The CDMO Biomay has worked closely with GEA to scale up the homogenization process from laboratory to production size and achieve the same cells disruption effect in the proteins and microorganisms manufacturing process.
Vienna-based contract development and manufacturing organization (CDMO) Biomay manufactures biomolecules for the global biopharmaceutical industry. The company has specialist expertise in GMP-grade production of recombinant proteins, plasmid DNA, and messenger RNA. Claiming to be one of just a handful of CDMOs that can manufacture all three types of these key biomolecules, the firm offers a full range of GMP services aligned along the biopharma pipeline, from cell banking, to process development, bulk production and release of drug products. Established in 1984, and operating as a CDMO since 2009, Biomay works with customers ranging from biotech start ups and SMEs, to multinational corporations.
Biomay manufactures proteins and other biomolecules using fermentation processes that involve growing engineered cells and microorganisms - such as the bacterium Escherichia coli - in bioreactors. When it came time to expand operations and build a new facility for special and customized production processes, Biomay chose GEA to supply homogenizer technology for the new site.
Homogenizers allow to release inner content of cells
The basic process for producing proteins involves first growing the engineered microorganisms in fermentation bioreactors, in which the microbial cells are provided with all the nutrients and other factors that they require to multiply rapidly. The bacteria are then harvested from the bioreactors and undergo homogenization, which breaks open - or disrupts - the cells to release their contents. The recombinant proteins that are released from the bacteria can then be isolated and purified for the client, who may use them, for example, as starting materials for further manufacturing steps, or as active pharmaceutical ingredients that may be either already on the market, or undergoing development.
High pressure homogenization is used by the pharma and biotech industry primarily for cell disruption, and, dependent on the product, GEA homogenizers can achieve more than 90% cell rupture.-Annalisa Malchiodi, Product Manager Pharmaceutical, GEA Business Unit Homogenizer
From Biomay’s perspective, one key feature of the GEA Ariete system is the VHP (very high pressure) compression block, which pumps the product into the homogenizing valve, reaching up to 1500 bar pressure, which is recommended for cell disruption. The compression block has also been configured with ceramic plungers, the most resistant material to wear from high pressure and abrasion. The GEA system is highly flexible to support variable throughput, and can by varying the motor speed can maintain exactly the right ratio between pressure and the flow rate.
A number of factors helped to ensure success of the project. There was mutual trust between the professional teams from both Biomay and GEA, which helped to address challenges caused by the CoVID pandemic, ensured that there was optimal technical clarification in the pre-sales phase, and that the we’ll-designed GEA skid met all of the customer’s expectations.-Dario Zappia, GEA CEE Sales Separation and Homogenizer Austria
Critical to design of the final solution at the new site was Biomay’s requirement to use the homogenizer in two different rooms, so the GEA team configured a compact, skid-mounted solution that could easily be moved between the two rooms. To keep the footprint compact and the system easily moved around, the homogenizer and human machine interface (HMI) are both mounted on the same skid, and the HMI panel can be rotated through 90 degrees.
I had the pleasure to be part of the process throughout commissioning of the homogenizer from the purchase through the factory acceptance testing and site acceptance testing to the completion of the functional qualifications.
The homogenizer is housed in a clean room, and also has been configured in aseptic execution to avoid the risk of contamination from the external environment. The homogenizer can be supplied completely sealed according to customer containment request. GEA knowhow, engineering expertise and process insight meant the final system offered the right level of customization required to fulfil all of Biomay’s expectations.
Importantly for Biomay, it was possible to carry out factory acceptance testing (FAT) of the new system remotely. Biomay could not travel to Italy, so the GEA team organized the FAT via Teams online, and Biomay was able to see the machine and the test as it happened, so all phases of the FAT process were documented and recorded live and in real time.
Throughout this time, cooperation with GEA's experts was faultless. Any technical questions were answered quickly, helpfully and competently. In terms of process technology, the Ariete homogenizer meets all the expectations placed on it, which allows us to process our products in a time-efficient manner.
Different production processes for the highest product quality
No two biomolecules are the same, and it’s generally not possible to apply exactly the same process for different applications, so Biomay configures the production process for each product, to help ensure the highest GMP manufacturing quality, efficiency and reproducibility for its clients.
At Biomay’s first manufacturing site, in Vienna, a tabletop GEA PandaPlus Lab Homogenizer 2000 was perfect for small-scale production of recombinant proteins in bacteria. However, company growth and customer demand for its products meant that by 2021 Biomay needed to expand, and the firm constructed a larger facility, also in the Vienna region of Austria, to house an enlarged production plant, along with R&D labs and offices.
Another special feature is that the Ariete was designed to be mobile despite its high performance. This means that the Ariete can be put into operation at different installation sites in our plant with little effort. This gives us additional flexibility in our processes. -Michael Wozonig, Biomay Team Leader Upstream 2
Already familiar with the GEA homogenizer technology, Biomay partnered with GEA experts to configure the best homogenization solution for scale up at its new facility. In fact, GEA was one of the only suppliers that could provide a system that would work at the required pressures, offer the right ratio of high pressure to flow rate, and demonstrate proven performance. At larger scales higher throughput is needed to streamline manufacturing, and the GEA 3 piston Pharma Skid Ariete Homogenizer 3015 is expected to shorten process times and increase economy of manufacture. The new pharma skid will enable batch production at approximately 300-400 l/h, at 1000-1200 bar.
With GEA, we found the right partner for our project. During work to finalise the detailed engineering of the homogenizer, GEA always gave us competent answers to our specific requirements. It was particularly important to us that the new homogenizer would meet all GMP guidelines and requirements. This was achieved to our complete satisfaction with the resulting Ariete homogenizer.
Demand is on the rapid rise for GMP-grade biomolecules that are being developed as potential drug therapies, or which are already approved and being commercialized. Biomay aims to respond to this challenge by offering parallel manufacturing lines in 50 liter-, 150 liter-, and 750 liter-scale bioreactors so that it can cater to each individual client’s needs, and also offer an economy of scale.
The new Biomay manufacturing facility was completed during the last quarter of 2021 and inaugurated in June 2022. Meanwhile, the company hasn’t abandoned its first, still validated facility, where smaller scale production is ongoing, and the GEA PandaPlus homogenizer technology continues to provide great service.
During the entire project phase, GEA took care of our concerns in a customer-focused manner, so that we were able to configure and purchase a homogenizer that meets our requirements. We are already looking forward to working with GEA again on future projects.-Dipl. Ing Gottfried Stegfellner, Biomay Vice President/Manufacturing Upstream