Major Big Pharma Moves, Pressures of Capital Markets at Intersection with Autologous Versus Allogeneic

Behind the Headlines Episode 25

Questions about Real-World Evidence and Supply Chain Security

Ask the Expert

Small Molecules, APIs, and Excipients—Trends, Challenges, and Opportunities

Drug Digest September 2025

The 100% tariff on imported drugs will pressure pharma companies to build manufacturing sites in the US or face significant costs.

How 100% Pharmaceutical Tariffs Will Impact Domestic Manufacturing and Supply Chains

Responses to the FDA draft guidance "Considerations for Complying with 21 CFR 211.110"

Stakeholders React to FDA's Push for Quality, Integrity, and Uniformity

Advancing Radiopharmaceutical Development

On Sept. 11, 2025, Medicines Discovery Catapult (MDC), a national life sciences service dedicated to drug discovery, and Crown Bioscience, a contract research organization, announced the companies were collaborating on an integrated translational biology platform for the development of radiopharmaceuticals (1). As part of the collaboration, MDC will provide knowledge in cell biology, high-resolution microscopy, radiochemistry, preclinical imaging, mass spectrometry, and multi-omic tissue analysis, and Crown Bioscience will provide discovery, preclinical, and translations platforms and services for oncology and immune-oncology products.

® spoke with Juliana Maynard, PhD, Head of Translational Imaging, at MDC, to find out what makes radiopharmaceuticals unique and how MDC’s collaboration with Crown Bioscience can help developers of these treatments for cancer. According to Maynard, radiopharmaceuticals have enormous potential that provide game-changing breakthroughs for cancer patients, and the collaboration with Crown Bioscience will create a fully integrated pre-clinical workflow for developing radiopharmaceuticals globally as well as explore new isotopes or optimize targeting agents.

“At their core, they are a class of medicines that contain both a radioactive form of a chemical element, something we call a radioisotope, and they can be used to both diagnose and also to treat cancers,” Maynard explains. “But what makes them so unique and so powerful is their precision, and what they will do is they will target radiation directly to the tumors. How it works is taking a targeting molecule that binds to that specific receptor on a cancer cell, it will carry the radioisotope then straight to the disease site. And once it's there, the gamma rays themselves will emit either alpha or beta particles and kill the cancer cells for therapy. And what it means is that we can both see the disease through the diagnostic tracer, but we can also treat it in a very targeted way, something we call a theranostic approach. So, it's highly individualized, and it's very much image-guided therapy. So instead of a one-size-fits-all, what we can do is get smarter, safer, and more patient-derived, stratified medicine approach to treatment.”

“Compared with traditional cancer therapies, radiopharmaceuticals themselves, they spare healthy tissue,” Maynard continues. “We don't get those side effects that we've seen with other cancer medicines. And because they're so precisely delivered to those cancer cells, the radiation dose to the rest of the body is significantly reduced, which lowers those side effects. And we've shown proven treatment effects already in some really difficult-to-treat cancers, cancers.”

Click the above video to watch the entire interview.

Juliana Maynard is Head of Translational Imaging at Medicines Discovery Catapult. She has a PhD from the University of Edinburgh, and was a postdoctoral researcher at the University of Manchester.

MDC and Crown Bioscience. Medicines Discovery Catapult and Crown Bioscience Form Strategic Global Alliance for Radiopharmaceutical Innovation. Press Release. Sept. 11, 2025. 

https://www.businesswire.com/news/home/20250911458780/en/Medicines-Discovery-Catapult-and-Crown-Bioscience-Form-Strategic-Global-Alliance-for-Radiopharmaceutical-Innovation

*Editor’s Note: This transcript is a direct, unedited rendering of the original audio/video content. It may contain errors, informal language, or omissions as spoken in the original recording.

My name is Juliana Maynard. I'm head of translational imaging at medicines discovery catapult. My background is in imaging science. I did my PhD at the University of Edinburgh, and then I moved to the University of Manchester as a postdoctoral researcher. And after that, I spent nine years in AstraZeneca before deciding to step out of industry to set up a commercial imaging service, and the aim there was to make imaging much more accessible to the wider drug discovery community. And that ambition led me to my career now in medicines discovery catapult, which is a national life sciences organization that's dedicated to turning drug discovery into meaningful commercial breakthroughs. And at MDC medicines discovery catapult, we work very closely with entrepreneur entrepreneurial scientists, and we help them validate their ideas. We derisk their investments, and ultimately, we drive productivity across the drug discovery sector and also impact to patients. And within my team, we focus on applying those translational imaging techniques, technologies like Positron Emission Tomography and computer tomography, to understand how medicines behave in real biological conditions, and this, in turn, helps accelerate drug development. It ensures that those medicines are developed to deliver the maximum therapeutic benefit to our patients. And we're also pioneering in the area of radio pharmaceutical development and translation. And here, we're combining our world class radio chemistry expertise with our state of art imaging technologies, including clinically the world's the UK's first total body PET scanner. So, alongside my role here as head of translational imaging at MDC, I'm also the director of operations and engagement for our national PET imaging platform, and this is a National Technology network that provides the UK research community with unprecedented access to total body pairs.

