Plastic Injection Molding under Cleanroom Conditions

This article outlines the challenges that have to be mastered during injection molding and the subsequent assembly and packaging in volume production, and which processes and control mechanisms are required.

You can find the subtopics of this article in condensed form here: cleanroom production to ISO 8 and ISO 7, maintaining the cleanroom outside production hours, and conduct within the cleanroom.

At RKT, we specialize in manufacturing demanding medical components under cleanroom conditions using the plastic injection molding process. The groundwork for this was laid in 2006 with the realization of production for the first medical components and the associated establishment of an ISO 8 cleanroom at the Roding site. Initially, this was a customer requirement for manufacturing plastic parts for insulin pens.

A new challenge arose with the inquiry for analyte-free production of PCR test cartridges. The PCR test enables immediate determination of results for the detection of pathogens – including the SARS-CoV-2 pathogen – at laboratory quality in less than an hour. With the microfluidic cartridges, extremely fine structures are created during injection molding. These cartridges are filled with reagents that respond specifically to, for example, SARS-CoV-2 and enable a fully automated analysis directly at the point of care.

In production, it is not only a matter of complying with certain particle parameters, but in particular of preventing the introduction of foreign DNA or RNA. In principle, the requirements for the cleanroom technology are the same as when the focus is on particles. However, for the air to achieve the required cleanliness and freedom from analytes, certain filters must be installed that regularly filter both the incoming air and the air inside. Technically, it is entirely possible to filter out microorganisms and viruses; nevertheless, it is problematic if the germs have already found their way into the cleanroom. As a rule, this happens via human skin and is difficult to prevent. To prevent the unwanted target nucleic acid sequence of the pathogens – which is to be detected later with the test cartridges – from entering the cleanroom, however, we have defined strict measures for the cleanroom staff: every employee who comes into contact with the product is tested for the target germ in advance, with their consent – in the case of the SARS-CoV-2 pathogen, by means of a daily rapid antigen test – to ensure that no introduction of this target RNA can occur here. Should an employee be carrying the pathogen, they receive a ban on entering this production cell.

Everything depends on the product when it comes to planning and designing a cleanroom. The customer generally defines the product risk and the hygiene requirements. Many customers can provide very precise specifications regarding classification and other requirements, while some start-up companies without experience in the industrial volume production of medical components need expertise and consulting from the plastics specialist. Once these basic requirements have been clarified, the available production area in the cleanroom can be planned. There may be especially sensitive process steps, as in the case of the PCR tests, where freedom from analytes was the highest requirement. In this case, a sterile bench was provided within the cleanroom that works with UV light and can kill germs at certain process steps by means of the UV light, thus representing yet another safety level. In this way, individual solutions can be found and tailored to the respective product. Such a workbench solution within an existing ISO 7 cleanroom also enables a higher cleanroom classification to ISO 6 for the respective manufacturing steps.

For more complex manufacturing operations involving several processes such as injection molding and subsequent assembly, it is advantageous if all work can be carried out within one cleanroom without passing items in and out through airlocks. In the production of a cartridge for a cell therapy for leukemia patients, these various process steps can—in terms of space capacity—be mapped within a single cleanroom, since the product is produced on demand and not held in stock.

Other products, such as the PCR cartridge for the detection of SARS-CoV-2, are produced for stock due to the varying call-off quantities – significantly fewer in summer than in fall/winter. But since clean storage space within the cleanroom would be far too costly – the upkeep conditions of a cleanroom mean a great deal of energy, electricity, and effort – the pre-produced plastic cartridges, which are only filled with their biochemical reagents and made ready for use later, must first be packaged and passed out through the airlock to be stored outside. For this purpose, the parts are double-bagged and stored in plastic containers in high-bay racking. For further processing in the next cleanroom, the outer bag is removed in the material airlock as part of the defined airlock-in procedure, and the inner bag with the component can be brought into the cleanroom, where it is opened and processed further. The cleanroom is therefore always planned and used exclusively as a production area, never as a storage area.

Overall, cleanroom production depends on a high level of commitment from employees. When employees identify with the cleanroom requirements, this is also reflected in inconspicuous monitoring results. A hygiene manager regularly checks compliance with the cleanroom rules on site and confirms a high degree of discipline among colleagues. The requirements are high: from day one, training sessions are part of the daily routine for new employees. Even the correct donning of protective clothing—without already contaminating the outsides of the suits in the process—takes practice. The slow, even movements that work in the cleanroom requires must also be trained. The removal of personal items (such as jewelry) and the observance of a certain waiting period after smoking, to avoid nicotine particles, are likewise among the obligatory behaviors in the cleanroom.

Depending on the cleanroom class, monitoring tracks either particles or germs. In an ISO 7 cleanroom, the focus is on avoiding particles and dirt. With GMP Class C, the aim is additionally to limit the microbial load. In principle, neither the cleanroom and ventilation technology nor the gowning concept differ for the two classes. The measurements that have to be carried out, however, differ fundamentally. Our ISO 7 cleanrooms are tested for both particles and germs, so that different components can be manufactured here according to requirements. For ISO 7, airborne particle measurements are decisive. For this purpose, the particle counter is placed in the cleanroom, draws in the air, and evaluates how many particles per cubic meter are contained in the air. Depending on the size of the cleanroom, several measurement points within the cleanroom must be evaluated.

Assessing the microbial load for GMP Class C is somewhat more involved. For contact plate samples, certain sampling locations in the cleanroom are defined using a risk-based approach, at which agar plates are applied as a culture medium. These are incubated in the laboratory for a few days to check whether the colony-forming units (CFUs) remain within the defined range.