Until a few years ago, the production of insulin was essentially in the hands of three pharmaceutical companies with international operations. Together, they covered up to 95% of the market. This situation has changed considerably recently, in line with globalization and the simultaneous upswing of emerging countries. China, India, Brazil, the Middle East, Poland, Russia and the Ukraine are the new countries involved in the production of insulin. In these regions, the pharmaceutical industry is responding to rising demand for insulin and is producing the active agent for diabetes sufferers at more favorable conditions. Demand is strong particularly in these parts of the world: rising prosperity is being accompanied by an increase in the prevalence of diabetes.
Expanding Markets and Production in the Emerging Nations
Being overweight and a lack of exercise mean that diabetes is becoming a global illness. Diabetes means that the human body does not produce sufficient insulin, is unresponsive or resistant to insulin. In its advanced stage, insulin is therefore administered in the correct dose to the patient as a life-saving measure. In general, the remaining life expectancy of patients is reduced by approximately one third after the point at which the illness is diagnosed.
"According to the fifth edition of the Diabetes Atlas, the International Diabetes Federation (IDF) expects to see a worldwide increase in the number of sufferers from 36 million in 2011 to approximately 552 million in 2030"
The diabetes market leader Novo Nordisk from Denmark accounts for an estimated more than 50% share of the worldwide market for insulin. Together with the French Sanofi-Aventis and the US manufacturer Eli Lilly, Novo Nordisk controls around 80% of the market. Other market players include newcomers and niche providers in the emerging countries, such as the Indian pharmaceutical manufacturer Biocon, the largest producer of insulin in Asia. Wanbang Biopharma for instance is the largest producer of insulin in its domestic market of China, accounting for almost half of the overall market. Mainly for exports to Europe and the USA, this Chinese producer now intends to build an insulin factory which, in its initial stage, will be able to produce around 130 million units annually.
Julphar to Commission a New Middle East Production Facility
In the United Arab Emirates, a new insulin factory is to be commissioned by Julphar (Gulf Pharmaceutical Industries) in mid-2012; in the same way as many other production facilities throughout the world, this facility will also be equipped with mechanical separating technology from GEA. As the largest producer of antibiotics delivered in oral form and in injectable form in the Middle East, Julphar produces its own brands and also operates as a subcontractor for worldwide demand under GMP conditions. The factories are also ISO-certified.
Julphar pioneered the production of insulin in the Middle East and Africa. The company has been distributing insulin in cooperation with a French manufacturer since 1998; at that time, Julphar imported the insulin crystals. In 2006, Julphar decided to manufacture the raw material for insulin itself. This is a logical decision because, according to the International Diabetes Federation (IDF), there are already an estimated 32.6 million diabetes sufferers in the region, and this figure is expected to double by the year 2030. The diabetes rates in the Middle East and North Africa are some of the highest in the world.
Core Processes from GEA
Julphar‘s new production facility in Ras Al Khaimah, north of Dubai, is one of the most modern in the world for manufacturing insulin crystals for human consumption. It covers a floor area of 20,000 m2, including clean rooms of 5000 m2. Fifteen kilometers of pipework have been installed. GEA was responsible for the engineering, delivery, commissioning and qualification of the entire systems for the production of ultra-pure media as well as various process equipment and cleaning installations. In addition, the delivery comprised all the necessary pipework and distribution systems for the production processes. In Ras Al Khaimah, Julphar uses the technology of recombinant DNA (r-DNA), by injecting the insulin gene into a suitable carrier substance, in this case Escherichia coli. Its genetic constitution is modified in such a way that it produces the human hormone insulin.
In various stages, the bacteria then multiply in fermenters, and are subsequently recovered and purified in separators. Separators thus constitute the core processes in the production of insulin. Because GEA is known as the worldwide technology leader in the production of insulin, Julphar decided to use the know-how of the company from Oelde with centrifugal technology in its new plant. GEA has installed a total of five separators in Ras Al Khaimah. A nozzle-type separator CFA 65with GEA viscon® technology is used for separating the coli bacteria from the fermentation broth; in this solution, the solids are continuously discharged with a constant concentration. Following the homogenization stage, two self-cleaning separators of the type CSE 80 separate the inclusion bodies from the cell fractions and wash them. Following the precipitation of the insulin crystals in the clean room, two chamber-type separators BKA 28 are then used to separate the crystals and thus produce concentrated insulin. Whereas the separators in the first two stages were supplied as compact package units, the chamber-type separators are stand-alone machines with the corresponding valve blocks and control unit. After GEA has provided intense training to the operating personnel, operations in Ras Al Khaimah will start providing product in mid-2012.
Hycon as an alternative
As an alternative to the production of insulin from Escherichia coli, other producers use yeast as the carrier substance. The process is similar, but the valuable substance in this case is not the solids, and instead is the clarified phase. In both methods, the Hycon machines can be used as an alternative to the chamber-type separator after the crystallization process. Hycon is a completely closed system which enables the separating process to be done under clean room conditions without contamination by the drive or motor.
Owing to the principle of the suspended bowl, this twin-room concept has the bowl with the hood and solids holding tank in the clean room, whereas the drive units can be housed in a separate room with a lower classification. The machine is designed in such a way that the solids are automatically discharged from the suspended separator into closed containers installed below the separator. GEA achieves very gentle product treatment which is appropriate for the high value material by means of two features: the hermetic feed and the gentle discharge at operating speed or lower speed of the machine. Whereas chamber-type separators are not sterilized and can only be cleaned manually, Hycon machines have fully automatic cleaning and, where necessary, sterilisation by means of CIP and SIP. Demand for the technologies of GEA for the production of insulin is very strong, particularly in the new markets of the emerging countries.