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

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

ICE Pharma, a producer of bile acid-derived APIs, excipients, and finished dosage forms, announced on Oct. 15, 2025, that it will showcase its innovations and sustainability strategies at Booth 9.1 A94 at 

, which is being held from Oct. 28–30. Highlights include the company’s ursodeoxycholic acid (UDCA) production and bile acid derivatives (1).

ICE’s products assist in the therapeutical applications for liver, metabolic, and neurological diseases and are developed in the company’s five R&D centers. The company also has a quality framework for ensuring traceability, viral inactivation, closed manufacturing systems, and regulatory compliance.

How is ICE Pharma meeting sustainability goals?

ICE Pharma will be presenting its four-pillar strategy for sustainability: Fighting Illness through Product Innovation, Caring for People, Accelerating Sustainable Operations, and Building Strong Relationships. The company is using this strategy to make decisions across resource management, waste reduction, energy sourcing, and stakeholder engagement. Following its reduce, reuse, recycle philosophy, ICE will be presenting an eco-designed booth at CPHI Frankfurt that has been built from recyclable materials from past events, minimizing environmental impact.

“At ICE Pharma, quality and environmental responsibility are inseparable,” said Agostino Barazza, Chief Executive Officer. “By mastering bile acids with rigorous controls and sustainable design, we are delivering medicines with impact and integrity.”

“Our sustainability roadmap strengthens operations and inspires confidence across our supply chain, empowering partners to deliver therapies benefiting from bile acid science,” added Roger Viney, Chief Commercial Officer.

What else is ICE Pharma showcasing at the event?

ICE will be celebrating the centennial of ABC Farmaceutici at CPHI Frankfurt, which was founded in 1925 in Turin and acquired by ICE in 2021 (2). ABC Farmaceutici will highlight its achievements and its research concentrations at the event. A special “100 Years” logo will also be unveiled at the conference.

“Reaching 100 years is not only a celebration of our past, but also a promise to the future,” said Severino Previtali, ABC Farmaceutici Business Unit director, in the press release (3). “This milestone reminds us of the generations of people who have contributed to our success, and it inspires us to continue driving innovation, building strong collaborations, and making a meaningful impact on global health.”

What is ICE Pharma’s approach to quality?

spoke with Roger Viney, chief commercial officer of ICE Pharma, aboutquality and compliance issues surrounding the use of animal-derived ingredients in the bio/pharma industry (4). In the interview, Viney talked about how regulatory harmonization is critical and increases the security of the supply chain. He also talked about the importance of traceability and knowing the origin of animal-derived material. 

ICE Pharma. ICE Pharma Highlights Sustainability and Bile Acid Expertise at CPhI Worldwide 2025. Press Release. Oct. 15, 2025.

Lavery, P. ABC Farmaceutici to Mark 100th Anniversary with CPHI Frankfurt Display. PharmTech.com. Sept. 18, 2025. 

https://www.pharmtech.com/view/abc-farmaceutici-mark-100th-anniversary-cphi-frankfurt-display

ICE Pharma. ABC Farmaceutici Celebrates 100 Years of Pharmaceutical Excellence and Innovation. Press Release. Sept. 17, 2025.

Thomas, F. DCAT Week 2025: Quality and Compliance for Animal-derived Products. PharmTech.com. March 18, 2025.

Articles

ICE Pharma, a producer of bile acid-derived APIs and excipients, will showcase its innovations and sustainability strategies at CPHI Frankfurt 2025. The company emphasizes its ursodeoxycholic acid production and bile acid derivatives for liver, metabolic, and neurological diseases. ICE Pharma's sustainability strategy includes product innovation, sustainable operations, and stakeholder engagement. The company will also celebrate the centennial of ABC Farmaceutici, acquired in 2021. ICE Pharma prioritizes quality and compliance, focusing on traceability and regulatory harmonization for animal-derived ingredients in the bio/pharma industry.

The company will also highlight its sustainability strategies and quality solutions at the event. 

