Digital Transformation in Pharma Manufacturing

Patent Cliff Deals, Tariff Pressures, and the In Vivo Cell Therapy Bet

Behind the Headlines, Episode 23

ICH Q12 and Post-Approval Changes

Speed, Flexibility Top Large-Molecule Manufacturing Trends

Drug Digest July 2025

Key Insights from Industry Survey Results

Bio/Pharma's Tariff Response

Patrick Lavery is an Editor for the MJH Life Sciences brands 

. Previously at MJH, he filled the same role for 

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The contract research organization (CRO) BDD Pharma (BDD) has opened a new, 122-square-meter (1313-square-foot) good manufacturing practice (GMP) manufacturing facility at BioCity near Glasgow, United Kingdom, BDD announced on April 8, 2025 (1).

Development of the state-of-the-art facility began in 2023, according to BDD, and was facilitated by a £2 million (US$2.6 million) round of funding from multiple investors, led by the angel investment syndicate Archangels along with Scottish Enterprise—BDD is a Scotland-based company—and British Business Bank, the latter of which had not been a pre-existing investor in BDD (1).

“The investment in the new facility strengthens BDD’s ability to offer end-to-end services to meet the growing market demand and dovetails the company’s clinical expansion,” Sarah Hardy, director and head of New Investments at Archangels, said in a BDD press release (1). “BDD uniquely supports pharmaceutical companies of any size that need to act quickly or accelerate plans enabling them to navigate the complex path of getting new therapies to patients.”

The facility was constructed by Guardtech Group, which specializes in cleanrooms, and according to the press release, will significantly expand BDD’s manufacturing and clinical testing capabilities (1). BDD said it adopts a lean clinical development approach in which clinical readouts are produced rapidly while quality is maintained from project to project. This helps the company to support R&D for small- to medium-sized pharmaceutical companies, specifically in the knowledge of how dosage forms work within the human body.

BDD reported that the new facility underwent a successful inspection by the UK Medicines and Healthcare products Regulatory Agency in March 2025.

“This new additional facility provides a wonderful opportunity to generate even quicker reliable data on the safety and effectiveness of these newly developed medicines,” Stephen Clarke, head of Quality at BDD, said in the company press release. “That in turn will lead to new medicines getting into patients quicker and so improve patient health sooner, which benefits all of society. The outcome of the recent UK government inspection provided a high level of independent confidence that we are doing all the correct things, in the correct way, consistently.”

 of its manufacturing and R&D presence in the United States on April 10, with an investment of $23 billion during the next five years (2). The company will build seven new facilities, bringing production of 100% of its key products to the US, and will also create a new research hub in San Diego to increase R&D activities. Three current sites will be invested in with approximately 1000 new jobs being created, with an additional 4000 new jobs in the US overall. Production capacity will be increased for APIs, biologics, and secondary production and packaging.

1. BDD. BDD Pharma Opens Brand-New GMP Manufacturing Facility Following £2m in Funding. Press Release. April 8, 2025.
2. Novartis. Novartis Plans to Expand its US-Based Manufacturing and R&D Footprint with a Total Investment of $23B Over the Next 5 Years. Press Release. April 10, 2025.

Articles

Development of the state-of-the-art facility was made possible by a £2 million (US$2.6 million) round of funding, and a successful inspection by MHRA was completed in March 2025.

BDD Opens GMP Manufacturing Facility in Scotland

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Novartis announced on April 10, 2025 the expansion of its manufacturing and R&D presence in the United States with the investment of $23 billion during the next five years. The company will build seven new facilities, bringing production of 100% of its key products to the US. Novartis will also create a new research hub in San Diego to increase R&D activities in the US.

In addition to the seven new facilities, three current sites will be invested in and approximately 1000 new jobs will be created at Novartis with an additional 4000 jobs in the US. Production capacity will be increased for APIs, biologics, and secondary production and packaging.

During the next five years, Novartis will create its second R&D hub in the US, to be located in San Diego; build four new manufacturing facilities, three of which will be dedicated to biologics manufacturing; build two new radioligand therapy (RLT) facilities to be located in Florida and Texas; and expand three of its RLT facilities in Indianapolis, Ind., Millburn, NJ, and Carlsbad, Calif. This investment creates manufacturing capacity of all the company’s core technology platforms in the US, including manufacturing of Novartis’ small interfering RNA (siRNA) technology, allowing for end-to-end production in the US.

"As a Swiss-based company with a significant presence in the US, these investments will enable us to fully bring our supply chain and key technology platforms into the US to support our strong US growth outlook. These investments also reflect the pro-innovation policy and regulatory environment in the US that supports our ability to find the next medical breakthroughs for patients," said Vas Narasimhan, CEO of Novartis, in a press release (1). "We are prepared for shifts in the external environment and fully confident in our 2025 guidance, mid- to long-term sales growth outlook and 2027 core margin guidance of 40%+."

The new research hub in San Diego, a $1.1 billion investment, will be a state-of-the art research facility with scientific infrastructure and drug discovery capabilities. The facility is planned to open between 2028 and 2029 and will serve as the epicenter of the Novartis West Coast Biomedical Research capabilities. The company has complementing hubs in Cambridge, Mass. and Basel, Switzerland.

In February 2025, Novartis announced another investment: a new viral vector production facility in Mengeš, Slovenia, the first specialized viral vector manufacturing facility in Europe. By investing €40 million (US$43 million) in the facility, the company expanded its research and production capabilities in the biopharmaceutical market (2).

