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Feliza Mirasol

Outsourcing ADCs development manufacturing partnerships

A CDMO’s Perspective on Outsourcing Challenges for ADCs–Part 1

®, Christian Morello, vice president and head of the Bioconjugates Business Unit at Lonza, discusses three challenges he sees with bringing new antibody-drug conjugates (ADCs) to market. The first challenge is tied in with the overall dynamic of innovation as much of this innovation is coming for small biotech firms, and those companies are not equipped with the internal capacity to produce product. Secondly, there is also a lack of expertise for the industrialization and scale up of ADC manufacturing, and thirdly is the complexity of the supply chain, Morello enumerates.

“[These are] the three main challenges that an ADC developer has to face and has to overcome to make clinical supply, or to make commercial supply,” Morello says. “And this is where a CDMO [contract development and manufacturing organization] [such as] Lonza brings in a lot of benefit.

The science of ADC manufacturing has evolved much over the past 20 years, Morello also emphasizes. There has been much improvement in the technology for making the monoclonal antibody (mAb) component (i.e., carrier) as well as in the linker technology. Therefore, Morello explains, “If you want to go fast, you need to make sure that you have the expertise to take care of your drug and the complexity of the manufacturing as well the experience to scale up and go through the different regulatory paths.”

Morello also points out that an ADC developer is not obliged to build in-house capacity, “because then you can allocate [that] money on the clinical development, [which is where] you will create and validate your concept associated to the development of the drug. So, clearly, when you look at the overall portfolio, 70 to 80% of the ADC portfolio is outsourcing.”

Christian Morello, Vice President and Head, Bioconjugates Business Unit, Lonza

Christian Morello is vice president and head of the Bioconjugates Business Unit at Lonza. He is responsible for establishing and driving strategy of the business unit developing bioconjugates/antibody-drug conjugate (ADC) manufacturing services for Lonza’s customers worldwide. Prior to joining Lonza, Morello was the head of Global Project Management at Sanofi where he oversaw the development portfolio execution. He is a biochemical engineer and has over 28 years of experience in drug development from discovery to registration, planning, manufacturing, and programs management.

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Christian Morello, vice president and head of the Bioconjugates Business Unit at Lonza, discusses the challenges and unmet needs in bringing ADCs to market. 

3d rendering of Antibody drug conjugates (ADCs) are targeted medicines that deliver chemotherapy agents to cancer cells | Image Credit: © Love Employee - stock.adobe.com

*Editor's note: article updated on March 3, 2025 to fix typographical errors.

Following a long road to success with antibody-drug conjugates (ADCs), developers today are seeing regulatory approvals for ADCs as a more common occurrence. Better success in the current environment is largely due to technology improvements that have helped minimize risk and enhance therapeutic efficacy for these complicated drugs. However, the manufacturing of ADCs remains a complex process, involving requirements for both the large-molecule and small-molecule components. The linker technology joining the two pieces also has its own requirements. Because of their manufacturing complexity, ADC development and production increasingly requires outsourcing services.

Three major challenges for drug developers trying to bring ADCs to market include lack of capacity, lack of expertise in scaling up, and the complexity of the supply chain, notes Christian Morello, vice-president and head of the Bioconjugates Business Unit at Lonza.

In looking at the overall dynamic of innovation in the ADC space, the majority of innovation is coming from small biotech companies, and those companies are not necessarily well equipped with the internal capacity to produce the product, Morello points out. “There is also a lack of knowledge about the industrialization and the scale up of ADCs,” he says. “And [there is also] the complexity of the supply chain; Indeed [we] within the bioconjugate field, we are bringing different pieces, like a puzzle, to produce the drug substance. It implies [much] complexity [and requires] management of different sourcing in order to make it happen.”

These challenges are what ADC developers have to face and overcome to produce clinical supply or commercial supply, Morello emphasizes. “This is where CDMOs [contract development and manufacturing organizations] bring a lot of benefit, because we have [experience with] different modalities. [Especially at Lonza,] we’re totally integrated, so we offer fully integrated services to make it happen and to accelerate [the developer’s] path to commercialization,” Morello says.