 What is unique about the use of radiopharmaceuticals to treat cancer?

So, radiopharmaceuticals really do have enormous potential in modern medicine, and they're already driving game, game changing breakthroughs to patients, and we're seeing that worldwide. And at their core, they are a class of medicines that contain both a radioactive form of a chemical element, something we call a radioisotope, and they can be used to both diagnose and also to treat cancers. But what makes them so unique and so powerful is their precision, and what they will do is they will target radiation directly to the tumors. How it works is taking a targeting molecule that binds to that specific receptor on a cancer cell, it will carry the radioisotope then straight to the disease site. And once it's there, the gamma rays themselves will emit either alpha or beta particles and kill the cancer cells for therapy. And what it means is that we can both see the disease through the diagnostic tracer, but we can also treat it in a very targeted way, something we call a theranostic approach, so it's highly individualized, and it's very much image-guided therapy. So instead of a one size fits all, what we can do is get smarter, safer and more patient derived, stratified medicine approach to treatment, and compared with traditional cancer therapies, radiopharmaceuticals themselves, they spare healthy tissue. We don't get those side effects that we've seen with other cancer medicines. And because they're so precisely delivered to those cancer cells, the radiation dose to the rest of the body is significantly reduced, which lowers those side effects? And we've shown proven treatment effects already in some really difficult to treat cancers, cancers. So, for example, prostate cancer and neuro endocrine tumors have shown huge traction. And also beyond the therapy, as I say, those radioactive traces and the technology advancements that we're seeing within the UK, we can see those incredibly detailed insights to give both earlier but also more accurate diagnostics. So, you know, really, what makes them so unique is that we can combine the diagnostic, diagnosis and the treatment into one, and we're offering earlier detection, you know, better more precise treatment. And ultimately, we should. Lead to better patient outcomes.

 What are some of the specific challenges associated with the development of radiopharmaceuticals?

That's a really important question, because radiopharmaceuticals themselves have enormous potential. We've seen that, but there are still some very real challenges, both in their development, but also delivery, delivery that we need to overcome. So firstly, the global demand for the radio pharmaceutical treatments themselves is rising fast, you know, around 5% per year currently and growing more and more. And here in the UK, every hospital is using them daily to help patients, but one of the biggest hurdles is the access to the radio isotopes themselves. And at the moment, there are currently no UK production routes for many of the key radionuclides that we need. And that means that our clinical trials and also the widespread use of these therapies are heavily dependent on imports from overseas and from reactors and cyclotrons. And naturally, that supply chain creates risks, and if those supply chains are disrupted, then the access to the treatment and for the patient is immediately effective. Secondly, there are regulatory and quality requirements themselves. So like all medicines ready, pharmaceuticals must be manufactured, transported and administered, and very strict standards to ensure patient safety. And patient safety is at the forefront of every medicine that's produced, but because these products are radioactive and the bar for handling them, and also the compliance and how we administer them, is even higher, and that can slow development and add significant complexity. And then there's also the challenge of the short half life. So the radio isotopes themselves, they do degrade very quickly. So often the medicines have to be produced on the day that they're needed for injection, and also any delay in that transport, the production or the administration, can mean that procedures need to be canceled. We have a wasted product, or worse, a patient could be missing out on a timely diagnostic or treatment. So while the promise of radio pharmaceuticals are huge, overcoming these challenges, particularly around that reliable isotope supply regulations and logistics is critical if we want to see the full impact for our patients, both here in the UK but also worldwide.

How will the new crown MDC platform accelerate the development of radio pharmaceuticals?

How will the new crown and MDC partnership develop? So the partnership between Crown Bioscience and Medicines Discovery Catapult it's an incredibly exciting opportunity because it creates a fully integrated pre-clinical workflow for companies that are developing radio pharmaceuticals globally, and whether they're advancing new radio therapeutics, or they're exploring new isotopes or optimizing their targeting agents. This partnership can encompass all of those parts of the delivery so here within medicines discovery catapult, we've built a national radio pharmaceutical platform that combines the cutting-edge imaging technologies with the world class radio chemistry and translational expertise within the team, but crown bioscience themselves, they bring that unrivaled strength in pre-clinical oncology models and drug discovery services. So together, that creates a seamless pathway right the way through from discovery through into pre-clinical validation, but also into those translational imaging studies. And what this means for drug developers is that they can carry out more efficient studies, they can generate that high quality translational data, and it will support their precision medicine strategies. The partnership really does enable that rapid and also reliable testing of how a radiopharmaceutical behaves within the body and also how the body responds to it and how effective the radiopharmaceutical itself is, all of which are absolutely critical to identifying those drug candidates and reducing that clinical development risk. We're also leveraging our expertise across other areas within our organization, our cell biology, high resolution microscopy and also multi omic tissue analysis, and that allows us to deliver robust comparator studies with approved standards of care, which in turn provides greater regulatory confidence and help those drug developers provide and prepare stronger and successful investigational new drug submissions. So, by combining all of our strengths, we're not only helping innovators develop radio pharmaceuticals more efficiently, we're giving them the tools to de risk their investment accelerate the time it will take to get them to clinic and ultimately improve patient outcomes. So, it's all about moving radio pharmaceuticals to market faster and. Doing so in a way that's smarter, safer and more impactful for our patients.

