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Feliza Mirasol

A discussion on aseptic sterile processing in pharmaceutical manufacturing with Simtra BioPharma Solutions' Lidia Serina.

A Discussion on Aseptic Processing for Sterile Injectable Manufacturing (DCAT Week 2025)

In an interview with the PharmTech Group ahead of DCAT Week 2025, Lidia Serina, PhD, head of Development Services at Simtra BioPharma Solutions, discusses the key challenges in aseptic processing for sterile injectables. Among the primary hurdles are the preservation of aseptic conditions throughout complex, multi-hour manufacturing processes while ensuring product stability, especially for sensitive molecules such as antibody-drug conjugates (ADCs); upholding cold chain logistics to maintain temperature-sensitive products during processing and shipping across global supply chains; and adherence to stringent safety standards for highly potent and cytotoxic molecules to protect both the workforce and the final drug product.

To address these challenges, Simtra is leveraging advanced automation, digitalization, and lean manufacturing practices. This includes enhanced digital monitoring, robust technology transfer protocols, and facility designs tailored to mitigate risks. The company is also expanding its capabilities in highly potent and cytotoxic manufacturing, as well as dedicated suites for ADCs.

"In parallel to the digitalization environment, we are also improving the way we do technology transfer … from when we receive a molecule and a process from a client [to when] we transfer this knowledge onto our aseptic filling lines … we need to make sure that we understand the critical process parameters [and] the quality attributes of the molecule, so we are actually able to keep the stability of this molecule along the manufacturing process [even to] the patient, right when we ship the product to the patient," Serina says.

DCAT Week is being held March 17–20, 2025 in New York City.

Lidia Serina, PhD, head of Development Services at Simtra BioPharma Solutions

Lidia Serina, PhD, is head of Development Services at Simtra BioPharma Solutions, leading a strategic area essential to the company’s mission. She partners with clients to develop high-quality injectable products and efficient manufacturing processes. With extensive experience in supply chain, vaccine R&D, quality and regulatory compliance, and both commercial and clinical manufacturing, Serina’s technical expertise spans a wide range of molecule types. Her leadership drives innovative solutions to the complex challenges of product development and manufacturing.

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Lidia Serina, PhD, head of Development Services at Simtra BioPharma Solutions, discusses the challenges with maintaining aseptic integrity in sterile injectable pharmaceutical manufacturing.

DCAT Week 2025: A Discussion on Aseptic Processing for Sterile Injectable Manufacturing

India-based Shilpa Biologicals, a fully owned subsidiary of Shilpa Medicare Limited, announced on March 17, 2025 that it has entered into a strategic partnership with Switzerland-based mAbTree Biologics. The companies will co-develop and commercialize mAbTree’s novel biologic asset—a checkpoint inhibitor for immuno-oncological applications.

Under the agreement, Shilpa Biologicals will support development—including clinical studies—and long-term commercial supply with good manufacturing practice (GMP) manufacturing. Meanwhile, Shilpa Group will provide mAbTree access to India and several global markets through its partner network (1).

The partners aim to develop a fully human monoclonal antibody (mAb) against a novel immune checkpoint protein. This protein enables T-cell activation and the generation of strong immune responses against tumors, similar to the more well-established blocking action of programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1).While blocking PD-1/PD-L1 has demonstrated significant clinical successes, recent studies suggest that Shilpa Biologicals’ and mAbTree’s novel target carries a highly attractive therapeutic potential in various immuno-oncological states as both a monotherapy and combinatorial therapy. Their approach has the potential to convert cold tumors (those with poor immune cell infiltration) to hot (having good immune infiltration). Their approach can also suppress tumor metastasis and make refractory tumors susceptible to chemotherapy. This target is applicable in various cancers, including lung cancer, head and neck squamous cell carcinoma, and hematologic malignancies, according to a company press release (1).

