SÜDPACK Verpackungen is a qualified supplier of plastic films to the biopharmaceutical industry. The company is the leading European manufacturer of packaging products for the food industry and also offers its expertise to the biopharmaceutical industry. In 2011, SÜDPACK created an exclusive cooperation partnership with Sartorius Stedim Biotech, a global technology provider for the pharmaceutical biotech industry, which has now been extended before its end date.
This article also tells the story of an industrial sector. There is nothing particularly spectacular or grandiose about it, but it does give some insights into how successful SMEs of the type that operate in Baden-Württemberg are preparing for the future. And it also shows how biotechnology is making a name for itself as a cross-sectoral technology that brings together new industries.
Around ten years ago, biologicals were mainly produced in stainless steel bioreactors. In the intervening period, there has been a gradual increase in the use of single-use systems (SUS) in biopharmaceutical development and production. Large fermenters of 2,000 litres and over are still made of stainless steel.
Why is the industry shifting from reusable stainless steel reactors to disposable plastic reactors? According to a recent press release (4th November 2016) published by Rentschler Biotechnologie, a leading contract development and manufacturing organisation in southern Germany, compared to stainless steel bioreactors, single-use systems are cheaper, have a lower contamination risk, can be implemented more quickly and offer huge flexibility in manufacturing processes. At the time, Rentschler Biotechnologie was opening its latest single-use bioreactor designed to expand its manufacturing capacity.
Let’s go back to before 2000 when plastics were starting to come to the fore as an alternative material for use in biopharmaceutical production. Ingo Schnellenbach, director at SÜDPACK Medica, says that the Remmele family who own the SÜDPACK Group were very interested in new technologies and were already looking for another foothold for the company. They contacted CDP Laboratories, a manufacturer of medical sterile packaging, which became a part of SÜDPACK Medica in 2003, and began expanding into a new business area.
The integration of CDP opened the door to new business partners such as Sartorius, which at the time tended to purchase mainly secondary packaging. “What initially started out as small projects, became a long-term collaboration in 2011,” recalls Schnellenbach. SÜDPACK's owners decided to become involved in a completely new area: the highly sophisticated biopharmaceutical business sector. In 2007, the biotechnology division of Sartorius had merged with the French biotech company Stedim to create Sartorius Stedim Biotech. Sartorius was hoping that this merger with Stedim, a company that it referred to as the “world’s leading single-use containers (bag technologies) for biopharmaceutical applications” would enable it to become a globally leading technology provider for the biopharmaceutical industry.
Contacts were gradually intensified, and the first development attempts eventually got underway. In 2011, Sartorius Stedim Biotech and SÜDPACK Medica signed an exclusive cooperation agreement for the development, manufacture and supply of polymer plastic films for the biopharmaceutical market. These plastic films are used to manufacture single-use bags and systems mainly for pharmaceutical industry customers for cell cultivation, transportation and storage of biopharmaceutical liquids. Nowadays, the Ochsenhausen-based company supplies the raw material that Sartorius Stedim Biotech uses to manufacture of 2D and 3D bags and bioreactors.
SÜDPACK invested a high single-digit million euro sum in pharmaceutical film production in its Ochsenhausen site. Nowadays, SÜDPACK produces films for use in the pharmaceutical industry in specially designed areas under controlled conditions. At overpressure and specific climatic conditions, wearing protective clothing and with a disproportionally high cleaning and control burden, the film experts from Ochsenhausen are able to meet the incredibly high requirements of the pharmaceutical industry. With these measures in place, biological contamination of a material (particles, germs, microorganisms) can be kept as low as possible. “The greatest change in comparison with the traditional manufacture of films for use in the food sector concerns the continuous, repetitive need to guarantee and check process and product safety,” says SÜDPACK manager Schnellenbach.
In principle, the manufacturing process of films for use in biopharmaceutical applications is comparable to that of films for use in food packaging, says Schnellenbach. Pharmaceutical suppliers also have to adhere to precisely defined controlled production processes that are subject to defined change control. This also applies to the formulation of the granules from which the films are extruded at the company site in Ochsenhausen. The supply chain and secure supply of identical granules, documentation, marketing authorisation procedure and the accompanying measurements throughout the controlled production processes have to meet pharmaceutical industry standards.
