Unpacking the Cost of Biomanufacturing
Strategic early planning, optimal CDMO selection, careful scale management, and stringent quality, along with greater industry collaboration, will ensure future biomanufacturing success.
Biologic-based therapeutics are increasingly in demand, thanks to their ability to provide more targeted and personalized treatment options for a variety of chronic and difficult-to-treat conditions. This surging demand for biologics is driving growth in biopharmaceutical manufacturing market, which is forecast to increase at a compound annual rate of 8.9% over the next eight years, reaching a market value of USD 967.7 billion by 2033 (1).
However, these therapies are much more complex than conventional drug products, and their manufacture can be associated with a greater number of challenges. Cost is always a major consideration for any company seeking to manufacture their product, but for complex, sensitive, and valuable biologic products, the initial expenditure and ongoing operational costs for manufacture can prove troublesome.
“The costs associated with drug development and manufacturing are largely due to the complexity of the manufacturing processes and the regulatory environment/strategy that the developers take,” notes Scott Broughton, CCO, Ascend. “Drug developers need to always develop with the end in mind, meaning that planning and strategy development early on can avoid costly mistakes. Using the end in mind, the developers can be sure to choose the right product characterization strategy, potency assay, standards, raw materials, right manufacturing platform, disposables costs, and so on.”
Extensive Capital Commitment
“Building and operating a biologics manufacturing facility requires extensive capital commitment that introduces significant fixed costs that remain constant regardless of how many batches are produced,” notes Magdalena Leszczyniecka, CEO of STC Biologics. Major costs to consider include facility construction (often in excess of USD 20–200 million), utility systems, cleanroom construction, maintenance and environmental monitoring, equipment validation, quality systems, and compliance infrastructure, she points out.
“Even more critical are the human resources,” Broughton emphasizes. “A full-time staff of highly trained operators, analytical chemists, process engineers, quality control and assurance professionals, and regulatory experts must be hired and retained, even when production demand is low or intermittent.”
Steve Lavezoli, VP, Curia Biologics at Curia Global, concurs that the initial investment is a huge consideration and adds that supply materials are also impactful on financial budgets. “In addition, many next generation technologies do not have a proven track record yet and could lead to costly mistakes,” he notes. “To offset these costs, it is imperative to find a CDMO with suitable facilities for the project at hand and a proven track record at those facilities.”
Companies need to consider a vast array of cost factors, from CapEx to operational costs, and total cost of ownership (TCO), adds Hanns-Christian Mahler, CEO, ten23 health. “When operating a facility, economy of scale will help to manage ‘per unit’ costs better. When working with CDMOs, a careful selection of CDMO capabilities is key for TCO,” he says.
Materials and Supply Burden
In terms of supply chain costs, Lavezoli recommends ordering all known materials that are needed for a project upfront rather than on an ‘as-needed’ basis. “Ordering in advance prevents project delays and the need to pay expedite fees, [and] also allows CDMOs to pivot in a timely manner if a supply chain issue arises,” he stresses. “With inflation, we also tend to see better pricing when we order materials at project initiation as material costs have been on the rise.”
Oftentimes, the cost burden of materials and supplies can exceed the actual production service costs in the manufacturing of biologics, remarks Leszczyniecka. “Key raw materials such as Protein A resins, and cell culture media, contribute heavily to overall expenses,” she notes. “As a result, process optimization is essential, including efforts to increase upstream titer (reducing the required bioreactor volume), streamline purification steps, and maximize resin loading capacity during chromatography.”
While base costs are high, industry is also facing import tariffs on raw materials and equipment, particularly is sourced internationally, continues Leszczyniecka. “This [aspect] is particularly relevant for resins, filters, and media components often produced in Europe or Asia. Managing sourcing strategies and understanding tariff impacts has become increasingly important for cost control in global biologics production,” she says.
According to Vinay Saluja, Global Head Development Services, Novartis Contract Manufacturing, constant negotiation on raw materials prices is crucial to maintain cost-efficiency. “Furthermore, reducing volume losses during the production process can significantly enhance line efficiency; by maximizing the line utilization minimizing idle times, companies can ensure operations activities to run smoothly,” Saluja adds.
Getting Scale Right
“Scale selection, and an eye to a future commercial scale can also result in smoother transition through the manufacturing scale,” Kenneth Holbourn, Senior Director of Technical Project Lead Group (PD), FUJIFILM Biotechnologies notes. “This can be assisted by selecting a manufacturing partner with dual-sourcing capabilities that offer seamless technology transfer across scales.”
For Saluja, ensuring the right scale is being used for drug production is essential in order to achieve tailored capital expenditure. “Very often, mid-sized production based on demand is the most efficient approach considering that business projections frequently prove unreliable for large-scale production,” Saluja says.