Videos

Pharmaceutical Technology® spoke with Juliana Maynard, PhD, Head of Translational Imaging, at Medicines Discovery Catapult, to find out what makes radiopharmaceuticals unique and how MDC’s collaboration with Crown Bioscience can help developers of these treatments for cancer.

Chris Spivey is director of Industry Relations and Strategic Partnership, MJH Life Sciences.

Pfizer re-balances weight loss portfolio with Metsera, Bristol Myers Squibb and Roche make Breast cancer progress, and Keytruda gets under your skin.

Behind the Headlines Episode 26: Clinical Advances, Weight-Loss Deals, and Swiss Startup Strength

Behind the Headlines bi-weekly episodes examine the ongoing trends, factors and fashions that cause pharmaceutical news to happen. Panelists are a mix of consultants, venture capitalists, scientists, patient advocates, journalists and editors. Each episode talks about the current headlines of the preceding weeks that are on everyone’s lips but seeks to highlight the more enduring lessons that hide behind these headlines.

In Episode 26, Sirpa Tsimal, Global Marketing Director, Switzerland Global Enterprise; Philip Just Larsen, MD, PhD, CEO, Six Peaks Bio; and Stephan Emmerth, Director of Business Development & Operations, BaseLaunch, take a close look at recent clinical trial progress, including Bristol Myers Squibb’s successful phase 3 results for relapsed refractory multiple myeloma (1) and Roche’s evERA study on advanced breast cancer (2), alongside Eli Lilly and Company's oral treatment for ESR1-mutated breast cancer (3) and Merck 's FDA approval for subcutaneous keytruda delivery (4).

Because of its very clear importance to Scandinavian countries, this all Swiss-based panel also examined the reasons behind Pfizer’s Metsera acquisition for $4.9Billion (5), a key move to re-shape the weight loss drug landscape, once again.

The panel also discussed what makes for a great set of accelerator business conditions for life sciences and scores Switzerland’s performance for several of the most important factors determining successful outcomes for the life science industry, most especially as they relate to innovative young companies, as well as the university systems that feed them, alongside the big pharma companies that help sustain the momentum being built.

Bristol Myers Squibb Announces Phase 3 EXCALIBER-RRMM Study Evaluating Iberdomide in Combination with Standard Therapies Demonstrated a Significant Improvement in Minimal Residual Disease Negativity Rates in Relapsed or Refractory Multiple Myeloma

Positive Phase III Results Show Roche’s Giredestrant Significantly Improved Progression-free Survival in ER-positive Advanced Breast Cancer

U.S. FDA Approves Inluriyo (Imlunestrant) for Adults with ER+, HER2-, ESR1-mutated Advanced or Metastatic Breast Cancer

FDA Approves Pembrolizumab and Berahyaluronidase Alfa-pmph for Subcutaneous Injection

Pfizer to Acquire Metsera and its Next-Generation Obesity Portfolio. Press Release

Pfizer re-balances weight loss portfolio with Metsera, Bristol Myers Squibb and Roche make breast cancer progress, and Keytruda gets under your skin.

.AI, Machine learning, Business analysis, Science and artificial intelligence technology, Cloud computing, Network, Big data, communication, Digital transformation, Innovation and futuristic. | Image Credit: ipopba -stock.adobe.com

For pharmaceutical scientists, the integration of artificial intelligence (AI) and machine learning (ML) into workflows represents a fundamental paradigm shift in how the industry discovers, develops, and manufactures medicines (1). AI is no longer a futuristic concept but a present-day reality, reshaping everything from early-stage drug discovery and clinical trial optimization to real-time process control on the factory floor (1). The synergy between groundbreaking science and innovative, AI-driven manufacturing may well define the next decade of bio/pharma, creating more personalized, effective, and accessible therapies.

How is AI accelerating discovery and streamlining development?

AI is looking to be invaluable during the early stages of drug development as it can rapidly screen vast compound libraries and predict a drug candidate's properties from just its chemical structure (2). ML algorithms can identify complex patterns in high-dimensional data, allowing scientists to de-risk projects by predicting absorption, distribution, metabolism, elimination, and toxicity (ADMET) properties 

 before committing to resources (2, 3). This capability is particularly crucial for complex molecules with poor solubility or narrow therapeutic windows, where traditional modeling may fall short (2).

Beyond initial screening, digital tools are creating a bridge between R&D and manufacturing (3). AI-powered analysis of preclinical data can help optimize formulation conditions, while virtual models of a process or product (i.e., digital twins) offer extensive 

 testing, scenario elaboration, and process optimization (1, 3, 4, 5). These tools have the potential to save time and resources by reducing the need for physical experiments. They also have the potential to accelerate tech transfer by capturing and standardizing process knowledge, ensuring consistency from a small lab batch to a large manufacturing run (3, 5).