“We are delighted to enter this strategic collaboration with mAbTree Biologics as we share a common vision to bring innovative solutions to address unmet medical needs around the globe, especially in the field of oncology where Shilpa has had a long history of providing affordable innovative solutions,” said Madhav Bhutada, director, Shilpa Biologicals, in the press release (1).

Shilpa Biologics’ large R&D teams will provide full-service capabilities, from cell line development to GMP drug product manufacturing. Manufacturing activities and the provision of clinical supply will be conducted at the company’s biomanufacturing facility at Dharwad, Karnataka, in India.

“mAbTree is excited to continue our strategic partnership with Shilpa Biologicals and our aim is to enable greater access to medicines for more patients across the world, especially focusing on India and ROW [rest of world] markets where access has been limited,” said Raj Andhuvan, CEO, mAbTree in the release. “But what really impresses us about Shilpa is their commitment and scientific expertise. We look forward to rapidly advancing therapeutic options in the NBE [new biological entity] space and to addressing emerging health challenges.”

mAbTree’s pipeline (including this asset under the partnership with Shilpa Biologicals) includes two oncology assets that have completed preclinical studies and two assets currently in the R&D phase, one multiple sclerosis and the other in psoriasis. The rest of the company’s pipeline includes two undisclosed candidates in the investigational new drug application-enabling phase, one in the 

 proof-of-concept phase, and two in the lead optimization phase (2).

Shilpa Biologicals’ pipeline primarily includes biosimilars in various stages of development. It has an adalimumab biosimilar that has complete Phase III trials, an aflibercept biosimilar entering Phase III trials, and a FC fusion protein biosimilar and another mAb biosimilar in preclinical studies. The company also has a new biological entity, recombinant human albumin, that has started Phase III trials (3).

1. Shilpa Biologicals. Shilpa Biologicals Pvt Ltd Signs Strategic Development Partnership with mAbTree Biologics AG for a Novel Immuno-Oncology Asset. Press Release. March 17, 2025.
2. mAbTree Biologics. Pipeline. 

 (accessed March 17, 2025).
3. Shilpa Biologicals. Product Portfolio. 

Articles

The partnership aims to develop and commercialize a novel checkpoint inhibitor for immuno-oncology applications.

Shilpa Biologicals and mAbTree Biologics to Collaborate on Novel Immuno-Oncology Asset

Advances in manufacturing for new biotherapeutics and small-molecule pharmaceuticals are often based on current trends and/or changes or upgrades in equipment and processes. As biotherapeutic modalities grow more complex and as API dosing forms increasingly aim for high potency/low dose formats, equipment and process trends must keep pace. An exploration of current trends in equipment and processes can shed light on how these changes are supporting the way bioprocessing and pharmaceutical manufacturing is advancing going forward.

Starting early in the manufacturing lifecycle, the challenges associated with bioprocess development for a new biotherapeutic can fall into a few major categories. For one, in bioprocess development today, more than ever, there is a need for bioprocesses to be well aligned with the manufacturing supply chain and distribution strategy that is intended for that product right from the get-go, says Smriti Khera, PhD, global head of life sciences strategy and marketing at Rockwell Automation.

“If you look at the industry today, there are two parallel but opposing mega trends. One is that the manufacturing scales needed today are very different across various drug classes,” Khera says.

The bioprocess development for follow-on drug candidates, she emphasizes, “… willoptimize process to boost yield and productivity of the manufacturing process and that might require increased use of automation and evaluating new digital tools and technologies such as digital twins, PAT [process analytical technology] solutions, and beyond. An increased use of automation will produce efficiencies across the process, plant, and personnel needed to support the large scale manufacture of blockbuster drugs,” Khera says.

The more traditional challenges in bioprocess development are around determining and monitoring set points for critical process parameters (CPPs) and critical quality attributes (CQAs). “To do this, [bioprocess developers] need to perturb and evaluate the design space around a process and get a better understanding of the process overall, and that will help them ultimately put a better process and control strategy together,” Khera observes.