Novartis also announced its potential purchase of Anthos Therapeutics, a Boston clinical-stage biopharmaceutical company, in February 2025. The pending acquisition has an upfront price of $925 million and includes abelacimab, a human monoclonal antibody in late-stage development for the prevention of stroke and systemic embolism in patients with atrial fibrillation (3).

“We are excited to join forces to advance the development of abelacimab, a potential first-in-class treatment and safer approach for stroke prevention in atrial fibrillation as well as cancer-associated thrombosis,” Shreeram Aradhye, MD, president, Development and chief medical officer, Novartis, said in the press release announcing the acquisition (3). “Welcoming Anthos Therapeutics strengthens our focus in the cardiovascular space and complements our portfolio of life-changing treatments, comprehensive clinical programs, and strategic collaborations that help thousands of patients with heart disease around the world.”

Novartis. Novartis Plans to Expand its US-Based Manufacturing and R&D Footprint with a Total Investment of $23B Over the Next 5 Years. Press Release. April 10, 2025.

In Slovenia, Novartis Opens Its First Specialized Viral Vector Production Facility in Europe

Novartis. Novartis Bolsters Late-Stage Cardiovascular Pipeline with Agreement to Acquire Anthos Therapeutics for USD 925 Million Upfront. Press Release. Feb. 11, 2025.

The company has plans to invest $23 billion during the next five years to expand manufacturing and R&D in the US, which will include seven new facilities.

Novartis to Expand US-Based R&D and Manufacturing

INTERPHEX Tariff Roundup

® Group was busy networking with industry leaders at INTERPHEX 2025 in New York City on April 2, United States President Donald Trump scheduled the announcement of what he called “Liberation Day” with a 10% baseline tariff on imported goods from most other countries in the world, effective April 5 (1).

One week later, in the early morning hours of April 9, Trump went ahead with levying reciprocal taxes on countries the president had felt engaged in unfair trading practices, 

 (1). Those tariffs were what, later that day, Trump then selected for a 90-day pause that briefly sent a boomerang through US and worldwide stock markets, which were sent reeling.

With news breaking in the middle of the three-day INTERPHEX conference, a prompt posed by PharmTech Group to several of its interviewees at the conference ran the risk of becoming quickly obsolete: If this may apply to your company, give us your thoughts on the current tariffs being enacted by the US and the reshoring expectations relative to this change in policy, and how you believe this may impact you or the industry.

While some of the interview subjects politely declined the question, several attacked it head-on and laid out their companies’ plans for both the short and long term.

Click the video above to view a compilation of those responses.

 for complete coverage of INTERPHEX 2025.

1. Wiseman, P. and Rugaber, C. Another U-Turn: Trump Reverses Tariffs That Caused Market Meltdown, But Companies Remain Bewildered. 

Videos

Even with, or perhaps because of, the rapidity with which changes in United States policy are developing, many in the bio/pharmaceutical industry are taking a longer view.

Tariff Pause Reinforces Uncertainty Among Biopharma Professionals

Felicity Thomas is the former Associate Editorial Director of Pharmaceutical Technology, Pharmaceutical Technology Europe, BioPharm International.

Industry Outlook 2025: Talent Up for Grabs

The post-COVID-19 era has seen the consequences of ambitious programs launched during the pandemic, according to Erik Wiklund, CEO of Circio, such as a lack of capital for small biotech and employee layoffs, and Wiklund sees this impacting the industry during 2025. “Many companies launch great ambitions, large valuations. People flow into the industry, and then the breaks set in, but then what happens is that the companies that survive, they then suddenly have access to a broad talent pool, and then the capital comes back,” Wiklund says. “So, I think the consequence of that is that you see some consolidation. You see access to talent, and you see new stronger companies emerge, and maybe that's what will happen now. After the reset in biotech, a broad set of companies are gone, but this may create fertile ground for the future successes once the capital markets and the industry start to normalize, and hopefully this will happen during 2025.”

This increase in available talent is a trend that Wiklund sees continuing in the coming year. “What we've seen is that there's been increasing cost levels in the [United States] in particular, strong dollar and increasing inflation has driven up prices,” Wiklund says. “Salaries are high, and I think that, to a certain degree, is starting to make European or other companies look elsewhere for development opportunities. It's become cheaper by comparison to develop drugs in Europe, Asia, and Australia, and I think maybe if that trend continues with a strong US economy and increasing prices, then you may see that kind of European, eastwards-oriented trend continuing.”

Click the above video to watch the interview.

Erik Wiklund, PhD, is CEO of Circio. He has deep scientific knowledge in RNA and cancer biology, and 13 years of pharma and biotech industry experience in a variety of functions including R&D, finance and business development. Previous employment includes the radiopharmaceutical company Algeta, which was acquired by Bayer in 2014, Aker Biomarine, and management consulting experience from the Pharma & Health Care practice of McKinsey & Company. Wiklund holds a PhD in Molecular Biology from Aarhus University, Denmark, and the Garvan Institute of Medical Research, Sydney, Australia

Pharmaceutical Technology® Group spoke with Erik Wiklund, CEO of Circio, about the impact of the post-COVID-19 world on the pharmaceutical industry and how that has shifted the talent pool.

Industry Outlook 2025: Cell Therapy Advancement

Edwin Stone, CEO of Cellular Origins, sees two themes having the biggest impact to the bio/pharma industry: the expansion of glucagon-like peptide-1 (GLP-1) and the growth of cell therapies from fourth- and third-line treatments to second-line treatments. “It really opens up that question of, when do we start to see first line treatments? And of course, part of that comes down to not just the safety and efficacy profiles, but the cost of goods, which still no one has a good answer to,” Stone says. “So, I think that really links the two parts that we've seen through this year, the GLP-1 and advanced therapies really all come down to that manufacturing piece.”