Looking at small interfering RNA (siRNA) in particular, Alison Moore, Chief Technical Officer, Codexis, reveals that current process limitations and the capital expenditure required for chemical synthesis are creating a significant barrier to scalable production. “The generation of toxic solvent waste presents additional costs in terms of disposal and the consequent negative environmental impact,” she says.
Criticality of Solid Quality Systems
Quality-by-design is a significant driver of cost for Holbourn. “A solid CMC [chemistry, manufacturing, and controls] strategy and use of a CDMO with experienced validation scientists can avoid the risk delays including clinical holds, unnecessary duplicative work or additional bridging studies that may result in expensive delays to market,” he asserts.
“A CDMOs ability to evaluate a manufacturing process for potential issues is key to mitigate risk for routine production,” Mahler confirms. “Just having produced three (or more) PPQ [process performance qualification] batches does not mean a process is robust for reliable commercial supply of a given product.”
Establishment of a solid quality system is essential, agrees Leszczyniecka. “This [quality system] includes implementing robust, well-documented standard operating procedures (SOPs), maintaining detailed batch records, and enforcing strong quality assurance oversight,” she states.
“Deviations from good manufacturing practices (GMPs) can compromise product quality, often leading to batch rejection or triggering regulatory actions such as a consent decree,” Leszczyniecka says. “To maintain compliance and product integrity, manufacturers must operate in controlled environments with validated processes and cleaning procedures, particularly for room changeovers. Operators must be qualified and properly trained to handle complex processes reliably. An effective change control and deviation management system is vital to detect and address any variability or departures from defined procedures.”
Regulatory Principles
“The regulatory principles for any GMP production process are uniform in the requirement for a control strategy that enables the routine production and release of consistent safe, pure, and effective product,” specifies Moore. “What is changing is the complexity of biomanufactured assets, the intensity of production capability, and our ability to describe critical quality attributes through improved analytical methods.”
Minni Aswath, VP of Process Development, Bionova, emphasizes the role of new modalities in the evolution of the industry and, as a result, the regulatory landscape. “New modalities, such as bispecifics, trispecifics, ADCs, cell and gene, nanobodies, and so on, are evolving at a rapid pace,” she notes. “Historically, regulators have been philosophically resistant to change; however, the faster the biopharma industry changes, the more the regulators are becoming accustomed to seeing change.”
As a result, regulators are more open into evaluating the underlying science and have been more accepting of flexible and creative ideas that are backed by sound science, Aswath explains. She adds that those involved in biomanufacturing should keep abreast of the following key regulatory areas: GMP compliance; ICH guidelines (Q8–10); FDA and EMA expectations; environmental monitoring and contamination control; and data integrity.
“A critical focus for regulators is on data integrity,” confirms Leszczyniecka. “Electronic systems used in manufacturing and quality operations must be validated to ensure that all data are traceable, securely stored, and access-controlled,” she says.
At a Pivotal Juncture
Agility, digitalization, and sustainability are tremendously important for the future of biomanufacturing, Aswath emphasizes. “Companies that invest in flexible infrastructure, robust supply chains, and advanced analytics will be best positioned to meet growing global demand, while ensuring cost-efficiency, compliance, and environmental responsibility,” she confirms.
Industry has made great strides forward in terms of technical progress; however, economic sustainability remains the biggest challenge, Broughton urges. “As manufacturers, we can only reduce costs so far while maintaining the profitability necessary to operate, improve, and retain talented teams. The real barrier to progress is that gene therapies costing USD 3–4 million per patient create an unsustainable system that limits access to those who need these treatments most,” he says.
To continue advancing, the industry needs to collaborate at unprecedented levels, Broughton asserts. “Companies, regulators, and healthcare providers must work together to fundamentally address the cost-access equation,” he states.
“The biomanufacturing industry is at a pivotal juncture, with significant advancements on one hand and pressing challenges on the other,” summarizes Saluja. “By leveraging technological innovations, optimizing production scales, maintaining regulatory compliance, and prioritizing sustainability, companies can navigate this complex landscape effectively. The future of biomanufacturing holds immense potential; with strategic efforts, the industry can continue to thrive and contribute to global healthcare advancements.”
Reference
IMARC. Biopharmaceutical Manufacturing Market Report by Cell Culture (Mammalian Cell Culture, Microbial Cell Culture), Class (Monoclonal Antibodies, Recombinant Proteins, Interferon, Granulocyte Colony-Stimulating Factor (G-CSF), Erythropoietin, Recombinant Human Insulin, Vaccines, Human Growth Hormones (HGH)), and Region 2025–2033. Market Research Report, December 2024.
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