CPPs can be dramatically different at different scales, so maintaining conditions correctly, such as homogeneity, temperature, and dissolved oxygen, can be very different at different scales and must be monitored. “Determining the right conditions is [typically] a very labor-intensive process within bioprocess development,” notes Khera. “If you put that into context of today’s extremely diverse and massive therapeutic pipelines, it creates a resource constriction and massive demand for the process development experts’ time. That’s where a big opportunity exists today to leverage available data and science together through mechanistic and data-driven machine learning (ML) models and be able to run process simulations to help cut down on the manual experiments and expensive pilot runs needed.”

In terms of key equipment, there are a variety of critical equipment applications in biotherapeutic manufacturing, including single-use bioreactors, cell culture equipment, viral vector production systems, purification systems, fill/finish equipment, and real-time analytics gathering, says Anthony Christopher, commercial manager of bioprocessing at Kent Elastomer Products (KEP).

Christopher emphasizes that one of the most prominent recent developments in the biomanufacturing space is the increased adoption of single-use technologies (SUTs). “Advances in disposable components and equipment in a range of applications can help to reduce contamination risks, streamline cleaning requirements, and enable faster changeovers,” he states.

Christopher points to tubing, specifically, which presents one of the critical applications for single-use systems. However, alternatives to traditional silicone tubing offer potential quality and cost optimization benefits that Christopher says can make a true impact on biopharmaceutical manufacturing operations. “Bioprocessors have the opportunity to evaluate and source high-performing elastomeric tubing options that can help bring overall costs down without sacrificing quality or accuracy issues,” he states.

“Elsewhere,” Christopher adds, “we’re monitoring other evolutions, including continuous manufacturing systems, modular production units, integrated chromatography systems, advanced sensor and monitoring systems, and more.”

Meanwhile, automation has been playing a big role in advancing the equipment supporting bioprocessing. Christopher highlights digital twin technology, integrated control systems, automated sampling and analysis, and smart bioreactors as some of the automation developments being witnessed in the biomanufacturing space.

Automation is also being increasingly used at a commercial level. “From what our team has seen, most commercial biomanufacturing processes are partially automated, with automation implemented in upstream (e.g., bioreactors, feeding systems) and downstream (e.g., chromatography, filtration) steps,” says Christopher. He interjects that manual intervention is needed for setup, troubleshooting, and quality control, but that many facilities now use automated systems for data collection, process monitoring, and quality assurance. “But,” he qualifies, “full end-to-end automation is rare.”

On the small-molecule manufacturing front, the pharmaceutical industry is seeing a paradigm shift in processing equipment, driven by automation, sustainability, and regulatory compliance, says Caterina Funaro, Competence Center manager at IMA Active. Industry 4.0, for example, is accelerating the adoption of smart machinery, interconnected sensors, and artificial intelligence (AI)-driven control systems, which are enabling real-time monitoring and data-driven decision-making.

“Predictive maintenance is a key application where equipment can self-monitor for wear and tear and alert operators before a breakdown occurs, minimizing downtime. Smart factories are becoming a reality, where data collected from machines optimize operations in real time,” Funaro states.

Meanwhile, sustainability is a key focus in the pharmaceutical industry as manufacturers face pressure to adopt more energy-efficient equipment that reduces their environmental footprint, notes Funaro. “This includes reducing water and energy consumption, lowering emissions, and improving waste management. Recyclable and reusable components in machinery, as well as the use of environmentally friendly materials, are becoming more widespread,” she observes.

When it comes to developing a manufacturing process for new biotherapeutics, process engineers and, in general, drug developers can benefit from implementing automated technologies into the manufacturing process.

“As an automation engineer,” says John Hatzis, global life sciences industry consultant at Rockwell Automation, “I’m always thinking about tech transfer from process development into GMP [good manufacturing practice] manufacturing, and it’s important to use automation technologies that can make that transition easy.”

