Biopharmaceuticals

Challenges and Opportunities

Basanta Behera

• Publisher: CRC Press
• Year: 2020
• ISBN:
  9781351013130
• Edition: 1
• Topic: Medicina
• Subtopic: Biochimica in medicina

Biopharmaceuticals: Challenges and Opportunities

This book highlights how the traditional microbial process technology has been upgraded for the production of biologic drugs how manufacturing processes have evolved to meet the global market demand with quality products under the guidelines of internally recognized regulatory bodies.

It also carries information on how, armed with a deeper understanding of life-threatening diseases, biopharmaceutical companies and the life sciences industry have developed formal and informal partnerships with researchers in institutes, universities, and other R&D organizations to fulfil timely, quality production with perfect safety and security. One of the most interesting aspects of this book is the conceptual development of personalized medicine (or precision medicine) to provide the right treatment to the right patient, at the right dose at an earlier stage of development, for genetic diseases. Besides this, it also highlights the most challenging aspects of modern biopharmaceutical science, focusing on the hot topics such as design and development of biologic drugs; the use of diversified groups of host cells belonging to animals, plants, microbes, insects, and mammals; stem cell therapy and gene therapy; supply chain management of biopharmaceuticals; and the future scope of biopharmaceutical industry development.

This book is the latest resource for a wide circle of scientists, students, and researchers involved in understanding and implementing the knowledge of biopharmaceuticals to develop life-saving biologic drugs and to bring awareness to the development of personalized treatment that can potentially offer patients a faster diagnosis, fewer side effects, and better outcomes.

Features:

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• Explains how the traditional cell culture methodology has been changed to a fully continuous or partially continuous process

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• Explains how to design and fabricate living organs of body by 3D bioprinting technology

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• Focuses on how a biopharmaceutical company deals with various problems of regulatory bodies and develops innovative biologic drugs

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• Narrates in detail the updated information on stem cell therapy and gene therapy

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• Explains the development strategies and clinical significance of biosimilars and biobetters

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• Highlights the supply chain management of biopharmaceuticals

1 Biopharmaceuticals – A New Frontier

Biopharmaceuticals are of biological origin, derived from host cells from plants, animals, or bacteria. They are also known as medical products, biologicals, or biologics (Valderrama-Rincon et al., 2012, Rodríguez et al., 2014). The science of drug discovery is moving towards larger molecules instead of small molecules derived either from biological systems such as host cells or semi-synthetically. These biopharmaceuticals have caused an archetype shift in disease cure and have led to an enhancement in the quality of life of patients with various diseases such as autoimmune diseases and refractory cancers. At present, biopharmaceuticals have occupied about 7.5% of all drugs in the global market and account for ~10% of the total expenses for marketed drugs. The awareness for biopharmaceuticals has been gaining popularity at the rate >20% per year. They are already being replaced 74% more than chemical or semi-synthetic pharmaceuticals, in life-saving or end-stage applications.

Furthermore, >30% of drug discovery programmes at global level is supposed to be of biopharmaceuticals. These biologics include all recombinant proteins, monoclonal antibodies, cytokines, peptides, vaccines, blood-/plasma-derived products, non-recombinant culture-derived proteins, nucleic acid-based products (DNA, RNA, or anti-sense oligonucleotides used for curative or in vivo diagnostic purposes), and cell and tissue cultures (Sekhon, 2010). In spite of using sophisticated host cells (mainly from animal, mammals, and plants), the preferential use of different genetically modified micro-organisms is in progress. Biomass processing is an integral part of biotechnology. With the rapid development of protein engineering technology and continuous process technology, it is expected that within the next 5–10 years, up to 50% of all drugs in development will be biopharmaceuticals. The best example is the production of recombinant proteins through microbial fermentation process. The development of continuous upstream process and downstream process, use of modern equipment for crude biologics separation, crystallization and polishing, and new therapeutic protein-based chimeric antigen receptor T cell (CAR-T) therapies have enormously upgraded biologics.

1.1 Continuous Manufacturing

In order to bring down the high cost of biopharmaceuticals, the present manufacturing process has been in the state of modification from batch process to continuous manufacturing process, either fully or partially on a need basis. In this process, the different steps in manufacturing are linked to each other, partially or continuously. Due to such linking, the manufacturing process cost gets reduced with minimum time, energy input, and manpower involvement.

Continuous processing is contrasted with batch production.

Continuous manufacturing process is operated for 24 hours a day, 7 days a week, and all around a year in non-stop mode of operation. With such a continuous operation process for 8,400 hours per year, a biopharmaceutical industry is expected to produce both quality and quantity products in a sustainable pattern. In practice, a biopharmaceutical industry takes 15% downtime for plant maintenance and unscheduled shutdown. As a result, a plant is supposed to run for 7,140 hours to produce a specific product on a yearly basis. Any deviation in this process of fermentation operation is not entitled to be a continuous process. Hardly a decade back had the pharmaceutical industries used to follow discrete steps and equipment present at multiple locations to produce active pharmaceutical ingredients (APIs) and finished products and used to waste $50 billion a year on an inefficient process. In order to overcome such a financial loss, continuous fermentation process is the best alternate. So it is time to encourage biopharmaceutical companies to introduce continuous manufacturing process for both quality and quantity products with minimum time and budget (Tanner, 1998; Reay et al., 2008; Anderson, 2001; Thomas, 2008; Fletcher, 2010; Laird, 2007).

In biopharmaceutical industries, the upstream process and downstream process are compliment to each other. Both the upstream and downstream processes can entirely be integrated to a continuous process, or as per the convenience and the nature of the products, one of the processes can entirely or partially be integrated to a continuous mode and the remaining steps can be operated in a traditional manner. Such hybrid systems are in practice with an encouraging performance.

1.1.1 Fully Integrated Continuous Process

The fully continuous bioprocessing technology is a noble amendment in biologics manufacturing for the production of quality- and quantity-based products within a stipulated time. This method of operation process (Figure 1.1) is widely acceptable today for commercial manufacturing of complex/labile proteins, such as enzymes, blood factors and, in some cases, mAbs. With the development of microchip-based advanced technology, the continuous manufacturing process has become a flexible technology, which can be designed and adapted based on the needs of the biopharmaceutical industry. On a need basis, the manufacturer can have various options such as precipitation (Hammerschmidt et al., 2014), flow-through purification (Xenopoulos, 2013), directly coupled chromatography columns without hold vessels in between (Landric-Burtin, 2013), and viral inactivation (Brower, 2013). Bioprocesses utilizing continuous chromatography for product capture offer significant direct cost savings in clinical material production, which can have a large impact considering the high clinical attrition rates (Pollock et al., 2013).

FIGURE 1.1 Continuous upstream and downstream processes for thera...