ADCs have unique manufacturing requirements, which is part of their complexity. “With ADC specificity, we are merging two worlds,” explains Morello. “We are merging the water and the solvent, the biologic and the chemistry. So, with this integration of two worlds, it requires specific skills.” Morello also cautions carefulness when dealing with the risks associated with the chemistry involved in ADC manufacture. “You need to take care about potential explosion or flammable risk associated [with] the chemistry, but you also need to take care about the potential contamination due to microbes if you’re not working with adequate procedure for clean environment. So, the operating model is very specific.”

The science of ADCs has evolved significantly over the past 20 years, Morello also points out. Many improvements can be seen in the carrier component (protein or peptide), the linker component, and the payload, all of which makes the conjugation technology more complex.

“There have been a lot of new developments in terms of conjugation and linker technologies,” agrees Nicolas Camper, senior director, Bioconjugation, at Abzena. “There is a definitive move towards site-specific conjugation technologies and away from stochastic conjugation approaches that allows [us] to prepare better-defined antibody-[drug] conjugates,” he says.

Camper also points out another new development that he’s observed over the past few years, which is that linker technology is becoming more sophisticated. “Quite often, when you conjugate cytotoxic drugs, they are quite hydrophobic, and that can impact the performance of your ADC. So, there has been a lot of effort put into developing more hydrophilic linkers,” he explains.

Another noticeable advancement has been in the development of branch linkers. These branch linkers give some options for preparing the ADC and modulating the drug loading. “[T]hat is something relatively new and should have an impact on the performance of ADCs and ultimately result in better ADCs and more programs,” he says.

Technological gaps are one area of unmet need in the ADC space. In Lonza’s case, the CDMO realized it needed a certain technology that would be valuable to its customers, which prompted it to acquire the Netherlands-based Synaffix in 2023 (1). Morello explains that the technology Synaffix brings offers a new way to do the conjugation “where we are connecting the linker at the glycan location on the mAb.”

“That is something that no one else has,” Morello emphasizes. This technology specifically addresses the challenge of how to manage the number of linkers and payload that can be connected to the carrier, the mAb. “So, it brings some solution to address the needs the customer has,” he says.

Morello also notes that Lonza is following the evolution of conjugation technology day-to-day to be able to capture new technologies and bring the best solutions to customers. “We have also created a toolbox [where we] identify very innovative companies/technology outside, bring them into the [Lonza] network, and identify where the customer may require this type of support, and then facilitating, connecting this technology at an early stage,” Morello states.

“When it is confirmed that [a] molecule is really interesting … then [we use] our ability to … master this very breakthrough technology [and bring it] into an industrial and GMP [good manufacturing practice] environment and to scale up this technology to support Phase I, Phase II, or Phase III [development], and then, later on, [scale up to] the commercialization of the drug,” Morello says.

ADC development has a robust future with much potential. Camper points out an important aspect currently driving ADC development: diversification. “I think that we’ve seen a lot of diversification. That’s a key word. The increased diversity can be noticed in the targeting moiety. Smaller targeting fragments, which allow for better penetration into the tumors, are being developed as targeting moieties; that can be nanobodies or fat fragments,” he explains.

“There is also diversity which is encompassed in the use of bispecific antibodies. They allow for targeting more selectively cancer cells,” Camper says. Camper also notes that there is a lot of diversity today in the payloads. “Traditionally, they were cytotoxic payloads, but, now, people are revisiting all potent small molecules, such as potent kinase inhibitors or payloads that have radically different mechanisms of action, such as molecular glues or PROTACs [proteolysis-targeting chimeras].”

Camper additionally observes how, in the past few years, there has been development of bioconjugates outside the area of oncology. “There are lots of antibody-drug conjugates being developed for the treatment of inflammation, for instance, or—something which is extremely hot at the moment—the development of antibody oligonucleotide conjugates for the treatment of genetic disorders,” he states. “Having access to more complex and linked payloads and conjugation technologies—more advanced conjugation technologies—that definitely results in better therapeutic profiles for antibody-drug conjugates, and we’ll see more and more of those in the future.”

