Behind the Headlines Episode 27

Ask the Expert

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

Drug Digest September 2025

Artificial intelligence, machine learning, and novel instruments are helping drug developers.

Enhancing Bioanalysis and Drug Development with Advanced Tools and Technologies

J.P. Morgan Report Lists Biologics, Obesity, China

Top Trends Reshaping Pharma R&D

Feliza Mirasol is the science editor for 

Discussion with Jerry Keybl, Avantor, about latest innovations in biomanufacturing and major industry trends coming out of INTERPHEX 2025.

INTERPHEX 2025: The Search for Pragmatic Solutions to Ground Industry Innovations

Contemporary biopharmaceutical production strategies emphasize three critical drivers: scalability, flexibility, and efficiency, says Jerry Keybl, senior vice-president, Biopharma Products and Strategy, Avantor. In addition, Keybl attended INTERPHEX 2025 last April and shared some of his impressions of the energy at that show around these themes.

Keybl emphasizes how the bioprocessing sector is experiencing significant transformation today, driven by supply chain disruptions, regionalization, and the emergence of diverse therapeutic modalities. He underscores the importance of developing future-proof bioprocessing technologies.

"Innovations today really have to be future-proof. They have to support manufacturing all the way from clinical trials to commercialization. Sometimes the challenges are different at different stages of the development, and the decisions you make early on can really impact the success as a commercialization approaches," he says.

Manufacturing flexibility is increasingly crucial, he also points out, explaining that facilities are transitioning from single-process to multi-product and multi-modality platforms. Therefore, there is a need for adaptable technologies that can accommodate diverse product requirements while maintaining operational efficiency.

Buffer management is also emerging as a crucial area for optimization, with solutions such as ready-to-use buffers and direct dispense packaging systems (solutions that Avantor offers) allowing for the reduction of labor costs and improved process efficiency.

One key takeaway from the show that made an impression on Keybl was that the bio/pharmaceutical industry is currently focused on practical innovation, balancing excitement about new modalities with a pragmatic approach to solving real-world manufacturing challenges.

Click the video above to view the full interview.

Jerry Keybl, Senior Vice-President, Biopharma Products and Strategy, Avantor

Jerry Keybl is senior vice-president of Biopharma Products and Strategy at Avantor, leading integrated product strategy and execution across traditional and novel biopharma modalities. He previously held product management, marketing, and strategy roles at MilliporeSigma, with a focus on cell and gene therapies, and served as a project leader at the Boston Consulting Group.

Videos

Jerry Keybl, senior vice-president, Biopharma Products and Strategy, Avantor, discusses innovations in biomanufacturing and recalls his impressions of INTERPHEX 2025 held this past April.

Discussing Pragmatic Solutions to Ground Industry Innovations with Avantor

Mike Hennessy Jr. is the Chairman and CEO of 

High Angle Shot of a Working Desk of an Successful Person in Office with Cityscape Window View. | Image credit: © Gorodenkoff - stock.adobe.com

As you read this note, pharmaceutical development and manufacturing are being redefined by collaboration, innovation, and the urgent need for agility. The throughline across this issue of 

® is unmistakable: success now depends on integration of systems, data, partnerships, and people.

Our cover story, “Customizable Relationships Enhance Speed to Market,” underscores this reality. As drug modalities become more complex, sponsor companies and CDMOs are moving away from traditional, transactional relationships. The new model is one of shared risk and long-term collaboration, driven by mutual investment in speed, quality, and innovation.

This spirit of innovation is reflected in the development space, where ocular drug delivery continues to challenge formulation scientists. As Cynthia Challener reports in “Advanced Solutions for Sustained Delivery of Ocular Therapies,” sustained-release technologies for eye care are gaining traction, improving compliance and outcomes in an area in which frequent dosing has long been a barrier.

“In-line UV Spectrometry Monitoring in Cleaning Validation” offers a timely look at how Pharma 4.0 principles are reshaping validation. The integration of in-line analytical tools enables real-time monitoring, greater data reliability, and stronger alignment with quality-by-design and digital manufacturing goals.

On the analytics front, “Overcoming PK/PD Modeling Challenges” explores how AI and machine learning are transforming PK/PD modeling. These tools enable faster, more accurate predictions of drug behavior, helping teams avoid costly delays and unnecessary experimentation.

We also examine the realities of small-batch fill/finish operations, including the technologies and process solutions emerging to meet the demands of low-volume, high-value production.

Finally, in “ICH Q12 and Post-Approval Changes,” Siegfried Schmitt sheds light on why streamlined post-approval change management remains elusive, and why it’s crucial for maintaining supply resilience.

Taken together, these articles offer a clear view of where pharmaceutical manufacturing is headed: toward smarter tools, deeper partnerships, and a renewed focus on compliance and quality at every stage of the product lifecycle.

