John Stewart, Vice President kojoX™ Strategy, Head of Global Process Development, Fujifilm Biotechnologies
The COVID-19 pandemic highlighted the critical need for resilient and adaptable manufacturing strategies in the biopharmaceutical industry. Key learnings include the importance of domestic onshoring, robust supply chains, and the ability to rapidly scale up production in response to emerging health crises. These vulnerabilities in biopharmaceutical manufacturing, now heightened by geopolitical uncertainty, require a new approach to ensure continuity of supply for medicines. Contract development manufacturing organizations (CDMOs) play a critical role, as a vital partner to pharma, in bridging the gap from clinical to commercialization phase.
CDMOs excel at scaling production, expediting the delivery of medications to the public quickly and safely. At FUJIFILM Biotechnologies, we are building the industry's largest interconnected network of biomanufacturing facilities, revolutionizing how complex medicines are developed and produced at scale. Our kojoX™ operational philosophy — a first-of-its-kind modular approach with standardized equipment, processes, and procedures across sites — bolsters supply chain resilience. This results in faster timelines, smoother tech transfers, and most importantly, the trust that comes from collaborating with the same production partner throughout the lifecycle of a drug. Our pharmaceutical partners can then focus on innovation and development rather than building significant internal production capacity and expertise.
Emily Schirmer, Ph.D., General Manager, Catalent Biologics
The significant manufacturing hurdles that biopharma faces can often serve as catalysts for innovation. The complexity of certain biologics, such as monoclonal antibodies and recombinant proteins, together with the variability in expression, purification, and stability, drives us to enhance efficiency, strengthen control strategies, and accelerate the timeline from lab to commercial production, all without compromising quality.
A structured, practical approach to process development is essential for overcoming these hurdles. Using high-yield, stable CHO cell lines built through targeted gene insertion helps drive consistency from the start. Strategies like N-1 perfusion can boost viable cell density and reduce production time. On the downstream side, process intensification must keep pace. Traditional purification methods often become bottlenecks when upstream titers increase. Adopting technologies such as multi-column chromatography increases throughput and resin efficiency while reducing buffer use and facility footprint.
Real-time monitoring and process analytical technology (PAT) tools enhance control and help identify issues early. Flexible, single-use systems and modular infrastructure allow faster transitions from clinical to commercial. Embedding regulatory expertise throughout development supports smoother global filings.
Catalent approaches these challenges with collaboration and focus. We work closely with our partners to apply the right tools and insights, moving programs forward without compromising quality or speed to clinic.
Joomyung Lee, Director of Downstream Manufacturing, Samsung Biologics
Managing risk mitigation and assessing manufacturing scalability are daily realities in drug development. Unlike commercial manufacturing, which benefits from standardized processes from technology transfer to final packaging, early-stage production often lacks the data necessary for biomanufacturers to design robust plans that effectively address uncertainties.
Incomplete criticality assessments of process parameters — such as cell culture trends —may engender the creation of stringent process ranges that fail to address potential errors in large-scale manufacturing. This, in turn, complicates root-cause analysis of issues and troubleshooting. Furthermore, insufficient understanding of equipment specifications and process variations between labs and large-scale facilities can exacerbate these challenges.
Collaboration is essential to overcoming such hurdles. Strategic partnerships among academia, drug developers, and biomanufacturers can accelerate timelines for process characterization, analysis, and design. Partnering with a trusted contract development and manufacturing organization (CDMO) can streamline process development and ensure consistent quality. Additionally, proactive sharing of scientific and project knowledge between CDMOs and their clients can expedite the development of rigorous technology transfer processes and risk mitigation strategies.
Robust interactions between CDMOs and their clients facilitate timely root-cause analysis and effective resolution of issues. The detection of unaccounted impurities during the purification stage — if not thoroughly and promptly addressed — could critically hinder progress toward achieving a project milestone. In high-pressure situations, CDMOs should establish real-time communication channels and work closely with clients to develop an effective issue-resolution method by combining knowledge and expertise. In tandem, CDMOs must provide up-to-date data and analysis from their project histories, ensuring clients that actionable data is available to help them rigorously implement the resolution method.
Grant Boldt, Ph.D., Chief Operating Officer, CPTx
Viral vectors remain the backbone of gene and cell therapy (GCT) delivery due to their ability to achieve high transduction efficiency in both dividing and non-dividing cells, enable stable gene integration when required (e.g., lentiviral vectors in T cells or hematopoietic stem cells), and support durable transgene expression in vivo (e.g., AAV vectors targeting liver, muscle, or central nervous system).