“The technology is now at the level of maturity that enable a lot of different things,” adds Morello. For instance, going back to Lonza’s Synaffix acquisition, Synaffix presents another type of linker technology in which the developer can define how many payloads it wants to have per mAb. “That is another possibility that will enable [the developer] to fine tune the benefits/risk ratio for the patient,” Morello states. “We can see [that] today for some cytotoxic compounds for oncology, for sure, but we also have radiolabeled compounds to facilitate diagnosis. [This is] also oncology treatment, but with a different approach.”

“We have nucleotide and mRNA [messenger RNA] that are more and more used for some applications. We have polysaccharides that are also used as a vaccine. So, the applications associated with bioconjugation is much broader than it was in the past,” Morello says.

In addition, Morello points out, when looking at the overall portfolio of clinical trials that are ongoing in the bioconjugates field, half of them is associated with oncology applications and the other half is associated with non-oncology products. The ability to tackle different type of disease is one clear direction where ADC development is heading. Another area is having the ability to improve the benefits/risk ratio to decrease side effects, particularly in oncology, while increasing efficiency. Being able to target a specific ratio of linker to payload to mAb is also an interesting area, he adds. 

“Last but not least is the ability to simplify the process, again, through more integration,” Morello states. “We will need to accelerate the time to market and will accelerate, as well, the time to commercialization.”

1. Lonza. Lonza to Acquire Synaffix and Strengthen Antibody-Drug Conjugates Offering. Press Release. June 1, 2023.

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Vol. 49, No. 1
January/February 2025
Pages: 29–30

When referring to this article, please cite it as Mirasol, F. Advancing ADCs to the Next Level. 

Articles

CDMOs who have integrated technologies can help further the advancement of ADC development.

Advancing ADCs to the Next Level

The winners of the 2025 Pharmapack Awards were announced on Jan. 22, 2025, according to Pharmapack Europe. The awards, which have been newly reformatted, recognize excellence in six key categories. In addition, this year’s awards used a new approach in which both commercialized products and groundbreaking innovations expected to shape pharma packaging's future were celebrated. For the first time, these awards were open to all participants in an effort to foster greater inclusivity and innovation, according to a press release (1).

The winners included many significant advancements, such as an autoinjector that eliminates the need for manual needle attachment, a fully recyclable and heat-sealable ultra-high barrier paper, and a multi-layered vial that is designed for storing gene therapy product. Other innovations included a prefilled syringe pack that reduces packaging waste by 62% and a non-electronic, eco-friendly label that can monitor both time and temperature. This year also saw the first “Women of the Year” commendations presented.

In the Delivery and Device Innovation category, the winner was Switzerland-based SHL Medical’s Elexy, a reusable electromechanical autoinjector, which was developed from years of innovative research. This autoinjector is drug-agnostic and has the widest range of primary container flexibility among autoinjectors, which means the device can caters to both prefilled syringe- and cartridge-based primary containers. The cartridge-based version of the autoinjector features SHL’s proprietary Needle Isolation Technology (NIT), which comprises a pre-installed needle housed within the cap of the autoinjector. This design eliminates the need for manual attachment of the needle and offers patients a more convenient device.

The winner of the Eco-Design category was Finland-based Huhtamaki’s fully recyclable, heat sealable, ultra-high barrier Omnilock Ultra Paper. This ultra paper is specially engineered to replace non-recyclable multi-layer laminates, including laminates made of paper, plastic, and aluminum. The product represents a significant innovation in sustainable packaging as it offers ultra-high barrier properties that were previously only found in non-recyclable multi-layer combinations of aluminum foil and plastic. Omnilock has a paper content ranging from 87–93% and is derived from FSC-certified fibers. The product maintains superior barrier performance while at the same time being environmentally friendly.

In the Packaging Innovation category, Japan-based Mitsubishi Gas Chemical (MGC) won for its new vial, the OXYCAPT Multilayer Plastic Vial, which is designed to store gene therapy products using dry ice and liquid nitrogen. Standard cyclic olefin polymer (COP) vials have a poor gas-barrier (2), making COP vials inadequate for drugs that are sensitive to oxygen (O

), according to the Pharmapack press release (1). The OXYCAPT consists of three layers: the drug contact layer, the outer layer (both made of COP), and the O

barrier layer, which is made an MGC novel polyester. OXYCAPT therefore provides an excellent O

, and ultraviolet (UV) barrier that is 20 times better than standard COP monolayer vials.