ICE Pharma to Showcase Bile Acid Expertise at CPHI Frankfurt 2025

Cheryl Barton is director of PharmaVision, 

Landkarte *** Europa | Image credit: ©beugdesign - Stock.adobe.com

On 2 July 2025, the European Commission (EC) announced a “bold and ambitious” new life science strategy to position the European Union (EU) as the world’s most attractive place for life sciences by 2030 (1). This strategy aims to positively impact public health, create jobs, and provide access to innovative, environmentally friendly technologies, thereby enhancing the EU's strategic resilience. Previously, President Ursula von der Leyen emphasized that the strategy for European life sciences was a priority in the political guidelines for 2024–2029, stating that, “we need to put research and innovation at the heart of our economy” (2). In January 2025, the EC also published the Competitiveness Compass, focusing on how to improve research and innovation (R&I) to boost competitiveness and promote innovation in biotechnology (3).

The EC has identified several strengths, including the presence of biotech clusters and leading academic institutions that operate with freedom and encourage diversity and inclusion. Additionally, the EU ranks second behind the United States (US) in terms of global high-value patents, holding 18% share of patents compared to 39% in the US (1). The life science industry continues to invest heavily in R&I, with 15% of the world’s top firms residing in the EU (1). However, the EC also recognizes that to improve R&I it must overcome numerous barriers, such as turning scientific breakthroughs into real-world applications, improving scalability in the EU, creating a more cohesive R&D ecosystem, utilizing healthcare data and artificial intelligence (AI) more effectively, and streamlining the regulatory process to reduce complexity and duplication (1).

How will this strategy unlock Europe’s life science potential?

To overcome these issues and achieve the life science strategy goals, the EC has outlined three interconnected phases that will impact the entire life science value chain:

optimising the R&I ecosystem to achieve a globally competitive life science sector

ensuring smooth and rapid market access for life science innovations

boosting the uptake and use of life science innovation.

The EC recognizes the need to optimize the R&I ecosystem and develop a globally competitive life science sector. This can be achieved through enhanced cooperation, more efficient resource use, and a comprehensive approach that leverages data and AI, develops adequate skills, and promotes a sustainable industry. The EC will provide new incentives for long-term multi-country clinical trials and rare disease research, strengthen EU bioclusters, and establish a network of European Centres of Excellence in advanced therapy medicinal products (ATMPs) (4). The EC also aims to establish a European Life Sciences R&I Data Assembly to improve cross-regulatory collaboration and enhance the interpretation of data regulations (5).

To ensure life science innovations reach the market smoothly and quickly, the European Medicines Agency (EMA) will need to establish more innovation-friendly regulations, and the EU will need to increase investments from both private and public sectors. A number of legislative changes and regulatory reforms are underway to simplify and modernize the approval processes, such as the Biotech Act and the EU Pharma Package, and these should help make the EU’s regulatory environment more conducive to biotech innovation (5–6). For instance, the Biotech Act, announced in July 2024, seeks to tackle barriers through legislative and policy changes across five key areas: regulation, financing, scale, skills, and data (7).

The creation of new knowledge is an essential basis for a vibrant life sciences ecosystem and for the development of technologies and innovations. The EC will invest more than €10 billion (US$11.9 billion) in various programs, such as Digital Europe, EU4Health, and Horizon Europe, to help build this knowledge base (8–10). Meanwhile, Member States and stakeholders must strengthen their connection with citizens to help reduce misinformation and build trust. They also need to collaborate more closely with end-users to ensure solutions meet their specific needs. Overall, this should help accelerate the adoption and use of life science innovations (1).

What is the future outlook for EU life sciences?

Although the EU is currently in a strong R&I position, the biotechnology sector remains highly competitive. In recent years, China has increased biotech investments following regulatory reforms, improvements in domestic manufacturing, and the implementation of the Healthy China 2030 initiative (11). Additionally, the implementation of US–EU framework on an agreement for reciprocal, fair, and balanced trade has resulted in a 15% tariff on pharmaceutical raw ingredients, APIs, and completed drug products imported into the US. This has raised expenses for branded pharmaceuticals developed by multinational corporations and created market uncertainty. Private investors are concerned that potential investments may slow due to pricing pressures, and biotech companies may hesitate to invest in new projects to expand operations, given the risks associated with tariffs (12–13).

