List of Excipients in Branded Drug BEVESPI AEROSPHERE

Company	Tradename	Ingredient	NDC	Excipient	Potential Generic Entry
AstraZeneca Pharmaceuticals LP	BEVESPI AEROSPHERE	glycopyrrolate and formoterol fumarate	0310-4600	1,2-DISTEAROYL-SN-GLYCERO-3-PHOSPHOCHOLINE	2030-05-28
AstraZeneca Pharmaceuticals LP	BEVESPI AEROSPHERE	glycopyrrolate and formoterol fumarate	0310-4600	CALCIUM CHLORIDE	2030-05-28
AstraZeneca Pharmaceuticals LP	BEVESPI AEROSPHERE	glycopyrrolate and formoterol fumarate	0310-4600	NORFLURANE	2030-05-28

BEVESPI AEROSPHERE Excipient Strategy and Commercial Opportunities

Last updated: August 10, 2026

BEVESPI AEROSPHERE is a pressurized metered-dose inhaler containing glycopyrrolate and formoterol fumarate for twice-daily maintenance treatment of chronic obstructive pulmonary disease. Its commercial differentiation depends on AstraZeneca's co-suspension formulation, which combines micronized active ingredients with porous DSPC phospholipid particles in an HFA-134a propellant system. The principal opportunities are inhaler-platform licensing, generic and authorized-generic development, low-global-warming-propellant reformulation, and supply of specialized phospholipid and device components.

What excipients are used in BEVESPI AEROSPHERE?

BEVESPI AEROSPHERE uses a narrow excipient system:

Component	Function	Commercial relevance
HFA-134a, also known as norflurane	Propellant for aerosol generation	Creates future reformulation exposure because of greenhouse-gas restrictions
DSPC, or 1,2-distearoyl-sn-glycero-3-phosphocholine	Porous phospholipid carrier particle	Supports co-suspension, dose uniformity and aerosol performance
Glycopyrrolate	Long-acting muscarinic antagonist	Active pharmaceutical ingredient
Formoterol fumarate	Long-acting beta-2 agonist	Active pharmaceutical ingredient

The FDA label describes the active ingredients as suspended in HFA-134a with porous particles composed of DSPC. The formulation does not rely on a conventional liquid cosolvent system such as ethanol for the principal suspension architecture.[1]

Each labeled actuation contains 9 mcg of glycopyrrolate and 4.8 mcg of formoterol fumarate. The recommended dose is two inhalations twice daily, providing 36 mcg of glycopyrrolate and 19.2 mcg of formoterol fumarate per day.[1]

How does the BEVESPI excipient system work?

Why DSPC is commercially important

DSPC is a saturated phospholipid used to create porous particles that carry micronized drug particles. The carrier system is designed to improve:

• Physical separation of drug particles during storage
• Uniformity of emitted dose
• Suspension stability
• Reproducibility of aerodynamic particle-size distribution
• Co-delivery of two chemically different active ingredients

The platform is generally referred to as a co-suspension delivery system. It differs from traditional suspension inhalers in which micronized drug particles are suspended directly in the propellant and stabilized mainly through particle engineering, surfactants or density control.

The porous carrier is intended to reduce strong drug-drug and drug-container interactions. That matters for a fixed-dose combination containing a hydrophobic antimuscarinic and a beta-2 agonist with different physical and chemical properties.

Why HFA-134a matters

HFA-134a is a well-established inhaler propellant with a long regulatory history. Its main advantages are manufacturing familiarity, broad device compatibility and extensive toxicology precedent. Its limitation is environmental: HFA-134a has a materially higher global-warming potential than newer hydrofluoroolefin propellants.

For BEVESPI, the propellant is not a freely interchangeable excipient. A change to HFO-1234ze(E), HFA-152a or another lower-impact propellant would affect:

• Vapor pressure
• Density
• Suspension behavior
• Valve metering
• Spray force
• Plume geometry
• Evaporation rate
• Particle growth during actuation
• Delivered dose and aerodynamic deposition

A propellant change would therefore be a reformulation program rather than a simple excipient substitution.

What formulation and device patents protect BEVESPI AEROSPHERE?

Protection for BEVESPI should be analyzed across four separate layers rather than through the product name alone.

1. Active-ingredient combination claims

These claims may cover the combination of glycopyrrolate and formoterol, including dose ratios and use in COPD maintenance therapy. Their commercial relevance is greater for early generic entrants than for later entrants with independent formulation approaches.