The impact of AI extends into manufacturing, where Industry 4.0 is driving the adoption of smart machinery, interconnected sensors, and AI-driven control systems (4). In both small-molecule and large-molecule manufacturing, the goal is to leverage data to achieve high levels of process understanding and control (4, 5). By combining AI/ML models with process analytical technology, manufacturers can monitor critical quality attributes in real time, moving toward real-time release (4, 5).

This integration enables a move from reactive to predictive—and eventually prescriptive—manufacturing (4). An AI/ML model can analyze real-time sensor data from a bioreactor, predict the final batch outcome, and drive a closed-loop optimization to adjust parameters before a deviation occurs (4,5). This can lead to improved yields, reduced variability, and more consistent product quality, when compared with standard, non-AI/ML approaches (4,5).

How can one navigate the data and regulatory landscape?

Realizing the full potential of AI hinges on high-quality, contextualized data (1,2). Process data from the factory floor is often unstructured, making it difficult for algorithms to use effectively (5). Adopting findable, accessible, interoperable, and reusable (FAIR) data principles and creating centralized data platforms are essential first steps to building a scalable, AI-ready environment (1,5). Without context, the value of data diminishes, hindering their ability to drive meaningful action (5).

Simultaneously, the regulatory landscape is rapidly evolving to keep pace with technology (6). While regulators may be open to AI-driven approaches, they emphasize the need for transparency, validation, and managing bias (2, 5, 6). The "black box" nature of some algorithms is a significant concern, pushing the industry toward hybrid models that combine the predictive power of AI with the interpretability of mechanistic models (2, 3). Establishing "good machine learning practice" will be crucial for ensuring these tools are fit-for-purpose and gaining regulatory confidence (2).

As the industry moves forward, AI will continue to augment human expertise, requiring a workforce upskilled in data analysis and robotics (1, 4). The journey ahead involves navigating these data and regulatory challenges, but the destination may be a more efficient, intelligent, and patient-centric pharmaceutical industry.

Visit PharmTech.com to watch industry experts discuss the use of AI/ML in pharma. Below is a selection of video interviews.


Susan J. Schniepp, Distinguished Fellow, Regulatory Compliance Associates, joins PDA CEO Glenn Wright and Melissa Seymour, Executive Vice President, Global Quality, Eli Lilly and Company, to talk about the regulatory and quality topics discussed at the 2025 PDA Regulatory Conference.


https://www.pharmtech.com/view/pda-regulatory-conference-2025-wrap-up

Industry Outlook 2025: Technology as a Supporting Element

® spoke with Alexander Seyf, CEO and co-founder of Autolomous, about the use of artificial intelligence and machine learning in pharmaceutical development and manufacturing.


https://www.pharmtech.com/view/industry-outlook-2025-technology-as-a-supporting-element

Drug Digest: Keeping Pace with Progressive Technologies in Biopharma Development


This episode of Drug Digest will discuss where the significant bottlenecks are in the development and manufacturing of new molecules resulting from progressive technologies, such as AI and ML, and how best to approach these challenges.


https://www.pharmtech.com/view/drug-digest-keeping-pace-with-progressive-technologies-in-biopharma-development

Quality Considerations for Using AI in Bio/Pharma


In this episode of the Ask the Expert video series, Susan J. Schniepp, distinguished fellow at Regulatory Compliance Associates, and Siegfried Schmitt, vice-president, Technical, at Parexel, discuss the quality requirements needed when incorporating AI in bio/pharmaceutical development and manufacturing.


https://www.pharmtech.com/view/quality-considerations-for-using-ai-in-bio-pharma

Thomas, F. Expanding Pharma’s Horizons Through AI and Acquisitions." 

Challener, C. A. Overcoming PK/PD Modeling Challenges. 

Haigney, S. Advancements in Biopharma Spur Innovation. 

Mirasol, F. Accelerating Adoption of Smart Tools to Advance Manufacturing." 

Markarian, J. Optimizing Data Use for Digital Transformation." 

Schmitt, S. Regulations in AI and Other Digital Technologies. 

Articles

AI and ML are transforming pharmaceutical workflows, from drug discovery to manufacturing, by enabling rapid screening of compounds, predicting drug properties, and optimizing processes. These technologies facilitate the transition from reactive to predictive manufacturing, enhancing process control and product quality. High-quality, contextualized data and evolving regulatory frameworks are crucial for maximizing AI's potential. The industry must address data challenges and regulatory concerns, such as algorithm transparency, to fully leverage AI's capabilities. Upskilling the workforce in data analysis and robotics is essential for future advancements.

This article takes a look at the developing use of AI in pharmaceutical development and manufacturing.