Now more than ever, the EU needs to boost its investment in the life sciences sector and tackle longstanding issues that have hindered the region’s competitiveness and limited European patients' access to the latest treatments. Plans to introduce the Biotech Act in 2025, along with enhanced support for small and medium-sized enterprises and improvements to the regulatory framework, are positive developments. The European Federation of Pharmaceutical Industries and Association (EFPIA) welcomed the news; although, Nathalie Moll, Director General of EFPIA, warned that “for Europe to truly lead, it needs to invest in medicines, attract investment, accelerate turning that investment into new treatments and economic growth, and ensure that patients across the EU have access to them at the same pace as other regions” (14).

EC. A Competitiveness Compass for the EU 

Five Facts to Know: EU Life Sciences Strategy

. https://www.edelmanglobaladvisory.com. 2 July 2025. https://www.edelmanglobaladvisory.com/insights/five-facts-know-eu-life-sciences-strategy

 May 2025. https://www.europarl.europa.eu/RegData/etudes/BRIE/2025/772866/EPRS_BRI(2025)772866_EN.pdf

The New EU “Pharma Package”: Preparing for the Trilogue

. Crowell.com. 30 June 2025. https://www.crowell.com/en/insights/client-alerts/the-new-eu-pharma-package-preparing-for-the-trilogues

European Commission Sets Out New EU Life Sciences Strategy

. 1 Aug. 2025. https://www.osborneclarke.com/insights/european-commission-sets-out-new-eu-life-sciences-strategy

EU4Health Programme 2021-2027–A Vision for a Healthier European Union

. EC.europa.eu. (accessed 30 Sept. 2025). https://health.ec.europa.eu/funding/eu4health-programme-2021-2027-vision-healthier-european-union_en

(accessed 30 Sept. 2025). https://research-and-innovation.ec.europa.eu/funding/funding-opportunities/funding-programmes-and-open-calls/horizon-europe_en

Healthy China 2030: A Vision for Health Care

. https://www.ispor.org/docs/default-source/publications/newsletter/commentary_health-care_china_2030.pdf

Assessing the Impact of Tariffs on the Pharmaceutical Industry

. https://www.pharmafocuseurope.com/articles/impact-of-tariffs-on-pharmaceutical-industry.

The Impact of Tariffs on the Life Sciences Industry - Healthcare & Life Sciences Blog

31 Mar. 2025. https://healthcarelifesciences.bakermckenzie.com/2025/03/13/the-impact-of-tariffs-on-the-life-sciences-industry/

EU Life Science Strategy: A Springboard for European Life Sciences

. Efpia.eu. 2 July 2025. https://www.efpia.eu/news-events/the-efpia-view/statements-press-releases/eu-life-science-strategy-a-springboard-for-european-life-sciences/

Cheryl Barton is the founder and director of PharmaVision, Pharmavision.co.uk.

The European Commission has unveiled a comprehensive life science strategy to establish the EU as a global leader in life sciences by 2030. This initiative aims to enhance public health, create jobs, and foster innovation through environmentally friendly technologies. The strategy focuses on optimizing the research and innovation ecosystem, ensuring rapid market access for innovations, and increasing the adoption of life science advancements. Key measures include regulatory reforms, increased investments, and the establishment of European Centres of Excellence. The strategy also addresses challenges such as scalability, data utilization, and regulatory complexity.

The European Union aims to become the most attractive place for life science by 2030.

European Union Life Science Strategy

Patrick Lavery is an Editor for the MJH Life Sciences brands 

. Previously at MJH, he filled the same role for 

Life sciences CEOs are boosting their AI spending.

KPMG CEO Outlook Recap

 CEO Outlook Survey, fielded in September 2025 and released on Oct. 14, 2025, captures the strategic views of more than 100 life sciences CEOs concerning artificial intelligence (AI) investment, workforce needs, and operational stability (1). The survey findings confirm that despite economic uncertainty, AI is a decisive and growing investment priority. A high degree of confidence exists, with 76% of leaders certain their organization is moving at the right pace to handle the speed of AI development and its effects.

