Cleanroom installation located at Createchnic AG (Nürensdorf, Switzerland). Photo courtesy of Dittel Cleanroom Engineering
This article is the first in a two-part series on the use of injection molding techniques for medical device production under cleanroom conditions. The first part focuses on design considerations. The second part will identify issues related to facilities qualification and process validation.
BASIC REQUIREMENTS FOR DEVICE PRODUCTION
Appendix I of the Medical Devices Directive contains the fundamental manufacturing requirements for all medical products marketed in Europe. Among other things, the directive states that microbiological and particulate cleanliness, and the surrounding conditions under which medical devices are manufactured, must be guaranteed. These requirements point out clearly that the air in premises where medical products are being made must be free from germs and particles.
For pharmaceutical or medical engineering enterprises, a commitment to maintaining appropriate cleanroom technology is obligatory as part of complying with normal regulations, such as the GMP requirements. Changes that occur in market conditions can also demand respective precautions from other industries. Under such circumstances, the extent of the commitment to cleanroom processing needed by injection molders depends on the product specifications. Optimal cleanroom solutions adapted to suit individual specifications must be cost-effective and leave room for expansion.
ENVIRONMENTAL SPECIFICATIONS FOR CLEANROOMS
When planning a cleanroom operation, particular attention must be paid to dust sources. Of course humans are the largest individual source of dust. Dust particles are produced by human beings and their activities in vast quantities, even though most particles produced are smaller than 0.5 µm. The number of particles measuring 0.3 µm or less produced per minute is subject to the speed and kind of movements being made. Table I illustrates the typical amount of particulate matter produced by humans making typical movements.
|Type of Movements||Numbers of Particles Produced per Minute|
|Seated or standing (not moving)||100,000|
|Seated (making slight movements)||500,000|
|Seated (moving arms or trunk)||1,000,000|
|Moving from sitting to standing||2,500,000|
|Walking up steps||10,000,000|
|Athletic activity||15,000,000 – 30,000,000|
Table I. Particulate matter produced by human activities.
In a room devoid of air currents, the human body emits dust particles continually in a radial direction. In this instance, however, dust particles larger than 5 µm are numerically unimportant, because they can be removed by appropriate cleaning methods. All the same, they must not be neglected, because their high speed of descent generally causes them to come to rest on horizontal surfaces and on or near the floor. Ultimately, they are raised as dust repeatedly by people walking around the area.
Because the constant production of dust is unavoidable, the overall number of particles must be reduced to a specified minimum using a suitable means. Subject to specific requirements, the lower the percentage of dust that will be permitted in a planned production plant, the higher the required investment for the design of the room and the selection of construction materials will be, and the more complex the instructions governing the conduct of the people who work there.
High categories of cleanliness are always associated with high investment costs. When planning, it is therefore important to ensure that the cleanroom conditions not only meet the specification profiles of the articles to be produced, but also those of the various production stations. Skillful planning can achieve different degrees of air purity at significantly reduced air volume inside a room. This will save on investment and utilization costs. After all, forward-looking planning offers a chance to design a flexible production layout. In most cases, expansion or organizational changes of a flexible layout can be put into practice at justifiable costs.
In Europe, cleanrooms of Class 6 (100,000 particles/cu ft) and those of Classes 5 to 3 (10,000 to 100 particles/cu ft) are generally specified for injection molding.
FUNDAMENTAL DESIGN CONSIDERATIONS
Cleanroom design, including the technical aspects of the premises and room, is generally a function of the cleanliness category and subsequently is subject to regulatory oversight. In order to prevent mistakes in planning, a project team should be established as early as possible. Apart from cleanroom experts and the customer's or user's representatives as well as those of the molder, the team should include specialists from the machinery manufacturer, mold maker, and material supplier. Subject to a planned production budget, it may also be expedient to consult experts from the raw materials, processing, packaging, and handling fields.
Modifying Injection Molding Machines for Device Production inside Cleanrooms. To integrate injection molding machines in a cleanroom-installed production line of Class 6 or better is comparatively easy in most cases. Machines can be equipped with either a horizontal or vertical clamping unit. Smooth, clean surfaces are required. Surfaces with nonslip or antislide coatings that cover walk-on surfaces must be removed because dirt particles will adhere to them. Connections for electrical supply lines should be installed in the machines' lower sections, close to the floor. All moving parts, particularly column bushes, should be self-lubricating and maintenance free.