Mike Hennessy Jr is Chairman and CEO of MJH Life Sciences®.

®
Vol. 49, No. 6
July/August 2025
Page: 8

When referring to this article, please cite it as Hennessy, M. The Future of Pharma: Connected, Continuous, and Compliant. 

Articles

Pharmaceutical development and manufacturing are evolving through collaboration, innovation, and agility. Success now hinges on integrating systems, data, partnerships, and people. The shift from traditional, transactional relationships to shared risk and long-term collaboration is crucial, especially as drug modalities grow more complex. Innovations in ocular drug delivery, in-line UV spectrometry for cleaning validation, and AI-driven PK/PD modeling are reshaping the industry. Small-batch fill/finish operations and streamlined post-approval change management are also critical for maintaining supply resilience and ensuring quality throughout the product lifecycle.

Pharma manufacturing is headed toward smarter tools, deeper partnerships, and a renewed focus on compliance and quality at every stage of the product lifecycle.

The Future of Pharma: Connected, Continuous, and Compliant

Communication between the manufacturing plant and retail stores. | Image Credit: © Cagkan - © Cagkan - stock.adobe.com

ESTEVE CDMO (actively operating under the Esteve Química brand) announced on July 31, 2025 that it has acquired Regis Technologies, an API contract development and manufacturing organization (CDMO) in Chicago. The acquisition expands ESTEVE’s API contract development and manufacturing services in the United States from pre-clinical to commercial manufacturing.

ESTEVE CDMO, headquartered in Barcelona, is a global pure-play CDMO that specializes in small-molecule APIs, intermediates, spray drying technologies, and high-potency API manufacturing. To these services, Regis Technologies brings process R&D; analytical and stability; current good manufacturing practice (GMP) API manufacturing; chemistry, manufacturing, and controls support; and chromatography products.

"We are proud to strengthen our CDMO solutions for pharmaceutical innovators through this acquisition, while welcoming around 70 skilled professionals to our US team," said Joan Petit, chief industrial operations officer of ESTEVE and general manager of Esteve CDMO (Esteve Química), in a press release (1).

"This acquisition enhances our early-stage development capabilities, and expands our global manufacturing footprint, allowing us to have an integrated service offering to better respond to our customers' needs," Andrea Oro, global head of Commercial Operations and Strategy, added.

"We are happy to join a company that shares our same values, a company that is also family-owned, with more than 90 years of experience, that is committed to people and focused on delivering long-term value to customers," said Scott Aladeen, president and CEO of Regis Technologies, in the release.

ESTEVE acquires symptomatic medullary thyroid cancer treatment

In June 2025, ESTEVE, the company’s pharmaceutical development division, acquired the rights to Caprelsa (vandetanib) in more than 50 countries from Sanofi. Caprelsa (vandetanib) is a treatment for adults and children five years of age and above with aggressive symptomatic medullary thyroid cancer.

"Medullary thyroid carcinoma is a rare neuroendocrine tumor that can produce calcitonin from parafollicular cells. The treatment of resectable disease is surgery (2). When the disease is not technically resectable, this treatment provides a long-lasting slowdown of disease progression. We at ESTEVE are proud to join the fighting effort of the patients diagnosed with this carcinoma and their healthcare professionals, with the ambition to continue improving patient's health and lives," José María Giménez-Arnau, chief scientific & medical officer of ESTEVE, said in a press release (3).

Other recent acquisitions by the company include the purchase of a business specializing in rare and ultra-rare endocrinology and onco-endocrinology diseases in April 2024 and a license for a biologic treatment for children and adolescents aged 2–18 years old with severe primary insulin-like growth factor 1 deficiency in April 2025.

"We are proud to announce that we are increasing our portfolio of highly specialized therapies. Caprelsa will help us improve the lives of patients all around the world. This is a step forward in ESTEVE's international journey focused on highly specialized treatments for high unmet medical needs of patients," Jacob Tolstrup, chief commercial officer of ESTEVE, said in the press release (3).

ESTEVE CDMO. ESTEVE CDMO Acquires Regis Technologies, Expanding US Presence and Capabilities. Press Release. July 31, 2025. 

https://www.esteve.com/global/media/news/esteve-acquires-regis-technologies-expanding-u-s-presence-and-capabilities

American Thyroid Association. Cancer of the Thyroid. Thyroid.org (accessed Aug.6, 2025). 

https://www.thyroid.org/medullary-thyroid-cancer/

ESTEVE. ESTEVE to Acquire Medicine to Treat Medullary Thyroid Cancer. Press Release. June 30, 2025. 

https://www.esteve.com/global/media/news/esteve-to-acquire-medicine-to-treat-medullary-thyroid-cancer

ESTEVE CDMO, operating under the Esteve Química brand, has acquired Regis Technologies, enhancing its API contract development and manufacturing services in the US. This acquisition strengthens ESTEVE's capabilities from pre-clinical to commercial manufacturing, adding process R&D, GMP API manufacturing, and more. Additionally, ESTEVE's pharmaceutical division acquired Caprelsa (vandetanib) for treating aggressive symptomatic medullary thyroid cancer, expanding its portfolio of specialized therapies. These strategic moves align with ESTEVE's focus on highly specialized treatments for unmet medical needs, reinforcing its global presence and commitment to patient care.