“Despite a climate of uncertainty, life science leaders are decisively investing in AI to drive innovation and product development,” said 

, KPMG United States Life Science Leader, in a statement provided along with the release of the report (2). “Success requires a dual focus: upskilling the workforce and ethical AI adoption while rethinking supply chain resilience to deliver breakthrough therapies with confidence worldwide.”

Following are some key findings reflecting the opinions and experiences of a high percentage of the CEOs surveyed.

AI is a top investment priority for 75% of life sciences CEOs, up sharply from 60% in 2024. Financially, 73% anticipate spending 10–20% of their budget on AI in the next 12 months.

A majority of leaders (65%) anticipate seeing a return on their AI implementation investment within one to three years.

Investment is highly concentrated in operational areas: 80% are investing in agentic AI, and 79% are investing in AI in products and services and for intelligent manufacturing.

AI workforce readiness or upskilling is cited by 85% of CEOs as a trend impacting organizational prosperity during the next three years.

More than three-quarters (77%) of organizations are modifying their long-term workforce strategy (2–5 years) to focus on retaining and re-training high potential talent.

Ethical challenges are cited by 66% of organizations as a barrier to AI implementation, an increase from 58% in 2024.

Regulatory demands are cited by 74% of CEOs as a trend that will impact prosperity during the next three years.

Six out of 10 CEOs are “extremely concerned” about fraud detection and prevention, and 47% are equally concerned about identity theft and data privacy.

. Provided via email correspondence on Oct. 13, 2025.
2. Statement provided via email correspondence on Oct. 13, 2025.

Videos

Life sciences CEOs are boosting AI spending, focusing on workforce upskilling, and tackling ethical challenges to drive innovation and product development.

KPMG CEO Outlook: How Pharma Is Navigating AI, Regulatory Demands, and Supply Chain Risk

AstraZeneca sign and logo on British-Swedish multinational pharmaceutical and biopharmaceutical company campus - South San Francisco, California, USA - 2020 | Image Credit: © MichaelVi - stock.adobe.com

Nearly 100 abstracts at the European Society for Medical Oncology 

 to be held Oct. 17–21 in Berlin, will feature 

 medications—both approved and potential—or pipeline molecules, but, prior to the conference, the company is spotlighting four major pivotal trials in particular, new data from which are intended to demonstrate AstraZeneca’s advancements in the field of cancer care (1).

What have the trials found? Which cancers are being addressed?

Two arms of a Phase III trial of trastuzumab deruxtecan, marketed as Enhertu, either followed by paclitaxel, trastuzumab, and pertuzumab in the neoadjuvant setting or as post-neoadjuvant therapy (DESTINY-Breast11 and DESTINY-Breast05, respectively), headline the findings that will be presented (1). These studies involved patients with high-risk, human epidermal growth factor receptor 2-positive early-stage breast cancer.

A Phase III trial of datopotamab deruxtecan (brand name Datroway) was performed as a first-line treatment in patients with locally recurrent inoperable or metastatic triple-negative breast cancer for whom immunotherapy was not an option (1). Another Phase III trial, of durvalumab (Imfinzi), combined that drug with standard-of-care bacillus Calmette-Guérin induction and maintenance therapy in patients with high-risk, non-muscle-invasive bladder cancer.

The specific findings from these trial data were not disclosed by AstraZeneca in the press release. Final overall survival results from a Phase III trial of perioperative durvalumab plus fluorouracil, leucovorin, oxaliplatin, and docetaxel chemotherapy in patients with resectable, early-stage and locally advanced gastric and gastroesophageal junction cancers will also be shared at the ESMO conference (1).

Among the abovementioned medications, AstraZeneca is collaborating with 

 to develop and commercialize its trastuzumab deruxtecan and datopotamab deruxtecan offerings, and also has partnerships in progress with 

 (known as MSD outside the United States and Canada) and 

What other AstraZeneca news has happened lately?

became the second major pharmaceutical company,

 after Pfizer, to reach an agreement with the White House to offer prescription drugs to patients in the United States at the lowest price among developed countries, a strategy known as most-favored-nation pricing (2). Fifteen other companies also received letters from US President Donald Trump on July 31, 2025, outlining the steps recommended to achieve this goal; no other deals have yet been announced.