Before installation and commissioning, the injection molding machine must be subjected to complete and thorough cleaning. To accomplish this, any contamination must initially be removed with conventional cleaning agents, followed by washing the machine down with cleaning spirits. From that time on, all persons working within that area must wear the apparel prescribed for that cleanliness level. For some levels, they must be dressed in special working clothes. This also applies to visitors, such as the machinery manufacturer's technicians. It is self-evident that all other cleanroom regulations must also be observed--such as absolutely no smoking within the room.
Ideally, the air-conditioning layout dictates machine installation in the production area. An optimum location for the clamping unit is directly underneath an air outlet to achieve a flow of cleaned air that is as uniform as possible over the mold.
Injection Molding Machines for Cleanroom Class 3. Injection molding machines must meet more extensive requirements for operating under Class 3 cleanroom conditions, with their outfitting governed by the products to be molded. Specifications for production plants manufacturing articles for the medical, biotech, or pharmaceutical industries are considerably more restrictive than those for other technical products. Application of a coat of antistatic paint and enclosure of the clamping unit may be necessary. Dead corners must be avoided to prevent dirt from collecting unchecked. Window frames and windows in covers must fit flush with the sheet metal on the inside to prevent dirt from collecting on protruding edges. In addition, all rubber hoses must be sheathed in plastic, and any tapped holes not used for mold retention in the platens should be closed.
In general, an almost laminar airflow is conducted through the clamping unit and thus the mold for a Class 3 cleanroom. The less obstructed the airflow through the machine, the easier it is to achieve and maintain the desired quality. That is why machine covers have to be smooth on the inside and tight at the sides. The introduction of air in a Class 3 cleanroom also affects the design of the clamping unit. In principle, an injection molding machine with a vertical clamping unit would also be suitable. In such a configuration, however, air introduction and extraction would become considerably more elaborate and therefore more expensive because the airflow must be conducted horizontally across or through the mold for extraction at the opposite side. It is possible that a different solution might be more cost-effective.
Such considerations are also of importance for the machine installation sites. If a complete molding shop is to be established in a Class 3 cleanroom, the machine siting plan must be determined in conjunction with space planning. A modular room-in-room solution is the most cost-effective and allows great flexibility. For that purpose, the machine hall can be established to conform to a lower cleanroom category, such as Class 6. On the injection molding machines, only the clamping units and any existing handling units must be enclosed by modular cabinets, if necessary. The cabinets must contain a ceiling filter for Class 3 and fans to supply precleaned air from the surroundings.
Electrical supply lines to the machines must be run as a function of the building's structural solution. If the entire shop is to be a Class 3 cleanroom, the lines must either be routed up through the floor for direct connection to the machines or enclosed and sealed within appropriate ducting. If the machines are enclosed, including partial enclosure in cabinets, lines must be run outside these cabinets. The actual connections must be close to the floor, which means below the mold area.
Before a machine intended for production in a Class 3 cleanroom may be installed, it must be given an overall, thorough cleaning outside that zone. Machine enclosure follows, if necessary, and another thorough cleaning is performed to achieve the "clean" status. From that point on, personnel must don regulation protective clothing, including hoods. Acceptance measurements that have also been specified can now be carried out.
Machine and Mold Maintenance. The maintenance of machines employed in cleanroom production is particularly important. Regular maintenance performed on the machines must be differentiated from cleaning jobs that must be completed just as frequently.
Machine maintenance is important because almost every malfunction can result in contamination of the machine, mold, or surroundings. Machine stoppages are considerably longer in these cases because of the necessary overall cleaning. It therefore makes sense to comply strictly with the maintenance intervals stipulated by the machine's manufacturer, including replacement of seals before they cause breakdowns through aging. Both machines and plants must be subjected to a weekly general cleaning to remove precipitation, dust particles, and other contamination. Depending on the article produced, cleaning may need to be more frequent. Gross contamination must be removed immediately, and if contamination should occur regularly, its source must be found and rectified.
The training of operators and maintenance personnel is also important. Experience has shown that the customary single instruction session is woefully inadequate. It is essential that employees receive follow-up instruction so that the necessary understanding is maintained and extended under difficult working conditions.
Injection Molding Tools for Cleanroom Production. The production of injection molding tools that meet relevant cleanroom specifications can be described as a specialty discipline mastered by only a few mold makers. One of the main difficulties is the restriction of lubricant use. In cases where this requirement is insurmountable, the lubricant must not be permitted to enter the mold cavity area under any circumstances; the lubricant must be diverted to the mold's inside by applying an appropriate pressure difference.
For obvious reasons, release agents are not allowed in cleanroom production. Pneumatic cylinders operated with cleanroom air are permitted for ejector movements; however, article demolding as such must not be supported by air blasts. Strippers actuated either mechanically or by pneumatic cylinders should be employed for that purpose. The positively guided mechanical version is preferred because it is more reliable, and ensures controlled demolding. With most of the other methods, a molding can stick in the mold and get deformed during subsequent mold closing, requiring the mold to be cleaned completely.