The Patient-Centric Design category winner was Belgium-based UCB Pharma’s redesigned BIMZELX 160mg autoinjector packaging, which consists of innovative features and takes a patient-focused approach. The redesigned packaging incorporates 15 new design elements and enhances the patient’s unboxing experience by prioritizing ease of use, sustainability, and functionality. Key design highlights include a “book style” carton construction that displays instructions better, an intuitive reclosing mechanism, a tamper-evident design, and a plastic tray consisting of 50% recycled polyethylene terephthalate material.

The winner in the Start-Up Innovation category was Italy-based Active Label for its non-electronic, environmentally friendly labels designed to monitor both time and temperature. These smart labels are activated with near-monochromatic UV light. They use engineered materials developed through research in collaboration with universities and research centers. Information from these labels is read using a compact reader that utilizes optically stimulated luminescence (OSL) and a proprietary algorithm that converts signals into time and temperature data. These data are stored in the cloud, which makes the data accessible remotely.

Pharmapack’s first inaugural Woman of the Year Award went to Asmita Khanolkar, senior director, Combination Products, Drug Delivery, Sterile Manufacturing, Device/Pharma Strategy and Commercialization, at US-based SMC Ltd. Khanolkar has more than two decades of experience, where she has managed and led various products from concept to commercial launch. Her product portfolio includes single-use, wearable and implantable devices, drug-device, device–biologic combination products for drug delivery, biotech, and biotherapeutics. The application of these products includes various indications such as diabetes, pain management, cell therapy, tissue regeneration, orthopedic, vascular, women’s health, oncology, surgical products, and more. She has made a significant contribution to advancing healthcare, having launched multiple medical devices and commissioning manufacturing lines for novel devices, including for first-in-human, single-use, on-body, and implantable cell therapy delivery devices.

“This year, we’ve seen a record number of award categories, yet the quality and innovation of entries continue to reach new heights. Notably, many submissions demonstrate a strong commitment to advancing sustainability through reduced raw material usage, improved recyclability, and lower carbon footprints, all while enhancing patient and user experiences,” said Tara Dougal, brand and content director—Pharma, at Informa, in the press release. “These efforts reflect the industry's determination to address critical challenges and shape the future of healthcare. We applaud the entire pharma packaging and drug delivery sector for its relentless drive toward innovation and transformative care standards.”

1. Pharmapack Europe. Pharmapack Award Winners 2025 Redefining Pharmaceutical Packaging and Drug Delivery. Press Release. Jan. 22, 2025.
2. Sarmadi, M.; Holmes, S.; Agha, R.; et al. A Comparative Study of Freeze-Drying Heat Transfer in Polymeric Vials and Glass Vials. 

Winners in this year's Pharmapack Awards include both commercial products and innovations that are shaping the future of pharmaceutical packaging. 

2025 Pharmapack Winners Showcase Innovations in Pharma Packaging and Drug Delivery

UK cloud-based, cell and gene therapy (CGT) software platform developer, Autolomous, has partnered with US-based Trenchant BioSystems, a CGT manufacturing platform developer for gene-modified cells, to combine technology platforms. The collaboration, announced on Jan. 20, 2025, will address timelines, costs, and challenges with CGT manufacturing.

Under the partnership, Trenchant will integrate Autolomous’ autoloMATE digital solution into their automated CGT manufacturing platform, which has been designed for distributed manufacturing at appropriate global medical facilities. The collaboration is aimed at delivering the first manufacturing process to the market encompassed in a single compact, fully automated chassis combined with a digital platform that generates automated batch records while capturing manufacturing performance and lot-release data in real time.

“The use of current cell and gene therapy manufacturing practices to deliver therapies to large-scale patient populations in an affordable manner is currently theoretically, but not practically, possible. Without significant changes, manufacturing is too lengthy, labor intensive, and costly to deliver CGTs to patients,” said Jon Ellis, CEO, Trenchant BioSystems, in a company press release (1). “Trenchant has developed a manufacturing platform that can reduce both manufacturing timelines to 2.5 days, and costs by over 80%. This can place CGTs for the first time as first-line therapies. To integrate digitalization into this development is critical, and this is why we have selected Autolomous’ autoloMATE as the most advanced CGT-specific digital platform to enable this transformation for the CGT marketplace.”