2. Co-suspension and porous-particle claims

These claims may cover:

• Porous DSPC particles
• Drug loading onto phospholipid particles
• Co-suspension of two active ingredients
• Particle-size distributions
• Surface-area or porosity parameters
• Ratios between active ingredients and carrier material
• Storage and redispersibility characteristics

This is the strongest formulation-specific barrier because a generic developer could need to design around both composition and process claims while preserving equivalent aerosol performance.

3. Inhaler and container-closure claims

The device estate can include:

• Metering valve geometry
• Canister and actuator configuration
• Dose-counter integration
• Drug-retaining surfaces
• Suspension delivery features
• Priming and repriming behavior

A non-infringing formulation placed into an infringing device would still create launch risk.

4. Manufacturing-process claims

Process protection may address:

• Micronization
• Preparation of porous phospholipid particles
• Drug loading
• Blending
• Filling into canisters
• Valve crimping
• Homogeneity testing
• Control of residual moisture and impurities

Manufacturing know-how can remain commercially important even where patent protection has expired. Inhaler performance is sensitive to small changes in particle morphology, blend energy, humidity and filling conditions.

A definitive patent-number and expiration-date schedule requires a current FDA Orange Book and jurisdiction-specific patent-register review. The FDA Orange Book remains the controlling starting point for U.S. listed patents and regulatory exclusivity analysis.[2]

When does BEVESPI lose regulatory exclusivity?

BEVESPI was approved by the FDA on June 24, 2016.[1] The likely regulatory exclusivity structure was:

Exclusivity type	Relevance to BEVESPI	Timing
New chemical entity exclusivity	Unlikely to apply to the combination as a whole because glycopyrrolate and formoterol were previously approved active ingredients	Not the primary barrier
Three-year exclusivity	Potentially applicable if the approval relied on sponsor-conducted clinical investigations supporting the new combination	Generally associated with the first three years after approval
Pediatric exclusivity	Possible only if separately awarded after completion of an FDA pediatric requirement	Must be confirmed in the current FDA listing
Patent protection	Can cover combination use, formulation, device or manufacturing	May extend beyond regulatory exclusivity

The end of regulatory exclusivity does not remove patent-based launch risk. An ANDA applicant can challenge listed patents through a Paragraph IV certification, while patents that are not listed in the Orange Book may still create litigation or freedom-to-operate exposure.

What is the Orange Book status of BEVESPI?

BEVESPI is an FDA-approved inhalation aerosol and its reference product is listed in Drugs@FDA and the Orange Book framework. The relevant reference product is the glycopyrrolate/formoterol fumarate inhalation aerosol marketed as BEVESPI AEROSPHERE.[1,2]

For generic applicants, the critical issues are likely to include:

• Whether a proposed product can qualify for the same dosage form and route
• Whether the ANDA must demonstrate equivalent delivered dose
• Whether the product can match aerodynamic particle-size distribution
• Whether the device is sufficiently similar or requires comparative performance testing
• Whether listed formulation, device or method-of-use patents require Paragraph IV certification
• Whether a first-filer can obtain 180-day generic exclusivity

Inhaled products are more difficult to copy than conventional oral tablets because pharmaceutical equivalence does not depend only on assay and dissolution. The applicant must control emitted dose, fine-particle dose, spray pattern, plume geometry, priming, tail-off and device resistance.

Which companies are challenging BEVESPI with generic or competing products?

The commercial competitive field includes both fixed-dose LAMA/LABA products and triple inhalers.

Product	Active ingredients	Device type	Strategic comparison
BEVESPI AEROSPHERE	Glycopyrrolate/formoterol	Pressurized MDI with co-suspension technology	Low-complexity excipient system but technically demanding aerosol platform
ANORO ELLIPTA	Umeclidinium/vilanterol	Dry-powder inhaler	Competes on once-daily dosing and DPI convenience
STIOLTO RESPIMAT	Tiotropium/olodaterol	Soft-mist inhaler	Competes on soft-mist delivery and once-daily administration
UTIBRON NEOHALER	Glycopyrrolate/indacaterol	Dry-powder capsule inhaler	Uses the same antimuscarinic class but a different device and excipient architecture
DUAKLIR PRESSAIR	Aclidinium/formoterol	Dry-powder inhaler	Competes in LAMA/LABA maintenance therapy
BREZTRI AEROSPHERE	Budesonide/glycopyrrolate/formoterol	Pressurized MDI with co-suspension technology	Uses the same delivery platform with an added inhaled corticosteroid
TRELEGY ELLIPTA	Fluticasone furoate/umeclidinium/vilanterol	Dry-powder inhaler	Competes as a once-daily triple therapy

BEVESPI's closest platform comparison is BREZTRI AEROSPHERE. Both use AstraZeneca's aerosol technology, but BREZTRI adds budesonide and addresses a broader treatment segment. That increases the strategic value of the platform because the same device and carrier technology can support multiple combinations.