One day prior, on Oct. 9, 2025, AstraZeneca 

 a total $4.5 billion in a new US manufacturing facility, near Charlottesville, Va., with the announced monetary amount representing a proposed increase of $500 million to be dedicated to enhanced manufacturing capability supporting a broader range of medicines, including cancer treatments (3). The tranche of money is part of a $50 billion overall investment in US manufacturing and R&D announced by AstraZeneca in July 2025.

Pharmaceutical companies, AstraZeneca included, have been re-examining their manufacturing operations in 2025 due to the changing tariff policies of the Trump administration, which as of October 2025 is imposing a 100% tariff on all imported branded or patented pharmaceutical products (4).

AstraZeneca Furthers Ambition to Redefine Cancer Care with First Data from Four Major Pivotal Trials at ESMO.

 Press Release. Oct. 13, 2025.
2. Lavery, P. 

AstraZeneca is Next to Reach MFN Deal with White House.

, last updated Oct. 13, 2025.
3. Lavery, P. 

AstraZeneca’s US Expansion Highlights AI, Automation, and Policy Pressure in Pharma Manufacturing.

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

AstraZeneca is set to present nearly 100 abstracts at the ESMO Congress 2025, focusing on four pivotal trials showcasing advancements in cancer care. These trials include studies on trastuzumab deruxtecan for HER2-positive early-stage breast cancer, datopotamab deruxtecan for triple-negative breast cancer, and durvalumab for bladder and gastric cancers. AstraZeneca is collaborating with Daiichi Sankyo, Merck & Co., and HUTCHMED. Additionally, AstraZeneca has agreed to most-favored-nation pricing with the White House and plans a $4.5 billion investment in a new US manufacturing facility.

Data from four major pivotal trials will be shared, but AstraZeneca medications and pipeline molecules appear in more than 90 abstracts for the upcoming conference in Berlin.

AstraZeneca’s Cancer Care Contributions to be Highlighted with Trial Data at ESMO Congress

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

The pharmaceutical industry is in a period of rapid transformation, driven by scientific innovation, regulatory expectations, and the increasing complexity of therapies. This issue highlights the most pressing trends shaping the sector and the strategies that organizations are adopting to stay competitive.

In our cover story, Susan Haigney explores innovative approaches to bioanalysis, in which automation and novel methodologies are expanding capabilities for faster and more reliable results. As the complexity of drug modalities increases, bioanalytical innovation is no longer optional; it is essential for ensuring product safety, regulatory compliance, and development speed.

Equally critical is formulation development. Cynthia Challener examines how artificial intelligence (AI) and machine learning are being applied to predictive modeling for small molecules, where drug candidates present formidable challenges in molecular complexity and delivery.

Advances in digitalization and automation of aseptic processing are helping organizations address the growing diversity of injectable drug products. Streamlined, technology-enabled approaches are reducing human intervention, improving sterility assurance, and enhancing scalability.

This issue also delves into mechanistic modeling of renal clearance, with Akanksha Prasad providing insights into optimizing dosing strategies for elderly patients. As patient populations age, this type of research is vital to balancing efficacy with safety in clinical care.

Data integration and digital transformation remain central to the industry’s progress. Jennifer Markarian highlights how better use of process data, enhanced by AI and advanced analytics, is enabling smarter process control and more connected manufacturing systems.

Patrick Lavery examines FDA’s push for greater quality, integrity, and uniformity, particularly in the context of advanced manufacturing and batch control. Our Ask the Expert section takes a look at the importance of real-world evidence used in pharmacovigilance.

As these articles show, the future of pharma lies in a careful balance: adopting cutting-edge technologies while upholding rigorous standards of quality and safety. The organizations that succeed will be those that embrace innovation while keeping patients at the center of every decision.

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

When referring to this article, please cite it as Hennessy, M. From Discovery to Delivery: Evolving Practices in Pharma. 

