Unlocking Potential in Pulmonary and Nasal Drug Delivery

While advancements are unlocking new possibilities in inhaled drug delivery and the pipeline is strong, the regulatory landscape is still challenging, highlighting the need for specialized partners to unlock future success.

Developing inhaled and nasal drug products is widely regarded as one of the most challenging undertakings in the pharmaceutical industry. Unlike oral solid doses, these products are governed by their status as drug–device combinations, requiring a multicenter regulatory review and rigorous human factor studies to ensure safe and effective use. The complexity is further magnified for new molecular entities and inhaled biologics, where specific guidance has yet to catch up to the pace of scientific innovation.

In this exclusive interview with The Pharma Navigator, Carolyn Berg, Vice President of Business Development for Catalent’s Inhalation Franchise, shares her insights into the intricate inhalation drug delivery sector.

Stand Out Advancements

TPN: Could you highlight some of the key advances, within both formulation and device technology, that have driven progress in the field of inhaled drug products?

Berg (Catalent): Particle engineering, especially spray drying, stands out as the foremost technological advance. Spray drying for dry powder inhaled (DPI) drugs has been around for over two decades, since the launch of the inhaled insulin in 2006. Spray drying allows for precise control over particle size, shape, density, and morphology — it is a useful tool for both small and large molecules as it allows for higher drug doses to be delivered to the lungs effectively.

Over the past two decades, there has been an enormous amount of knowledge in the public domain regarding the use of specialized excipients and additives (especially leucine, trehalose and magnesium stearate) that help prevent powder agglomeration and improve powder flowability. 

Another advancement is in the field of lipid nanoparticles (LNPs) and polymeric nanoparticles (PNPs) which allow targeted delivery within the lungs by protecting the API. This has been crucial for delivering complex molecules like biologics — messenger RNA (mRNA) for vaccines and gene therapies. These nanoparticle-based systems can be used in dry powders but are more often seen in liquid formulations for delivery via a nebulizer or a soft mist inhaler (SMI). 

Device technology has advanced tremendously to suit the changing pipeline. For DPIs, the key advance has been higher payload devices that enable one inhalation vs. multiple inhalations using capsule-based DPIs devices. For liquid formulations, there have been many advances in vibrating mesh nebulizers and SMIs that allow for improved particle dispersion and deposition, reduced medication waste, improved treatment time, comfort, and ease of use (breath actuation) for patients. Some newer technologies, such as acoustic nebulizers, have emerged that promise better control over droplet size.  

Unique Regulatory Challenges

TPN: What are the primary regulatory considerations for inhalation drug products and their delivery?

Berg (Catalent): All inhalation drug products — such as pressurized metered dose inhalers (pMDIs), DPIs, nebulized/soft mist drugs and nasal liquids and powders —present unique regulatory challenges and complexity due to their classification as drug/device combination products under the FDA’s Code of Federal Regulations  21 CFR 3.2 (e) defined as ‘a product comprised of two or more regulated components, i.e., drug/device, biologic/device, drug/biologic, or drug/device/biologic, that are physically, chemically, or otherwise combined or mixed and produced as a single entity.’ This definition applies to both small and large molecules   

The effectiveness of drug delivery is significantly influenced by both the design of the device and the patient's proficiency in its proper usage. All devices, whether marketed or novel, must undergo extensive product characterization testing to demonstrate the drug/device robustness and performance, and to support labeling instructions related to proper use. Novel devices may face a steeper hurdle as the FDA may require additional safety and effectiveness data rather than merely a 510(k) clearance that is required if a device is deemed to be of substantial equivalence to a predicate device. Additionally, the devices involve multi-center review from CBER, CDER, and CDRH. 

Analytical considerations are not to be undermined — both in method development and testing. Pulmonary and nasal drug–device combination products have far greater stability testing requirements and release testing requirements vs. oral solid drug dosage forms. Human factor studies are also mandated to demonstrate the device can be safely and effectively used.

Updated Guidance

TPN: Have there been any recent updates to regulatory requirements, or any major challenges with regards to current requirements, around inhalation drug development and delivery that companies should consider?