How AI is Accelerating Pharmaceutical Development

Patrick Lavery is an Editor for the MJH Life Sciences brands 

. Previously at MJH, he filled the same role for 

STEIN, SWITZERLAND - FEBRUARY 18, 2020: Novartis is the second largest pharmaceutical company in the world. Novartis Pharma in Stein produces new medicaments and delivers them in 150 countries. | Image Credit: © Taljat - stock.adobe.com

For the first time, FDA has approved a Bruton’s tyrosine kinase inhibitor (BTKi) for chronic spontaneous urticaria (CSU), giving the green light to 

’ twice-daily oral treatment remibrutinib (brand name Rhapsido) (1). The approval, announced by Novartis on Sept. 30, 2025, was granted for adult patients with CSU who remain symptomatic despite H1 antihistamine treatment.

According to information provided by Novartis, CSU is a mast cell-driven condition that is believed to be brought on by immune dysregulation, with patients’ immune systems becoming activated through either allergic or autoimmune pathways (1). When this happens, immune cells, such as mast cells and basophils, activate the BTK protein; although this process is not fully understood, it can ultimately result in a release of histamine or other, proinflammatory mediators that cause red, swollen, and/or itchy hives.

Onset of symptoms like these hives are often unpredictable in patients with CSU, Novartis said, recurring for six weeks or more with no warning, making diagnosis difficult—sometimes taking up to 24 months (1). Patients report CSU symptoms negatively affecting their sleep, work, and mental health.

Even after first-line antihistamine treatment, more than half of patients still exhibit symptoms, including after being administered higher doses (1). For those who do not respond to antihistamine treatment, injectable treatments do exist, but Novartis said fewer than 20% of eligible patients receive them.

What’s the larger implication of the remibrutinib approval for the industry?

FDA’s approval of remibrutinib may represent a new phase in the application of BTK inhibitors beyond hematologic malignancies. While BTK inhibitors have become a mainstay in oncology, their expansion into immunology demonstrates the versatility of the drug class and underscores a broader trend of repositioning targeted therapies to address inflammatory and autoimmune conditions. For drug developers, this approval highlights the regulatory willingness to consider well-established mechanisms of action in new therapeutic areas when the unmet need is clearly defined.

The decision also stands to set a precedent for competition in the CSU space, which has historically relied heavily on injectable biologics. The availability of a twice-daily oral treatment offers a more convenient alternative, potentially shifting prescribing patterns and influencing payer considerations. This shift could encourage other manufacturers to accelerate development of small-molecule therapies in areas traditionally dominated by biologics, further blurring the lines between the two modalities.

For the bio/pharmaceutical industry more broadly, the approval reflects the growing emphasis on precision immunology and the push toward diversifying portfolios across therapeutic classes. As more companies pursue BTK inhibitors for non-oncologic conditions, the long-term impact will likely extend beyond CSU, shaping investment strategies, clinical trial designs, and regulatory pathways for next-generation targeted therapies.

Have other CSU treatments or BTK inhibitors been approved recently?

’s Omlyclo (omalizumab-igec) as the first interchangeable biosimilar to 

 and Novartis’ Xolair (omalizumab), both treatments being indicated for a number of conditions, including CSU in those aged 12 and older whose hives have continued uncontrolled by H1 antihistamine treatment (2).

Meanwhile, two BTK inhibitors have been advanced by the European Medicines Agency (EMA) in 2025. In February, EMA’s Committee for Medicinal Products for Human Use 

’s Jaypirca (pirtobrutinib), a non-covalent or reversible BTK inhibitor, for treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia previously treated with a BTK inhibitor (3).

 to rilzabrutinib, an investigational, oral BTK inhibitor from 

, for the treatment of IgG4-related disease (4).

, advancing a previously announced merger plan. In parallel, Novartis also said a direct-to-patient platform would launch in the United States Nov. 1, 2025, providing secukinumab (brand name Cosentyx)—Novartis’ top-selling biologic in the US, approved to treat psoriasis, psoriatic arthritis, hidradenitis suppurativa, and other immune-mediated inflammatory diseases—at a 55% discount off list price for cash-paying patients (5).

Anecdotally, Novartis was one of 17 pharmaceutical companies 

 on July 31, 2025, outlining the step-by-step process US President Donald Trump said the companies must take to lower prescription drug prices in the US to the lowest price offered among other developed nations, a strategy known as the most-favored-nation price (6). 

 with the White House, on Sept. 30, 2025 (7).

 focused on developing novel degraders for immune-mediated diseases, building on the companies’ initial 2024 licensing agreement for vav guanine nucleotide exchange factor 1 degraders, including MRT-6160, a candidate advancing toward multiple Phase II studies (8).

Novartis Receives FDA Approval for Rhapsido (remibrutinib), the Only Oral, Targeted BTKi Treatment for Chronic Spontaneous Urticaria (CSU).

 Press Release. Sept. 30, 2025.
2. Lavery, P. 

FDA Approves Celltrion’s Omalizumab Biosimilar.

, March 13, 2025.
3. Eli Lilly and Company. 

Lilly's Jaypirca (pirtobrutinib) Recommended by CHMP for Approval in the European Union for Adults with Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) Previously Treated with a BTK Inhibitor.