Trenchant is currently validating an Alpha Prototype of its platform, which the company said takes a fresh approach to CGT manufacturing. The prototype delivers an accumulated cell processing efficiency across all washing, selection, activation, and transduction steps that results in an eight-fold improvement over current practices. The company’s CGT manufacturing process involves a proprietary cell selection and activation technology, spinoculation, and cell washing technologies that remove the current requirement of 

 expansion of chimeric antigen receptor T (CAR-T) cells, which is a costly and lengthy process to produce clinical doses (2).

Trenchant’s platform was designed with digital integration at its core which is meant to reduce the duration of CAR-T manufacturing and lower the cost of goods and labor, both of which have been barriers to patient access. Autolomous offers its expertise in delivering solutions for the CGT space across an international user base that includes academics, contract development and manufacturing organizations, and biotechs. Trenchant selected Autolomous for this advantage as well as Autolomous’ extensive experience in integrating with systems and devices.

Trenchant expects to release internal performance data on the integrated platforms in the first quarter of 2025, after which data generated by a third party currently manufacturing CAR-T cells for clinical use will be released. Trenchant plans to offer its early access programs by the end of the third quarter of 2026.

“Current costs of CGTs, and CAR-Ts specifically, are way beyond the resources of societies to pay for them. Significant highly qualified labor is required to manufacture, review, and release each CAR-T batch. As a result, digitization is essential for CGTs to realistically realize their dramatic therapeutic potential to provide new solutions for a range of patients with no alternative therapeutic options,” said Alexander Seyf, CEO, Autolomous, in the press release. “Trenchant has now devised a new CAR-T manufacturing modality in its own right that will alter the way CGTs are created. This is why Autolomous has entered a partnership agreement with Trenchant to ensure therapies reach unprecedented patient numbers.”

Trenchant BioSystems and Autolomous Partner to Integrate Automated Cell and Gene Therapy Manufacturing and Digital Solutions

. Press Release. Jan. 20, 2025.
2. Cliff, E. R. S.; Kelkar, A. H.; Russler-Germain, D. A.; et al., High Cost of Chimeric Antigen Receptor T-Cells: Challenges and Solutions. 

The collaboration will combine fully automated and digitalized technologies to reduce CGT manufacturing timelines to 2.5 days. 

Trenchant BioSystems Partners with Autolomous to Form Integrated Automated CGT Manufacturing Platform

Cytiva and Cellular Origins, a TTP company based in the UK that specializes in advancing scalable and cost-effective cell and gene therapy (CGT) manufacturing, have partnered to combine technology platforms that will offer automated, robotic manufacturing of CGTs, Cytiva announced on Jan. 16, 2025. Under the agreement, Cytiva will combine its automated Sefia platform with Cellular Origin’s Constellation, an automated robotic platform. The integration of these two technologies aims to enable scale-up of CGT manufacturing to industrial levels without changing the initial manufacturing process used during discovery phases or clinical trials, according to a company press release (1).

The two systems are expected to have a seamless interface, which will provide complete digital interconnection. This interconnection will encompass quality control systems, fully remote digital controls, and analytics. The integration will remove the need for manual intervention between and within CGT manufacturing steps. The companies expect that the combined technologies will help drive new standards of automation and manufacturing productivities.

“The manufacturing of cell and gene therapies must evolve from personalized and small batch medicine to industrialization if these therapies are to reach their potential for patients. At Cellular Origins, we are working to make this a reality. By collaborating with Cytiva … we are building a unified automation platform that can meet the sector's large-scale industrial needs,” said Edwin Stone, CEO, Cellular Origins, in the press release (1).

Work is already underway to integrate the platform technologies, and the first systems are set for process and biological testing in early 2025. Good manufacturing practice systems are expected to be available by the end of 2025 for clinical use.

The companies estimate that 47% of referred patients currently get access to chimeric antigen receptor T cell (CAR-T) therapies (2). Current manufacturing practices for CAR-T therapies heavily rely on manual labor, which adds to the complexity and variability of its production process. Meanwhile, limited manufacturing capacity, significant risk of batch failures, and the expected increase of regulatory approvals for wider indications are expected to present more challenges for drug developers to satisfy the growing patient demand.