“The other big thing on cell therapies that I think has been really important this year, and I think really hopefully points to future … moving now into new indications, particularly solid tumor. Again, we don't have to go back that far for there to be real questions with Iovance’s approval in that space and then later Adaptimmune. Solid tumors now are right [on] the cutting edge of where cell therapies are at, and I think that gives great excitement for their potential. Again, we're going to need to make sure we can show that we can manufacture those,” Stone adds.

Stone also sees messenger RNA, the diversity of biologics, and new biological mechanisms as areas to pay attention to for the future of the industry. “I think the thing … we're perhaps just at the start of now, is being able to really broaden our ability to harness biology to go after diseases that we previously haven't been able to tackle. And of course, that's incredibly exciting,” Stone says.

Click the video above to watch the full interview.

The PharmTech Group interviewed Edwin Stone, CEO of Cellular Origins, about the bio/pharmaceutical trends from 2024 that continue to impact the industry in 2025.

Collaborating with a CDMO that has the necessary expertise, equipment, and systems in place is
crucial to optimizing the scale-up process and accelerating timelines.

Executive Summary: Commercial Tech Transfers in OSD Manufacturing

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Siemens has announced an agreement to acquire Boston-based life sciences R&D software provider Dotmatics for $5.1 billion, saying the transaction is a “strategic milestone” that extends Siemens’ artificial intelligence (AI)-powered product lifecycle management (PLM) portfolio into the life sciences market (1).

In a press release on April 2, 2025, Siemens referred to life sciences as an “attractive complementary software market opportunity,” with the Dotmatics acquisition expanding the company’s industrial software total addressable market by $11 billion (1). Siemens said the market is driven by certain structural shifts: an increased need for medication by aging populations, improved access to medicine and new treatment options, and a desire for increased collaboration and visibility, all of which Siemens expects to double software spending in the next five years.

“By acquiring Dotmatics, we’re strategically strengthening our position in Life Sciences and creating a world-leading AI-powered PLM software portfolio as part of Siemens Xcelerator,” Roland Busch, president and CEO of Siemens AG, said in the release (1). “Artificial Intelligence has emerged as a transformative force across various industries, and its application in life sciences is becoming increasingly important. The Dotmatics acquisition is part of our ONE Tech Company growth program, enhancing our leading position in industrial software and helping our customers to innovate even faster.”

“The acquisition of Dotmatics drives strong revenue synergies and is highly profitable and cash generative. Financing will be provided primarily through the sale of shares in listed companies, including Siemens Healthineers,” said Ralf P. Thomas, chief financial officer of Siemens, also in the release.

 in December 2021, the company formerly known as Insightful Science rebranded itself to Dotmatics—which had been among Insightful Science’s portfolio of scientific R&D software solutions—in April 2022 (2,3).

“Following an exciting journey with Insight Partners, where Dotmatics achieved remarkable growth and portfolio expansion, we are thrilled to announce our new chapter with Siemens,” said Thomas Swalla, CEO of Dotmatics, in the Siemens press release. “Combining our next-generation scientific intelligence platform and industry-leading scientific applications together with Siemens' Digital Twin and AI capabilities, we’ll drive a new wave of innovation in life sciences R&D. Together, we'll accelerate innovation cycles for our customers and help scientists make breakthrough discoveries faster than ever before shaping the future of scientific innovation.”

® published a commentary from Stephen Tharp, Dotmatics senior vice-president, Customer Operations, suggesting how companies can optimize their AI budgets for the year ahead (4).

“We know most companies are spending money on AI—but are you spending it efficiently?” Tharp wrote (4). “Companies need a spend strategy or else costs will escalate without control. At its core, there are a few large drivers of cost when we think about AI, which include data, compute, and people (i.e., the scientists). You can’t simply dump data in a data lake. ‘Garbage in, garbage out’ is a tale as old as time. GenAI can’t deliver expected results unless a proper data architecture and infrastructure is in place. You want to maximize storage, compute, security, GPUs [graphics processing units], training, and storage costs. That means seeking out smart, integrated data strategies that enhance an organization's existing software spend.”

1. Siemens. Siemens Acquires Dotmatics to Extend AI-Powered Software Portfolio to Life Sciences. Press Release. April 2, 2025.
2. Insightful Science. Insightful Science Acquires Protein Metrics to Expand its R&D Solution to Include Proteomics. Press Release. Dec. 21, 2021.
3. Dotmatics. Dotmatics, Previously Insightful Science, Set to Transform the Future of Scientific Software and Data Management. Press Release. April 26, 2022.
4. Tharp, S. 

Mastering Your AI Budget for 2025 Success.

Siemens said spending on AI software is predicted to double by the end of the 2020s, in a market increasingly driven by structural shifts that underscore a need for digital transformation.

Siemens Acquires Dotmatics, Extending AI Software Portfolio into Life Sciences

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SkyCell announced on April 7, 2025 that it is collaborating with Microsoft to integrate SkyMind, SkyCell’s artificial intelligence (AI)-powered supply chain solution, with Microsoft Teams and Copilot based on Azure OpenAI Service. The collaboration will enable those working in the pharmaceutical supply chain to access real-time shipment data, predictive insights, and automated alerts within a Microsoft system, according to SkyCell (1).