The acquisition expands the CDMO’s small-molecule API development and manufacturing services in the US.

ESTEVE CDMO Acquires Regis Technologies

Patrick Lavery is an Editor for the MJH Life Sciences brands 

. Previously at MJH, he filled the same role for 

gemstones using infrared spectroscopy | Image Credit: © poco_bw - stock.adobe.com

 series, FDA details how a newly developed nuclear magnetic resonance (NMR) spectroscopy method enabled researchers at the agency’s Center for Drug Evaluation and Research (CDER) to characterize—crucially, in a non-invasive way—microstructure properties in complex, oil-in-water nanoemulsion ophthalmic formulations (1).

The research centered around difluprednate, which has been approved as an orphan drug to treat post-operative ocular pain and inflammation (1). It is insoluble in water and, as such, was formulated as an oil-in-water nanoemulsion.

CDER researchers have been developing NMR spectroscopy to characterize such formulations since 2018, and, according to FDA, the researchers’ work culminated in correlated microstructure changes being observed for the first time in nanoemulsion formulations.

® also explores applications of spectroscopy, namely ultraviolet (UV) spectroscopy as a continuous, in-line method to monitor cleaning processes to confirm cleanliness of equipment surfaces through final rinse water analysis (2).

“Results showed that in-line monitoring capability of UV spectroscopy enables continuous monitoring of the entire cleaning cycle and applicability to quality by design, process analytical technology, process digitalization, and sustainability goals of a Pharma 4.0 manufacturing facility,” the authors wrote.

Below are further implications of CDER’s work for formulation scientists, analytical chemists, and manufacturers of complex drug products.

For formulation scientists, the ability to noninvasively monitor nanoemulsion dynamics could lead to more robust excipient selection, formulation optimization, and stability prediction. For manufacturers, intact NMR may offer a quality control tool that minimizes sample manipulation while enhancing sensitivity to early signs of instability.

The study also demonstrated that different NMR relaxation times and diffusion coefficients can serve as surrogate indicators for microstructural changes, suggesting possible future development of NMR-based specifications for complex generics and innovator products alike.

Relevance for complex generics, quality assessment

FDA's emphasis on intact NMR aligns with its broader goals to facilitate the development of complex generics, particularly those containing nano-sized active or excipient particles. By enabling more precise characterization of reference listed drugs and their generic counterparts, this approach may support bioequivalence determinations and post-approval change assessments.

Furthermore, FDA noted that the study aligns with quality by design principles, offering a means to better understand critical quality attributes of nanoemulsions without disrupting the formulation environment.

The adoption of intact NMR as a regulatory science tool represents a meaningful step in enhancing FDA’s analytical capabilities for complex dosage forms. As nanotechnology-based drug products continue to enter the market, advanced tools like these will likely become essential in supporting both premarket evaluations and ongoing quality assurance.

“Based on data obtained in this study, intact NMR methods for characterization of nanoemulsion can now be recommended to generic drug sponsors,” FDA said in the blog post (1). “These sensitive and accurate analytical methods may save resources for [the] pharmaceutical industry, accelerate generic drug development, and enhance the quality assessment of these drugs, ultimately resulting in lower costs to [the] American public.”

Modern Intact NMR Approach Reveals Synchronized Microstructural Changes in Nanoemulsion Drug Formulations.

, last updated Aug. 4, 2025 (accessed Aug. 5, 2025).
2. Schallom, J, et al. 

In-Line UV Spectrometry Monitoring in Cleaning Validation.

The FDA has developed a nuclear magnetic resonance (NMR) spectroscopy method to non-invasively characterize microstructure properties in oil-in-water nanoemulsion ophthalmic formulations. This advancement, particularly for difluprednate, an orphan drug for post-operative ocular pain, marks the first observation of correlated microstructure changes in such formulations. The method offers potential for robust excipient selection, formulation optimization, and stability prediction. It aligns with FDA's goals for complex generics development, supporting bioequivalence determinations and quality assessments, and is recommended for generic drug sponsors to enhance quality and reduce costs.

A new nuclear magnetic resonance method reveals real-time, coordinated changes in nanoemulsion drugs, improving noninvasive analysis and regulatory evaluation.

