Medical Device Link.

Automated systems for the manufacture and quality control of IVDs consist of a combination of mechanical, electrical, and software components whose nature and mode of integration into a system must be specified in light of what the system will be expected to do. The manufacturer needs to thoroughly evaluate and define the tasks to be performed by the system and related process parameters.

Often, manufacturing processes for a range of related products are similar. It is natural to seek a single piece of automation equipment that can be used to perform all of these processes, but challenging to define the requirements of each process and decide how best to integrate them into one system. The development of a requirements definition, however, is central to specifying manufacturing automation systems. The key components of a complete requirements definition are:

• A specification of the operating environment.

• A specification of capacity objectives.

• A definition of the sequence of tasks to be performed by the automation solution.

• A definition of operating parameter values and tolerances for each task.

• A summary of documentation and resources required to effect implementation.

Specifying the Operating Environment

It is important that the IVD manufacturer considering adding an automated system look at the resources currently available in the production facility and determine whether those must constrain the system design. The choice between specifying according to present conditions and specifying with the intention to upgrade systematically as necessary to support the project objectives must be made.

In terms of the operating environment, the first considerations to take into account are the skill level and qualifications of those who will be operating and maintaining the equipment regularly, safety issues raised by the nature of the processes or the materials being used, and the characteristics of the materials that will be processed—such as, for example, temperature, pH, viscosity, sterility, and sensitivity to particular conditions—that may dictate production system features and materials of construction. Also important is that the space required for the automation equipment and all activities related to its installation and operation be available.

Installation logistics include planning the equipment delivery path from the loading dock, through elevators, hallways, and doorways, to its place on the production floor. The manufacturer may have to decide between having the system delivered in sections and modifying the facility to clear a path to the use location, but either is better than the stress of making unplanned equipment or facility modifications at delivery time.

Something often overlooked is planning for the staging and handling of production materials. Automation projects usually come about because of a desire to scale up manufacturing capacity, which will increase the volume of product components being moved into and out of the production area. The manufacturer should define and simulate (on paper at least) the worst-case situation, involving largest planned batch sizes. Material staging carts and the flow of material through the area can be drawn to scale in the planned automation space. And so can the space required for operating, QC, and related support personnel and their workstations. Besides planning the flow of material and personnel through the space, the manufacturer can also consider interaction with other equipment and processes. This exercise will result in an optimal specification for the new system and greatly reduced head scratching at the time of implementation.

Also requiring consideration is the capacity to deliver all of the necessary utilities to the workspace. Utility requirements may include electrical power at various voltages (single- and three-phase), compressed air, plumbing for water (for equipment and for cleaning and setup stations), waste drainage or removal, and ducting for airflow or waste air. The system will need what it needs, of course, but many design alternatives relative to the available or preferred utilities can be considered.

If an aseptic or sterile operating environment will be required for the automated equipment, it should be specified, since it will likely affect system design. Sometimes it is more cost-effective to enclose the system and maintain the clean environment within this enclosure. If a positive- or negative-pressure environment is to be maintained, then the system’s exhaust air requirements have to be considered.

Perhaps certain product components have to be maintained at defined temperature or humidity levels during processing. Sometimes, this is best handled locally within the automated system. In other cases, the entire workspace is controlled at the specified levels. The manufacturer should weigh these alternatives and include the desired solution in the system specification.

Specifying Capacity Objectives

Manufacturing capacity objectives can be described in terms of the expected range of batch sizes and the time within which batches must be produced. Of course, allowances should be made for the time required to set up and clear the area for a run and for that needed to shut down and clean up at the end of the run. Available run time sometimes can be increased by bringing in specialized startup staff earlier and providing shutdown and cleanup staff later. And run periods can span multiple shifts. The batch size divided by the number of hours available for system operation yields the minimum rate, in units per hour, at which the machine must run.

Care should be taken to represent capacity objectives realistically, since system design and cost are greatly influenced by these. Providing an expected-frequency or distribution curve along with the range of batch sizes helps. If batch sizes are frequently small, quick setup and changeover and lower priming volumes will be design priorities. If batches are frequently large, design priorities will favor speed and greater automation of material-handling tasks.

A well-planned, well-designed automation solution can be expected to serve needs for well over 10 years. While predicting capacity and functional requirements that far out is difficult, contingency plans can be made for staged implementation of functionality and capacity. This is the occasion for considering what might be needed in a few years as well as what is needed now. Future requirements can be factored into the system design. For example, the system could be designed to allow for processing 10 product units at once even though initial population of system functions might accommodate only half that number. Provision will have been made for adding later the system components required to double throughput when needed.

Defining the System’s Task Sequence

In addition to basic material-handling and product assembly steps, the functions of an automated system can include product identification or labeling steps, inspections of product ingredients and the assembly, and process monitoring and feedback. All required functions should be identified and sorted into a single machine-configuration specification. Tabulating the tasks required to complete each process is a helpful organizational tool in this regard. In such a tabulation, each process would be assigned a column and each task a row, tasks being listed in the order they are performed. Not all tasks will be relevant to each process, but automated systems can easily skip tasks when they are not needed. To make clear how processes and tasks will proceed in a system being defined, the system designers might place a check mark in cells that apply and a dash in those that do not.

