Trend Report: Containment
Containment Calls for Paradigm Change in Solids Production
Reach may be forcing chemical producers to pay careful attention to occupational safety, but the number one market driver for containment solutions is the pharmaceutical industry, according to Fred Lonzer, Head of Sales and Marketing at the Müller Group which specializes in packaging and handling systems. Mass production is being replaced to an increasing extent with smaller batches and greater flexibility coupled of course with maximum safety. "We are working closely with isolator manufacturers in this segment to develop packaging units which have two interfaces. Reducing the number of interfaces makes the process safer," explained Lonzer.
Fritz Martin Scholz, Product Manager at the Bosch Packaging Technology subsidiary Hüttlin, also reported that the pharmaceutical industry in particular (e.g. for cancer drugs) has been driving demand for containment systems in recent years. For companies which have production operations in high growth regions, the active ingredient and the sales market were important considerations when decisions are made to produce with local or European equipment. Scholz is convinced that process systems "Made in Germany" offered leading-edge quality.
State-of-the-art systems offer features which are important for containment. According to Scholz they were able, for example, to detect possible faults and interruptions in the product flow and initiate corrective action without the need for manual intervention. It is often the small details which cause real problems. Plant operators tend to underestimate the problem potential and then find themselves confronted with unexpected situations. For example, where does the waste water go after cleaning? Then there is a crucial decision to make: Do I choose steel or single-use applications? Companies such as Hecht market isolator systems with disposable foil, but "throw-away" technology is not the solution of choice for some manufacturers. Hecht's emphasis is still on stainless steel systems.
Containment Alone Is Not Enough
Plants operators have to clean all components which they will reuse. Again, there are two options/philosophies: removal of everything for cleaning or systems that can be cleaned in-line, in other words manual cleaning or CIP/SIP systems. Andreas Bürckert, design engineering team leader at the packaging machine manufacturer Bausch+Ströbel, explained the advantage of the latter approach: With CIP/SIP, the process could be validated because the operations took place under machine control. The result is uniform cleaning quality and a defined time sequence.
Also less manual intervention is needed by workers who would otherwise have to remove the components for cleaning by hand. There are fewer potential hazards and less time and effort are needed. Bürckert reports that for efficiency reasons, more and more plants operators are running their systems in parallel. While the CIP/SIP program is running on one system, production continues on the other system, and this reduces changeover time. If a plant operator decides to use automatic cleaning, this does not necessarily mean that the technology is deployed throughout the entire production line. CIP/SIP could also be part of hybrid systems, where some of the equipment is cleaned and other equipment is single-use based, he added.
However well-designed the solution is, no technical system provides 100 % containment. Appropriate measurements must be taken prior to commissioning to assess compliance with the specified limits. The Ispe Good Practice Guide "Assessing the Particulate Containment Performance of Pharmaceutical Equipment" describes how users can measure the air concentration and surface contamination and compare them with the threshold value. Even on what is thought to be the best containment system in the world, caution is advised. Be confident, but check things anyway.
It cannot be stressed often enough that containment is primarily about interfaces or, to be more precise, avoiding them. Any break in containment when moving the product from one process step to the next puts humans and the end product at risk. Ispe has obviously given serious thought to this, for example with the Pharma 2025 initiative which provides recommendations for future development: It is essential that containment is integrated into the process and not adapted to the process. At the moment, in many cases process systems are not self-discharging and have to be opened, and that creates a break in containment. There is a need here for new, innovative solutions. Another key question is what role humans will play in future production environments for highly-active substances.
Denk adds, that the threshold values were now approaching the current limit of 1 ng/m3. Current cancer therapeutics designed for targeted treatment, which contain substances that are extremely active, were getting closer and closer to the single-digit nanogram range. The specification for two new products recently introduced in the US is 0.1 ng/m3. Measurement methods also continued to improve, and it was only a question of time before it is possible to detect such low threshold values. Finding suitable containment systems was likely to present the same challenges. Unattended, robot-controlled systems were one possible option.