FDA Adopts Intact NMR to Advance Nanoemulsion Drug Quality Assessment

Eli Lilly and Company (Lilly) announced on July 30, 2025 results from a long-term extension (LTE) of a Phase III study (TRAILBLAZER-ALZ 2), which showed that participants treated with donanemab-azbt (brand name Kisunla) demonstrated slowing of decline (1)—a benefit that continued to grow over a span of three years, compared to an untreated external cohort from the Alzheimer's Disease Neuroimaging Initiative (ADNI) (2). Under the brand name Kisunla, donanemab-azbt was 

 for treating Alzheimer’s disease (AD) (3).

Participants in the Phase III study who began treatment at a later time still saw benefit; however, study participants who started treatment earlier significantly reduced the risk of progression to the next stage of AD compared to those who received treatment later (2). Data from the study were presented at the 2025 Alzheimer's Association International Conference (AAIC) in Toronto, Canada, which occurred on July 27–30.

"The TRAILBLAZER-ALZ 2 long-term extension reaffirms that Kisunla delivered sustained clinical benefit that continued to increase over three years and a consistent safety profile," said Mark Mintun, MD, group vice-president, Neuroscience Research & Development, Eli Lilly and Company, in a company press release (1). "Participants continued to show meaningful outcomes, reinforcing the long-term value of early intervention."

This Phase III LTE study (TRAILBLAZER-ALZ 2 LTE) was a double-blind extension of the original Phase III clinical trial (TRAILBLAZER-ALZ 2) designed to evaluate the efficacy and safety of donanemab-azbt in individuals with early symptomatic AD (2). Participants originally treated with donanemab-azbt were either continued on the same treatment or were switched to placebo, while those initially on placebo began treatment with donanemab-azbt in a blinded manner. To assess outcomes against a matched, untreated population, an external comparator group from ADNI was used.

The key preliminary results from the LTE study include:

The demonstration that the donanemab-azbt benefit continued to grow over the course of three years in study participants treated with the therapy compared to those in the matched ADNI group. The data show that donanemab-azbt reduced cognitive decline by -0.6 at 18 months and -1.2 at 36 months based on the Clinical Dementia Rating Sum of Boxes (CDR-SB). These data came from patients initially treated with the therapy in the core study compared to the ADNI group.

An earlier start of treatment with donanemab-azbt reduced the risk of disease progression to the next stage by 27% on the Clinical Dementia Rating-Global Score (CDR-G) compared to the group who had delayed initiation of treatment.

More than 75% of participants treated with donanemab-azbt achieved amyloid clearance within 76 weeks from the start of treatment.

Observed data gathered after up to 2.5 years in participants who had completed treatment showed that the reaccumulation of amyloid plaque remained slow at a rate of approximately 2.4 CL/year, which was consistent with prior observations and modeling.

No new safety signals were observed in the study over the three-year period, which supports the established safety profile for donanemab-azbt.

Side effects include amyloid-related imaging abnormalities (ARIA) with edema/effusion (ARIA-E) and with hemorrhage/with hemosiderin deposition. These are side effects within the class of amyloid targeting therapies that do not usually cause any symptoms; however, serious and life-threatening symptoms can occur. ARIA can be fatal, according to Lilly in the release.

Lilly’s Kisunla (donanemab-azbt) Showed Growing Benefit Over Three Years in Early Symptomatic Alzheimer’s Disease

. Press Release. July 30, 2025.
2. National Library of Medicine. 

A Study of Donanemab (LY3002813) in Participants with Early Alzheimer's Disease (TRAILBLAZER-ALZ 2)

, May 4, 2025 (accessed Aug. 5, 2025).
3. FDA. 

Eli Lilly's long-term extension of the Phase III TRAILBLAZER-ALZ 2 study demonstrated that donanemab-azbt (Kisunla) significantly slowed cognitive decline in Alzheimer's patients over three years. Early treatment initiation notably reduced disease progression risk compared to delayed treatment. The study, presented at the 2025 Alzheimer's Association International Conference, confirmed sustained clinical benefits and a consistent safety profile. More than 75% of participants achieved amyloid clearance within 76 weeks, with slow amyloid plaque reaccumulation. No new safety concerns were identified, although amyloid-related imaging abnormalities remain a potential risk.

Findings from a Phase III study highlight the demonstrated action of donanemab-azbt (brand name Kisunla) in slowing the decline of patients exhibiting early symptomatic Alzheimer’s disease. 

Lilly’s Kisunla Demonstrates Growing Benefit in Treating Early Alzheimer’s Disease

Chemical molecular formula hormone serotonin. Silhouette of a man head. Connected lines with dots background. | Image Credit: © JEGAS RA - stock.adobe.com

 has received final approval from FDA for an abbreviated new drug application (ANDA) for sertraline hydrochloride capsules, in 150mg and 200mg doses, as selective serotonin reuptake inhibitors (SSRIs) for the treatment of major depressive disorder (MDD) in adults and obsessive-compulsive disorder (OCD) in both adults and pediatric patients aged six and older (1).