The pharmaceutical industry is undergoing rapid transformation due to scientific innovation, regulatory demands, and complex therapies. Key trends include bioanalytical advancements, AI in formulation development, and digitalization in aseptic processing. These innovations are crucial for ensuring safety, compliance, and efficiency. Mechanistic modeling is optimizing dosing for aging populations, while data integration enhances process control. The FDA emphasizes quality and uniformity in advanced manufacturing. Success in the industry hinges on adopting new technologies while maintaining high standards of quality and patient-centered care.

This issue showcases strategies that organizations are adopting to stay competitive as pressing industry trends shape the sector.

From Discovery to Delivery: Evolving Practices in Pharma

Akanksha Prasad, MS, is a chemical and bioprocess engineer with over nine years of experience in chemical, biologics, and pharmaceutical process development. Her expertise spans mRNA, vaccines, and biologics, with a focus on technology transfer, PAT, scale-up, purification, and regulatory compliance. She holds a Master’s in Chemical Engineering with a biopharma specialization from the Illinois Institute of Technology, Chicago, and a Bachelor’s in Chemical Engineering from India.

Many multi-colored pills in a Senior's hands. Painful old age. Caring for the health of the elderly | Image Credit: ©perfectlab - stock.adobe.com

The kidneys serve as the primary excretory organs responsible for eliminating endogenous waste products and xenobiotics, including pharmaceutical agents and their metabolites, through urine formation. Understanding the mechanistic basis of renal drug excretion is crucial for optimizing therapeutic efficacy and minimizing toxicity. This paper provides an in-depth overview of the anatomical structure and functional dynamics of renal filtration, secretion, and reabsorption processes that govern drug clearance. Blood is delivered to the kidneys via the renal artery, and filtration begins at the glomerulus where small molecules pass into the nephron while larger components remain in circulation. The filtrate undergoes further refinement through selective tubular reabsorption and active secretion, culminating in urine formation. The role of the nephron in modulating drug excretion is modeled mathematically using key pharmacokinetic parameters, including the glomerular filtration rate, free drug fraction, intrinsic tubular clearance, and the area under the plasma drug concentration-time curve. This work also presents fundamental equations describing renal clearance pathways and explores factors influencing drug reabsorption and secretion. Together, these insights offer a quantitative framework for predicting renal drug clearance and guiding rational drug design and dosage regimen development.

Blood is composed of plasma, red blood cells, white blood cells, and platelets. The normal 70-kg adult has 5 L of blood (0.07 L/kg), roughly 55% of which is a liquid called plasma, and 45% is cells and platelets. The kidney is the primary organ of discharge of the body’s byproducts, and of medications and medication metabolites. Urine is the main liquid for the discharge of waste materials (coming out from different cell processes), as well as medications and metabolites, from the body.

The kidney is the primary organ for excretion of the body’s byproducts, medications, and medication metabolites (see 

). Urine serves as the final pathway for eliminating metabolic byproducts, drugs, and their metabolites from the body.

Figure 1: Mechanistic model of renal clearance processes for daptomycin. Figures created with AI and courtesy of the author

Blood flows into the kidney through the renal artery. This large blood vessel branches into smaller vessels until the blood reaches the nephrons. In the nephron, blood is filtered by the tiny vessels of the glomeruli and then flows out of the kidney through the renal vein. In a single day, the kidneys filter about 140 L of blood. Most of the water and other substances that filter through the glomeruli are returned to the blood by the tubules. Only 1–2 L become urine (1).

Each nephron is divided into two sections: the renal corpuscle and renal tubule. As blood flows into each nephron, it enters a cluster of tiny blood vessels—the glomerulus. The thin walls of the glomerulus allow smaller molecules, wastes, and fluid—mostly water—to pass into the tubule. Larger molecules, such as proteins and blood cells, stay in the blood vessel.

Reabsorption and secretion adjust the composition and volume of glomerular filtrate as it travels down the nephron to the collecting tubule. When these processes are completed, the concentrated filtrate, now called urine, is moved to the bladder for storage until it is eliminated from the body.

As the global population ages, integrating physiological modeling into early stage drug development and dose planning has become essential for tailoring therapies to vulnerable subpopulations.