SkyCell will use Microsoft’s ecosystem to enhance monitoring and provide full visibility of the supply chain using Azure AI Foundry. It will also use SkyCell’s K.AI intelligent assistant, which monitors shipments, assesses risks, and suggests real-time solutions. It also allows for the streamlining of product release through automated reporting and electronic resource planning integration. Data can be quickly accessed by stakeholders, who can then share that data with relevant parties, making communication more seamless. The partnership is combined with SkyCell’s 24/7 AI-enabled control tower and support team.

“SkyCell’s intelligent assistant, K.AI, along with Microsoft's Teams and Copilot, are revolutionizing the pharmaceutical logistics industry by ensuring real-time monitoring, risk assessment, and seamless communication,” ‍Richard Ettl, CEO of SkyCell, said in a press release (1). “This collaboration is crucial for transforming data into actionable insights, thus preventing product loss and enhancing efficiency in the supply chain.”

“Pharma companies already have established platforms and workflows that they use to manage their operations efficiently,” Nico Ros, CTO of SkyCell, said in the release. “We understand this, which is why our collaboration with Microsoft ensures that pharma companies and supply chain teams can leverage SkyMind’s power directly within Microsoft Teams and Copilot.”

"By harnessing the transformative power of AI through Microsoft Azure OpenAI, SkyCell is advancing pharmaceutical logistics to create safer, more efficient supply chains,” Elena González-Blanco García, EMEA Digital Natives Technical Director at Microsoft, said in the release. “This approach will ensure that vital treatments reach patients swiftly and securely, ultimately driving impactful progress in the industry."

SkyCell currently monitors five million shipments a year and believes the collaboration with Microsoft will accelerate digitalization in the pharma industry.

Automation, AI, and machine learning are hot topics in the pharma industry. At INTERPHEX 2025, held in New York City in April, “Pharma 4.0” was discussed heavily. Data collected as part of CRB’s Horizon Life Sciences report showed that 31% of industry stakeholders saw automation and digital transformation as key priorities for capital investment projects presently or in the near future. In a presentation at 

, Peter Walters, fellow, advanced therapies at CRB, discussed additional results from the report that shed light on priorities in both the lab and on the production floor, including AI, 

There is still caution around the use of AI in pharma, however (2). “I know for some people the idea of AI in a cGMP [current good manufacturing practice]-regulated setting could be a little unnerving, but it doesn't mean that we're handing over the sole finish to our robot overlords; it's a lot more like mechanical systems that have AIs on board to moderate themselves and look for mechanical issues in advance of them happening,” Walters explained. “I think where we also are seeing it is where you've got manufacturing steps that have to have very complex decision trees; you're still having a person make those decisions, but you're having AI models that can support that decision-making.”

Automation is being utilized in the areas of quality, throughput, and operator autonomy within the pharmaceutical industry, according to Peter Sarvey, head of Sales for Automation NTH, and the cost of using automation has decreased in the past two years. Meanwhile, the accuracy of these tools is increasing. The use of AI, which has been used in the “vision side” of automation according to Sarvey, is also increasingly starting to be used in the inspection side of manufacturing (3).

 interviewed Sarvey at INTERPHEX 2025. The full interview can be found on 

1. SkyCell. SkyCell and Microsoft Announce Collaboration to Bring Copilot into Pharma Supply Chains. Press Release. April 7, 2025.

2. Bigica, A. Pharma 4.0: What are Industry Leaders Prioritizing in the Modernization of Pharmaceutical Manufacturing? PharmTech.com. April 3, 2025. 

https://www.pharmtech.com/view/pharma-40-what-are-industry-leaders-prioritizing-in-the-modernization-of-pharmaceutical-manufacturing-

3. Lavery, P. and Haigney, S. INTERPHEX 2025: 

SkyCell is working with Microsoft to incorporate SkyCell’s AI-powered supply chain solution into Microsoft Teams and Copilot.

Microsoft and SkyCell Collaborate on Pharma Supply Chain Logistics

New survey data released jointly by The Pistoia Alliance, a global nonprofit that focuses on engendering better collaboration in life sciences R&D, and the Copyright Clearance Center (CCC), suggests that agentic—something that is able to independently achieve outcomes, functioning like an agent—artificial intelligence (AI) is identified by pharmaceutical industry leaders as the technology that will have the most significant impact on the field in the next two to three years (1).

That opinion, presented at the Pistoia Alliance’s annual European conference held in London on March 26, 2025, reflects the work of those involved in the group’s just-completed large language model project, as well as speakers at the conference from the United Kingdom Medicines & Healthcare products Regulatory Agency, AbbVie, AstraZeneca, and Amino Data (1).

However, more than half (51%) of those surveyed in the data collected and released by the Pistoia Alliance said that resistance to change with regard to AI is the biggest barrier to innovation, with lack of skills a distant second (17%) (1). Nearly four in 10 respondents (39%) said that AI models producing incorrect answers is the biggest concern about the technology, with reputational risk cited by 37% as a reason why companies might not want to build, choose, or use AI technologies.

“The poll confirms what many of our members are experiencing—that progress depends on people, culture, and skills, not just technology,” Becky Upton, PhD, Pistoia Alliance president, said in a press release (1). “The goal of digital transformation is to accelerate the development of better treatments and improve patient outcomes. That means we must empower the people behind the science—from researchers to C-suite leaders—with the right skills and mindset to embrace innovation. The Alliance is uniquely placed to lead this effort, connecting individuals and uniting organizations across pharma, technology, and regulation.”