FDA’s approval is the first in the United States for a generic form of the reference sertraline hydrochloride drug marketed by Almatica Pharma (1). US sales of the reference product in the 12 months ending in June 2025 totaled $35.5 million, according to IQVIA.

Zenara’s version has also been granted competitive generic therapy designation, under the terms of which Zenara’s ANDA has 180 days of marketing exclusivity in the US, commencing with the product’s launch.

"Receiving the first generic approval for sertraline hydrochloride capsules highlights Zenara's strong R&D capabilities and operational excellence,” Srinivas Arutla, PhD, CEO of Zenara, said in a press release (1). “We remain committed to our mission of delivering to patients early access to high-quality, affordable pharmaceuticals."

Finding suitable treatments for MDD has been a goal for drug developers in recent years. In 2023, Evecxia Therapeutics and Quotient Sciences 

 of a Phase I clinical testing program for Evecxia’s EVX-101, an adjunctive treatment for MDD for patients who experienced an inadequate response to first-line antidepressants such as SSRIs (2).

Below are some broader impacts to the pharmaceutical industry based on the news from Zenara.

FDA’s cell and gene therapy (CGT) pathway aims to incentivize applicants to pursue competitive generics in markets with insufficient generic competition. Companies achieving first‑approval status can secure a six‑month exclusivity window in the US. For R&D teams, this underlines the value of strategic application timing and patent‑challenge readiness, especially for legacy molecules with high sales but limited generic entrants.

Scientific teams should note the therapeutic significance of sertraline as a widely prescribed SSRI. Generics in this space must replicate key pharmaceutical properties—dissolution profile, impurity thresholds, and bioequivalence performance—to qualify for FDA approval.

Zenara’s successful development and scale‑up suggest strong end‑to‑end capabilities in formulation and manufacturing. Vertical integration appears central to their competitive positioning, enabling efficient API sourcing, scale‑up validation, and good manufacturing practice compliance to support timely ANDA filing and commercial launch. For drug manufacturing organizations, this vertical integration moves beyond a simple reference drug copy strategy toward more strategic, agile platforms that prioritize rapid ANDA execution and commercial readiness to capture CGT incentives.

Strategic considerations for stakeholders

 Companies working in drug discovery should monitor FDA CGT designations and Orange Book listings to identify potential high‑value targets for generic development when exclusivities expire.

 Intellectual property teams must assess active patents and exclusivities early to establish first‑to‑file status and preserve eligibility for CGT exclusivity.

 Launch timing is critical. To avoid forfeiture of CGT exclusivity, first approved applicants must commercially market within 75 days of approval. Coordination between regulatory, manufacturing, and commercial functions is therefore imperative.

The approval won by Zenara illustrates how generic developers can harness regulatory incentives to bring affordable versions of widely used molecules to market. For drug discovery and development professionals, it exemplifies an emerging business model: targeting established, high‑volume drugs through accelerated pathways, leveraging robust formulation science and tight regulatory execution, rather than pursuing novel chemical entities exclusively.

Zenara Pharma Receives US FDA Approval for First Generic of Sertraline Hydrochloride Capsules with 180-Day CGT Exclusivity.

 Press Release. Aug. 1, 2025.
2. Quotient Sciences. 

Evecxia Therapeutics Reports Favorable Data from a Phase I SAD/MAD Trial.

Zenara Pharma, a subsidiary of Biophore, has received FDA approval for the first generic version of sertraline hydrochloride capsules, used to treat major depressive disorder and obsessive-compulsive disorder. This approval grants Zenara 180 days of marketing exclusivity in the US. The development underscores Zenara's R&D capabilities and highlights the strategic importance of FDA's competitive generic therapy pathway. The approval exemplifies a business model focusing on established drugs through accelerated pathways, emphasizing formulation science and regulatory execution over novel chemical entities.

The company’s FDA-approved first generic sertraline capsules secured a 180‑day exclusivity period, highlighting strategic generic development pathways.

Zenara Secures First Generic Sertraline Approval from FDA, Plus Six Months of Market Exclusivity

The Evolving Field of Radiopharmaceuticals

Radiopharmaceuticals have been traditionally used to treat superficial tumors, according to Mike Ritchie, CCO at 

. As they have evolved, they have been used to treat internal tumors, and now the technology is transforming to be directed specifically so that they only impact the tumor and not other cells in the body.