Berg (Catalent): In 2023, the FDA/Center for Research on Complex Generics (CRCG) issued a guidance titled, ‘Considerations for and Alternatives to Comparative Clinical Endpoint and Pharmacodynamic Bioequivalence Studies for Generic Orally Inhaled Drug Products.’ In 2025, the FDA published a multitude of Product Specific Guidance’s (PSGs) for inhaled drugs. The purpose of these guidance documents is to facilitate the entry of generic products by offering streamlined pathways to demonstrate bioequivalence.

On the new molecular entity (NME) front, however, there have not been any regulatory updates, nor is there any specific FDA guidance for inhaled biologics, which is a growing part of the inhalation pipeline, especially in liquid formulations. 

Drug development is already a challenging undertaking, and this is heightened in inhalation (nasal/pulmonary) product development and even more complex if the drug is a macromolecule. Fortunately, there is an ecosystem of service providers in this field who have the required expertise to aid drug developers in this path.

Advances in Sustainable Devices

TPN: Sustainability is a growing concern for regulators and other industry stakeholders, including patients. So, what approaches are being used to improve sustainability of orally inhaled and nasal drug products and their associated delivery devices?

Berg (Catalent): The pharmaceutical and devices industries have been focused on sustainability for over a decade. For inhaled products in particular, there have been many advances in terms of sustainable devices. 

For SMIs, many new device developers have adopted an interchangeable cartridge design whereby a patient inserts daily medication cartridges into the device, enabling the device to be used for a period of six months to one year. This is in contrast to previous designs where the drug cartridge was not interchangeable and the device was discarded weekly or monthly. This is also true for nasal soft mist devices.

Other efforts for sustainability involve recycling programs. Some European pharmaceutical companies have partnered with health authorities to offer inhaler recycling programs whereby patients can dispose of their empty, unwanted or out-of-date inhalers and these can be recycled.

Pipeline Progression

TPN: How are next-generation therapeutics impacting inhalation drug delivery development?

Berg (Catalent): The pipeline for inhaled drugs has radically changed in the past decade from one that was predominately small molecule to one that is increasingly large molecule. For dry powders, approximately 30% of the pipeline is in large molecule where for the nebulization/SMI pipeline that figure is over 50%. The former is comprised mainly of proteins, peptides, and adeno-associated viruses (AAVs), whereas the latter encompasses additional modalities such as gene therapies, mRNA, and other vector technologies. 

Large molecules are inherently more complex and costly to develop than small molecules. Besides the rigorous analytical methods and testing — which is already complex for any inhalation product — large molecules mandate significantly more. An example would be a monoclonal antibody (mAb) where additional development (and equipment) is needed in drug product potency methods (such as cell-based assays) and ID and protein purity. Not only does this add to costs and time of development, but it presents challenges to drug developers in finding suitable partners that are specialized and have capabilities and specialization in both inhalation and large molecule drugs.

The pipeline for pulmonary and nasal drugs is the strongest it has ever been in many decades with many exciting trends such as Nose to Brain (N2B) delivery for nasal drug products, higher therapeutic doses possible by particle engineering and formulation technologies, the emergence of novel devices on the liquid and powder side and a growing macromolecule pipeline that makes tackling rare or complicated diseases possible. 

Ultimately, as this pipeline progresses, this benefits patients by tackling disease with an improved route of administration that can improve clinical outcomes, provide greater safety (less adverse effects as compared to oral RoA) or offer greater patient convenience for the administration of these therapies. 

About the Interviewee

Carolyn Berg is currently the Vice President of Business Development for Catalent’s Inhalation franchise where she is responsible for driving the sales and strategy growth of Catalent’s inhaled drug delivery solutions. Carolyn began her career in the pharma industry in 1992 with Merck and has specialized in the respiratory/inhalation space since 2004 with Teva and, later, Cipla before joining Catalent in early 2021. 

As with all companies and service providers in this specialized field, Carolyn’s goal is to help customers accelerate their development programs as well as grow the overall pipeline by making companies aware of the benefits nasal and pulmonary routes of administration (RoA). 

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