Upton previously provided context for those comments in an interview with 

“To successfully harness AI in the pharmaceutical industry, vision and leadership from the top are essential,” Upton said at the time. “Leadership must understand that AI thrives on well-structured, high-quality data. Without proper data organization and governance, AI models cannot deliver accurate insights or drive innovation. For AI to be effective, data must be structured, standardized, and interoperable across systems. This requires a strategic commitment to robust data management, ensuring that data are not only accessible but also curated for AI readiness. In addition, leaders should foster a culture that values cross-functional collaboration and data sharing, while supporting investments in advanced infrastructure and training to realize AI’s full potential.”

“Companies know that increased AI regulation is on the horizon—in fact, 59% of our respondents expect increased government regulation in the next five years,” comments Neal Dunkinson, senior director of Solution Sales at CCC, in the Pistoia Alliance press release (1). “Now is the time to embed rigorous AI risk assessments into everyday practice. Events [such as] the Alliance’s conference are key for bridging the gap between pharma and regulators, helping the industry align on shared frameworks that support trustworthy and responsible AI use. By laying these foundations today, organizations can both stay ahead of evolving regulation and safely unlock AI’s potential.”

 held from April 1–3, 2025 in New York City, 

® Group interviewed Peter Sarvey, head of Sales for Automation NTH, about the increasing use of AI on the inspection side of manufacturing.

“There are a lot of inspections that previously were done manually, because it's not a simple pattern match for if this medical device or this pharmaceutical component is a reject,” Sarvey said in the interview (3). “Now we can teach the AI what a good part looks like, what a bad part looks like, and then over time, shift that area too, all in the nature of increasing throughput and decreasing yield loss.”

 for the full video interview with Peter Sarvey at INTERPHEX.

1. The Pistoia Alliance. Life Science Professionals say Agentic AI to Have Most Impact in Next 2-3 Years, but 51% Cite Resistance to Change as Biggest Barrier to Innovation. Press Release. April 3, 2025.
2. Hollan, M. 

Security and Data Sharing: Q&A with The Pistoia’s Alliance’s Dr. Becky Upton.

, Oct. 30, 2024.
3. Lavery, P. and Haigney, S. 

INTERPHEX 2025: AI and Automation in Pharma.

Lack of skills in the AI realm was a distant second among those surveyed about the biggest barrier to innovation while using the technology.

Agentic AI Growth Predicted, but More Than Half of Pharma Still Resisting Change: Report

Cynthia A. Challener is a contributing editor to Pharmaceutical Technology.

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The global population is aging, and the prevalence of chronic illnesses is on the rise, meaning that bio/pharmaceutical companies are seeking out new therapeutic approaches that may not only provide relief from disease symptoms but may also offer a real cure. Emerging therapies, such as genetic medicines, cell therapies, multispecific antibodies, and other novel modalities, are providing viable therapeutic options to a whole host of disease areas. However, these therapeutic modalities are highly complex and present numerous challenges to their development across formulation, manufacturing, analysis, regulatory compliance, and other activities. While significant advances have been made in the past decade, new hurdles continue to emerge as drug companies seek to bring promising candidates through the clinic and to the market more rapidly and at lower cost.

Both small and large biopharmaceutical companies developing emerging therapies must overcome a wide range of hurdles as they seek to bring their candidates forward, regardless of the modality. One of the major challenges heavily emphasized by Kate Broderick, chief innovation officer at Maravai Life Sciences, is limited access to funding. “In the current environment, finding the funding essential for supporting projects from initial discovery to first-in-human trials is extremely difficult,” she states.

A big issue for Yochi Slonim, CEO and cofounder of Anima Biotech, is the current limited understanding of disease biology, which combined with traditional drug-discovery methods and existing datasets, leads to reinforcement of pre-existing hypotheses rather than mechanistic insights.

“Genes and proteins play a critical role in the onset and progression of disease, but the conventional drug-development approach still fails to account for the complex interplay at the molecular and cellular levels, which leads to poor translatability for emerging therapies,” agrees Asim Siddiqui, senior vice president and scientific fellow at Seer.

Slonim also highlights the fact that many key disease-driving proteins, including transcription factors, scaffolding proteins, and intrinsically disordered proteins, are well established in disease pathology but remain undruggable using conventional small-molecule or biologic approaches. Furthermore, he notes that while powerful, phenotypic screening is often unable to elucidate the mechanism of action (MoA) of promising compounds.

“For these reasons,” says Slonim, “researchers often lack a clear understanding of how compounds function within disease biology, and as a result many promising molecules fail to progress, even when they demonstrate strong initial effects.”

The complexity of development due to the involvement of cutting-edge technologies such as gene editing and cell engineering that require deep scientific expertise, precise control, and extensive validation—and, therefore, longer development timelines and increased costs—is another general challenge, according to Jeng Her, founder and CEO of AP Biosciences. The lack of translationally relevant preclinical models that accurately predict treatment response in humans is an additional important issue.

Material sourcing is also often a hurdle in the development of emerging therapies. Access to plasmid DNA is often cited as a limiting factor for many genetic medicines. Ensuring the necessary supply of excipients crucial for the stability and efficacy of novel formulations that meet stringent purity, regulatory compliance, and functional requirements remains a persistent bottleneck as well, according to Marie-Sophie Quittet, head of customer relationships for Adragos Pharma.

Development of cost-effective, robust, scalable processes that afford high yields of high-quality drug substances and drug products is a key challenge for most new modalities. “Many novel therapies require intricate processes that must be efficiently scaled while ensuring batch-to-batch consistency, particularly bispecific antibodies,” observes Her. Cell therapies and viral vector-based gene therapies are also complex and difficult to manufacture, causing very high manufacturing costs and patient access issues, according to Jens Vogel, president and COO at Mirai Bio.