 Press Release. Feb. 28, 2025.
4. Sanofi. 

Sanofi’s Rilzabrutinib Earns Orphan Designation in the EU for IgG4-Related Disease.

 Press Release. Aug. 14, 2025.
5. Mirasol, F. 

Novartis Advances Pipeline and Redefines Distribution with Tourmaline Acquisition and DTP Platform.

Trump Sends Letters to 17 Leading Pharma Companies Outlining Most-Favored-Nation Drug Pricing Protocol.

Pfizer Reaches First Agreement with White House on MFN Pricing; Who Will Be Next?

Monte Rosa and Novartis Partner to Target Undruggable Immunology Pathways with Degraders.

The FDA has approved Novartis' remibrutinib, a Bruton’s tyrosine kinase inhibitor, for chronic spontaneous urticaria (CSU) in adults unresponsive to H1 antihistamines. CSU is a mast cell-driven condition causing unpredictable hives, affecting patients' quality of life. This approval marks a significant expansion of BTK inhibitors into immunology, offering a convenient oral alternative to injectable biologics. It may influence prescribing patterns and encourage development of small-molecule therapies. Novartis is also advancing strategic initiatives, including acquisitions and direct-to-patient platforms, amidst regulatory pressures on drug pricing.

The go-ahead for Novartis’ oral treatment marks a new option for patients with spontaneous urticaria who remain symptomatic despite antihistamine therapy.

What FDA’s Remibrutinib Approval Reveals About the Future of BTK Inhibitors

The Story of Nitrosamines

Nitrosamines occurring in pharmaceuticals became a developing problem in 2018, and regulatory agencies have been working with pharmaceutical companies since to mitigate the risk of these cancer-causing chemicals in drug products. Over the years, 

® has covered the issue through news reports, interviews, and technical articles. PharmTech's nitrosamine coverage can be found in the reference list below. 

Click the above audio summary to learn about how the nitrosamines situation began and is continuing. And check out the video summary below.

 This media was created using NotebookLM using articles found on PharmTech.com. Please see below list of references. AI-generated content may not be correct.

The graphic below breaks down some of the basics involved and what manufacturers should look out for. 

Nitrosamines Contamination. Image Credit: Created using Canva AI

The discovery of nitrosamine impurities in pharmaceutical drugs, beginning in 2018, has prompted extensive regulatory action and industry-wide changes to ensure patient safety (1,2). The issue first came to light when N-nitrosodimethylamine (NDMA), a probable human carcinogen, was found in valsartan, an angiotensin receptor blocker (ARB), from a Chinese active pharmaceutical ingredient (API) manufacturer, Zhejiang Huahai Pharmaceutical Company (1, 3). This led to widespread recalls of sartan-based medicines (1).

Investigations soon revealed other nitrosamines, like N-nitrosodiethylamine (NDEA), in different sartan drugs, including losartan and irbesartan (1,4). The contamination was traced to specific manufacturing processes, particularly those involving certain solvents, reagents, and recycled materials (5, 6,7). The problem was not isolated to sartans; NDMA was later found in other widely used drugs such as ranitidine (Zantac), metformin, and pioglitazone, triggering further recalls and investigations (3,9). One study suggested the ranitidine molecule itself might be inherently unstable, capable of forming NDMA under conditions mimicking the human stomach (9).

In response, global regulators, including the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), have issued comprehensive guidance (10, 11). They now require pharmaceutical companies to conduct rigorous risk assessments for all chemically synthesized APIs to identify and mitigate nitrosamine risks (3, 10, 7). Both agencies have established acceptable daily intake limits for various nitrosamines and mandated confirmatory testing if a risk is identified (3, 12). The FDA has also developed advanced analytical methods, such as liquid chromatography-mass spectrometry (LC-MS), to detect trace levels of these impurities and avoid false positives that could occur with older testing protocols (1, 9, 13). This ongoing challenge has underscored the critical need for continuous safety surveillance and robust quality control throughout the pharmaceutical supply chain (3, 14).

 This summary was created with NotebookLM using articles found on PharmTech.com. AI-generated content may not be correct.

After Valsartan Recalls, Regulators Grapple with Nitrosamine Contamination in APIs

Detecting Apparent Total Nitrosamine Content in Pharmaceutical Drugs.

Complying Confidently? Learning Lessons from Nitrosamine Impurities

FDA Hits Valsartan Manufacturer with Warning Letter. 

5. PharmTech Editors. FDA Gives Update on NDMA Investigation. 

FDA Releases List of 'Safe' Valsartan and ARBs While Experts Explore and Debate Root Causes of Contamination. 

 Investigating NDMA Impurities at EMA’s Request.

Pharma Industry Contends with Contamination-Based Recalls.

Problems With Ranitidine May Transcend Manufacturing Issues

EMA Issues Final Opinion on Nitrosamines.

FDA Publishes Guidance on Control of Nitrosamines

Nitrosamine Impurities in Medicinal Products. 