However, viral vectors also represent one of the most significant manufacturing challenges in biopharma. Their production is costly, complex, and time-intensive, with stringent quality control requirements that can delay development timelines. These hurdles contribute to the high cost of many approved therapies, which frequently range from $400,000 to $1 million per patient.
Non-viral delivery offers a transformative alternative. By eliminating the need for viral vectors — particularly in ex vivo applications — non-viral approaches are already streamlining manufacturing, reducing costs, and accelerating development. Importantly, in vivo therapies utilizing non-viral methods are also gaining momentum as these methods provide greater control over gene insertion and mitigate risks such as excessive transgene expression and insertional mutagenesis.
A key enabler of non-viral GCT is single-stranded DNA (ssDNA). Single-stranded DNA templates enable precise and efficient gene insertion with minimal toxicity. Compared to double-stranded DNA, ssDNA elicits fewer immune responses and supports higher editing efficiency. Gxstrands’ fermentation-based synthesis enables scalable production of long-chain, custom ssDNA sequences with clonal sequence fidelity, leveraging microbial repair mechanisms — critical for advancing high-quality therapies from lab to clinic.
As non-viral delivery efficiencies continue to approach those of viral methods, ssDNA is driving the adoption of non-viral strategies — enabling next-generation GCT to become safer, more accessible, and cost-efficient to manufacturable at scale, helping to democratize advanced therapies for broader patient populations.
Vanee Pho, Vice President Global Marketing, Mission Bio
With new therapeutic modalities come new manufacturing paradigms, and the most significant challenges today are for cutting-edge tech like cell therapies, which require manufacturing processes unlike anything biopharma has ever seen before. This is especially true for therapies leveraging gene-editing technologies like CRISPR. And while novel manufacturing methods can accelerate the production of a dose, analytics must keep pace.
For both safety and efficacy, we need reliable and efficient assays to ensure the consistent quality of final therapeutic products before administering to the patient. For vector-mediated therapies, there can be variability within a lot due to cell-to-cell differences in vector copies. For gene-editing therapies, it is crucial to know how well therapeutic genes have been transduced into target cells within a lot and to ensure on editing efficiencies are maintained. In both instances, bulk assays lack the specificity and resolution required to ensure the safety of a batch, in terms of confirming the expected distribution of genetic material. Furthermore, data from multiple assays on different instruments must be combined to determine critical quality attributes.
For these reasons, high-throughput single-cell DNA sequencing is becoming a necessary tool to ensure the safety of each CGT dose, particularly gene-edited therapies. Multiple attributes, such as on- and off-target editing, zygosity and co-occurrence of edits, and surface protein expression can be combined into one assay for a more precise and accurate measurement.
Jordan Hunter, Ph.D., Senior Product Manager, Cell & Gene Therapy, BioIVT
The journey from lab to market for advanced therapies and cell and gene therapies (CGTs) is fraught with manufacturing hurdles. A primary challenge is scalability; these are often personalized medicines, making traditional large-batch production impractical. Manual processes, which are still prevalent, can lead to high variability in quality, labor costs, and batch failures. The need for specialized, costly cleanroom facilities and highly trained personnel further exacerbates economic burdens, translating into prohibitive per patient costs.
Supply chain fragility is another critical concern. Sourcing consistent, high-quality starting materials and critical reagents can be challenging. There are single suppliers for many components, which creates vulnerability. Moreover, the ultra-cold chain logistics required for many CGTs add significant complexity and risk of product degradation.
To facilitate this journey, the industry must embrace streamlined, scalable manufacturing technologies. Automated, closed-system manufacturing platforms can reduce manual intervention, improve consistency, lower contamination risk, and enable greater scalability. Implementing digital solutions like electronic batch records and advanced data analytics will enhance process control, optimize yields, and facilitate regulatory compliance. Fostering talent development and strategic partnerships with critical raw material suppliers and contract manufacturing organizations will be crucial to overcoming capacity constraints and accelerating delivery of these life-changing therapies to patients.
