High-performance biomanufacturing processes are needed to accelerate the time-to-market of safe and efficient drugs, reaching thousands of patients worldwide. The unique biological properties of insulin make it a key growth-supporting ingredient in many different cell culture processes. Recombinant insulin improves cell proliferation and boosts the production of therapeutic proteins for various applications, viral vectors for advanced therapies, and viruses for vaccines.
From monoclonal antibodies to cell and gene therapies, and vaccines, Novo Nordisk Pharmatech recombinant insulin is contributing to improving the lives of people living with arthritis, cancer, multiple sclerosis, and many more medical conditions.
Today, the central pillar of the pharmaceutical industry is represented by the development of biological drugs manufactured from engineered mammalian cell lines. Compared to small molecule drugs, biotherapeutics show exceptional specificity with fewer off-target interactions and improved safety profiles.
The standard process to produce high quantities of therapeutic proteins in biopharma is represented by fed-batch cultures of Chinese Hamster Ovary cells. These cells, genetically engineered to express high amounts of recombinant protein, can be grown in serum-free and chemically defined media, and have lower risks of propagating human viruses. For all these reasons, today CHO cells provide the platform for about 70% of biological drugs.
With the continuing expansion of the biotherapeutics market, the biopharmaceutical industry is facing the challenge of efficiently producing therapeutic proteins in large quantities. To keep up with the demand while driving manufacturing costs down, mammalian cell production expectations are rising every year, with product titers reaching 10 g of protein/L of culture. Combined efforts in improving host cells and optimizing the cell culture media contribute to the high yields obtained.
Recombinant Insulin is an essential supplement in chemically defined media cell cultures of CHO cells, producing monoclonal antibodies. When supplemented to the media, insulin is improving monoclonal antibody yield from 4g/L to 6g/L in fed-batch culture of CHO-K1 cells. Recombinant Insulin is currently used in the biomanufacturing of more than 100 therapeutic drugs, some of them being blockbusters.
Over the past years, advanced therapies, such as cell and gene therapies, have gained much interest, extending their applications beyond the treatment of rare diseases. Viral vectors are at the heart of advanced therapies, representing the standard vehicle for gene delivery. A variety of gene therapy drugs, based on viral vectors, have obtained regulatory approval within the past 5 years. The applications of these drugs range from vector-based cancer therapies to treating monogenic diseases with life-altering outcomes. At present, the three key vector strategies are based on adenoviruses, adeno-associated viruses (AAV), and lentiviruses (LV). To address the increased demand for advanced therapies in the commercial space, viral-vector manufacturing requires rapid expansion.
Unlike the production of monoclonal antibodies, viral-vector manufacturing is not standardized across the industry, with biopharma companies using different production systems and downstream processes. The diversity in manufacturing modalities among advanced therapy companies rises concerns about the regulatory standards for manufacturing and quality control.
In particular, the quality of the raw materials used for the manufacturing of these therapies represents a critical aspect influencing future development and approval of the final product. Making the right choice early is critical for gaining regulatory approval and achieving patient access faster.
Manufactured under GMP regulatory requirements, Recombinant insulin is the best candidate to support the production of viral vectors in the cell culture of mammalian cells. Supplementing insulin to chemically defined cell culture media can significantly improve the production of both AAV and LV in HEK293 cells, adapted to grow in suspension. A study found that the production of AAV was increased up to 1.5-fold and the production of LV up to 2-fold when insulin was added to the cell culture medium.
Traditionally, the manufacture of vaccines, such as the annual flu vaccine, relies on the use of chicken fertilized eggs, used to grow the virus. Over the past decade, however, increased efforts have been made to develop eggless manufacturing technologies, in to produce more vaccines quicker.
Cell-based virus production offers a faster and more stable production of vaccines compared to embryonic chicken eggs, which only produce 1-2 vaccine doses per chicken egg. Cell culture technology is more flexible and may allow for multiple viral vaccines to be produced in the same production platforms, in a more sterile environment. In addition, the use of cell-based systems in vaccine production has the potential to offer better protection compared to egg-based flu vaccines.
In the cell culture-based production system, the candidate vaccine viruses are grown in mammalian, avian or insect cell cultures. Typically, these cells are Madin-Darby Canine Kidney cells, or monkey cell lines, like pMK and Vero, and human cell lines HEK 293, MRC 5, Per.C6, PMK, and WI-38. The virus replicates exploiting the cellular pathways and is then extracted from the cell culture media and purified.
Among the cell lines used for vaccine preparation, HEK293 is widely utilized due to its high transfectivity, rapid growth rate, and ability to grow in a serum-free, suspension culture. To maximize the production of viruses in cell-based systems, optimal cell growth conditions must be identified, supporting cell proliferation and viral replication. A study found that recombinant insulin added to chemically defined media, increased the production of flu virus by up to 2-fold, compared to the medium without insulin.