To optimize manufacturing efficiency, system functions should be organized into a sequence that enables one-way flow of product through the processing steps. What is important in building a table to represent system functions is to list all the tasks required for each process in their flow sequence. In some cases, the sequence will not be strictly defined; for example, a label might be applied at various points in a process. A cap, on the other hand, must not be applied before a container has been filled. Tasks listed in the system design table may be able to be rearranged later as necessary to optimize the system configuration. Occasionally, functions may have to be duplicated in order to maintain one-way flow of product through the system.

Potential future requirements can be considered when defining the system. Spare positions in the system design can be specified to allow for later addition of functions that will come into play only when products under development are launched eventually.

In general, it is good practice to organize process sequences according to GMP objectives and the way value is added. Automated product container and component inspections can be done early on, for instance, before costly ingredients are added. After this, and still prior to adding expensive ingredients, product labeling and identification can be performed and inspected. Container surfaces can then be cleaned or treated, ingredients added, and so on. Related tasks ought to be in adjacent rows in the process table. For example, product identification might involve paper labels and, in other cases, direct ink-jet printing onto the product container or device. These machine functions can be situated adjacently, and either or both can be used as the process requires. Placing them near each other enables a single vision system downstream to inspect the results of either application.

Some tasks—general-overhead tasks rather than in-line machine functions—are not sequence specific. Examples of these are environmental monitoring, air-pressure or vacuum-level control, and reservoir level maintenance. These might best be listed in a table separate from the task sequence table, but one with columns for product processes to allow indication of when the tasks do and do not apply.

The table building is an iterative optimization process that leads from a listing of all process steps used in manufacturing for each product to a specific machine configuration. The designers review the results and seek opportunities to bring process sequences into alignment such that task sequences for all processes are similar. That will make for a simpler, more efficient automation system design. Such simplification of manufacturing processes also makes it easier to manage manufacturing activities and product quality, an important advantage.

There will be trade-offs between the implementation of process changes and efficiency objectives. A tabular system development process also serves as a means of communicating among interested parties, who will include not only technical people but also such corporate functions such as facilities management, safety, QC, and regulatory affairs. Process sequence changes should be negotiated and agreed to before proceeding so that, eventually, an automated production system design acceptable to all parties is settled on. The early involvement and continuing inclusion of every company function with an interest in the endeavor is an important component of project success.

Still, it is best to jump-start the process by having technical personnel first approach other interested company departments with a well-prepared draft tabulation of current production processes and a well-organized list of suggested changes with reasons and impacts for each change. The other parties can then identify additional impacts and considerations and negotiate an agreement regarding what will be specified for the automation system. This way, all parties will be supportive of the system that is implemented.

Defining Operating Parameters, Tolerances

For each of the automated manufacturing process steps, performance parameters and tolerances should be defined. Value ranges will vary among processes for different products. Device or container size may differ from product to product, for example. Ingredient volumes may vary likewise. The dimensions and placement of labels may shift among various products. Ideally, however, there will be enough similarity among all the requirements to allow for a single-system solution. Sometimes, of course, to accommodate the full range of requirements, it will prove more cost-effective to build multiple systems.

In specifying the task parameters and tolerances for each task at each station on the machine, the company should consider both present and future requirements. It is important to be realistic here: overstating requirements will inflate the system cost while limiting design options.

The task sequence table described previously can be supplemented with a second, more complex version that includes the parameters and tolerances for each task pertinent to each process. Two columns added to each process column create spaces for entering, in additional performance parameter rows for each task, the parameter value range and the performance tolerance allowed at a given value. For example, the tool temperature required for a given process at a particular task station might range between 100° and 150°C, and the tolerance at any given set point might be ±1°C. These figures occupy the appropriate cells. Other applicable task parameters might be component dimensions, liquid fill levels, dryness levels, vacuum levels, and so on.

This enhanced form of the table will serve to outline the capabilities required at each machine function. The simpler system function table can be a basic reference for use in fundamental discussions of system task sequences. If the automated production system consists of many processes, it may be more practical to create separate tables for each process. A final step in creating the tabular representation of system functions and performance parameters is to consolidate the parameter value ranges for each system task parameter across all processes, showing the overall minimum-to-maximum value range and its respective system tolerance.

Qualifying the System

In the IVD industry, implementing a new automated production line requires that the equipment, and the processes to be run on that equipment, be qualified. It is useful for the manufacturer to become familiar with the documentation and resource requirements for implementation and qualification when engaged in the process of defining system requirements. Suppliers of automation solutions and system components may be able to help in this effort.

Conclusion

Well-thought-out specification of automation system requirements, prepared with the involvement of all interested parties, sets the stage for smooth system and component selection and successful implementation. Who is to be included among the interested parties will depend on the nature of the project. Involving the purchasing department early on enables these expert professionals to spot relevant sourcing opportunities and provide helpful input toward choosing more-feasible design paths. Their engagement in the entire development process will also prepare them well to perform their role in system component selection immediately upon completion of the requirements definition project. In this as in everything else, communication contributes strongly to the realization of great results.