.
• Module independence and system design flexibility make it easier for OEMs to meet specific customer requirements.
• Improved equipment quality leads to higher customer satisfaction.
• The potential for increased revenue is significant.

Robust Testing. Each type, or class, of module is constructed and qualified independently. Then, modular units from specific tested classes are combined to form higher levels of functionality, and these combinations are tested. This procedure ensures that the fundamental components used to construct bigger components, at any system level, have all been proven to work. The testing of the combined components focuses on the integration points rather than exhaustively covering all functionality, which is unnecessary. Most important, this testing strategy enables defects to be discovered early in the automation system building project, when the cost of fixing problems is lower.

Because modularization facilitates a stage-by-stage testing process that culminates at integration points and with system testing, that testing—that is, those validation and qualification activities—should not be viewed as an add-on element of equipment development and delivery. Rather, it is central to the construction of the optimal processing system.

Replicability. Modularization provides a big opportunity to copy existing modules exactly, both within one project and from project to project. By replicating modules (and the corresponding documentation) wherever possible, manufacturers minimize development and implementation time. Also, module replication reduces the risk of quality and delivery inadequacies, since the modules have already been tested and may even have been operated extensively.

Even in cases in which modules cannot be copied exactly, procedures can be developed to take advantage of work already developed and to keep the overall development and delivery processes maximally efficient. For example, while an impact assessment of changes to a module will indicate new testing required, the original documentation package for that module may still be highly serviceable, speeding the generation of up-to-date new documentation.

The bottom line is that, by replicating modules, what is known to work one place can be reused in another without concern or extra testing labor. The manufacturer’s focus can remain on system validation and qualification activities. This in turn helps IVD producers maintain compliance with the section of FDA’s quality system regulation (QSR) calling for process equipment to be appropriately designed, constructed, and installed.⁶

Maintenance and Troubleshooting. The self-contained nature of processing-system modules allows for quick troubleshooting and pinpointing of root causes of errors or inefficiencies. In addition, in this type of architecture changes to one module are much less likely to harm the functions of other modules. Because changes can be accomplished quickly with relatively little risk, manufacturers experience less downtime, both planned or unplanned. Long-term support benefits derive from applying this approach across multiple systems or projects, as well. Having a system architecture and components that are standard accelerates the learning curve and allows support personnel to be transferred among projects much more easily.

Process Flexibility. Modules designed to operate independently with configurable parameters will require far fewer hard-coded software changes when they need to be adjusted than will complex engineered systems. Productivity improves with this approach, too, because revising parameters instead of design (or code, in the case of software) takes less time to implement and involves less associated risk.

OEMs that supply IVD manufacturers also experience these benefits of a modular approach, but they enjoy certain other advantages more visible from their own point of view.

Custom Requirements. Though an OEM may offer the market a line of variously configured standard solutions, customers always have specific needs not fulfilled by the standard equipment as is. Those needs often require that changes be made to the equipment before it is shipped. A modular design enables changes in a process component to be made faster and more smoothly because modules can be swapped in and out easily to meet differing user requirements. Also, if software modules have been designed to be highly configurable, then configuration changes will be more common than code changes.

Customer Satisfaction. An OEM’s reputation can sink or soar based on its perceived ability to provide customer satisfaction. The industry is not big enough to allow successive mistakes or delivery failures to be hidden. If a customer has specific user requirements that require changes to be made in the OEM’s standard solution, a modular approach helps minimize the risk that a change to one part of the process will unexpectedly affect another. Regardless of whether changes were made or not, everyone involved wants to minimize start-up problems and see a ramp-up to full production as rapidly as possible. A modular approach produces greater confidence that the customer will find no lurking bugs days, weeks, or months after delivery.

OEM Productivity. A modularity-minded OEM can finish more projects in a given period because the projects advance more quickly or more projects can be executed simultaneously. Designs that are more flexible and robust and involve a lower defect risk provide an equipment supplier with a competitive edge and result in that OEM winning more projects. An OEM using a modular approach is well positioned to meet customers’ requirements, deliver product quickly, or simply offer a better design.

Vendor Management

Figure 4. A robust process of equipment procurement that is organized in logical sequence (click to enlarge).

IVD manufacturers very commonly build a new manufacturing or packaging process entirely or partly through OEM equipment purchases. Carefully structuring vendor management will help ensure the success of any project. IVD companies often select a vendor and then let them work too independently. Manufacturers may intend to provide oversight, but their planning and distribution of resources can fall short, or not be documented or communicated well enough.

Although most OEMs have keen expertise with their own processes or equipment, their understanding of process control and equipment automation, which may not be a core competency, can be deficient. What results is a tendency for the OEM to construct automation solutions that are not very flexible or extensible, using work practices that are less than ideal. Many OEMs engage in inefficient engineering practices. They may design a new solution for every order or develop monolithic code that is very difficult to troubleshoot and change. Delivered systems produced this way typically require relatively frequent automation software updates to correct flawed complex logic. Changes to unstructured or monolithic programming can be difficult to test thoroughly. What’s more, equipment operators have a tendency to do things unexpectedly, which introduces more exposure to software issues.

