Minimizing Contamination in Tubes
Pharmaceutical tubes demand the utmost in low-germ and low-particle purity to protect sensitive pharmaceutical ingredients. Tube makers must keep this in mind during manufacturing. That is why Karl Höll GmbH & Company KG (Langenfeld, Germany) has developed a three-zone concept for manufacturing the tubes that minimizes the levels of chemical, biological, and particulate contamination.
The manufacturing of collapsible aluminum tubes can be divided into different steps: blank tube fabrication, the coating of both the inside and outside of the tube and the printing of the tube, tube coning and closure application, and the packing of the finished tubes. By performing these steps in separate zones and by controlling the environment in which the steps take place, tube manufacturers can nearly eliminate contamination.
During manufacturing, the tubes are subjected to extremely high temperatures: about 212°F during predrying and 750°–840°F while in the annealing oven. Postdrying temperatures are usually above 320°F. All bacteria are killed at these temperatures. The clean area begins at this point, namely at the transition from the drying oven to the capping station. From this point, the tubes are subjected to only minimum levels of contamination and no production steps are permitted that could significantly raise such levels.
The only machines inside the cleanroom area are the automatic capper, the latex sprayer for sealing ends, and, if necessary, the coning station and the packing system.
Transfers from the black production area to the cleanroom area are only possible via transfer locks, which are defined as gray areas. The doors on either side of the transfer locks are designed to open one at a time in order to maintain the isolated atmosphere. In addition to these transfer locks, there are also others designed for the transportation of materials in and out of the zones. The three zones are the black production area, the cleanroom area, and the gray areas.
What maintains the clean environment is the air-conditioning and ventilation system that works in conjunction with special filters. This system maintains the air purity at 100,000 particles/cu ft in the cleanroom and down to 10,000 particles/cu ft at the packing stations.
A mixture of outside air and recy-cled cleanroom air is fed to the air-conditioning and ventilation system. This air—nearly 953,500 cu ft/hr—is first prefiltered in a ventilation device and is either cooled or heated, depending upon requirements, before being fed to the cleanroom via a central system of ducts and filter hoods with high-efficiency submicron particulate air filters. A defined difference between the parameters for feeding and extracting air secures an overpressure in the cleanroom. This overpressure ensures that no unfiltered, contaminated air from the black area can get into the cleanroom. In addition, particles that may still be present in the filtered and conditioned air are kept close to the floor by the overpressure. Laminar-flow devices positioned above the packing stations filter the air further to provide the best possible protection.
Analysis of the air at the packing stations as well as from other cleanroom areas has shown that contamination is well below the required limits. Microbiological examinations of the tubes revealed no fungal or bacterial contamination and found particulate in a very low concentration, well within GMP guidelines.
Such data demonstrate that the three-zone concept can effectively minimize contamination. While some pharmaceutical products may not need such pristine tubes, the process is ideal for those that require the lowest level of contamination possible.