Model framework. Renal clearance (2) was modeled as the sum of three components as shown in 

CLfiltration = clearance via glomerular filtration

CLsecretion = clearance via tubular secretion

CLreabsorption = reabsorption (negative contribution to clearance).

A schematic representation of method for glomerular filtration, tubular secretion, and reabsorption is shown in 

Figure 2: Schematic representation of renal clearance model. Figures created with AI and courtesy of the author

 expresses total renal clearance as the net result of filtration, active secretion, and reabsorption. Mechanistic renal clearance is shown in 

Fr = fraction of compound reabsorbed from tubule.

defines the fraction of unbound (free) drug in plasma. Only unbound drug is pharmacologically active and subject to filtration, secretion, or metabolism.

 shows that the clearance due to glomerular filtration is directly proportional to the free fraction and the glomerular filtration rate.

 models active secretion into the renal tubule, where QR′ is renal plasma flow, CLu_int is intrinsic unbound renal clearance, and C is the drug’s plasma concentration.

 shows the influence of urinary pH and drug pKa on passive reabsorption. Non-ionized (lipophilic) species are more readily reabsorbed.

Overall renal clearance (CLr). Equation 7

 allows the calculation of the net renal clearance based on the excretion rate or total excreted amount (Ae) relative to plasma exposure (AUC), with the method shown in 

Daptomycin is a cyclic lipopeptide antibiotic indicated for the treatment of complicated skin and skin-structure infections, Staphylococcus aureus (S. aureus) bacteremia, and right-sided infective endocarditis caused by susceptible Gram-positive organisms, including methicillin-resistant S. aureus (MRSA) (3). It is administered intravenously and is particularly valuable for patients who cannot tolerate or have failed other antibiotic therapies.

However, the following physicochemical properties (4) limit daptomycin’s oral absorption and influence its pharmacokinetics:

Model calibration and validation. Model parameters, including volume of distribution (Vd), glomerular filtration rate (GFR), and tubular secretion capacity, were obtained from published pharmacokinetic studies on daptomycin (5). These values were iteratively adjusted within physiological bounds to achieve close agreement with observed plasma concentration-time profiles.

Simulations were conducted for two populations:

young adults (18–30 years): assumed normal GFR (~125 mL/min/1.73 m²) and intact tubular function

geriatric adults (>70 years): modeled with a 30% decline in GFR and reduced tubular secretion, reflecting known physiological changes with aging.

The model outputs, including renal clearance (CLr) and plasma concentration profiles, were compared against reported clinical pharmacokinetic data to validate predictive accuracy.

Clearance was calculated for two populations:

young adults (18–30 years): normal GFR and secretion

geriatrics (>70 years): 30% reduction in tubular secretion, age-related decline in GFR.

Volume of distribution (Vd) and other parameters were taken from literature values and adjusted to fit experimental data.

The modeled clearance for young adults was CLr = 16.2 mL/min/kg. Predicted clearance aligned well with reported pharmacokinetic data for daptomycin in healthy adult volunteers.

 In this analysis, the young adult group refers to individuals aged 18–30 years. Using the slope of the plasma concentration–time curve together with the estimated volume of distribution (Vd​), the renal clearance (CLr​) was calculated according to 

. This calculation resulted in a CLr​ value of 16.2 mL/min/kg for the young adult population.

depict the mean plasma concentration–time profiles of Daptomycin in young and elderly adults, respectively, modeled using the renal clearance equation (Eq. 1). In this analysis, the geriatric group refers to individuals over 70 years of age. Using the same calculation method described in 

, the CLr for this group was determined to be 9.2 mL/min/kg as shown in 

Figure 3: Daptomycin plasma concentration in young adults (mean profile). Figures created with AI and courtesy of the author

Table I. Modeled and documented renal clearance (CLr ) and percent error for young and elderly populations.

 Initial model over-predicted clearance: CLr = 12.8 mL/min/kg (calculated using 

). After incorporating a 30% reduction in tubular secretion, CLr = 9.2 mL/min/kg. This adjustment brought the model into closer agreement with known clearance values for elderly patients.