“It’s all about leveraging industry standards out-of-the-box so as to avoid the need to reprogram the system or retrain personnel when your therapy gets approved,” Hatzis explains. “If you adopt an automation platform that applies standards [such as] ISA-101 and ISA-88 earlier in your manufacturing, you can seamlessly transition your operations into GMP without costly retraining of personnel or re-architecting your automated systems. Having the features built into the platform that can be easily configured to comply with the regulations for data integrity when you need them is really important.”

For example, Hatzis points out, a developer that builds up a repertoire of automation software for a piece of equipment that does not have “off-the-shelf” features may need to undergo significant reworking when the time comes for tech transfer into a clinical manufacturing, where data integrity becomes crucially important. “All of these things are going to be really important to make tech transfer easy and efficient [going] into clinical or GMP manufacturing,” he states.

Nicolas Pivet, vice-president and general manager, Manufacturing Capacity & Digital Solutions, Cytiva, shares the company’s experience in working with partners to develop bioprocesses for new biotherapeutics. “What we’ve been experiencing is that many of our customers actually use a platform approach for process development, which is great for speed but sometimes is not optimized for everything,” he explains, noting that it was this gap between speed and optimization that prompted Cytiva to develop a software simulation tool (GoSilico). “[This tool] helps to characterize and optimize large sets of chromatography resins, for instance, and saves a lot of time,” says Pivet.

Pivet also brings up the automation layer, which is a layer that allows equipment information to be viewed together. “Over the past seven years,” he explains, “we’ve been developing [an] automation offering (Figurate), which is a wide range of automation solution and libraries—from historian to control systems with Unicorn [control software] to SCADA [supervisory conrol and data acquisition] with Wonderware [automation platform] and to distributed control systems [e.g., DeltaV, PlantPax].”

Developing an automation library for cell culture and purification steps and improving control over CPPs such as pH, oxygen, and temperature, enables parallel processing, which can ease scale-up from lab to production, Pivet explains. Meanwhile, applying automation to downstream chromatography and filtration steps helps optimize product purification, improving purity and yield.

The improvement in process PAT has also been key in the implementation of automation in bioprocessing, Pivet notes. “Today, it’s really about outlier technologies that are used in the industry—[Raman] spectroscopy with chromatography and mass spectrometry [for example]—to monitor product quality, but those solutions have been quite cumbersome on the [manufacturing] floor, so we are working on new and breakthrough technologies [as well as] simulation[s] to avoid the burden of physical experiments,” Pivet says.

Pivet also notes that in-silico process development tools are a game changer. For example, he discusses the development of a bioreactor scaler using computational fluid dynamics capabilities, which helps with scaling up or scaling down between processes. “We’ve shown that we can save up to 50% of the time to run characterization optimization studies, and we can also achieve up to five points higher yield. Truly, I think that automation benefits the whole workflow, the operations—from seed production … to [cell] harvesting and downstream processing, even fill/finish,” he explains.

Furthermore, PAT enhances monitoring at “moments of truth,” where critical control points impact drug quality, safety, and efficacy, Pivet also explains. Integration with manufacturing execution systems and laboratory information management systems ensures full process visibility.

Automation technologies, including PAT, are important now and will be crucial to the industry moving forward. “I think, in the area of process analytical technology, the industry needs to move faster. [Regarding] PAT sensors [for example], there’s the emergence of improved sensing technology. And measuring CQAs, for instance, in line or online is really the holy grail of the biopharma industry right now, so the industry needs to get there in being able to measure CQAs in line and helping with real-time release, or right-time release, of the drug,” Pivet states.

“At the end, we need a software orchestration to take all those sensor data, manage them in real-time, and, using artificial intelligence [AI]/ML modeling, drive a real closed-loop optimization of the batch to end up with a batch that’s prescriptive, where you can really intervene on the batch before it’s too late and maximize the outcome of the batch. So, that’s where the industry is going,” Pivet concludes.

Meanwhile, Christopher observes that, from the research his company’s team has performed and from what is being seen among the customer base, “fully automated commercial-scale biologics manufacturing is not yet common, but the industry is rapidly moving in that direction.”