What commercial opportunities exist for BEVESPI excipients?

Opportunity 1: Co-suspension platform licensing

The most valuable opportunity is likely the delivery platform rather than DSPC as a commodity excipient. A platform license could provide:

• Formulation development support
• Porous-particle manufacturing know-how
• Device integration
• Analytical methods
• Stability protocols
• Clinical bridging strategy
• Regulatory documentation

Potential licensees include originator companies developing new pMDI combinations, specialty respiratory companies and generic manufacturers seeking a lower-risk route to complex inhaled products.

A licensing deal would likely be structured around milestone payments, territory rights, product royalties and manufacturing obligations. Public product materials do not establish a separate, publicly disclosed excipient-only license for BEVESPI.

Opportunity 2: Generic formulation development

A generic company could pursue either:

1. A close co-suspension design using DSPC or a comparable phospholipid carrier; or
2. A different formulation architecture with equivalent in vitro and in vivo performance.

The second path may offer greater patent-design flexibility but creates higher development risk. A direct DSPC-based design may simplify performance matching while increasing exposure to formulation and process claims.

Opportunity 3: Low-global-warming-propellant reformulation

HFA replacement is the largest medium-term excipient opportunity. A lower-emission BEVESPI product could preserve the active ingredients and potentially maintain the established dosing regimen while updating the propellant system.

The development program would need to establish:

• Chemical stability
• Valve and canister compatibility
• Microbial and particulate control
• Dose uniformity
• Aerodynamic equivalence
• Human-use performance
• Container-closure integrity
• Extractables and leachables
• Environmental and toxicological acceptability

The FDA has issued guidance addressing development of orally inhaled and nasal drug products, including performance and quality considerations relevant to propellant-based systems.[3] The EPA has also adopted restrictions affecting high-global-warming-potential HFC uses, creating commercial pressure for inhaler reformulation.[4]

Opportunity 4: Specialized DSPC supply

DSPC supply is a narrower but defensible opportunity. Pharmaceutical-grade suppliers can compete on:

• Purity
• Oxidation control
• Lot-to-lot particle morphology
• Residual solvent profile
• Sterility or bioburden control
• Regulatory documentation
• Global supply continuity

The relevant value is not simply phospholipid availability. The supplier must reproduce the particle structure and surface characteristics required for aerodynamic performance.

Opportunity 5: Contract manufacturing

Contract development and manufacturing organizations can offer integrated services covering:

• API micronization
• Porous-particle preparation
• Suspension manufacture
• Canister filling
• Valve crimping
• Actuator assembly
• Dose-content uniformity testing
• Cascade impaction
• Stability testing

Inhaler manufacturing capacity is strategically valuable because many pharmaceutical companies have oral-dose infrastructure but lack validated pMDI filling and aerodynamic testing capabilities.

How strong is the BEVESPI formulation patent estate?

The formulation estate is commercially stronger than the ingredient combination alone because performance depends on an integrated system. A competing developer must reproduce a clinically usable aerosol while avoiding claims that may cover:

• Carrier-particle composition
• Drug-to-carrier ratio
• Particle morphology
• Suspension behavior
• Device configuration
• Filling process
• Dose delivery

The estate's practical strength depends on claim breadth, remaining patent term, Orange Book listing status, prosecution history and the ability of a generic applicant to establish equivalence through a different formulation. Narrow claims to specific DSPC particles may be easier to design around than broader claims to co-suspension systems and aerosol performance.

The most significant non-patent barriers are analytical and manufacturing reproducibility. A product can be chemically equivalent yet fail to match inhalation performance.

What Paragraph IV and generic-launch scenarios exist?

