The landscape of the biopharmaceutical industry is evolving at a remarkable pace, bringing forth numerous innovations that can help to improve the lives of patients. This rapid growth brings with it immense opportunities, but also creates new challenges, as research teams are put under pressure to accelerate the development of novel biotherapeutic drugs. Many companies find themselves grappling with constraints of time, space, resources and even the necessary expertise to explore the diverse range of therapeutic targets available, or to develop new cell lines or manufacturing technologies in-house. This article delves into the indispensable role played by contract development and manufacturing organizations (CDMOs) in driving forward the biopharmaceutical industry, offering a helping hand with the specialized support, knowledge, and infrastructure crucial to accelerate the drug development process and get new biologics to the market sooner.

Biopharmaceuticals: the backbone of modern medicine

Biopharmaceuticals are a pinnacle of scientific achievement, harnessing the power of living cells to produce complex therapeutic molecules. Unlike conventional synthetic drugs made using chemicals, these bio-based treatments boast molecular and physiological similarities to human compounds. These can translate into heightened specificity for therapeutic targets, greater efficacy and minimized side effects,^1,2 improving patient outcomes.

The advent of biopharmaceuticals has also enabled the treatment of patients who respond poorly to traditional synthetic drugs and is paving the way for the future of personalized medicine. Switching from the production of synthetic therapeutics to biopharmaceutical manufacturing can also have benefits for the environment, by turning to more renewable sources of input materials and reducing the industry’s reliance on chemicals. The numerous benefits of biopharmaceuticals have led to significant interest and growth in this industry, which makes up 20 percent of the total pharmaceutical market today.¹ The sector’s growth trajectory, currently exceeding eight percent annually, outpaces that of conventional drug manufacturing,^1,3 signifying a shift towards bio-based therapeutics as the cornerstone of modern medicine.

The complex journey of biopharmaceutical development

Unfortunately, the journey toward creating a viable biopharmaceutical product is riddled with operational and technological complexities. Designing the desired therapeutic begins with the meticulous selection and genetic modification of a suitable biological host—usually bacteria, yeast or mammalian cells²—to produce a protein or other biomolecule of interest. Once a cell line capable of  producing the desired product in the necessary quantities has been established, it is then cultured in the carefully controlled environment of a reactor vessel under specific conditions that enable it to thrive.¹ The resulting therapeutic molecules must then be separated from the cells, the production media and other impurities, followed by meticulous formulation adjustments, before entering the pre-clinical and clinical trial stages of drug development. Manufacturing large molecules for therapeutic use at an industrial scale requires significant bioengineering expertise, cutting-edge manufacturing capabilities and advanced infrastructure, which can often come with a prohibitive price tag or time commitment. Considering that there is no guarantee that the chosen organism will produce the desired product at the quantities needed to meet target cost of goods (COGs), there is always a risk to investing in new resources.

Unlocking potential through collaboration

This is where CDMOs can help, by offering an abundance of pre-existing resources dedicated to biopharmaceutical development. From state-of-the-art facilities to teams of specialist scientists adept at working with a range of organisms, these resources come without the need for hefty upfront investment by pharmaceutical organizations, allowing them to explore new avenues of research while mitigating the risk of losses. It is therefore no wonder that 44 percent of life sciences companies currently outsource a significant portion—if not all—of their drug development processes.⁴ Partnering with a reliable and reputable CDMO equips biopharmaceutical companies with the capacity and flexibility to navigate the complexities of drug development pipelines, resulting in cost and time savings to optimize resource use.

Expediting drug development
Partnering with a CDMO to outsource the infrastructure, technologies and expertise integral to biopharmaceutical manufacturing streamlines the arduous drug development pathway. A proficient CDMO should seamlessly support its clients across every stage of this journey, from host selection to bioprocess development, manufacturing, and analytical testing.

Mitigating risk
Beyond accelerating drug development, CDMO collaborations also mitigate some of the risks inherent in bringing novel therapeutics to market. The financial commitment and uncertainty associated with developing a new therapeutic product in-house, and subsequently bringing it to market, poses a significant challenge for pharmaceutical companies, without any guarantee of achieving a successful clinical outcome. By outsourcing to a CDMO that boasts an arsenal of specialized equipment, dedicated manufacturing spaces, and experienced personnel, companies effectively hedge against potential setbacks, significantly reducing risk.

Regulatory navigation
CDMOs can support projects from the initial stages of development right through to supporting complex regulatory approvals. Staying up to date with evolving regulations can be daunting, time consuming and resource intensive, and failing to do so can have significant negative consequences for biopharmaceutical companies, damaging their reputation and taking projects back to the drawing board. A comprehensive CDMO offering will include regulatory support to help biopharmaceutical companies navigate complex and time-consuming submission processes, ensuring that products adhere to all the necessary regulatory requirements. Partnering with a CDMO therefore provides a significant advantage in a competitive biopharmaceutical market, accelerating regulatory approval to avoid delays and ensure timely market entry for innovative products.

Scaling for success
Some biopharmaceutical companies may master bioengineering processes at a small scale in a laboratory, but scaling up these same processes to generate larger volumes of product can be both challenging and expensive. This is a crucial step in ensuring that the product is commercially viable beyond the laboratory. Seasoned CDMOs are primed for the optimization of high throughput fermentation processes, enabling seamless technology transfer and GMP-compliant drug production. This ensures the smooth scale-up of processes to help a novel biotherapeutic reach a global audience and have a real-world impact on the lives of patients.

Exemplifying CDMO excellence in the COVID-19 pandemic

The pivotal role of collaborations between CDMOs and biopharmaceutical companies gained newfound momentum during the COVID-19 pandemic, when the industry was pushed to develop vaccines and antivirals in record time. Backed by extensive prior research and substantial public funding, there was an unprecedented number of biopharmaceutical companies looking to fast-track new drugs to market, and regulatory departments were inundated with requests to enable swift COVID-19 vaccine development with internationally agreed benchmarks for safety and efficacy.