He points to advances in robotics, AI, and ML accelerating progress. “But, plenty of challenges stand in the way, including cost of implementation, regulatory compliance, and more.We have heard from experts who anticipate that fully automated, ‘lights-out’ biomanufacturing facilities could become a reality within the next five to 10 years,” Christopher adds.

In small-molecule pharmaceuticals manufacturing, automated production lines minimize downtime, increase throughput, and enable continuous manufacturing. “Automated material handling, packaging, and processing reduce the need for human intervention, leading to faster cycle times. In continuous manufacturing—especially in pharmaceuticals and chemicals—automation enables uninterrupted processes, reducing the need for manual batch handling and improving scalability,” says Funaro.

“As automation becomes more advanced,” Funaro adds, “the workforce will need new skills in data analysis, robotics operation, and AI systems management. Upskilling employees to work alongside advanced automation systems will be critical.”

®
Vol. 49, No. 2
March 2025
Pages: 10–13

When referring to this article, please cite it as Mirasol, F. Accelerating Adoption of Smart Tools to Advance Manufacturing. 

Industry 4.0 is driving adoption in the pharma industry for smart equipment 
and tools that will advance manufacturing.

Accelerating Adoption of Smart Tools to Advance Manufacturing 

The forward movement of the bio/pharmaceutical industry is driven by fast-paced advancements in manufacturing technology innovations. As manufacturing technology advances, so does the shift to continuous manufacturing (CM), a process that enables real-time monitoring, improved scalability, and enhanced quality control. As the industry increasingly adopts CM, it is undergoing a transformative shift.

In the current environment, one of the most significant applications of CM is in the production of RNA-based therapeutics, including messenger RNA (mRNA), self-amplifying RNA (saRNA), and circular RNA. In an interview with Aaron Cowley, chief scientific officer at ReciBioPharm (1), Cowley noted how industry leaders have spearheaded the development of CM platforms for RNA manufacturing with funding from FDA. These CM platforms hold the promise of significantly increasing production efficiency while maintaining rigorous quality standards.

In particular, the COVID-19 pandemic sharply highlighted the necessity of having rapid and scalable RNA manufacturing to meet global vaccine demand at the time. Traditional batch manufacturing poses bottlenecks that hinder timely drug availability. In comparison, CM integrates all unit operations into a seamless and continuous process and allows for real-time release and significant reduction in production timelines (2).

One of the key advantages of CM in RNA therapeutics is its ability to maintain small-scale yet high-throughput production. And, unlike monoclonal antibodies or conventional biologics that require thousands of liters in bioreactors, RNA production runs at much smaller scales—typically a few hundred milliliters to several liters per batch (3). CM becomes an ideal approach to tackling production of RNA-based products because it facilitates rapid adaptation and scale-up while at the same time minimizing waste and inefficiencies.

A significant innovation in CM for RNA therapeutics is the integration of in-vitro transcription (IVT) into a continuous process. Traditionally, IVT reactions are performed in batch mode, in which RNA synthesis is followed by downstream purification and formulation. But the continuous integration of IVT with purification and fill/finish operations allows for real-time monitoring and control, which leads to enhanced product consistency and yield (4).

“Being able to have eyes on the process and the product as it goes along, the full train of manufacturing, and be able to release that real time—is the overall goal that we are after,” said Cowley in the interview (1), explaining that if another pandemic comes along there won’t be a bottleneck in manufacturing, and that an RNA-based vaccine, for example, will be available and the manufacturing process will still be able to produce extra material.

On the small-molecule side, there is a trend toward higher potency and smaller dosing of APIs as, for the past 20 years, development and innovation in the pharma industry have focused on patient safety, meaning product quality, while also addressing cost efficiency and promoting greater sustainability, says Guia Bertuzzi, product manager of processing equipment for oral solid dosage (OSD) at IMA Active, the specialized division of the Italian company IMA Group.

