Choosing and Using Clean-in-Place and Sterilize-in-Place Systems

Sterilize-in-place (SIP) and clean-in-place (CIP) systems can be used in various pharmaceutical manufacturing operations to automate cleaning and sterilization. Pharmaceutical Technology spoke with Klaus H. Schreiber, marketing and sales for Pharmatec, a Bosch Packaging Technology Company, andKlaus Ullherr, product manager at Bosch Packaging Technology, about the key considerations for choosing and using such systems in aseptic filling.

PharmTech: What are the key considerations for using/installing CIP/SIP systems in an aseptic filling process?

Schreiber (Bosch): An SIP system is usually combined with a CIP system to ensure the final and automatic sterilization of modules or a complete system before the next batch is produced. In general, SIP systems reduce the handling of parts or modules to be sterilized. SIP may be required if the production exceeds a certain size, weight, and level of complexity. The automated SIP process with validated parameters ensures a reproducible result and at the same time monitors and records critical process parameters, which is a must in industrial pharmaceutical production.

Aseptic handling is always critical at the interfaces between different systems or whenever human interference is required. Potential contamination by humans, as well as faulty operations or non-compliance with standard operating procedures in aseptic processing, is considered a risk. Automated processes (like CIP and SIP) can significantly reduce the need for, and thus impact of, human interference and ensure sterility. When highly potent or toxic ingredients or APIs are handled, CIP systems help protect both the operators and also the environment from exposure. Prior to disposal, any liquid waste will be chemically and thermally inactivated.

Ullherr (Bosch): When it comes to the actual aseptic filling process, the benefits of a CIP/SIP system primarily depend on the level of production. From a pharmaceutical point of view, it makes more sense to sterilize filling paths when they are already installed rather than to install them after sterilization. The latter has to be carried out manually and is more prone to human errors. Using a CIP/SIP system removes the operator as a cause for possible contamination. Aseptic handling is reduced and the system does not have to be dismounted.

The use of CIP/SIP systems is recommended for the production of large batches and toxic products since the initial investment for implementing CIP/SIP systems is comparatively high. Such systems need space, and the process can require a considerable amount of time. For smaller batches, the installation of CIP/SIP systems is not efficient, as downtimes might be too long. Contract manufacturers are also less likely to use CIP/SIP systems since a large number of different products and formats require higher validation efforts.

As an alternative, single-use, prevalidated, preassembled and presterilized parts, including hoses, product bags, filling needles, and tubing, can eliminate the loss of capacity resulting from lengthy cleaning validation as well as the risk of contamination between batch runs. They also reduce the amount of cleaning media and energy. Eventually, each customer’s decision depends on the following factors: economic evaluation, anticipated risks, and established processes.

PharmTech: SMB, a Bosch Packaging Technology Company, recently introduced a patented energy-recovery concept for hot-water shower sterilizers, which is described in Pharmaceutical Technology's Equipment & Processing Report.