Processing Technology for Ready-to-Use Containers for the Filling Lines of Low Performance
Unica Engineering professionals prepared the text for the publication based on the article published in CleanRoom Technology, October 2016
In his article, Mr. S. Morley, vice-president of Noxilizer, describes a new technology of biological treatment of the outer surfaces of containers with disposable Ready-to-Use syringes while passing through the insulating barrier of the filling line.
Why does the cGMP abbreviation contain a small letter "c", which means "current", i.e. current Good Manufacturing Practice?
Current technologies are being improved, new technologies are being developed to improve quality, reliability and safety.
Several years ago, “Getinge La Calhene” presented new system SterStar, using a directed electron beams to biologically clean external surfaces of RTU-containers (RTU - Ready ÒîUse), containing ready-to-fill / use disposable syringes while passing through the insulating barrier of the filling line.
It used to be a revolutionary solution, allowing the use of high-performance production equipment operating at a rate of 6 containers / min or 600 syringes / min. The main problem was to provide the same 6-fold reduction in spore formation under the edge of the lid, where Tyvec material was adhered to the flange of the container. When the lid was removed immediately before filling, the actual barrier created from the material immediately disappeared and allowed contamination to enter the container.
Electron beams proved to be an acceptable solution only for high-performance pharmaceutical productions, and Getinge has installed more than 20 such systems since 2002.
The electron beam system is a complex equipment. As a rule, three electron beam accelerators are used to create a triangular curtain through which the containers enter the conveyor belt. When the electron beam reaches the metal surfaces, X-rays are formed, so the entire system must be shielded with materials containing lead, and the conveyor belt must be in a "labyrinth", from the point of view of personnel safety. Apart from that, some ozone is generated during the process and it must be removed by the ventilation system.
The system is rather cumbersome (dimensions: 1m x 2m x 3m), heavy (more than 3 tons) and requires significant capital investment. It requires a lot of space and the connection to the energy. Such investments and energy costs are fully justified at high productivity of filling lines (400-600 syringes / min). However, it is difficult to assert that such costs will be adequate for lines with lower productivity (100-200 syringes / min or 1-2 containers / min).
Modern solutions for filling lines with low performance (<4 containers / min)
For biological cleaning of containers, when they fall into isolated filling lines, automated chemical processing can be used.
Gas plasma with low temperature and pressure can also be used, but this process is not only time-demanding, but it does not provide a 6-fold decrease in spore formation, and only reaches 4-fold, which does not always suit the manufacturer.
An alternative to automated processes can be a combination of manual processing and chemical decontamination. However, it should be kept in mind that any process performed manually is unstable and involves a greater potential risk than automated. While using this combination, the initial costs are not large, but the current costs (staff costs) and the costs of re-validation and ongoing monitoring can be significant.
Over the last year, Noxilizer has developed a solution for lines with low capacity, allowing 6-fold reduction in sporulation on all external surfaces, including critical contact points for Tyvec material with the lid of the container. This technology is based on the use of nitrogen dioxide (N02) as a sterilizing agent. Its effectiveness was proved: the substance is used to sterilize medical devices (the FDA has confirmed this use).
Being a gas that does not condense on evaporation, N02 is easily and evenly dispersed, and then removed during airing. Some publications provide a comparative analysis of the use of hydrogen peroxide and N02 in terms of biological decontamination and, if we add up to the above, N02 has the following advantages:
• the total time of the disinfection process using N02 is 50% less than when using hydrogen peroxide
• 6-fold decrease in spore formation (G.stearother-mophiles was used as an indicator)
• rapid airing time (aeration) with a decrease in concentration to 1 ppm, and then in just a few minutes, a decrease in the concentration to levels ppb
• possibility of use for oxidative sensitive biological products
• the simple and safe production of N02 from air using electricity, no need for the operator for the production, storage and transport of hazardous substances
• N02 penetrates better into various cavities of surfaces, taking into account their geometry, than hydrogen peroxide
• easy-to-use decontamination equipment.
In order to demonstrate 6-fold reduction in spore formation at the junction of the lid of the container with the Tyvec cover material (worst case), it was directly treated with liquid spore suspension and then dried and indicated with a bioindicator as "B1" at a concentration of 106 spores / sample. After that, all samples were subjected to the decontamination process with N02 and tested. All samples were inactivated.
The total process time was 15 minutes:
- 1 minute - total humidification
- 8 minutes - dosage
- 6 minutes - ventilating to a concentration of 1 ppm.
Thus, innovative development meets all the necessary criteria. It is relatively compact, requires a minimum of energy carriers, and investment in it is adequate for the manufacturers who use filling lines with low performance. The development provides 6-fold reduction in spore formation for all surfaces. Disinfection is carried out automatically, it can be easily validated taking into account the small amount of oxidants (in terms of environmental protection) and does not require high costs. ■