It is self-evident that sprue must be avoided. This can be achieved with pin-gating, for instance. Hot-runner molds are not always expedient because nozzles tend to leak, allowing contamination through melt or gases.
With cleanroom production, mold changes can be time-consuming and costly--particularly so in classified cleanroom areas. This becomes apparent with the preparations. Initially, the mold must be dismantled completely and cleaned under cleanroom conditions. A laminar-flow box that stands outside the cleanroom would be suitable for this purpose. The box can also be used for subsequent reassembly of the mold. After that, the mold is either encapsulated in a triple layer of film, which is then sealed by welding, or it is packed in a special transport box. The outer layer of film may only be removed in the cleanroom antechamber. The second wrap is taken off in the air lock between the two different clean zones. The inner, third wrap is only removed at the machine.
Raw Materials and Raw Material Supply. For the production of articles in classified cleanroom areas, only those plastic materials that have been produced under particularly clean conditions are allowed to be used. The characteristic profile of the molding materials employed is subject to the user's or customer's specifications, as well as the planned application for the finished articles. Some of the criteria for plastics used in medical applications are listed as: cleanliness, good rheological properties and physiological performance, biological compatibility, and color tolerance. Materials should be delivered in appropriate containers that have been sealed airtight by welding.
It is expedient for processing material to be fed to the machines by a centralized enclosed conveying system with an integrated, special extraction system. Alternatively, vacuum-operated feed systems attached to machines are feasible. All metering units must be operated with clean air. Even pipeline installations must conform to cleanroom conditions because abrasion fines must not be allowed to contaminate the plastic material. Pipe systems must be grounded to prevent them from becoming electrostatically charged.
Before they are processed, hydrophilic plastics must be dehydrated in special dryers outside the cleanroom. Under certain circumstances, it may be necessary to apply clean, dry air to the dehydrated granulate in order to remove any dust particles.
Molding and Downstream Processing. Once the machine has been equipped and the raw-material feed system has been set up, production can start. Depending on individual cases and particular regulations in force at the time, articles can either free-fall out of the machine on demolding or be removed by a handling unit. In a cleanroom production situation, a handling unit is usually mandatory. The reason: despite special protective clothing and every precaution, human beings are still the greatest source of generated dust and contaminants. Either special containers that can be sealed gas tight, gas tight bags, or pneumatic tubular conveying systems are suitable for catching free-falling articles. If bags are used, three of them must always be employed, nesting one inside the other. Each bag must be individually weld-sealed before being transported to areas outside the production zone. Pneumatic or vacuum conveying systems can be used where articles are conducted directly to workstations for finishing. These finishing stations are subject to the same basic conditions as those governing injection molding machines in cleanrooms.
Production Monitoring and Documentation. Cleanroom production without documentation would be unthinkable. The extent to which documentation needs to be applied ultimately depends on the actual use of the completed component, and the customer's specifications. All cleanroom production monitoring is, in principle, based on optimum aspects, in the interest of trouble-free operation alone.
Aside from the material-specific, article-related monitoring and checking actions, other forms of control are also required with cleanroom production. These concern regular analysis of the cleanroom air, for instance, to ensure that purity class is maintained, or special random checks of machine and article surfaces when producing moldings for the medical industry.
The correct attitude of factory employees should not be underestimated as an important criterion for quality-conscious production. This also expressly includes top management, which must comply with the same strict regulations that will become self-evident for the operators after appropriate and regular training.
Rules of Conduct for Personnel. Cleanroom working conditions cannot be compared with those maintained at normal workstations. Apart from the special rules of conduct and statutory regulations, the strain on personnel health must not be underestimated. Climatic and other conditions in cleanrooms, such as the continuous draft, can increase stress.
Cleanrooms are restricted areas and access must only be allowed to authorized persons. In general, people entering cleanrooms must be wearing protective clothing. Under no circumstances should this clothing be worn outside cleanrooms, and the clothing must be changed immediately after becoming contaminated. Naturally, smoking and the presence of food in cleanrooms is prohibited.
The mental attitude of all employees is of great importance, including the top echelons. Teams employed in cleanrooms must be prepared to accept without objection the specific demands that cleanroom operations entail. It is essential in cleanroom facilities to develop and strengthen a distinctive cleanroom conscientiousness. Accordingly, all other areas in the factory must be considered as contaminated, and for personnel to be aware of contamination is important.