The vendor evaluation process gives the IVD manufacturer an opportunity to educate an OEM on key aspects of the industry, including quality requirements. If the vendor is not usually involved with equipping FDA-regulated companies, the manufacturer can conduct training in QSR awareness just as it does in-house, and document that activity, as part of the vendor selection process. IVD manufacturers sometimes settle for companies that have the technical muscle but not the compliance background. The result is often a tension between, on the one hand, programming on the fly and constructing without drawings and, on the other, the needs and critical quality requirements of the IVD business.

OEMs should be more attentive to hiring employees with skills in system architecture rather than just programming. There is a tendency for some OEMs to rely on software programming resources to pull the operation of the system together. In response, IVD manufacturers should elevate the importance of the automation architecture when carrying out the process of vendor evaluation and equipment selection, validation, and design. That architecture plays a key role in the success of the development and delivery of process equipment, as well as in its use, operator control, and maintenance.

Structured vendor management allows for better understanding a vendor’s capabilities, including its quality practices, technological expertise, and engineering methodology, and then implementing compensating controls to address any capability gaps that exist. The process is documented in a vendor management plan that also clearly articulates the roles and responsibilities of both the IVD manufacturer and the OEM. This plan should include an anticipatory communication strategy designed to prevent eleventh-hour scrambling caused by failure to bring up apparent issues in a timely manner. Problems with vendors are too often discovered only after equipment is well into development or is actually delivered, making changes or remediation very costly.

A vendor management plan should set requirements for the use of standards, for quality-management practices, for support after equipment is delivered, and for communicating the discovery of defects after the project has been completed. It would not be unreasonable for the plan to be included as an attachment to the commercial contract between the IVD manufacturer and the OEM.

When a modular approach to new equipment procurement is taken, it may be that existing modules can be reused for a new process. The vendor management plan should indicate how modules will be incorporated by the vendor, including identifying required training and addressing confidentiality issues. Company or site standards on unit and integration testing and design and documentation requirements can be used to communicate expectations to the OEM. This will help ensure consistency within the manufacturer’s site or global module library and thus its manufacturing processes.

Finally, ownership of new modules created, and of related documentation, should be agreed upon by the IVD manufacturer and the OEM. The approach taken should be aligned with the support and maintenance strategy of the IVD manufacturer.

A Robust Delivery Process

Choosing to leverage standards, use a modular approach, and actively manage vendors is important for project success and, ultimately, for improving manufacturing productivity. However, to achieve sure and complete success requires establishing a unified production equipment delivery process that coordinates all three practices.

Equipment procurement as commonly practiced is a process that is easy to schematize simply (see Figure 3). The box at the left of the figure, labeled “Procure equipment,” represents all of the commercial activities involved, including purchasing negotiations. This is the first step in the traditional process.

The fundamental problem with this approach is the improper order of activities. User requirements have not been defined up front; therefore, what the vendor quotes may risk failing to meet the needs of the customer. Also, no vendor evaluation is performed early enough in the process, before the authorization to construct. Assumptions made by the IVD manufacturer about the capabilities of the OEM thus carry risks of higher-than-anticipated costs, late deliveries, or gaps in functionality or quality between what was needed and what was delivered.

Because negotiations are conducted first, both the IVD manufacturer and the OEM lose commercial leverage. Someone will pay more than expected, get less than expected, or deliver more than expected in this situation.

It is not unheard of for a manufacturer to select a vendor for the reason that “they’ve done it before” and then pay less attention to the vendor’s development and delivery methodologies than is prudent. This approach is risky. A considerable refinement of the process depicted in Figure 3 has been devised, which gets around the problems just noted (see Figure 4).

The first key aspect of the refined equipment procurement process is that the user requirements and validation plan are developed before any commercial steps are undertaken. Although these deliverables may evolve during the project, establishing these important pieces of the process at the outset will help to identify specific costs and later deliverables prior to the manufacturer entering any agreement with an OEM. They are essential for ensuring conformance to QSR production and process controls from a time before selection of the OEM. In cases in which a technology is available from only a specialized OEM, this is even more critical. The user requirements specification (URS) and validation plan could very well be included as attachments to a request for proposal presented to OEMs.

IVD manufacturers would benefit from practicing the discipline to establish clear user requirements and vendor expectations at the very start of a production system development project. Engineers sometimes are pushed into developing user requirements too quickly, without much analysis and input, so that the vendor can be selected and the purchase made within a short time frame. However, when that occurs, a meaningful requirements analysis and validation planning exercise is short-circuited, which will almost always have a negative impact on the design of the equipment, its cost, or the schedule of its delivery.

