The use of containment solutions serves to prevent contamination in three directions: contamination of the product by the operator, contamination of the operator by the product and cross-contamination between different products. In addition to the safety aspect for workers at the production site and economic losses due to loss of substance, consumer protection also contributes to the need for a containment system. A suitable containment concept can ensure that products in the food industry are suitable for allergy sufferers and that no cross-contamination has occurred from a previous process. Locally separated production lines, for example, are out of the question for many operators, as a combination of a lack of space and the variety of foodstuffs and luxury foods demanded by consumers makes it necessary to produce several products on the same line alternately.
How is the effectiveness of containment measured?
The efficiency of containment is mainly indicated by two classifications: the “Occupational Exposure Band” (OEB) and the “Occupational Exposure Limit” (OEL). The OEB describes the toxicology of the pure substance and the OEL the average concentration exposure of personnel to the active substance during an 8-hour shift.
An example: OEB-5, the current standard for many applications, corresponds to an exposure – and therefore an OEL – of less than 1 µg/m3. If this were extrapolated to the size of the Empire State Building in New York, there would be no more than one-twentieth of a teaspoon of the active ingredient in the entire building.
However, it becomes problematic when individual companies develop their own standards. Some of their requirements are higher than those fulfilled by an OEB 5 solution. To name just one example: At Roche, the equivalent to OEB-5 is called 3B. Without uniform standards, processes are more difficult to compare and incorrect information may be generated.
How is the effectiveness of containment documented?
While OEB and OEL generally specify containment targets, measurements are required to measure the effectiveness of containment systems and to document the effectiveness of these systems. The Smepac system (Standardized Measurement for Equipment Particulate Airborne Concentrations) is a method used to measure the concentration of particles emitted from a system. It defines the repeatable test processes and parameters required to assess and compare different containment processes in a plant.
The accepted test procedure uses lactose of a defined grade (other substances are possible), sets the equipment in a specific environment (humidity, temperature, number of air exchanges) and places the specified samplers at different positions. The test involves performing the designated operation and collecting air (via the samplers’ filters) for 15 min. The analysis of the filters gives the amount of lactose in a measured volume of air, which corresponds to the containment performance of the equipment. As the test is run over an average time of 15 min, this performance is called STTWA (Short Term Time Weighted Average). It is important to note that this method captures the total amount of escaping powder.
When working with potent active ingredients, often only a small percentage of the powder mixture is active, while the rest is carrier material. It is therefore important to distinguish between intermittent exposure, which occurs for example when a container with raw materials is docked onto a fluidized bed, and permanent exposure, for example from a tablet press, which is not completely safe.
Correctly performing containment exposure measurements is key to the safe handling of highly hazardous pharmaceutical substances. Fette Compacting has developed a Containment Guard procedure for exposure measurement on a tablet press. This not only allows the performance of a containment system to be tested, but also reliably planned, which increases planning reliability in corresponding projects and thus reduces costs. The method is based on the well-known ISPE guideline (International Society for Pharmaceutical Engineering). The guideline has been specified much more precisely for use on tablet presses in order to enable repeatable and, above all, comparable measurements. The basis for certification is a standardized test procedure in which the retention performance of the entire system, including the process and safety equipment, is determined on the basis of the Smepac guideline. Richard Denk, Chairman of the ISPE Containment Working Group, explains the new features of the second edition of the ISPE manual in an interview.
Other factors in Containment Guard are the positioning of the measuring probes, the location of the operators during the measuring process, the number of tablet samples and the possible operating conditions, including potential error situations. This extended procedure enables a reproducible evaluation especially for containment tableting systems. As a result, pharmaceutical manufacturers can reduce the time and effort required for set-up, testing and any improvements prior to commissioning. After successful testing, the systems receive the Containment Guard certificate. The levels of the certificate are based on the OEB limits of the containment pyramid and the values for the permitted daily exposure (PDE). The measurement logs form the basis for the risk assessment by the operator and also significantly reduce the ongoing workload after the system has been commissioned.
How does containment work in practice?
When looking at a system and its components, it becomes clear that containment is primarily a question of interfaces and how to avoid them. This is because every transition between one component and the next is a potential leak. Selecting a suitable and economical containment solution for the application requires know-how. For example, to answer the question of whether the process should be set up classically in stainless steel or with single-use technology. In addition to permanently installed isolators and production systems that have to be cleaned after use, complete processes can now also be set up with flexible film systems that are not cleaned after use but disposed of.
Operators who want to reuse their components must clean them reliably. Here, too, there are two options or philosophies available: Remove and clean everything or implement inline cleanable systems. All variants have advantages and disadvantages, and which solution is better suited to a specific application depends on many parameters – such as product characteristics, production volumes or economic considerations. In the regulated environment of pharmaceutical production, every change to the process requires revalidation – an expense that pharmaceutical companies try to avoid. This technical article describes what this can look like in solids production. In this interview, containment expert Michael Maintok, Business Development Key Technologies at Glatt, discusses the fundamental differences between various approaches. An example of a modern high-containment production facility is the recently established Pfizer site in Freiburg, whose concept was implemented with partner companies such as Siemens and GEA.
When it comes to containment, companies have a range of options to choose from and must decide which are suitable for their individual production. The basic principle here is to keep the quantity of substances escaping from the production plant to an absolute minimum. Primarily for the health of the workers and, in the case of non-hazardous substances, also for economic reasons. Technical solutions include, for example, extraction equipment at dust workstations and suitable filter solutions. Processes for filling and transferring powdery substances are particularly important, as these naturally involve open interfaces that must be kept closed to hazardous substances. You can also find help with your selection in our latest product focus on containment solutions.
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