New production processes promise to lower cost of biopharmaceuticals
Drugs derived from biological sources play a major role in modern healthcare, but producing them cost-effectively to keep up with rising demand is a major challenge for the pharmaceutical industry. EU-funded researchers are developing more efficient biopharmaceutical manufacturing processes that should expand patients' access to these highly effective therapies.
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Biopharmaceuticals have been used against many health conditions since biosynthetic human insulin was first approved as a therapy for diabetes in 1982.
Developed using recombinant DNA (rDNA) technology to produce molecules with novel genetic traits, bio-drugs are usually divided into different subgroups: substances that are virtually identical to the body’s own key signalling proteins such as the hormones insulin and erythropoietin; monoclonal antibodies with the same structure as the body’s own antibodies produced by immune cells; and fusion proteins formed from two or more genes. All play essential roles in modern medicine, often as treatments for life-threatening and disabling diseases such as cancer, diabetes or rheumatoid arthritis.
As applications for biopharmaceuticals such as vaccines have increased and demand has risen, the manufacturing challenges have also grown. The costly and time-consuming processes involved in capturing and purifying the proteins and other biological molecules that form the basis of all biopharmaceuticals constitute a major production bottleneck, while advanced analytical technologies are needed to better control product content and quality.
These downstream production issues are being addressed in the nextBioPharmDSP project, which is developing optimised manufacturing tools and techniques to lower production costs, increase production volumes and flexibility, and lower the industry’s environmental impact.
“Flexible biopharmaceutical production solutions that can be implemented at different manufacturing sites will help address variations in capacity needs and enable sustained drug supply. One of the main benefits is also the possibility to more easily replicate different processes and therefore substantially increase future biopharmaceutical production,” explains Gorazd Hribar, the nextBioPharmDSP project manager at Lek Pharmaceuticals in Slovenia.
Hribar points out that increased production flexibility will be particularly beneficial to manufacturers of biosimilars, follow-on drugs that replicate the effects of original biopharmaceuticals now that their patents have expired.
Flexible solutions for continuous drug production
The nextBioPharmDSP researchers are evaluating a range of innovative technologies that, in combination, should result in a continuous downstream production process for biopharmaceuticals, especially biosimilars.
Among other technologies, the team is exploring optimised flocculation (binding particles together in liquids) and tangential flow filtration processes for the primary separation of cells from biological products, which show clear advantages compared to traditional processes that rely on time-consuming centrifugation.
Capturing and purification of the desired products has been further enhanced with the development of innovative chromatography techniques – a technology commonly used for separating a mixture of desired biological products from unwanted impurities. The research has led to the development of multi-column continuous chromatography and flow-through processes to remove impurities continuously at very high flow rates, enabling faster and more efficient production streams with substantially reduced manufacturing costs.
A novel continuous chromatography system using adaptable and disposable elements is now being developed at manufacturing scale as part of the project. The team is also exploring non-chromatographic approaches, such as continuous precipitation, as possible alternative techniques for the initial separation stage.
The project’s work on advanced analytical tools for process monitoring, meanwhile, has already led to one publication and two patent applications, one for a method of in-line detection of product content, and another for a prototype device for real-time measurement of molecules.
Towards the end of the project, the technologies will be combined to build a holistic and integrated continuous downstream process incorporating the advanced analytical tools.
Hribar points out that some of the industry partners are interested in commercialising the new materials, devices and equipment, while others intend to use those materials and commercialise the processes, for example in the production of biosimilars.
These complementary fields of interest and the overall strength of the existing industrial partners provide ample opportunities for post-project commercialisation activities, according to the project manager.
“This should enable continuous manufacturing of biopharmaceuticals which, with the implementation of disposable elements, will increase the flexibility of manufacturers to supply high-quality medicines, minimise the industry’s environmental footprint, lower capital investments in downstream processing and reduce overall production costs,” he concludes.