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Valves for the pharmaceutical industry: How valves ensure the quality of medication

 

Valves for the pharmaceutical industry: How valves ensure the quality of medication

The average age of the world’s population is rising, and so is the need for new medication and progressive production processes in the pharmaceutical industry. Diaphragm valves play a key role in securing efficient and contamination-free production.

Infographic demonstrating the increase in the global use of medicines

We need new approaches for medication

The average age of humans is rising – and so is the demand for medication. The United Nations estimate that the number of people older than 65 years will have increased to 2.2 billion by 2070, when they will outnumber children for the first time. This development will lead to higher numbers of patients with non-infectious diseases, such as cancer or diabetes. The European Cancer Information System expects the number of cancer cases in the EU to have grown by 18 percent by 2040. Also, living standards are rising in countries such as China, India and the Asia-Pacific region. Global demand for medication has grown by 14 percent in the last five years, and is forecast to rise by another 12 percent by 2028. This equals an annual 3.8 trillion defined daily doses. To cope with these developments we need new approaches for medications – and reliable, safe procedures for producing them.

Biologics offer new opportunities

An especially dynamic field of developing new medication is that of biologics. These medicines are produced using living cells into which human genes have been introduced. They enable highly precise and often very effective treatment approaches that could not be achieved with conventional medicines. For example, gaining insulin from bacteria or yeast cells rather than from the pancreas of animals has made its production more reliable and efficient. Another example is that of monoclonal antibodies that are used to treat cancer and autoimmune diseases, e.g. Trastuzumab for breast cancer and Adalimumab for rheumatoid arthritis.

As biologics are often large, complex molecules such as proteins or antibodies, produced in living cells, their production differs considerably from the chemical synthesis of conventional medication. Biologics production is a complex process that requires precise control and specialised technologies.

The first step is to identify and isolate the gene for the required protein or antibody. This gene is then integrated in a human or animal host cell, a bacterium or a yeast cell. This is what will produce the required protein. About 80 percent of all biologics are made using CHO cells (Chinese hamster ovary cells), all of which are traced back to cells from the ovaries of a single Chinese hamster that were extracted at the University of Colorado in 1957.

During cultivation, also called the upstream process, the altered cells are cultivated in bioreactors, where they produce the required protein. Bioreactors may comprise several thousand litres and are designed allowing for precise control of factors such as temperature, pH, oxygen feed and nutrient concentration. After the cultivation, the cells and the culture medium are harvested.

Biologic medicines account for 46 % of the total medications sold worldwide.
Biopharmaceuticals have a share of 59 % of newly authorised drugs in Germany

This is followed by the downstream process, where the culture medium with the cells is purified. Filtration, centrifugation or chromatography remove cell debris, by-products and other contamination. Finally, the protein is processed to achieve a stable formulation. It is then filled into small bottles, syringes or other administration types under sterile conditions. In all these processes, valves such as KSB’s SISTO-C diaphragm valve are key in providing accurate control.

Infographic illustrating the share of biologics among global medicine sales

Biologics are growing in significance

Biologics have largely gained in significance over the last decades. By now, they make up 46 percent or almost half of all medicine expenses worldwide, and their market share is growing quicker than that of other drugs. They are distinctly ground-breaking in treating complex diseases such as cancer, autoimmune diseases and genetic disorders. In Germany, they accounted for about 59 percent of all newly approved active substances in 2023. A growing number of biologics start-ups is driving innovation further and is now responsible for 65 percent of all molecules in the research and development pipeline. Progress in gene therapy, cell therapy and mRNA technology has opened up new opportunities of treating previously incurable diseases, including hereditary disorders and degenerative diseases. With these technologies developing further, the impact of biologics in medicine will keep increasing. It will fundamentally change the way we treat diseases.

Complex processes require precise control

The production of biologics is a complex process that places high demands on valves. As modern bioreactors are usually fully automated, they require valves than can be integrated in a process control system for all production steps to be precisely monitored and controlled. The content of oxygen, CO₂ and nutrients in the bioreactors has to be controlled accurately as any fluctuations could impair the growth of cells and the quality of medicines produced.

Hygiene is particularly important for pharmaceutical valves because contamination with bacteria, fungi or viruses can lead to costly production failures. Right from the development phase, attention has to be paid to cleanability, self-draining ability, zero dead volume, and suitable materials. During production, high quality standards have to be met to ensure the required surface quality. Also, the valves should be suitable for clean-in-place (CIP) and sterilise-in-place (SIP) processes, enabling them to be cleaned and sterilised without removing them from the system. To meet these requirements, pharmaceutical systems are subject to stringent validation processes, for example to the Good Manufacturing Practices of the EU or the Guidelines of the International Society for Pharmaceutical Engineering (ISPE).

SISTO-C diaphragm valve in T-pattern and straight-way pattern

SISTO valves for special requirements

SISTO Armaturen S. A., which is part of the KSB Group, is specialised in manufacturing diaphragm valves, many of which are used in the pharmaceutical industry. In these valves a flexible element made of elastomer or plastomer, also called a diaphragm, regulates the throughflow and ensures that no mechanical parts will come into contact with the fluid. The SISTO-C valve, for example, has been specially developed for the high demands of medicines production. The diaphragm is made of EPDM or TFM. They are resistant to high temperatures and aggressive cleaning agents in CIP and SIP processes. Their smooth surfaces prevent the collection of microorganisms or deposits. The valve is self-draining and without dead volumes, making sure that no residues remain after operating or cleaning. With the option of pneumatic control and an interface for limit switches, the valve is ready for integration in a process automation system. Among SISTO’s core competencies are the design and production of so-called multi-port valves, integrating several valves in a single block. This saves space and reduces wetted inner surfaces.

Shorter delivery times by innovative manufacturing

KSB not only uses its know-how to produce high-quality valves but also to shorten their delivery times. Pharmaceutical valves are typically milled from forged blanks made of very high-quality nickel-base alloys, such as the material 2.4605. Especially in the case of such special materials, the availability of forged bars for producing blanks can be limited and long delivery times may apply. KSB speeds up production with additive manufacturing using powder bed fusion. The valve bodies manufactured in this way have also got a lower weight, a space-saving design, and offer excellent flexibility regarding planning and design. This enables geometries with undercuts, e.g. integrated cooling channels, which would hardly be possible using a milling process. Body parts made by additive manufacturing have further got a higher material homogeneity. Their suitability is checked and documented by the German Association for Technical Supervision (TÜV). They fulfil all required standards, for example the requirements of the European Pressure Equipment Directive (PED) 2014/68/EU.

3D-printed multiway diaphragm valve bodies for the pharmaceutical industry, prior to surface treatment

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