“Modernizing the pharmaceutical industry requires both a more robust drug formulation design and better control of the production process, ensuring the highest quality and availability of the drug throughout its entire life cycle,” Bertuzzi states, adding that, “This concept strongly aligns with the adoption of the quality-by-design (QbD) approach, which prioritizes quality in drug development, as recommended by regulatory authorities. Furthermore, it paves the way for CM and other emerging technologies.”

Bertuzzi points to how CM fully supports the growing trend toward low-dose OSD forms and the increasing need for process containment and accuracy in quality control. “By definition, CM systems are designed for high-containment processes: they are typically compact, closed systems with a smaller process surface compared to batch manufacturing systems of equivalent productivity,” she explains. “Additionally, CM enables the integration of different production technologies in series, allowing for an uninterrupted material flow, from raw materials to the final pharmaceutical form, within a closed system that eliminates the need for product transfers between equipment, thereby minimizing the risk of product leakage.”

Because the CM process is continuously monitored in real-time with advanced instrumentation and an advanced control philosophy (i.e., process analytical technology [PAT]), the critical quality attributes (CQAs) of the product is also instantly monitored, allowing for increased sampling frequency without requiring physical sample collection, Bertuzzi states.

Modular and flexible manufacturing systems

The flexibility of CM, meanwhile, allows for modular process design, which enables manufacturers to switch between different modalities without major overhaul of infrastructure. The ability to switch between modalities is particularly important in RNA manufacturing as RNA therapeutics expand beyond vaccines to include gene therapies, cancer immunotherapies, and rare disease treatments. Having the ability to modify purification steps—such as adjusting the number of chromatography columns (based on impurity profiles)—will ensure that different RNA therapeutics can be produced efficiently and on a single platform (5).

However, despite the advantages that CM has demonstrated so far, the transition from traditional manufacturing to fully CM processes will continue to present challenges. Small and medium-sized enterprises (SMEs) will particularly face obstacles, including high initial investment costs, integration complexities, and the need for specialized expertise—factors that remain barriers to widespread adoption.

“Adopting CM requires a significant initial effort, including cultural and organizational changes within most pharmaceutical companies,” Bertuzzi says. “A company looking to implement CM must adequately prepare and structure itself. Beyond simply acquiring and integrating machinery in series, production and quality must be designed with a QbD approach, incorporating a higher level of automation and ensuring seamless integration between various technologies. This necessitates a strong orientation toward digitalization.”

Continuous manufacturing has gained increasing recognition by regulatory agencies such as FDA and the International Council for Harmonisation (ICH), which acknowledge CM’s potential and have issued guidelines (e.g., ICH Q13) to facilitate implementation (6).

“The drive toward CM will undoubtedly intensify due to the recent publication of regulatory guidelines (ICH Q13, FDA Q13, etc.) by major global authorities. Additionally, ongoing global challenges—such as pandemics, wars, and raw material shortages—further highlight the need for more efficient and resilient manufacturing processes,” Bertuzzi emphasizes.

Overcoming the challenges to full CM adoption will require strategic collaborations between biopharmaceutical companies, contract manufacturing organizations/contract development and manufacturing organizations, and technology providers. These collaborations will be crucial moving forward. In addition, standardization of CM technology platforms, especially those that incorporate modular automation, AI-driven process control, and cloud-based data analytics, will further enable CM adoption (7).

“From an equipment vendor’s perspective, we are actively driving the transition toward CM, particularly for SMEs, by providing process engineering support to facilitate adoption and implementation,” adds Bertuzzi.

1. Spivey, C. Biopharma’s Progress with Continuous Manufacturing in mRNA (BIO 2024). 

, Sept. 27, 2024.
2. Plumb, K. Continuous Processing in the Pharmaceutical Industry. 

 (A6), 730–738.
3. Kempf, H.; et al. RNA Manufacturing and Process Development: Current Trends and Future Outlook. 

