Chiesi on Sustainability in Asthma and COPD R&D

Asthma and chronic obstructive pulmonary disease (COPD) remain major global health challenges. Asthma affected an estimated 363 million people in 2023, while COPD is the fourth leading cause of death worldwide. While inhaled therapies are central to disease management, the next era of respiratory innovation is increasingly focused on more than the active drug molecule alone.

For patients with chronic respiratory diseases, the formulation, device, inhalation technique and manufacturing strategy can all influence whether a therapy works as intended. At the same time, healthcare systems and pharma companies are under growing pressure to reduce the environmental footprint of care without compromising clinical outcomes.

Diego Ardigò, MD, PhD
Global Head of R&D
Chiesi Group

This creates a complex challenge for respiratory R&D: how to introduce more sustainable inhaler technologies while preserving the treatment experience for patients who are already stable on therapy.

To explore these questions, Xtalks spoke with Diego Ardigò, MD, PhD, Global Head of R&D at Chiesi Group, about sustainable inhaler innovation, the science of extrafine formulations and the future of asthma and COPD treatment.

Where Drug, Device and Formulation Converge

In respiratory medicine, innovation increasingly extends beyond the active ingredient. The formulation, propellant, device and manufacturing process all need to work together as a single delivery system.

Ardigò said this systems-based approach is central to Chiesi’s R&D strategy.

For pressurized metered-dose inhalers, the propellant is not simply a carrier. It is a critical excipient that can influence chemical stability, aerosol plume behavior and particle size distribution. Reformulating an inhaler with a next-generation, lower-carbon propellant therefore requires re-engineering the entire drug-propellant system.

That includes ensuring that active molecules remain stable in solution or suspension, that aerosol performance is maintained and that the formulation continues to deliver the extrafine particles needed for effective lung deposition.

“Respiratory R&D has shifted to a model where formulation, device and manufacturing are treated as integral components of a single delivery system. Each element affects therapeutic outcome.”

— Dr. Diego Ardigò

Manufacturing is also part of the R&D equation. Next-generation propellants can require specialized production infrastructure, including facilities designed to safely handle new propellant properties at industrial scale.

For Chiesi, this has involved major investment in dedicated manufacturing sites in Europe to support next-generation inhaler production. Ardigò described manufacturing not as a downstream operational issue, but as a core part of respiratory innovation.

The Science Behind Extrafine Inhaled Therapies

One of the central scientific priorities in inhaler development is particle size. Chiesi’s respiratory research has focused on extrafine formulations, which are designed to generate particles with a mass median aerodynamic diameter below 2 microns.

This matters because asthma and COPD are not confined to the large central airways. The small airways, often defined as airways with an internal diameter below 2 millimeters, are a key site of inflammation, remodeling and obstruction.

Larger particles may deposit mainly in the throat or central airways. By contrast, extrafine particles can penetrate more deeply into the bronchial tree and reach peripheral regions of the lung that conventional inhaled therapies may not adequately target.

Ardigò said this has both biological and practical implications.

“Extrafine formulations matter because of where the disease actually lives,” he said. “In asthma and COPD, the small airways are a primary site of inflammation and remodeling.”

Smaller particles may also make inhaled therapies more forgiving in real-world use. Because extrafine particles have lower velocity and remain suspended in the aerosol plume longer, they can be less dependent on perfect hand-breath coordination and inspiratory flow.

That is important in chronic respiratory disease, where inhaler technique remains a persistent challenge. Ardigò noted that real-world data suggest a high proportion of patients make clinically meaningful inhaler technique errors, despite decades of device evolution.

In this context, formulation science can help reduce the gap between how a product performs in a controlled study and how it performs in daily life.

Evidence Needed to Support Inhaler Switching

When an established inhaler is reformulated with a more sustainable propellant, the scientific question is not only whether the new formulation works. It is whether it performs in a way that is clinically equivalent to the existing therapy.

For Chiesi, this begins with in vitro characterization. Advanced in silico mathematical modeling is used to predict aerosol plume behavior and particle deposition before clinical testing begins. Laboratory studies then assess formulation stability and particle size distribution.

The next step is pharmacokinetic evaluation. Ardigò said these studies are used to assess lung availability as a surrogate for efficacy and total systemic exposure as a primary marker of safety.

The goal is to show that the reformulated inhaler falls within the accepted bioequivalence range relative to the reference therapy. For combination inhalers, this must be demonstrated for each active component, adding to the technical complexity.

“The primary clinical requirement is demonstration of therapeutic equivalence,” Ardigò said.

Safety evidence is also needed for the new propellant itself. Dedicated clinical studies are required to evaluate respiratory tolerability, including whether repeated exposure affects bronchial function or mucociliary clearance.

This layered evidence package is designed to give clinicians and patients confidence that a lower-carbon inhaler can preserve the expected standard of care.

Why Familiarity Matters for Stable Patients

For patients who are already stable on inhaled therapy, even small changes to the device or sensory experience can matter. Taste, mouthfeel, actuation force and inhalation behavior may all influence adherence and technique.

“Our strategic philosophy is, ‘We’re changing, so patients don’t have to.’”

— Dr. Diego Ardigò

Ardigò said Chiesi’s approach is guided by the principle that sustainable innovation should not disrupt stable care.