Ossama Eissa, Chief Operating Officer, Cellares
In cell therapy, the most critical manufacturing challenge has always been throughput. Especially for autologous therapies — where every patient gets their own batch — traditional scale-up models simply don’t apply. The result is a system where even approved, lifesaving therapies reach only a fraction of eligible patients. Not because of scientific limitations or reimbursement barriers, but because the manufacturing and quality control infrastructure wasn’t designed for this kind of medicine.
The good news is we’re finally starting to shift from incremental fixes to foundational change. Fully automated, closed systems are coming online — platforms purpose-built to run multiple patient batches in parallel, in a fraction of the footprint and with dramatically less manual intervention. These are not just efficiency upgrades. They’re a reimagining of how we bring advanced therapies to life.
Smart factories with integrated automation and in-line QC are driving orders-of-magnitude improvements in throughput. They’re enabling faster tech transfer, more consistent product, reduced labor dependency, and streamlined regulatory pathways. This isn’t about doing what we’ve always done slightly better. It’s about building the infrastructure that makes it possible to keep pace with the science — and with the patients waiting on the other side of approval.
Ahmad Hussin, Vice President, CDMO, Charles River Laboratories
The industry faces several complex manufacturing challenges, including scalability, batch-to-batch consistency, supply chain fragility, and evolving regulatory expectations. The transition from small-scale lab production to full-scale GMP and commercial manufacturing often exposes process gaps and inefficiencies — particularly in biologics, where living systems are involved. Even minor process variations can impact product quality and potentially compromise patient safety.
At Charles River, we recognize that overcoming these hurdles requires early, integrated support across the drug development life cycle. That’s why we continue to invest in robust, scalable platforms aligned with quality-by-design (QbD) principles, as well as modular and single-use technologies that enhance flexibility and reduce contamination risk. Our use of digital tools, data-driven systems, and strategic partnerships with innovator companies helps clients optimize process development, improve yields and consistency, and accelerate timelines to clinic or market.
Mitigating supply chain risks through dual sourcing, advanced logistics planning, and key collaborations is key to protecting development and technology transfer timelines. Additionally, partnering with regulatory agencies during development —leveraging accelerated pathways and enabling continuous manufacturing approaches — can further reduce time to market.
Ultimately, combining early-stage integration, digital innovation, resilient supply chain planning, and proactive regulatory engagement is key to streamlining manufacturing and accelerating the delivery of safe, effective therapies to patients.
Daniel Hawkins, Aseptic Manufacturing Director, Lifecore Biomedical
In recent years, growth in autoinjector technologies that allow for self-administration of therapeutics has fueled a trend toward higher concentration formulations designed for subcutaneous delivery. While the move to these new technologies can increase patient compliance and convenience, it does introduce some manufacturing challenges.
Biologics are inherently sensitive molecules that are at risk of damage from several factors, including shear stress. Compounding this issue, higher concentrations correlate to an increase in viscosity, meaning formulations can be more challenging to handle and fill. Manufacturers must incorporate precise process controls and optimize equipment to successfully formulate and fill these highly sensitive, viscous formulations. This includes consideration of special mixers for formulation and the use of peristaltic pumps on the fillers.
In addition, biologic products cannot be terminally sterilized. At times, biologic formulations can reach more extreme viscosities, and few manufacturers possess the ability to perform sterile filtration of highly viscous formulations. Over several decades, Lifecore Biomedical has established a leadership position within the CDMO space for the capability to sterile filter and manufacture highly viscous injectable products of all types, including biologics. Selecting a partner that has the right expertise and equipment from the start can help drug sponsors streamline their efforts to bring their products from the lab to the market.
Andrew Henderson, Ph.D., Chief Operating Officer, Sterling Pharma Solutions
From a manufacturing perspective, there are two broad challenges to streamlining a drug’s journey towards commercialization. Firstly — and this depends on each product’s individual characteristics — the extent of the process development and scale-up required can have a major impact on drug development timelines. Secondly, enhanced analytical testing and validation demands continue to increase the quantity of data needed to support the chemistry, manufacturing, and controls (CMC) section of New Drug Applications (NDAs), which subsequently can impact drug development timelines.
Patient safety is key, and it is obviously within the innovators’ and regulators’ remits to ensure products are both effective and safe, but the burden on manufacturers to provide extensive data is at the cost of expediency.