Researchers grappling with the challenge of complex vaccine production sought CDMO guidance to quickly advance processes and enhance scalability to accelerate drugs to market. For instance, researchers at the California Institute of Technology (Caltech) and the University of Oxford embarked on a partnership to develop a groundbreaking, futureproofed coronavirus vaccine. Their quest led to the identification of a promising ‘mosaic-8’ nanoparticle’ vaccine candidate that displays SARS-CoV-2 spike protein receptor binding domains (RBDs) alongside RBDs from seven other SARS-like betacoronaviruses.5 However, the production process was first developed using mammalian cells and Escherichia coli (E. coli), but this was prohibitively costly and too complex to rapidly generate large quantities of product. In addition, the resulting nanoparticles were contaminated with endotoxins produced by the E. coli host, requiring extensive downstream purification steps. With limited time and funding available, the researchers required input from a CDMO to streamline, scale up, and reduce costs in the vaccine production process.

Harnessing external expertise

Partnering with a CDMO provided researchers with access to a multidisciplinary team boasting a wide breadth of knowledge and expertise in the biopharmaceutical space. This experience of working with a wide range of different hosts—including mammalian cell lines and various microorganisms—as well as capabilities in bioprocess development and analytical processes, helped the CDMO team to overcome several issues that were hindering successful vaccine development. For example, they were able to establish scalable manufacturing upstream and downstream processes, develop supporting analytical methods and in-process controls, and provide material required for preclinical activities to ensure that the candidate vaccine could induce broad-spectrum immunity. The CDMO’s extensive understanding of diverse host organisms, including Pichia pastoris and Bacillus subtilis, also enabled the joint team to successfully transfer production of the RBDs and nanoparticles to new host organisms, optimizing the affordability, scalability, and adaptability of the vaccine production process. Having access to the wide variety of technologies that the CDMO had to offer also helped to boost the speed and success of strain productivity and downstream processing. Researchers were able to achieve fast, accurate and streamlined GMP-compliant purification of the vaccine components at high purity, laying the groundwork for a next-generation coronavirus vaccine.

With the help of an expert CDMO, each step in the vaccine production pathway was enhanced and optimized, and the researchers successfully developed an affordable, commercially viable and scalable manufacturing process for the large-scale production of a broad-spectrum betacoronavirus vaccine.6 This project highlights the transformative impact of CDMO partnerships across the biopharmaceutical industry, and how these collaborations can help to propel healthcare innovation forward.

Expanding horizons with CDMOs in biopharmaceutical development

This vaccine production project is just one example of a therapeutic venture that benefitted significantly from CDMO intervention. Looking ahead, the role of CDMOs is poised to expand even further, having a positive impact in each corner of the biopharmaceutical development workflow. With rapid advancements in technology and an increasingly complex regulatory landscape, pharmaceutical companies will continue to rely on CDMOs for specialized expertise, advanced infrastructure, and flexibility, avoiding hefty upfront investment costs and mitigating risks in future projects. Each emerging development within biotechnology presents a new frontier for CDMOs to explore, offering groundbreaking collaborations and advancements that benefit all parties.

In conclusion, CDMOs are indispensable allies in the development of novel biologics, offering strategic advantages to companies wishing to navigate the intricate pathways of producing biopharmaceuticals at the commercial scale. By harnessing the expertise, infrastructure, and resources of CDMOs, companies can expedite processes, mitigate risk and realize the potential of innovative therapies, thereby shaping the future of healthcare.

References
1. Otto R, Santagostino A, Schrader U. Rapid growth in biopharma: Challenges and opportunities. McKinsey & Company. 2014. Accessed September 22, 2023. https://www.mckinsey.com/industries/life-sciences/our-insights/rapid-growth-in-biopharma.
2. Kesik‐Brodacka M. Progress in biopharmaceutical development. Biotechnology and Applied Biochemistry. 2017;65(3):306-322. doi:10.1002/bab.1617.
3. Biopharmaceutical industry – Demand, Overview & Trends. Mordor Intelligence. 2023. Accessed September 22, 2023. https://www.mordorintelligence.com/industry-reports/global-biopharmaceuticals-market-industry.
4. Van Arnum P. CDMO outsourcing trends: cell and gene therapies. DCAT Value Chain Insights. 2022. Accessed September 22, 2023. https://www.dcatvci.org/features/cdmo-outsourcing-trends-cell-and-gene-therapies/.
5. Cohen, A.A. et al. Mosaic RBD nanoparticles protect against challenge by diverse sarbecoviruses in animal models. Science. 2022;377(6606). doi:10.1126/science.abq0839.
6. Ingenza collaboration with Caltech, Oxford University and CPI & secures $32M CEPI funding to advance next-generation coronavirus vaccine. Ingenza. 2022. Accessed September 22, 2023. https://www.ingenza.com/ingenza-collaboration-with-caltech-oxford-university-and-cpi-secures-32m-cepi-funding-to-advance-next-generation-coronavirus-vaccine/.

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Leonardo Magneschi, PhD, has over 13 years of experience in molecular biology and the engineering of plants and microorganisms. He completed his PhD in plant and microbial biotechnology in 2011, at the Sant’Anna School of Advanced Studies in Tuscany, in collaboration with the Carnegie Institution for Science, part of Stanford University. Following his postdoctoral research—funded by the Alexander von Humboldt Foundation—he transitioned to the world of industrial biotechnology. Leonardo joined Ingenza in 2016, where he heads up the molecular biology team, strategically driving the core mission of the company to deliver world-class biotechnology solutions.