“Countless patients have benefited from Cytiva's cell processing systems, and we remain enthusiastic about the therapeutic potential of CAR-T. We firmly believe that automating these processes will unlock wider access to these life-changing therapies. The open nature of Cellular Origins’ design fits seamlessly with Cytiva's Sefia platform and potentially benefits a wide array of therapeutic developers. We are excited to see what the combined potential of our collaboration brings to the future of medicine,” said Emmanuel Abate, president Genomic Medicine, Cytiva, in the release.

The companies realize that a modular robotic approach will help manufacturers scale up from thousands to hundreds of thousands of CGT doses per year, according to the press release. With the integration of the two technology platforms into existing customer workflows, those workflows will be enabled to manufacture commercially approved and late-stage CGT products around the clock without the need to change systems or redesign approved processes.

Cellular Origins and Cytiva are Collaborating to Deliver Automated Robotic Manufacturing Capabilities for Cell and Gene Therapies

. Press Release. Jan. 16, 2025.
2. IQVIA. 

Strengthening Pathways for Cell and Gene Therapies: Current State and Future Scenarios

Cytiva will combine its CGT manufacturing technologies with Cellular Origins' robotic manufacturing platform.

Cytiva Collaborates with Cellular Origins to Deliver Automated Manufacturing for CGTs

In a public disclosure issued on Jan. 13, 2025, Samsung Biologics said it has signed a contract manufacturing agreement worth more than $1.4 billion with a Europe-based pharmaceutical company, whose name was not disclosed. Production will take place at Samsung Biologics’ Songdo, South Korea, manufacturing site, and the agreement is expected to run through December 2030, subject to change (1).

The agreement bodes well for Samsung Biologics’ prospects for 2025. At a presentation given during the J.P. Morgan Healthcare Conference held Jan. 13–16, 2025 in San Francisco, Calif., the company highlighted several key updates coming up in 2025.

In April 2025, the company expects to complete construction of its fifth biomanufacturing plant, which will be housed on its new Bio Campus II, also expected to open in April. The new plant will add 180,000 L of biomanufacturing capacity, bringing the company’s total global capacity to 784,000 L. The company is also considering constructing a sixth plant as a proactive response to the rising demand for biologics. A sixth plant would raise its total production capacity to 964,000 L, pending board approval.

The company also began offering new services this year to support antibody-drug conjugates (ADCs). These ADC services build on the company’s expertise in large-scale antibody manufacturing and process engineering and spans late discovery, development, and conjugation.

“Despite industry challenges, Samsung Biologics is well positioned to kick-start a new phase of growth in 2025 with the opening of Bio Campus II and launch of antibody-drug conjugate (ADC) services,” John Rim, CEO and president, Samsung Biologics, said at the presentation given in the conference (2). “We’ll continue to invest in new modalities and technologies to better address client needs, maximizing satisfaction and ensuring the delivery of highest-quality products.”

Expanded drug product (DP) services: the company is investing in pre-filled syringe (PFS) capabilities and expects to have a fully automated PFS DP line will be current good manufacturing practice-ready capabilities by 2027.

Enhanced development capabilities: To better support global pharma and emerging biotech companies, Samsung Biologics is investing in core development capabilities and plans to offer services that incorporate new technology platforms, including its S-HiCon, S-Tensify, S-AfuCHO, and S-OptiCharge platforms to ensure increased productivity and higher quality of molecule.

Digital transformation: the company also intends to continue investing in further building its integrated digital systems in order to maximize operational efficiency by incorporating artificial intelligence and digital twin technology.

Furthermore, the company announced that it plans to open a regional office in Tokyo this year to boost its ability to offer local support and grow its partnerships in Japan.

1. Samsung Biologics. Samsung Biologics Signs Manufacturing Deal with Europe-based Pharma. Fact Sheet. Jan. 13, 2025.
2. Samsung Biologics. Samsung Biologics Presents Business Updates at 2025 J.P. Morgan Healthcare Conference. Press Release. Jan. 15, 2025.

Production is set to take place at Samsung Biologics’ Songdo, South Korea, site, and the agreement will run through December 2030, subject to change.