Understanding Nitrosamine Impurities in the Pharmaceutical Industry

What Goes Wrong When API Quality is Compromised? 

Development of a Validated Method of Testing for NDMA in Ranitidine. 

• Curran, T. and Bercu, J. P. (2021, March 15).

 Managing the Risk of Nitrosamine Impurities

European Pharmacopoeia Updates: EDQM Tackles Nitrosamine Impurities

N-Nitrosamine Impurities and FDA’s Recommendations for Acceptable Intake Limits

Strategies for Mitigating Nitrosamine Risk

FDA Releases Guidance on Intake Limits for Nitrosamine Drug Substance-Related Impurities. 

European Authorities Continue Work to Prevent and Manage Nitrosamine Impurities.

. Sartan Manufacturers Should Review Manufacturing Processes, Says EMA

FDA Approves New Generic Valsartan. Pharmaceutical Technology. 

EMA Provides Guidance on How to Avoid Nitrosamines in Human Medicines

FDA Expands Scope of API Impurity Investigation.

Latest ARB Recall Triggered by New Impurity. 

Metformin HCl Extended Release Tablets Recalled.

Nostrum Laboratories Expands Recall of Metformin HCl Extended Release Tablets

What Does the FDA's Recent Update of the Nitrosamine Guidance Convey?

Nitrosamides–Should They Be Treated the Same as Nitrosamines?

This review of the nitrosamines contamination problem in pharmaceuticals takes a look at how the crisis started and developed.

Pfizer logo sign New York, NY, USA - May 4, 2021: Closeup of Pfizer sign and logo on the side its corporate building in New York City. | Image Credit: © Kathy images - stock.adobe.com

 has become the first major pharmaceutical company to voluntarily agree to a July 31, 2025 mandate from the White House to lower prescription drug prices in the United States to the lowest price offered among other developed nations, a strategy known as most-favored-nation (MFN) pricing (1,2). US President Donald Trump’s administration and Pfizer both issued press releases announcing the deal on Sept. 30, 2025.

That date marked 61 days since July 31, one day over 

 to follow a step-by-step process his office outlined—following 

—or else the president said the federal government would “deploy every tool in our arsenal to protect American families from continued abusive drug pricing practices” should companies fail to act (3,4).

As detailed by the White House, every state Medicaid program in the US will be given access to MFN prices on Pfizer products—ensuring that foreign countries will no longer be able to do the same (1). Pfizer will be required to repatriate increased foreign revenue on existing products that may be realized as part of the new arrangement, and Pfizer medicines will be offered at deep discounts off the list price when sold directly to US patients.

Pfizer said it will also participate in a direct purchasing platform, TrumpRx.gov (not yet live), and that savings on most of the company’s primary care treatments and select specialty brands will average 50% but could be as high as 85% (2).

More specific terms of the agreement have been kept confidential, but in Pfizer’s press release, chairman and CEO 

, DVM, PhD, said that the company will also be granted a three-year grace period during which Pfizer products under a Section 232 investigation will not be subject to tariffs provided that Pfizer further invests in manufacturing in the US (2).

What are some of the broader implications for bio/pharma?

This first domino to fall in the push for MFN pricing has the potential to result in significant shifts across the bio/pharmaceutical landscape, affecting everything from R&D priorities to manufacturing strategies.

For those in drug discovery and development, it may necessitate a re-evaluation of investment strategies. Should the US no longer shoulder a disproportionate share of global pharmaceutical profits, the financial calculus for R&D likely changes. In its announcement, Pfizer stated the agreement allows it to "fully focus on delivering the next generation of cures" in high-value areas such as oncology, obesity, vaccines, and immunology (2). This suggests that companies may increasingly prioritize therapeutic areas with the potential for pioneering breakthroughs to justify investments under the new pricing framework.

In drug manufacturing, the agreement could spur a significant increase in domestic investment. The key component of Pfizer's deal—the tariff grace period—comes as the company has committed an additional $70 billion to US research, development, and capital projects in the coming years, aiming to fuel growth, create jobs, and reshore manufacturing (2).

In theory, the agreement stands to set a precedent for other major companies in the industry, potentially leading to a broader onshoring of manufacturing and supply chain infrastructure. The stability and certainty on pricing and tariffs provided by the agreement are seen by Pfizer's leadership as critical factors that will enable more bold investment in the US bio/pharmaceutical ecosystem (2).

Have any other companies responded to the White House’s demand?

Pfizer was one of 17 pharmaceutical companies to receive letters from the Trump administration on July 31, along with AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly and Company, EMD Serono, Genentech, Gilead Sciences, GSK, Johnson & Johnson, Merck & Co., Novartis, Novo Nordisk, Regeneron, and Sanofi (3).

Among those, Lilly was one company that had 

 to comply with the MFN directive, saying it expected to make necessary pricing adjustments by Sept. 1, 2025 (5). But with the entire month of September having now elapsed since that announcement was made on Aug. 14, no agreement has been disclosed by either Lilly or the White House.