Difficulties with integration of automation technologies and rapid analytics is an important contributor to this issue, says Mike Paglia, chief technology officer with ElevateBio BaseCamp. He also notes that the shift to platform processes can help address some manufacturing issues, but maintaining flexibility and adaptability is also essential in optimal processes developed to produce novel therapies.

. Many regulatory hurdles exist as well. Navigating regulatory landscapes is particularly challenging, as existing guidelines were primarily designed for small molecules and biologics rather than these newer, more complex modalities, according to Her.

“Pioneering new science requires forging a new regulatory path, which for both regulatory authorities and developers can be complex and time-consuming,” Broderick comments.

Striking a balance between the technical expectations of customers and regulatory constraints is a significant obstacle, Quittet adds. “Each innovation brings unique requirements and specifications that must be harmonized with the evolving regulatory guidelines to ensure safety and efficacy,” she says.

An example highlighted by Brian Pepin, CEO of Rune Labs, is the reliance of regulators on existing clinical assessment tools for clinical endpoint validation that were developed before digital technologies and artificial intelligence (AI)/machine learning (ML), which he believes do not offer the scalability or precision required to demonstrate the effectiveness of emerging therapies.

For novel modalities, summarizes Chris Learn, senior vice-president and head of Parexel International’s Cell and Gene Center of Excellence, regulatory guidance can be limiting, constantly evolving, and differ from one agency to another. He does emphasize, though, that while the uncertainty is challenging, it also presents opportunities for developers if they take the right approach.

 Many people today are also wary about the new technologies upon which emerging therapies are based. As an example, Rajiv Gangurde, vice-president, technical at Parexel points out that patients may hesitate to enroll in clinical trials that require an invasive, investigative procedure—particularly with irreversible, single-dose administrations. He adds that emerging therapies also face the challenges common to all new medicines associated with misinformation, its influence on public opinion, and its downstream effects.

Given the diversity of novel modalities advancing in the clinic today, it should not be surprising that some development challenges are uniquely associated with specific classes of compounds. For bispecific antibodies and bispecific antibody-drug conjugates (ADCs), target selection, engineering, and safety profile management present hurdles due to the fact these molecules engage two different targets simultaneously, according to Her. “Some of the difficulties lie in identifying target pairs that work synergistically without triggering unwanted immune activation or systemic toxicity, maintaining structural integrity and ensuring proper antigen engagement, and fine-tuning protein engineering to prevent mispairing and aggregation while optimizing batch consistency,” he says.

For nucleic acid-based candidates, the biggest challenge according to Broderick is finding manufacturers that can produce products in the desired form at the appropriate quality and yield in a specified timeframe. “A lot of companies claim they can do all of these things, but in actual practice producing these drugs is much more complex than most people think,” she observes.

Small molecules that modulate messenger RNA (mRNA) biology regulators without introducing synthetic mRNA are a new approach in the RNA field. They enable disease-specific control of mRNA expression and have the potential to treat conditions that previously have been considered undruggable, according to Slonim, but present a new set of challenges, such as identifying the precise regulatory mechanisms that control mRNA function in disease, ensuring target specificity, developing new screening methods for mRNA regulation, and understanding the complex functional impact of modulating mRNA pathways.

In the field of radiopharmaceuticals, Kathy Spencer-Pike, chief commercial officer for Nucleus RadioPharma, notes that one of the biggest challenges is talent acquisition and retention, because trained nuclear pharmacists, radio and analytical chemists, microbiologists, and radiation safety experts are often not easy to find in the exact locations and in the proper timelines. She also notes that due to the short half-lives of radiopharmaceuticals, they must be administered to patients within days or sometimes hours of production. “In addition to the special equipment and knowledge needed to handle radiopharmaceuticals, developers must have a foolproof plan leveraging a complex combination of production, quality control, proper handling, and transportation capabilities to bring these therapeutics and patients together,” Spencer-Pike contends.

Stability, solubility, and pharmacokinetic (PK) optimization are three important formulation challenges for emerging therapies, according to Her. Solubility and viscosity problems can be problematic in high-concentration formulations intended for subcutaneous administration, Her adds. “Innovative strategies for use of novel excipients, predictive modeling for sequence optimization, and advanced drug-delivery systems are needed to address many of these formulation issues,” he comments.

While lipid nanoparticles (LNPs) have proved useful for the delivery of the COVID-19 mRNA vaccines, they do suffer from several limitations with respect to unwanted side effects and delivery, largely to the liver. “The challenge,” says Broderick, “is to develop delivery systems that can, for instance, target the right muscles, the brain, or nerves to treat Huntington’s, Alzheimer’s, and multiple sclerosis, respectively. However, pioneering new opportunities requires proving new technologies are safe and effective and garnering regulatory acceptance, both of which can be challenging, arduous, and time-consuming,” she says.

Vogel agrees. “Delivering nucleic acid medicines involves multiple steps once the drugs are injected, each of which is impacted by the design of the delivery vehicle, the chemistry of the various components, the size and polydispersity of the particles, the placement of any shielding and targeting moieties, and the specific formulation in terms of the ratio of the different components used. Formulation optimization therefore needs to holistically take all parameters into account,” he notes.

Formulation challenges also arise for many emerging therapies due to the need for careful control of storage conditions, according to Quittet. Storage at ultra-low temperatures requires not only specialized equipment, but formulations designed to mitigate risks. That necessitates at the least, she says, selection of materials that align with the sensitivity of these therapies and the development of sensitive, robust, and sophisticated material testing protocols to ensure the compatibility and stability of products.

