The advantages of single-use systems in pharmaceutical production

Published: 22-Jul-2014

Traditionally stainless steel has been the containment material of choice in pharmaceutical production, but the use of single-use systems is growing. Richard Denk and Matthias Hänsel, Hecht Technologie, describe how disposable liner systems are now being employed

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The biotechnical industry has been a pioneer in the use of single-use equipment and has shown that it works well in an industrial setting and, more importantly, that cost savings of up to 40% are possible in some cases. In the US, some companies are looking at using more disposable facilities because it offers the opportunity to reduce production and cleaning costs and the issues of production residues and cross contamination no longer come into play (see cost comparisons in Figures 1a and 1b).

At many pharmaceutical manufacturing sites the active pharmaceutical ingredients (APIs) used today are more potent than in the past and thus more dangerous. Many of these substances are categorised as being in the Occupational Exposure Band (OEB) 5. This means that the operators must be effectively protected against exposure to the APIs and the contamination level must not exceed 1µg/m3.

The following analogy illustrates how potentially dangerous these substances are considered to be: if one were to take the volume of air in the Empire State Building, only one twentieth of a teaspoon of a toxic material would be allowed in the building to remain within the OEB 5 limits. Often there is only one possibility – to work inside an isolator. Most isolators are made from rigid stainless steel, which can be an expensive and not very flexible material to handle. The use of rigid stainless steel structures for API production gives rise to issues such as the need to clean the isolator, especially in multi-purpose facilities, which is usually a task for the quality management teams.

Hecht Technologie has developed a solution that takes the advantages of isolators and combines them with the benefits and flexibility of plastic liners. As a result, the company has designed and built a number of single-use systems.

Single-use systems can be the most effective solution when companies are faced with frequent product changes and thus frequent cleaning procedures

Single-use systems can be the most effective solution when companies are faced with frequent product changes and thus frequent cleaning procedures. For companies that handle cytostatic, carcinogenic, mutagenic and teratogenic materials, or substances such as hormones and antibiotics, the toxicity of these substances means that the operators need to be actively protected, and the cleaning procedures need to be of the highest standard and regularly validated.

In the sector of bulk solid transport, especially the discharging and filling of process equipment, single-use systems are already being employed. In an API or pharmaceutical production site, the first contact with the active substances is in the goods arrival facility. The substances are held here while samples are taken for analysis and quality control. Single-use systems are currently being field-tested for use in this area. Additional application fields are in the weighing and preparation for production or research and development departments.

In the sampling area, laminar air flow systems are commonly used. These systems protect the raw materials from contamination through the use of HEPA filtered air, but while working with the opened materials the operator is not protected against the dangers of coming into contact with the product, which must be avoided when handling highly active substances.

The Expendable Powder Sampling (EPS) system provides a solution. The samples that have to be checked are connected via liner technology to the EPS. The sampling takes place within the flexible isolator, to ensure the operator is permanently protected while working. Due to the closed sampling, neither the operator, the room, nor other samples are at risk of contamination. The cleaning requirement is reduced and the documentation process is faster. The disposable isolator can be removed and disposed of once the sampling procedure has been carried out.

Disposable weighing isolators

After sampling and approval, the substances are ready to be prepared for production and a defined amount of the product has to be extracted. In this application, worker protection also has to be controlled.

Figure 1: Example of a high containment installation comparing investment costs for a multiple-use vs single-use solution

Figure 1: Example of a high containment installation comparing investment costs for a multiple-use vs single-use solution

Figure 2: Example of a high containment installation comparing consumable costs for a rigid vs flexible disposable solution

Figure 2: Example of a high containment installation comparing consumable costs for a rigid vs flexible disposable solution

Using a similar technique to the sampling procedure, the material containers are connected via liners to the isolator. An additional lifting unit supports the handling inside the isolator. A completely new feature is the active-passive-weighing unit. Hecht has developed a system in which the weighing platform is outside the isolator while the weighing scale is inside. Using this unit products can be weighed inside the isolator even though the weighing platform is outside the liner. The weighing platform and scale are connected using a special technology that enables an accuracy up to +/-1g to be achieved. A compensator compensates for the possible pressure differences and any unwanted influence on the scale can be excluded from measurements. An integrated HEPA filter additionally supports the system.

In co-operation with Hosokawa Alpine, Hecht has also developed the world’s first manufacturing process in a disposable system, in which APIs can be micronised with the support of a disposable air separation mill. This system is used in the R&D department, where frequent product changes are required. Particularly in research labs, the toxicity of a substance is often unknown during the initial handling or contact. Therefore optimal operator protection has to be guaranteed at every point. The disposable isolator systems can manage all these tasks and many more.

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