And while no apparent headway has been made with Johnson & Johnson regarding MFN pricing, US health officials have had former J&J property Tylenol (spun off under Kenvue Brands in 2021) in their crosshairs during September 2025, as the Trump administration 

 between the use of acetaminophen during pregnancy and development of autism spectrum disorder and attention-deficit/hyperactivity disorder in children (6).

How else have we covered this story so far?

 on Sept. 10, 2025 that brought together a panel of experts with perspectives from economics, investment, law and the payer sector to help unpack the potential impacts of future pharmaceutical costs in the US (7).

The panel was moderated by Ned Milenkovich, PharmD, JD, chair of the Health Care Practice Much Shelist, P.C., and included Brian Corvino, principal and Global Market Access Practice leader, Deloitte US; Neal Masia, PhD, co-founder and chief executive officer, EntityRisk, Inc.; Ali Pashazadeh, founder, chairman, and chief executive officer, Treehill Partners; and George Van Antwerp, MBA, senior vice-president, Prime Therapeutics.

 to register for free and watch the full panel, on demand.

Fact Sheet: President Donald J. Trump Announces First Deal to Bring Most-Favored-Nation Pricing to American Patients.

Pfizer Reaches Landmark Agreement with US Government to Lower Drug Costs for American Patients.

 Press Release. Sept. 30, 2025.
3. Lavery, P. 

Trump Issues Executive Order Aimed at Reducing Prescription Drug Prices for US Patients.

Lilly Statement: MFN Pricing Targeted for September 1, Pushback on Pharma Tariffs.

Acetaminophen and Autism: Industry Impacts of the White House Statement.

, Sept. 23, 2025.
7. Medical Economics Staff. 

Trump’s ‘Most-Favored Nation’ Drug Price Push: Key Takeaways from Our Expert Panel.

Pfizer has agreed to a mandate from the White House to lower US prescription drug prices to match the lowest prices offered in other developed nations, known as most-favored-nation pricing. This agreement includes providing state Medicaid programs access to these prices and offering significant discounts to US patients. The deal also involves a tariff grace period for Pfizer, contingent on increased US investment. This move could influence the bio/pharmaceutical industry, potentially altering R&D priorities and encouraging domestic manufacturing. Other pharmaceutical companies have yet to finalize similar agreements.

Sept. 30 marked 61 days since July 31, one day past the timeframe President Donald Trump had set forth for companies to lower prescription drug prices in the United States.

Text sign showing Industry News. Business photo text delivering news to the general public or a target public | Image Credit: © Artur - © Artur - stock.adobe.com

The European Medicines Agency (EMA) announced on Sept. 29, 2025 that it has published a draft reflection paper on the use of patient experience data in the regulation of drugs (1,2). The reflection paper was written to encourage drug developers to gather and include data on real-life experiences of patients throughout a drug’s lifecycle so that regulators can use that insight in regulatory decisions. The draft reflection paper is open for public consultation until Jan. 31, 2026.

What can the patient perspective provide?

According to EMA, patient perspectives are of “great value” and include data such as cancer patients choosing quality of life over clinical endpoints. These data can play a “complementary role” to other scientific data during the regulatory review process. These types of data can be provided through Patient Reported Outcomes (PROs), Patient Preference Studies, and other patient engagement activities.

“Recent years have seen efforts by regulators internationally to steer medicine development toward programs that not only meet the requirements for quality, safety and efficacy of individual products, but also incorporate the broader perspectives of patients and carers. This is because patients may value different aspects of their disease and available treatments than medicine developers, including the type of relevant outcome measures to be assessed (e.g., quality of life), populations or stages of disease to be studied, or risk tolerability. An optimal patient-relevant medicine development program incorporates patients’ perspectives and documents their experience. Such patient experience data are directly collected from patients or carers experienced in managing the disease and capture their needs and preferences,” the paper states.

The reflection paper provides drug developers with principles on the generation, collection, and analyzation of these data. The paper also provides sources for where the data can be obtained, such as clinical trials and real-world data from safety surveillance systems. Also included in the paper are discussions on training and capacity building, challenges related to using PROs, study design, transparency issues, and considerations for systemic implantation of these data.

The paper does not include detailed methodological guidance; however, EMA is working with the International Council for Harmonisation (ICH) to harmonize existing global methodological guidelines. The EMA reflection paper is a complement to the ICH work and focuses on development programs and regulatory submissions in the European Union. EMA is supporting developers by offering early interaction platforms to discuss development plans and proposals for regulatory submissions.

What is the importance of real-world evidence?

The European Medicines Agency (EMA) has released a draft reflection paper to encourage the integration of patient experience data in drug regulation. This initiative aims to incorporate real-life patient insights throughout a drug's lifecycle, enhancing regulatory decisions. Patient perspectives, including quality of life considerations, are deemed valuable and can complement scientific data. The paper outlines principles for data collection and analysis, emphasizing real-world evidence's role in ongoing drug safety assessment. The EMA collaborates with the International Council for Harmonisation to align global methodological guidelines.

A draft reflection paper on patient experience data is up for public consultation until Jan. 31, 2026.

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