This reflects a broader concern in respiratory medicine: poorly managed switching can create anxiety, alter inhalation technique and potentially lead to loss of disease control.

For a patient with asthma or COPD, that can have clinical consequences, including increased rescue medication use, exacerbations, emergency visits or hospitalization.

Human factor studies therefore play an important role in the evidence package. These studies evaluate whether patients perceive the reformulated inhaler as familiar and usable, including whether sensory characteristics such as taste and mouthfeel remain consistent.

The goal is to ensure that a lower-carbon inhaler is not only equivalent in a controlled setting, but also experienced as seamless by the patient.

Sustainability Without Removing Therapeutic Choice

Sustainable respiratory care is sometimes framed as a choice between pressurized metered-dose inhalers and dry powder inhalers. Ardigò said this is too simplistic.

Dry powder inhalers have an important role because they do not require a propellant. However, they are not appropriate for every patient. Children, older adults and people with more severe COPD may not be able to generate the inspiratory flow needed to use a dry powder inhaler effectively.

For these patients, a pressurized metered-dose inhaler may be a clinical necessity rather than a preference.

“The ‘greenest’ inhaler is the one a patient can and will use effectively.”

— Dr. Diego Ardigò

This is why lower-carbon propellants are important. They could allow pressurized metered-dose inhalers to reach a carbon footprint closer to dry powder inhalers while preserving a treatment option for patients who need it.

Ardigò said the priority should be optimal inhaler selection for the individual patient.

This also has implications beyond the inhaler itself. Poor disease control can lead to higher use of rescue medication and more healthcare utilization, including emergency care and hospitalization. In that sense, maintaining control is both a clinical and environmental objective.

Evidence Beyond the Controlled Trial

Clinical trials remain essential to evaluating reformulated inhalers, but Ardigò emphasized that real-world evidence is needed to understand how these products perform in routine care.

A useful evidence package includes several layers: in vitro characterization, pharmacokinetic bioequivalence, clinical safety and tolerability studies, human factor assessments and long-term real-world data.

Real-world evidence can help assess adherence, inhaler technique, disease control, rescue medication use and patient confidence after transition. These data are particularly important in respiratory medicine, where technique and behavior can strongly affect outcomes.

Ardigò said controlled studies show what a formulation can do under optimal conditions, while real-world evidence shows what it actually does in everyday practice.

This is especially relevant for extrafine formulations, where the key clinical questions include whether improved small-airway deposition translates into measurable benefits. These may include changes in peripheral airway resistance, air trapping, distal lung function, exacerbation rates, disease control scores and reduced reliance on rescue medication.

The Manufacturing and Access Challenge

Bringing sustainable inhaler innovation into routine clinical use requires more than successful formulation science.

One major challenge is manufacturing scale. Reformulating established products with next-generation propellants requires specialized facilities, new safety procedures and reliable supply chains. This is particularly important as environmental regulations continue to reduce the availability of high-global-warming-potential propellants over time.

Ardigò said supply chain resilience is essential so that decarbonizing respiratory care does not create medicine shortages.

Economic access is another consideration. Sustainable inhalers cannot become a premium option available only to healthcare systems that can absorb additional cost. Chiesi has invested substantially in the transition, with the goal of making lower-carbon inhaler options available without incremental cost to patients or national health systems.

For Ardigò, this is part of the broader value proposition.

“The value being created extends well beyond the environmental gain,” he said.

The aim is to make sustainable respiratory care part of the standard of care rather than a separate or restricted option.

Sustainability as a Pharmaceutical R&D Strategy

Chiesi’s inhaler transition also offers broader lessons for the pharmaceutical industry.

Ardigò said sustainability must be embedded in company strategy, rather than treated as a parallel corporate objective. For Chiesi, this includes its B Corp certification, its adoption of Benefit Corporation status in several countries and its sustainability standards for partners across the supply chain.

He also emphasized that climate change is already a health issue for people with respiratory disease. Rising temperatures and worsening air quality can exacerbate lung conditions and increase the risk of hospitalization.

In that context, reducing the environmental footprint of respiratory care is not only a corporate responsibility goal. It is connected to the clinical mission of improving respiratory health.

“No company can reach net zero in isolation,” Ardigò said.

For pharmaceutical companies, this means working with manufacturing partners, distributors and suppliers to align sustainability expectations across the value chain.

The Future of Asthma and COPD Treatment

Looking ahead, Ardigò sees respiratory medicine moving toward a more human-centered model of care.

One area of innovation is precision medicine. Rather than treating asthma or COPD as single disease categories, future therapies may increasingly target specific biological endotypes that drive disease in individual patients.

Another area is the use of New Alternative Methodologies, including human lung-on-a-chip models. These systems use human cells to generate data that may be more predictive of human biology than traditional animal models, with the potential to support safer, faster and more ethical drug development.

“Carbon-minimal inhalers becoming the new standard is concrete proof that caring for patients and caring for the planet are not competing priorities.”

— Dr. Diego Ardigò

Digital health and smart drug delivery are also expected to play a larger role. Sensors embedded in inhalers could provide real-time feedback on technique, track adherence and share information with clinical teams. This could help address one of the most persistent problems in respiratory care: ensuring that the drug reaches the lungs consistently.

For Ardigò, the future of respiratory innovation sits at the intersection of precision, ethics, digital health and sustainability.