Safety is the key to biopharmaceutical development and production. So-called extractables and leachables that can migrate from the polymer material into the active ingredients are considered the greatest of all potential risks. Extractables are compounds that can migrate from polymers over a prolonged period of time, at high temperatures or in situations when solvents are used. Leachables are considered a greater danger as they can occur under normal process conditions. Additives that are produced and released from the polymer during the extrusion process or during gamma sterilisation are the main source of leachables. These water-soluble compounds can interfere with cell cultivation, promote protein aggregation and endanger patients when administered parenterally (Dechema, Recommendation, p. 6f).
SÜDPACK has implemented measures to prevent potential risks arising from such materials. The material used for producing single-use reactors must have as little interaction as possible with the biological material and the process medium in order to stop unwanted interactions in the form of extractables, leachables, absorption, by-products and degradation products from occurring.
Risk management commences as early as possible, not just when the material is processed in Ochsenhausen. It starts in the company that supplies the granules, explains Schnellenbach. This clearly shows how the two development partners benefit from each other, although understandably they do not wish to disclose details of their partnership. With SÜDPACK, the pharmaceutical industry has found a competent partner in the plastics industry. This may lead to further developments in the production of single-use bioreactors. It can certainly be expected that the long-term experience of SÜDPACK's partner, Sartorius Stedim Biotech, in dealing with leachables and extractables will benefit the development of polymers suitable for application in biopharmaceutical production.
“The excellent technical and scientific collaboration between the two companies has not only resulted in new films and applications for the biopharmaceutical industry, but also provides the basis for the further development of new films with improved properties, for example in terms of robustness, biocompatibility and purity,” said Prof. Oscar-Werner Reif, Head of Research and Development at Sartorius Stedim Biotech.
Plastic films for use in the biopharmaceutical market are not exactly a mass product or a volume business. SÜDPACK focuses on development and production know-how. “We are supplying a high-tech industry where the market has been growing for years. Our employees are well aware of the company's responsibility as well as the opportunities,” said Schnellenbach. Production quantity for biopharmaceutical films is in the kilogram range. Compared with the tons of films SÜDPACK supplies to the food industry, the quantity of biopharmaceutical films produced is a relatively small business.
SÜDPACK's management in Ochsenhausen is convinced that the partnership with Sartorius is well on the way to success. The fact that the cooperation partnership has been extended before its end date tends to confirm the chosen approach. The Remmele/Grimbacher families and Ingo Schnellenbach were convinced from the word go that the necessary long-term commitment would one day bear fruit: “Harvesting is a process that comes many years later.” It can therefore be concluded that this reflects the families’ entrepreneurial thinking, i.e. the courage to create something completely new rather than something similar to an already existing product.
Dechema (Ed.): Recommendation for a risk analysis for production processes with disposable bioreactors, Working Group Single-Use-Technology, Frankfurt/Main, October 2015.
Assuring film quality, in: European Biotechnology, Autumn Edition, Vol. 13, 2014, p. 70f.
Transkript 10/2014: Immer der gleiche Film. Interview with Stefan Schlack, https://www.sartorius.de/fileadmin/media/global/company/2014_10_article_technical_press_transkript_interview_schlack.pdf
Jean-Marc Cappia, Magali Barbaroux, Elisabeth Vachette, Carole Langlois and Heiko Hackel: Enhanced Assurance of Supply for Single-Use Bags: Based on Material Science, Quality By Design, and Partnership with Suppliers, Bioprocess International, 23. September 2014, in: http://www.bioprocessintl.com/manufacturing/supply-chain/enhanced-assurance-supply-single-use-bags-based-material-science-quality-design-partnership-suppliers/
Dechema (Ed.): Recommendation for leachables studies - Standardized cell culture test for the early identification of critical films (1st edition), http://dechema.de/dechema_media/SingleUse_Leachables_2014_en-p-4734.pdf
Dechema (Ed..): Single-Use Technology in Biopharmaceutical Production. Report of the Temporary Working Group, Frankfurt/Main 2012, 2nd Editon, http://dechema.de/dechema_media/StatPap_SingleUse_2011_englisch-p-4298-view_image-1-called_by-dechema-original_site-dechema_eV-original_page-124930.pdf
Sartorius Stedim Biotech and Südpack Medica AG sign exclusive cooperation agreement, press release by Südpack and Sartorius Stedim Biotech, 14th June 2011.
Dechema (Ed.): Single-Use-Technologie von A bis Z, Frankfurt/Main Januar 2016, online at: http://a-z-singleuse.org/
Sartorius Stedim Biotech launches new generation of single-use bags, Flexsafe, in: Biopharm International, 4th June 2014,
Extractables and Leachables Safety Information Exchange - Consortium comprised of 18 pharmaceutical, biotechnology, and medical device companies. http://www.elsiedata.org/