While timelines through development to launch can be significantly impacted by manufacturing challenges, the duration of clinical trials tends to be the rate-limiting factor to achieve a timely launch. However, by ensuring the appropriate time is spent making the process as robust as possible, and front-loading the development of programs to ensure clinical batches are made with suitable processes for commercial-scale launch batches, delays from manufacturing can be minimized by alleviating the need to undertake additional process/manufacturing scale-up and revalidation work post successful trials milestones.
Spandan Mishra, Global Director- Technical Marketing- Cell Culture Solutions, Evonik Health Care
There are several manufacturing challenges in biopharma. One significant hurdle is identifying the right clones of cells that have high producibility. Bioprocess efficiency at lab to commercial scale is also one more challenge which leads to difficulty in achieving cost-effectiveness at commercial scales.
For cell line screening and correct clone selection, high-throughput screening assays (HTS) such as CRISPR/Cas9 are playing an important role in identifying clones of cells with high growth and production rates.
In terms of bioprocess efficiency, this issue can be addressed by developing and executing a robust bioprocess that considers each step of the upstream and downstream process from lab to commercial scale.
Productivity and cost-effectiveness at commercial scale depends on the cumulative success in clone selection and bioprocess efficiency. The selection of the right raw materials and supplements for bioprocesses, robustness of supply chain, bioreactor efficiency, final formulation and drug delivery methods, operator competency and efficiency.
To help intensify, simplify and increase the productivity of a bioprocess from lab to commercial scale, Evonik offers a portfolio of peptides and keto acids. These high-quality, high-performance ingredients are used as raw materials and supplements in the cell culture (upstream) process. For more information see: https://healthcare.evonik.com/en/biopharma/cell-culture
References:
Thompson, Paul. “Bioprocessing Challenges and Solutions in Modern Drug Manufacturing.” Pharmaceutical Bioprocessing. 11: 74–76 (2023).
Thomas, Megan. “Where do we stand with cell line development?” DDW Online. 5 Mar 2025.
Wei Guo, Ph.D., Senior Vice President, Head of Global Manufacturing, WuXi Biologics
From the perspective of a contract research, development, and manufacturing organization (CRDMO), the biopharma industry faces three significant challenges in scaling from lab to market: process scalability, regulatory complexity, and supply chain resilience.
Scalability: Scaling up from small-scale to commercial production risks process drift, impacting product quality. Solutions including continuous manufacturing and process intensification (e.g., high-density cell cultures) reduce scale-up timelines while maintaining consistency. By combining the benefits of single-use technology with a scale-out strategy (increasing the number of bioreactors used in parallel), WuXi Biologics can effectively address scale-up risks, enabling rapid growth that aligns directly with demand, while also supporting emergency production and accommodating various process types.
Regulatory agility: The emerging modalities and delivery systems, such as antibody–drug conjugates (ADCs) and autoinjectors, impose new demands for specialized expertise and GMP adherence. To navigate these complexities, companies must proactively build interdisciplinary teams to accumulate institutional knowledge, ideally established early in development cycles to ensure seamless integration of quality systems and regulatory alignment.
Supply chain vulnerabilities: Geopolitical disruptions pose uncertainty and threaten timelines. Diversifying suppliers with different priorities in speed and cost for the initial and secondary launch can be helpful. With facilities in Ireland, Germany, the United States, Singapore, and China, we offer our global clients access to a reliable and premier-quality global supply chain network. By implementing a global dual sourcing strategy, WuXi Biologics ensures that materials can be sourced and products can be manufactured at multiple locations across the world.
Marie-Sophie Quittet, Ph.D., Head of Customer Relationship, Adragos Pharma
The biopharma industry faces several significant manufacturing hurdles, particularly in keeping with the ambition to streamline and accelerate the process from laboratory to market.
One of the most pressing challenges in this area is managing potential impurities from leachables. These substances can originate from packaging materials and equipment in the production process, and can compromise both the efficacy of the product and its safety to patients. To address this, the industry must implement rigorous material selection processes, and conduct thorough testing to identify and minimize such impurities. Establishing stringent guidelines and adopting materials with proven biocompatibility are crucial in mitigating these risks.
Another constraint is the ability to filter final drug products. Effective filtration is vital for the sterility of products, especially when terminal sterilization is impossible for biological products. However, manufacturers must balance filtration efficiency with the preservation of product integrity, which can be challenging. To overcome this, the biopharma sector must continue to innovate in filtration technologies, ensuring that high levels of purity can be achieved without compromising the therapeutic properties of biologics.