“There's so much [that goes] into pharmaceutical development into making something that can be manufactured at scale. It can sit on a shelf for a while. We can administer it to a patient, and it behaves in the way that we want,” says Ritchie. “We're just learning how to apply what we learn from anybody drug conjugatesinto radio drug conjugates, so the chemistry of how to link this radio ligand to an antibody, something that will continue to evolve, and there's a real opportunity there to improve that, to improve the therapeutic activity.From the biology perspective, again, we're in our infancy and understanding what are the tumor types, or the molecular cohorts within a tumor that are more sensitive to radio ligands. Like any chemotherapy or any therapy, certain tumors will respond. Others will not. They'll develop resistance. And so really understanding the right cohorts of patients to treat is something that we're still learning, and I think we'll continue to learn as the clinical development of these programs evolves.”

Click the video above to watch the interview.

Radiopharmaceuticals are moving from their standard use of treating superficial tumors into radio drug conjugates that target tumors without impacting other cells in the body.

Futuristic health tech. A smartwatch projects a holographic health dashboard, providing real-time body analytics and vital signs monitoring anytime, anywhere. | Image Credit: © woravut - stock.adobe.com

FDA’s Innovative Science and Technology Approaches for New Drugs (ISTAND) pilot program, launched in November 2020 as a pathway to qualify novel drug development tools (DDTs) not fitting within existing agency qualification parameters, is transitioning to a permanent DDT qualification program, according to an FDA Voices blog post published July 31, 2025 by ShaAvhrée Buckman-Garner, MD, PhD, director of the Office of Translational Services at FDA’s Center for Drug Evaluation and Research (CDER), and Mary Thanh Hai, MD, acting director of CDER’s Office of New Drugs (1,2).

FDA defines DDTs as “methods, materials, or measures” with the potential to facilitate drug development, counting among them tools that may: help to enable remote or decentralized trials (e.g., patient-performed digital photography in dermatology trials), advance understanding of drugs (using tissue chips to assess safety or efficacy, or developing novel, nonclinical pharmacology or toxicology assays), or leverage digital health technologies—such as artificial intelligence (AI)-based algorithms or wearables used for patient assessment (2).

DDTs evaluated to be “qualified” have a proven, specific use, and can be incorporated into any drug development program for a particular purpose (1). FDA maintains a 

 of DDT qualification projects under the umbrella of both CDER and the Center for Biologics Evaluation and Research.

ISTAND is being transitioned to a permanent program based on a total of eight accepted submissions over its nearly five-year pilot phase: three AI-based tools, two animal-free tools to assess preclinical safety, two novel methods involving tissues, and a novel statistical approach (1). Some examples of advanced tools the program has helped facilitate the integration of include organ-on-a-chip models, digital health technologies like fitness trackers, and complex 

As FDA continues to provide feedback on the submissions that have been accepted, the transition of ISTAND to a permanent program has numerous potential effects on drug developers and manufacturers.

For those involved in early-stage drug discovery, ISTAND’s permanency offers a clearer regulatory pathway for leveraging unconventional tools to generate and validate drug candidates. This includes, for example, the use of machine learning algorithms to identify promising compounds or targets, or the application of wearable devices to monitor real-world outcomes in preclinical and early clinical studies.

Drug development teams stand to benefit through more consistent engagement with FDA scientists, potentially reducing regulatory uncertainty associated with novel methodologies. This regulatory support may lead to greater investment in, and adoption of, innovative approaches to trial design, patient stratification, endpoint selection, and safety monitoring.

While ISTAND is not directly focused on manufacturing processes, its emphasis on novel data collection and analysis techniques could influence manufacturing by fostering tools that enhance process monitoring, quality assurance, and continuous manufacturing. For instance, digital sensors that monitor physiochemical parameters during production, or AI models that optimize process controls, could eventually be submitted through ISTAND for qualification, if their intended use supports a regulatory decision related to a new drug application.

A key feature of the ISTAND program is its transparency and collaborative engagement with stakeholders. The qualification process involves public posting of DDT submissions, feedback from FDA reviewers, and potential publication of qualified tools for broader industry use. This not only facilitates innovation within individual sponsors’ programs but also accelerates collective learning across the sector.

The formal establishment of ISTAND reflects FDA’s evolving approach to supporting scientific innovation in drug development. By offering a defined path for the qualification of nontraditional tools, the program is expected to expand the toolkit available to researchers and developers, thereby enabling more efficient and patient-centric drug development.

FDA Advances Drug Development Innovation by Establishing ISTAND as Permanent Qualification Program.

, July 31, 2025 (accessed Aug. 4, 2025).
2. FDA. 

Innovative Science and Technology Approaches for New Drugs (ISTAND) Program.

, last updated July 31, 2025 (accessed Aug. 4, 2025).

The FDA's ISTAND pilot program, initiated in 2020 to qualify novel drug development tools (DDTs), is transitioning to a permanent qualification program. DDTs, defined as methods, materials, or measures, facilitate drug development through tools like AI algorithms and digital health technologies. Over its pilot phase, ISTAND accepted eight submissions, including AI-based tools and novel statistical approaches. The program's permanency offers a clearer regulatory pathway for unconventional tools, enhancing drug discovery, development, and manufacturing. ISTAND emphasizes transparency and collaboration, fostering innovation and expanding the toolkit for researchers and developers.