As a next step, the OEM should provide a gap assessment that specifies which user requirements or activities in the validation plan cannot be accommodated. In response to this assessment, the IVD manufacturer should update the user requirements and validation plan. (Even if the updates are minimal, this review of the gap assessment and consequent activity are essential for ensuring that the system to be purchased is agreed upon, and that the defined validation strategy can be implemented.) For those requirements that cannot be met, a further assessment of criticality should be performed. It may be possible to implement appropriate procedural controls for some requirements that are not pertinent to the critical aspects of the system.

Perhaps some user requirements can be met if more financial resources or time is expended. If this is the case, the IVD company should diligently consider whether the OEM’s current offering is good enough to meet its actual manufacturing needs, even if that means relaxing, appropriately, one or more user requirements. Moving away from a standard solution toward a custom one drives up the risk of encountering design or implementation issues. An IVD manufacturer asking for changes is deviating from a design, architecture, or set of code that may have years of proven operational success. To compensate for the risk may require increasing the scope of the design qualification or testing deliverables, both of which will cost time and money.

Strategically important to the business success of both the IVD manufacturer and its OEM suppliers is to establish long-term relationships. For example, in the event that user requirements cannot be met in the short term, specific encouragement by the IVD manufacturer may result in the OEM upgrading its modules or the manufacturer finding fewer performance gaps in future equipment purchases.

The formal vendor evaluation follows the URS and validation plan review and update. As part of the purchasing controls specified in the QSR, the IVD company must establish requirements for the supplier or vendor.⁷ These requirements may be spelled out in the URS, in a validation plan, or in a separate deliverable. Only at this point is it appropriate to conduct commercial negotiations for equipment purchase.

Design reviews should be conducted jointly by the OEM and IVD manufacturer during development of a production system. A design qualification is a way to document that requirements will be met by the OEM design. Additionally, design changes should be part of the review process so that any effect they may have on requirements or other validation deliverables can be assessed.⁸

Conclusion

A modular approach to developing and building IVD manufacturing systems should result in a more robust system design, easier implementation of validation activities, and more reuse across a company’s manufacturing lines. Over time, this will lead to higher efficiency and less time spent on the development of similar systems or of systems that incorporate similar processes, equipment, or monitoring.

To introduce a modular philosophy into an IVD company to which such a concept is new may be a challenge if the proposal is seen as a change from the way things are usually done. But when engineering, quality, and maintenance personnel gain knowledge and understanding of the long-term benefits of this kind of strategy, they will appreciate the efficiency displayed in timely system development, module reuse, and subsystem testability.

A key element of this approach is the selection, qualification, and management of vendors and OEMs. The vendor evaluation and the relationship between the IVD manufacturer and each OEM are important factors for procuring needed equipment on a satisfactory schedule. Overall, incorporating the use of standards, developing or reusing system modules, being involved in design reviews and design qualification, and managing vendors systematically are choices that help ensure efficient processes and consistency in development costs.

Maintaining a qualified and validated production process according to the QSR is critical in the IVD manufacturing environment. The modular approach described here provides an efficient way to secure that state of validation. Through replication, the facilitation of robust testing, and simplified troubleshooting and maintenance, it can improve manufacturing quality. Business advantages to be realized are lower implementation costs, process flexibility, faster optimization, and, ultimately, higher revenues.

References

1. ANSI/ISA-88.01-1995, “Batch Control Part 1: Models and Terminology” (Research Triangle Park, NC: ISA Press, 1995).

2. ANSI/ISA-50.02, Part 6-1998, “Fieldbus Standard for Use in Industrial Control Systems Part 6: Application Layer Protocol Specification” (Research Triangle Park, NC: ISA Press, 1998).

3. ISA-5.1-1984, “Instrument Symbols and Identification” (Research Triangle Park, NC: ISA Press, 1984).

4. The Good Automated Manufacturing Practice (GAMP) Guide for Validation of Automated Systems in Pharmaceutical Manufacture (Tampa, FL: International Society for Pharmaceutical Engineering, 2001).

5. JH Parshall and LB Lamb, Applying S88: Batch Control from a User’s Perspective (Research Triangle Park, NC: ISA Press, 2000).

6. Code of Federal Regulations, 21 CFR 820.70.

7. Code of Federal Regulations, 21 CFR 820.50.

8. Code of Federal Regulations, 21 CFR 820. 70(g).

Associations of Interest

Several industry associations made up of OEMs and end-user companies address manufacturing-process standards and aspects of modular manufacturing. Readers interested in learning more about these topics are encouraged to review the activities and upcoming conferences of the following organizations:

ISA—The Instrumentation, Systems, and Automation Society
www.isa.org

World Batch Forum
www.wbf.org

Open Modular Architecture Controls User’s Group (recently agreed to merge with ISA)
www.omac.org

David A. Zier is a principal consultant at Quintiles Consulting (Indianapolis), and James H. Parshall is an automation department head at Eli Lilly and Co. (Indianapolis). The authors can be reached at david.zier@quintiles.com and parshall@lilly.com, respectively.

Copyright ©2005 IVD Technology