 (10), 1168–1180.
4. Karmakar, S.; et al. Continuous Manufacturing of RNA Therapeutics: Opportunities and Challenges. 

, 107840.
4. Uhl, P.; et al. Flexible Manufacturing Strategies for RNA-Based Therapeutics. 

Guidance for Industry, ICH Q13 Continuous Manufacturing of Drug Substances and Drug Products

 (CDER, March 2023).
6. Konakovsky, S.; et al. Smart Manufacturing Approaches for Continuous Biopharmaceutical Production. 

®
Vol. 49, No. 2
March 2025
Pages: 24–26

When referring to this article, please cite it as Mirasol, F. How Continuous Manufacturing is Advancing Bio/Pharma Production. 

Continuous manufacturing offers advantages in both biotherapeutic and API manufacturing but still poses challenges.

How Continuous Manufacturing is Advancing Bio/Pharma Production

Next-generation biotherapeutics pose challenges to the development of manufacturing processes and analytical characterization because of their complexity and, in some cases, novelty. From cell and gene therapies (CGTs) and new vaccines to antibody-drug conjugates (ADCs), successful development and commercialization of these next-generation therapies may hinge on partnerships with service providers that offer specific focus, expertise, and technological experience. At certain points in the discovery and development process, developers—especially smaller firms—come to realize the unmet needs that prompt them to seek an outsourcing provider and/or partnership.The first order of business would be to bring in a partner with the correct expertise and technology to tackle the challenges of bringing a complex biotherapeutic to market. 

Outsourcing Next-Gen Therapies Relies on Expertise and Technology

Bringing next-generation therapies to market brings up multiple challenges, according to Monika Paule, CEO, Caszyme. These challenges range from scientific and technical hurdles to regulatory and societal barriers. “One of the major obstacles is the social perception and acceptance of novel technologies such as CRISPR [clustered regularly interspaced short palindromic repeats]. Addressing public concerns, providing accurate information, and engaging in meaningful dialogue about the benefits, risks, and ethical considerations of these technologies are crucial,” Paule says.

Ali Pashazadeh, CEO, Treehill Partners, a transaction and drug development advisory firm focused on the biotech industry, points to the fact that the biopharmaceutical industry is currently experiencing its fourth year of financial drought, which has been one of the biggest challenges lately to bringing next-generation therapies to market. “Whilst next-generation technologies are incredibly exciting in their potential, these really require, for the first time, excellence in drug development to be combined with excellence in manufacturing,” Pashazadeh says.

Speaking specifically on nucleic acid-based therapies, Bernard Sagaert, CEO of etherna, emphasizes that the challenges are still big, even after the success of the COVID-19 vaccines. The challenges on the RNA front are tied in with RNA quality, where sometimes an inferior quality of RNA is used, which always leads to project failure in discovery or preclinical stages, cost of goods, or duration of expression, he explains. “On the delivery side, targeted expression and off-target expression reduction, balancing immune expression (regulate up or down, or be immune-neutral), and stability are the main challenges. All of these challenges can be different based on the therapeutic area where the products need to be used, whether it is in prophylactic or therapeutic vaccines, autoimmune diseases, gene editing, oncology, protein replacement, etc.,” Sagaert says.

Meanwhile, other challenges include technical and regulatory complexities, such as optimizing gene-editing precision and efficiency, ensuring scalable and cost-effective manufacturing, navigating complex regulatory requirements, and addressing safety and ethical considerations. “Overcoming these hurdles requires broad scientific expertise, strong analytical capabilities, and strategic collaborations among key ‘players’ to accelerate development while minimizing risks,” says Paule.

For the most part, it is the complexity of manufacturing involved in next-generation biotherapies that drives outsourcing in this sector. “These therapies require specialized expertise in areas such as gene and cell therapy production, advanced analytics, and regulatory compliance—expertise that many biopharma companies do not have in-house. Of course, everyone would love to do everything in-house, but the amount of initial investment needed, the need for speed in development, cost efficiency, and enhanced scalability are the main factors driving outsourcing,” says Paule.