The program has been transitioned to a permanent pathway that is designed to support innovative tools like artificial intelligence, wearables, and biomarkers in drug development and trials.

How FDA’s ISTAND Initiative Supports Innovative Tools in Drug Discovery and Development

Roche announced on July 28, 2025 that it presented new data from its development portfolio for Alzheimer’s disease (AD) at the 2025 Alzheimer’s Association International Conference (AAIC), held in Toronto, Canada, on July 27–30. The company is conducting research on AD across both its pharmaceutical and diagnostics portfolios (1).

On the pharmaceutical portfolio front, the company’s presentations at the conference included the latest results from an ongoing Phase Ib/IIa Brainshuttle AD study, which continue to support the rapid and robust reduction of amyloid plaques, and the design of Phase III studies (TRONTIER 1 and 2) using trontinemab—an investigational Brainshuttle bispecific 2+1 amyloid-beta targeting monoclonal antibody—for early symptomatic AD. These Phase III studies are planned to start later in 2025. In addition, Roche also plans to conduct an additional Phase III trial that will investigate the use of trontinemab in preclinical AD as part of its growing programs for the disease. This additional trial will focus on individuals at risk of cognitive decline. The goal will be to potentially delay or prevent the progression of AD to the symptomatic stages.

“Alzheimer’s disease represents one of the greatest challenges in healthcare today, and tackling it requires early detection and effective therapeutics,” said 

, chief medical officer and head of Global Product Development, Roche, in a company press release (1). “Trontinemab is designed to target a key driver of Alzheimer’s disease biology more effectively in the brain.Combining new treatment avenues with advanced diagnostics may enable earlier and potentially more effective intervention. With plans for Phase III trials in both early symptomatic and preclinical Alzheimer’s disease, we are advancing science with the goal of delaying—and ultimately preventing—progression of this devastating condition.”

On the diagnostic portfolio front and using both oral and poster presentations at AAIC 2025, Roche highlighted the potential of its Elecsys pTau217 product as a reliable and accessible blood-based biomarker test, which can provide comparable results to positron emission tomography (PET) scans and cerebrospinal fluid diagnostics for rule-in and rule-out diagnosis of amyloid pathology, a hallmark of AD, across care settings. Elecsys pTau217 will be used in the planned additional Phase III studies (TRONTIER).

“Blood based testing for Alzheimer’s disease has the potential to greatly improve patient access and decrease the time to definitive disease diagnosis,” said Matt Sause, CEO of Roche Diagnostics, in the press release. “Our data show that the Elecsys pTau217 test performs comparably to PET scans but can be performed with a simple blood draw and analyzed in a routine clinical laboratory. This has the potential to transform the diagnosis of Alzheimer's and provide clear answers to caregivers, patients, and their families.”

Roche cites that up to 75% of people living with symptoms of AD globally have not been diagnosed. Meanwhile, those who have been diagnosed were said to have waited an average of 2.8 years to get the diagnosis (2). Even fewer have received any form of treatment, according to Roche in the release. The company stated in the release that “[d]iagnostics play a crucial role in addressing the global challenge of Alzheimer’s, not only to detect and identify people with the disease early, even before the first symptoms, but also to rule out those who may or may not benefit from specific treatments” (1).

Roche Presents New Insights in Alzheimer’s Disease Research Across Its Diagnostics and Pharmaceutical Portfolios at AAIC.

 Press Release. July 27, 2025.
2. Johns Hopkins Bloomberg School of Public Health. Life Expectancy Following Diagnosis of Alzheimer’s Disease Depends on Age at Diagnosis. 

https://publichealth.jhu.edu/2002/alzheimer-age

Roche has unveiled new data on Alzheimer's disease (AD) research at the 2025 Alzheimer's Association International Conference. The company is advancing its pharmaceutical and diagnostic portfolios, focusing on trontinemab, a bispecific monoclonal antibody targeting amyloid-beta, with Phase III trials planned for early symptomatic and preclinical AD. Roche's Elecsys pTau217 test, a blood-based biomarker, shows promise as a reliable alternative to PET scans for diagnosing amyloid pathology. The company emphasizes the importance of early detection and effective therapeutics in addressing the global AD challenge.

The company presented new data from its Alzheimer’s disease research efforts across its diagnostics and pharmaceutical portfolios at this year’s AAIC.