Figure 4: Daptomycin plasma concentration in geriatric adults (mean profile). Figures created with AI and courtesy of the author

Table II. Why the Error? (As per Figures 3 and 4). Summary of model error sources for young and elderly populations.

Model performance and clinical implications. The model effectively reproduced published plasma concentration–time data for both young and elderly populations, with a percent error (6) of <10% for young adults and <16% for geriatrics after incorporating age-related declines in tubular function.

These findings underscore the importance of modeling tubular secretion decline in elderly patients, which is often overlooked in simpler renal clearance models.

 For drugs such as daptomycin that are primarily eliminated renally, failure to adjust dosing in geriatric populations may lead to drug accumulation, prolonged exposure, and increased toxicity risk. Model-guided predictions can aid in personalized dosing and safer therapeutic outcomes in age-diverse patient populations.

Renal drug excretion is critical for optimizing therapeutic efficacy and minimizing toxicity. The kidneys filter blood, reabsorb essential substances, and secrete waste, including drugs and metabolites, into urine. This study models renal clearance using pharmacokinetic parameters like glomerular filtration rate and tubular secretion. Daptomycin, a renally excreted antibiotic, was used to validate the model, highlighting age-related clearance variability. The model accurately predicted renal clearance in young and elderly populations, emphasizing the need for dose adjustments in geriatric patients to prevent drug accumulation and toxicity.

This paper provides an in-depth overview of the anatomical structure and functional dynamics of renal filtration, secretion, and reabsorption processes that govern drug clearance.

Mechanistic Modeling of Renal Clearance: Optimizing Dosing Strategies for Elderly Patients

 has agreed to offer drugs at a lower, “most-favored-nation” (MFN) price to patients in the United States through the federal government’s not-yet-live TrumpRx.gov platform, the White House announced on Oct. 10, 2025 (1).

What details have been reported about the AstraZeneca agreement?

AstraZeneca’s reported deal to lower drug prices in the US stands to make prescriptions more affordable for patients with lower incomes, including those on Medicaid (1). The TrumpRx platform will allow any companies that reach an MFN deal with the White House to sell their drugs directly to consumers at deep discounts, but the website is not expected to be made live until 2026.

 was the first pharmaceutical company to announce an MFN agreement with the White House, 

 on Sept. 30, 2025 (2). That was one day after the end of a 60-day timeframe 

 for companies to comply with the step-by-step process, provided by his administration, to lower prescription drug prices in the US to the lowest price offered among other developed nations, or the federal government would “deploy every tool in our arsenal to protect American families from continued abusive drug pricing practices” (3).

Aside from AstraZeneca and Pfizer, the other 15 companies to receive letters outlining those plans were 

What other commitments does AstraZeneca have in the US?

The deal with the White House was the second major piece of news involving AstraZeneca in as many days. On Oct. 9, 2025, the company said it would be 

 in a new US manufacturing facility, near Charlottesville, Va., with that monetary amount representing a proposed increase of $500 million that will be dedicated to enhanced manufacturing capability supporting a broader range of medicines, including cancer treatments (4). The investment is just a portion of AstraZeneca’s $50 billion overall commitment to US manufacturing and R&D that was first announced in July 2025, part of an industry-wide re-examining of manufacturing operations due to the changing tariff policies of the Trump administration.

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

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

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

AstraZeneca has agreed to offer drugs at a reduced "most-favored-nation" price in the US through the TrumpRx.gov platform, which is expected to launch in 2026. This initiative aims to make prescriptions more affordable, particularly for low-income patients, including those on Medicaid. AstraZeneca's CEO is set to meet with President Trump for an official announcement. This agreement follows Pfizer's similar deal and is part of a broader effort to lower drug prices. Additionally, AstraZeneca plans a $4.5 billion investment in a new US manufacturing facility.

US President Donald Trump made the announcement that AstraZeneca is the second of 17 major pharmaceutical companies, after Pfizer, to agree to most-favored-nation pricing protocols.

AstraZeneca Is Next to Reach MFN Deal with White House

We highlight the week’s industry news in an easy-to-consume, fun format.

PharmTech Weekly News Roundup — Week of October 6, 2025

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