The complexity of novel modalities and their manufacturing processes create hurdles for all emerging therapies, particularly those with compositions that differ greatly from traditional small-molecule and biologic drugs. A key challenge in emerging therapies, contends Mercedes Segura, vice-president of process development with ElevateBio, is the need to develop robust and scalable manufacturing processes from the start, ensuring a smooth transition into GMP manufacturing while supporting commercial readiness in the future.

The issue, adds Paglia, is not only to develop processes that are rapid, robust, and potent, but that can be consistently reproduced and scaled in multiple locations/regions to ensure global commercial success. He emphasizes the value of advanced digital quality and control systems and the need to have an overarching quality and control system that allows for standardization across many manufacturing locations.

That issue ties into the question of whether to conduct process development work in-house or outsource. If the latter is selected, one challenge then becomes choosing the right contract service provider, which, according to Christiane Niederlaender, vice-president, technical with Parexel, “depends on the scope, complexity, and timeline for manufacturing an advanced therapy asset as well as the financial, geographical, and scaling considerations that a sponsor must reconcile often without the benefit of certainty or assurances.” She does agree that moving to a decentralized manufacturing model involving distributed production across multiple, geographically dispersed locations may result in reduced transportation costs and lead times, increased flexibility and responsiveness, and enhanced opportunities for customization, but does require robust and reproducible processes.

Manufacture of nanoparticles, says Quittet, requires meticulous processes to ensure sterilization while avoiding sedimentation during filling, which can be particularly difficult for gene-modified particles and ADCs. Similarly, the need to achieve extremely high purities for gene-editing therapies and the challenges associated with developing processes that can meet these expectations while also affording high yields in a cost-effective manner are highlighted by Broderick. Quittet also notes that development of efficient and industrially feasible scalable lyophilization cycles complicates manufacturing for many emerging therapies.

When it comes to adoptive cell therapies, Segura believes that “investing early in process development (PD) with experienced PD teams and leveraging their extensive processing and testing capabilities, optimized workflows, and manufacturing platforms for both cell products and gene-modifying components not only mitigates chemistry, manufacturing, and control (CMC) risks—such as process failures, costly comparability exercises, and scale-up challenges—but also paves the way for long-term success.”

The advent of personalized mRNA-based cancer vaccines, meanwhile, poses challenges related to downscaling rather than upscaling, according to Broderick. The same is true for autologous cell therapies, for which the biggest challenge is that one batch equals one patient, and manufacturing can only be scaled out, not up, observes Vogel.

These therapies, says John Tomtishen, Cellares’ senior vice-president and Integrated Development and Manufacturing Organization general manager, require highly skilled professionals to operate in large cleanroom facilities leveraging manual benchtop equipment to produce one therapy for a patient at a time. “Automation and integrated manufacturing approaches that can lower costs, accelerate timelines, and enable commercial-scale manufacturing are pivotal to transforming the cell therapy manufacturing paradigm,” he states.

While Vogel recognizes that allogenic cell therapies enable some scale-up, he also expects the continued need for partial human leukocyte antigen (HLA) matching to present supply-chain challenges. The solution, he believes, is to replace complex ex vivo engineering and manufacturing of cells with targeted engineering of cells in vivo.

Developing fit-for-purpose analytical assays for novel therapies is complicated by many factors ranging from regulatory uncertainty to material availability and assay performance issues. “The timeline for regulatory agencies to publish analytical development guidelines can be quite lengthy, and for many emerging therapies, including those for which preliminary guidance has been published, clarity is often lacking regarding many issues, including which assays are acceptable,” Broderick comments.

One example highlighted by Quittet is the lack of validated methods for nanoparticle suspensions intended for injectable use. For instance, endotoxin testing is challenging for solutions that are already turbid; although, alternative methods are being explored when the turbidity is manageable. “Establishing reliable analytical methods involves leveraging prior knowledge and adapting to product-specific and regulatory requirements, while developing novel approaches validated over time,” she says.

Material (i.e., drug substance, drug product) availability can be problematic as well. “Material must be produced to develop an assay, but material production in turn relies heavily on analysis, (e.g., methods to assess purity and yield). So, process and analytical development need to be coupled and appropriately balanced,” Niederlaender explains. He also notes that development activities require heavy investments in terms of time and resources, which can be difficult, particularly at the onset of a project.

Of particular concern for Tomtishen is the development of potency assays for novel therapeutic modalities. He points to assays for cell therapies as being particularly challenging due to the inherent variability of cell-based products, including patient-to-patient variability and complex MoAs.

Lack of comprehensive analytical guidance is just one challenge derived from regulatory uncertainty. A more overarching issue, according to Barbara Abissi, manager of regulatory affairs for Parexel, is the lack of regulatory frameworks in many countries, which makes it difficult to properly categorize and evaluate emerging therapies. “Different regulatory authorities often operate independently without effective communication, and the resultant lack of coordination can lead to inconsistent evaluations, requirements, and timelines without predictability. These regulatory challenges underscore the need for harmonized approaches and clear guidelines to ensure the safe and efficient development of emerging therapies while maintaining rigorous oversight,” she contends.

With so many different challenges to overcome, there is no one single strategy that developers can pursue to ensure successful advance of their promising drug candidates. In fact, while some strategies apply across different challenges, in many cases different approaches are needed to address each individual challenge.