Roche Reveals New Data from Alzheimer’s Disease Research at AAIC 2025

United States President Donald Trump has contacted 17 pharmaceutical companies, providing them with the step-by-step process he says they must take to lower prescription drug prices in the US to the lowest price offered among other developed nations (1). This strategy, known as the most-favored-nation (MFN) price, was first detailed by the White House 

Conversations began after executive order

The companies receiving letters on July 31 were 

According to the White House, following the issuing of the May 12 executive order, the Trump administration began discussions with pharmaceutical manufacturers about ways to achieve MFN pricing in the US. The issuing of the letters is an indication that the administration feels that proposals from the industry have fallen short (1).

A fact sheet summarizing the content of the letters said that the federal government will “deploy every tool in our arsenal to protect American families from continued abusive drug pricing practices” if these companies fail to act (1). The letters set 

The White House lists four main steps it is requesting the 17 companies to take:

MFN prices must be offered to every Medicaid patient.

Manufacturers must specify that they will not offer better prices for new drugs to other developed nations than those offered in the US.

Efforts should be made to eliminate middlemen and sell medicines directly to patients, provided at prices no higher than the best price available in developed nations.

Raising of international prices should be supported by trade policy, with increased revenues from abroad directly reinvested into lowering prices for Americans.

This apparently imminent shift in US drug pricing policy has wide-ranging potential impacts across the pharmaceutical industry. Here are a few to watch for as this story develops.

The action may introduce substantial uncertainty into historical pricing models previously used to justify high initial launch prices in the US market. Specifically, drug developers pursuing novel therapies with high R&D costs could face additional hurdles in projecting return on investment. Companies may begin to rethink early-stage decisions, including therapeutic areas of focus, prioritization of pipelines, and clinical trial design, especially when working on therapies expected to launch first in the US.

Moreover, the directive to directly reinvest international revenue gains—if global prices increase—into US price reductions could discourage investment in markets with tighter pricing controls, thereby reshaping global clinical trial strategies and potentially delaying drug availability abroad. These tradeoffs could incentivize firms to prioritize assets with clearer pathways to MFN-compliant pricing structures.

Manufacturing and market access challenges

Adapting to MFN pricing may necessitate pharmaceutical companies making fundamental changes to their global pricing and market access strategies. Numerous multinational companies engage in tiered pricing, meaning country-specific prices are negotiated based on local healthcare infrastructure and purchasing power. The proposed MFN policy could undermine this model by disincentivizing offering lower prices abroad unless US prices are also reduced accordingly.

Manufacturing decisions, specially around scale and site selection, may be affected as well, as companies adjust to anticipated changes in demand—particularly if pricing pressures cause shifts in product access or payer coverage. Manufacturers may need to invest in enhanced cost-control measures and supply chain optimization to preserve margins under more uniform, globally benchmarked pricing.

Eliminating middlemen, such as pharmacy benefit managers, and enabling direct-to-patient sales could disrupt traditional distribution models. For established firms, compliance may require restructuring commercial operations, including patient support programs, channel strategies, and pricing transparency initiatives. Companies may need to invest further in digital infrastructure or third-party partnerships.

For smaller or emerging companies, these demands could increase the financial and logistical barriers to market entry, intensifying the need for strategic alliances with larger firms that possess the operational capacity to meet evolving federal expectations.

The 60-day window issued by the administration presents a relatively short timeframe for manufacturers to respond meaningfully. Firms will likely need to evaluate their current and upcoming pricing agreements globally, analyze the revenue impact of MFN pricing, and consider potential litigation or policy engagement strategies. While the administration has not outlined explicit enforcement mechanisms, the language in the fact sheet suggests the possibility of regulatory or trade-related consequences should manufacturers not comply voluntarily.

Still, this stands to be a potentially transformative moment for pharmaceutical pricing policy in the US. Stakeholders in discovery, development, and manufacturing will need to closely monitor policy developments and prepare for scenarios that may affect global revenue planning, R&D prioritization, and commercial model evolution.

Fact Sheet: President Donald J. Trump Announces Actions to Get Americans the Best Prices in the World for Prescription Drugs.

Fact Sheet: President Donald J. Trump Announces Actions to Put American Patients First by Lowering Drug Prices and Stopping Foreign Free-Riding on American Pharmaceutical Innovation.

 WhiteHouse.gov, May 12, 2025.
3. Hollan, M. 

President Trump Issues Letters to 17 Major Pharma Companies Demanding Action on Most-Favored-Nation Order.

President Trump has directed 17 pharmaceutical companies to adopt the most-favored-nation (MFN) pricing strategy, ensuring US drug prices match the lowest among developed nations. The administration's letters, following a May 2025 executive order, demand action within 60 days, threatening regulatory measures if unmet. The MFN policy could disrupt traditional pricing models, affecting drug discovery, manufacturing, and market access strategies. Companies may face challenges in maintaining margins and adapting distribution models, with potential impacts on global clinical trial strategies and investment in markets with strict pricing controls.

If action is not taken within 60 days, the White House said it would “deploy every tool in our arsenal” to improve drug pricing practices for American patients.

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