“A certain level of complexity multiplies directly in line with” the scale of manufacturing capacity,” adds Jason Jones, global business development lead, Cellular Origins. Jones explains that if processes are complex, variable, and expensive when manufacturing 1000 doses of a next-generation therapy, then these processes will be 100x more complex, variable, and expensive if they are continued to be produced the same way as production scales up 100x.

When referring to this article, please cite it as Mirasol, F. Outsourcing Next-Gen Therapies Relies on Expertise and Technology. 

Pharmaceutical Technology Bio/Pharma Outsourcing Innovation

The value of outsourcing partnerships for next-gen biotherapeutics rests in the expertise and technologies that service providers bring to the table.

FDA has approved a new drug application for Roche’s Evrysdi (risdiplam) tablet for treating people living with spinal muscular atrophy (SMA), which makes the drug the first and only tablet for treating SMA, Roche announced on Feb. 12, 2025. Risdiplam, offered in a 5 mg tablet that can be swallowed whole or dispersed in water, is also the only non-invasive disease-modifying treatment in this indication, according to Roche in a company press release (1).

FDA’s approval was based on the results of a bioequivalence study. This study demonstrated that the 5 mg tablet—swallowed whole or dispersed in non-chlorinated drinking water (e.g., filtered water)—provided comparable exposure to risdiplam compared with the original risdiplam oral solution. Thus, patients who take the tablet can expect the same efficacy and safety that is established with the oral solution. The oral solution will remain available for those taking other doses of the drug and for those who may prefer the oral solution.

"Evrysdi has robust potential to modify the SMA disease trajectory and has already been used to treat thousands of patients to date. This approval marks another significant step forward," said Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development, Roche, in the press release (1). "The Evrysdi tablet combines established efficacy with convenience, providing an additional flexible option for SMA management."

The new 5 mg tablet is expected to be made available in the coming weeks following its approval. It is suitable for use in people two years of age or older who weigh more than 20 kg (44 lbs). Roche is responsible for the clinical development of risdiplam (under the brand name Evrysdi) as part of a collaboration with the SMA Foundation and PTC Therapeutics.

"We cannot underestimate the value that comes with simplifying treatment administration and disease management for people who are living with SMA or those caring for them,” said Kenneth Hobby, president of Cure SMA. "This new room temperature stable formulation option offers an additional choice that may more conveniently fit into daily living activities such as working, traveling, and education."

Risdiplam (under the brand name Evrysdi) is approved in more than 100 countries. An important benefit of the tablet formation is that it can be stored at room temperature, compared to the oral formulation. This benefit may provide greater freedom and independence for people dealing with SMA.

Risdiplam is a survival motor neuron 2 (SMN2) pre-messenger RNA splicing modifier. It is a small-molecule drug (2) designed to treat SMA resulting from mutations in chromosome 5q. Such mutations can lead to survival of motor neuron (SMN) protein deficiency. The drug is administered daily either at home or in transit. In oral solution form, it is administered by mouth or via a feeding tube; with the new tablet form it is administered by mouth only, either swallowed whole or dispersed in water.

The European Medicines Agency granted risdiplam priority medicines (PRIME) designation in 2018, and FDA granted it orphan drug designation in 2017. The drug is currently being, or has been, evaluated in a number of global multicenter trials in people with SMA (1).

FDA Approves Roche’s Evrysdi Tablet as First and Only Tablet for Spinal Muscular Atrophy (SMA)

. Press Release. Feb. 12, 2025.
2. Ratni, H.; Scalco, R. S.; Stephan, A.H. Risdiplam, the First Approved Small Molecule Splicing Modifier Drug as a Blueprint for Future Transformative Medicines. 

 (6), 874–877. DOI: 10.1021/acsmedchemlett.0c00659

The approval makes Evrysdi the first and only tablet for treating spinal muscular atrophy.