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Jennifer Markarian is manufacturing editor of Pharmaceutical Technology.
Engineering controls and safe practices for containment protect both operator and product in tablet and capsule production.
This article was published in Pharmaceutical Technology Europe, Volume 30, Issue 10, October 2018
When handling highly potent materials in oral-solid dosage (OSD) manufacturing, appropriately designed equipment and safe practices are crucial for protecting the operator from exposure and for protecting the drug product from potential cross-contamination. Containment of airborne particles (i.e., dust) is important when producing capsules and especially when making tablets. Pharmaceutical Technology spoke with Jörg Stadelmann, head of Technical Sales at Bosch Packaging Technology, about some best practices in this area.
PharmTech:What are the primary considerations for designing containment in OSD manufacturing facilities? Are there different considerations for capsule filling vs. tableting?
Stadelmann (Bosch): Containment in OSD facilities is all about maintaining the required occupational exposure limit (OEL) during production, cleaning, and maintenance. First of all, a safe product transfer into the machine is essential, as well as the transfer of the finished product from the machine to the following peripheral equipment.
During production, safe sampling and troubleshootingare important. Sampling can be done, for instance, by integrating split valves with a washing cap or with a suction point on the active valve to minimize the so-called ‘ring of concern,’ whichis the ring on the split valve between active and passive containment parts of the machine.
The use of endless hose ejection systems, glove ports, rapid transfer ports (RTP), and H13/H14 high-efficiency particulate air filter systems are further options that are important not only for sampling but for the complete containment process.
To uphold the required OEL during cleaning between and at the end of batches, the machine can be accessed via gloves, while the remaining product can be pre-cleaned with an integrated suction hose. Fine mist from the spray nozzles binds airborne particles. Manual or fully automated washing-in-place (WIP) processes can be used.
As far as maintenance activities are concerned, it is important to seal the drive section room, for example through bellows, double, or air-flushed seals, as well as negative pressure in the production room.
The more a machine is automated, the less operator intervention is required, which naturally reduces the risk of exposure to highly potent products. With some of our fully automated capsule filling machines, intervention is not required at all, apart from very rare interventions. Bosch has also developed a ‘closing force detection’ to ensure that only completely closed capsules are transferred into the good capsule ejection area, so that the contents of open capsules will not contaminate this area.
In general, the main considerations for containment capsule filling and tablet pressing are identical. However, tablets will create additional dust before coating due to additional transportation and handling processes. Hence, the processes following tablet compression must be designed carefully to avoid contamination of the environment.
PharmTech: What types of engineering controls are available?
Stadelmann (Bosch):Engineering controls include monitoring of the negative pressure in the cabin and the overpressure of the inflatable seals. Redundant systems can be designed in many different ways; two examples are a combination of inflatable and static seals and establishing negative pressure in the production cabin by an exhaust system and vacuum pump. In the event of a system failure, warnings should be issued. Before production starts, the production cabin must be checked for leaks, and a glove testing unit performs pressure decay tests of the gloves before the batch starts. In any case, a room contamination control process must be established, which includes cleaning procedures, swabbing, personnel protective equipment (PPE), and personal monitoring.
PharmTech:What are some best practices for handling dust created during manufacturing with highly potent materials?
Stadelmann (Bosch):My main credo would be to avoid or at least minimize dust as much as possible. A ‘no cap, no fill’ function on the dosing stations definitely helps. Otherwise, additional suction points in the machine chamber and integrated suction hoses for pre-cleaning after batch completion are a good option. One of the most important factors of containment machine design is negative pressure in the production chamber. At Bosch, we have created a sophisticated zone concept with pressure barriers during production.
Hygiene and cleaning ability are also important factors, which can be influenced by the choice of surface material and cleaning media. Wetting (i.e., creating fine mist in the machine chamber to bind airborne particles before opening the equipment) is another possibility to reduce dust development, as well as surface pre-cleaning by WIP. And, most importantly, the use of suitable peripheral equipment (e.g., dedusters) can help a lot. It is extremely important to always check the entire system for adequate product handling.
PharmTech: What are some best practices for containment during sampling?
Stadelmann (Bosch):Sampling is a crucial step that requires systematic monitoring by the technical staff. For sampling there are both manual and automated samplers.
With our Bosch GKF capsule filling machines, we use an integrated in-process control (IPC). Samples are taken automatically, weighed, and transported to a sample container-of course, all contained. The weight results are recorded in the batch report.
There are several possible systems that can be used for containment during sampling. For instance, an endless hose system offers the possibility of crimping or cutting off during production. Other options are a contamination-free removal of the complete sampling system, rinsing the complete system at the end of production, or attaching a split-butterfly system.
PharmTech: What are some best practices for cleaning and maintenance of equipment in containment? Can you describe best practices for manual cleaning and explain when automated, wash-in-place systems should be used?
Stadelmann (Bosch):After the end of a batch, the first step is preparing the machine for cleaning. Glove ports allow the operator to access the machine through the closed machine doors. The safe transfer of size parts out of the production chamber can be done via RTP, while the remaining product is pre-cleaned with an integrated suction hose. Fine mist from the spray nozzles binds airborne particles.
If products with an OEL < 1 µg/m³ are manufactured, a WIP process is mandatory. It should therefore also be considered to wash the interfaces, pipe work, and peripheral equipment. Apart from occupational safety, it is paramount that product safety is considered and cross-contamination from one product to another is avoided. For this reason, validated cleaning procedures must be performed, monitored, and documented.
Pharmaceutical Technology Europe
Vol. 30, No. 10
When referring to this article, please cite it as J. Markarian, "Optimizing Containment in OSD Manufacturing," Pharmaceutical Technology Europe 30 (10) 2018.