The first step is to enhance understanding of biology and human health. Siddiqui points to the promise of integrating deep proteomic insights with genomic research, known as proteogenomics, for revealing the relationships between proteins and genetic information and pinpointing the underlying drivers of disease. “Integrated proteomic workflow technologies coupled with mass spectrometry offer enhanced protein coverage beyond the limitations of affinity-based methods for known proteins on a panel. With this approach, it is possible to conduct unbiased proteomic analyses to study the effects of emerging therapies, such as profiling xenotransplantation and immune dynamics or targeting cancer vulnerabilities with RNA-based treatments,” he says. Ultimately, Siddiqui believes that by better identifying how drug interactions affect the proteome, therapies can be designed that will dramatically improve patient outcomes.

The next step is collaborating with experienced service providers, both contract research and contract manufacturing and development organizations. “Engaging with such partners as early as possible in development allows process development and regulatory expectations to be aligned,” Quittet states. She adds that proactive collaboration ensures that manufacturing processes are robust and compliant and support the complex, often bespoke, needs of novel therapeutic modalities and can streamline the transition from development to commercialization.

Due to the unique manufacturing challenges posed by radiopharmaceuticals, in fact, Spencer-Pike believes that outsourcing to established service providers with expertise in handling radioactive materials and a comprehensive distribution network can be a viable option for developers of all sizes. “Smaller biotechs can find the flexibility helpful, while Big Pharma companies can use outside partners to mitigate the uncertainty and wasted capacity that can come with building too much of their own manufacturing infrastructure,” she comments.

Another general strategy being pursed to overcome manufacturing challenges is the development and implementation of platform processes. This approach has been highly effective for increasing the efficiency and productivity and reducing the cost of recombinant protein and monoclonal antibody production, and many emerging therapy developers are seeking to establish platform solutions for novel modalities with the same goals in mind.

Such efforts are being encouraged by FDA, which published draft guidance on its Platform Technology Designation Program for Drug Development in May 2024 (1). “Reviewing and adjudicating safety and efficacy profiles across dozens of new therapy submissions each year that are each produced with custom processes and technologies is extraordinarily challenging for regulators. By moving to platform approaches, both development and approval times are reduced,” Learn observes.

Indeed, such platform technologies can allow for standardized and modular approaches to manufacturing, formulation, and delivery, according to Her. Once a product has been approved that is developed and manufactured using such platform technologies, some requirements can be reduced and review can be achieved more quickly for future products developed and produced using the same technologies, Broderick says.

In the end, Tomtishen believes that use of platform technologies within drug development, particularly for complex and diverse emerging therapies, will have a profound impact on reducing time-to-market while also ensuring patient access to safe, efficacious, and high-quality drug products.

Leveraging AI and predictive modeling tools

Underlying many strategies for overcoming development challenges posed by novel modalities is the application of AI and other digital technologies, which today are being leveraged to improve drug discovery, lead selection and optimization, process development, and manufacturing in many different respects.

“Automation, modeling, and AI when combined are impacting various stages of advanced therapy development, from initial research to patient care,” says Gangurde. He points to advances in target identification/drug design, manufacturing optimization, quality control, patient stratification, and treatment optimization algorithms.

The power of AI, ML, and other predictive modeling tools, believes Vogel, is manifested in their capacity to analyze very large and complex datasets and find patterns amidst the noise. “This new ability to leverage high-throughput platforms to generate high-quantity and high-quality data sets, particularly of in vivo data, is accelerating and derisking the development of emerging therapies. By leveraging data lakes and advanced machine intelligence, we are enabling the rapid implementation of learnings into drug and cargo design. This is creating an immense opportunity to crack the code of delivery and pioneer cures for patients in need,” he concludes.

One key example for Slonim is the analysis with AI of proprietary deep data (large-scale experimental datasets generated directly from both healthy and diseased cells), which he notes is providing unique insights into disease mechanisms and thus supporting more effective drug discovery. He highlights visual biology as an important advance that integrates experimental biology with large-scale pathway visualization. “This approach generates millions of high-content images for a given disease, capturing hundreds of cellular pathways and uncovering mechanistic insights that traditional methods cannot access and allows for building of evolving AI models that further enhance disease understanding and target discovery,” he explains.

AI and predictive modeling tools are also being used to enhance process design, augment training, and allow for rapid reporting of key performance indicators and process data, which in turn support automation of routine activities, reduction of costs, and increased consistency, according to Paglia. “The ability to have data collection, analysis, and reporting fully automated allows for reduced operating expenses, which has a direct impact on product cost of goods and allows for more rapid release of a product for treatment,” he says.

Broderick is also excited about the potential for real-time data analysis in clinical trials, which she believes will “completely change the dynamics of drug discovery and development.”

Leveraging AI and moving from subjective and episodic assessments to objective, continuous real-world monitoring with digital biomarkers could accelerate regulatory approval and improve clinical decision-making, Pepin agrees. AI models are also being used to match patients with the right therapies to optimize patient recruitment for clinical studies. The use of predictive algorithms to anticipate symptoms, such as off-times in Parkinson’s, can, furthermore, enable proactive care adjustments, he says.

Caution around the application of AI and other advanced technologies is warranted, though. “For these efforts to be meaningful, notable acceleration and efficiencies gained will have to be demonstrably shown in terms of research advancements, personalized treatment, and improved clinical outcomes,” Learn cautions.

Draft Guidance for Industry: Platform Technology Designation Program for Drug Development 

Cynthia A. Challener, PhD, is a contributing editor to 

®
Vol. 49, No. 3
April 2025
Pages: 10–15

When referring to this article, please cite it as Challener, C.A. Navigating the Complexities of Emerging Therapy Development. 

Advancement of emerging therapies faces hurdles across all aspects and phases of drug development and manufacturing.


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