A generic BEVESPI applicant could pursue several launch scenarios:

Scenario	Description	Commercial effect
Non-Paragraph IV filing	Wait for relevant patents to expire	Lower litigation exposure, later market entry
Paragraph IV challenge	Assert that listed patents are invalid, unenforceable or not infringed	Earlier potential launch with litigation risk
Authorized generic	Originator or licensee supplies an equivalent product	Reduces price erosion from an independent generic
Formulation design-around	Uses a different carrier, propellant or device	May reduce patent exposure but raises equivalence risk
505(b)(2) pathway	Uses the reference product while introducing a material formulation or device change	Potentially useful for propellant or delivery-system reformulation

A first-filer may obtain 180-day exclusivity if statutory requirements are satisfied. Inhaled products can also face regulatory delays because FDA review may require extensive device and performance data beyond standard pharmaceutical equivalence.

What FDA regulatory issues affect excipient commercialization?

The FDA does not treat an inhalation excipient as interchangeable merely because it is accepted in another dosage form. For a new pulmonary excipient or materially changed concentration, the sponsor must address local tolerance, systemic exposure, impurity control and compatibility with the delivery device.

For a lower-global-warming-propellant product, the regulatory strategy should treat the propellant as a critical quality attribute. The sponsor must demonstrate that changing the propellant does not alter dose delivery, lung deposition, safety or clinical performance.

The principal regulatory pathways are:

• ANDA for a therapeutically equivalent generic
• 505(b)(2) NDA for a material formulation or device modification
• Full NDA for a new combination or new clinical use
• Supplemental NDA for a sponsor-controlled reformulation of the marketed product

What revenue exposure and commercial positioning does BEVESPI have?

BEVESPI competes in a large COPD maintenance market but faces pressure from once-daily therapies, triple combinations and formulary substitution. Its two-inhalations-twice-daily regimen creates adherence friction relative to once-daily products.

The commercial value of its excipient strategy is therefore greater as a reusable platform than as a single-product defense. The same co-suspension technology can support:

• LAMA/LABA products
• Inhaled corticosteroid/LAMA/LABA combinations
• Future rescue or maintenance combinations
• Lower-emission propellant versions
• Regional products using the same device architecture

Revenue exposure is highest if a generic can reproduce the product with a different formulation and obtain broad formulary access. Exposure is lower if the relevant patents cover broad platform elements and the manufacturing process remains difficult to replicate.

Key Takeaways

• BEVESPI uses HFA-134a and porous DSPC phospholipid particles as its principal excipient system.
• DSPC is strategically important because it enables co-suspension of glycopyrrolate and formoterol and supports dose uniformity.
• The primary commercial moat is the combined formulation-device-process system, not DSPC alone.
• HFA-134a creates a reformulation opportunity because lower-global-warming propellants may become commercially and regulatory priorities.
• Generic competition will face substantial analytical and manufacturing barriers even after regulatory exclusivity ends.
• The most attractive licensing opportunity is the co-suspension platform, particularly for fixed-dose respiratory combinations.
• BREZTRI AEROSPHERE provides the closest evidence that the platform can support higher-value triple therapy products.
• A current Orange Book and patent-register review is required for a final Paragraph IV, launch-date and patent-expiration assessment.

FAQs

Can BEVESPI use ethanol as a replacement for DSPC?

Not as a direct substitution. Ethanol would create a different formulation architecture and could change suspension stability, valve performance, evaporation behavior and lung deposition.

Is DSPC an FDA-approved inhalation excipient?

DSPC has pharmaceutical and pulmonary-use precedent, but acceptance in one inhaled product does not automatically approve every concentration, particle morphology or route-specific application.

Could a generic BEVESPI use a dry-powder inhaler?

A dry-powder product would generally require a different regulatory and equivalence strategy. It would not be a straightforward ANDA copy of the reference pMDI presentation.

What is the most valuable patentable feature in the BEVESPI platform?

The highest-value subject matter is likely the combination of porous phospholipid carrier particles, active-ingredient loading, suspension properties and device delivery controls.

Will a lower-GWP BEVESPI propellant create a new exclusivity period?

A propellant reformulation may support new patent protection and, depending on the regulatory basis and clinical investigations, could support limited regulatory exclusivity. It would not automatically recreate new chemical entity exclusivity.

References

1. U.S. Food and Drug Administration. (2016). BEVESPI AEROSPHERE prescribing information. AstraZeneca Pharmaceuticals LP. https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208294s000lbl.pdf

2. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.accessdata.fda.gov/scripts/cder/ob/

3. U.S. Food and Drug Administration. (2009). Guidance for industry: Metered dose inhaler and dry powder inhaler drug products: Chemistry, manufacturing, and controls documentation. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/metered-dose-inhaler-and-dry-powder-inhaler-drug-products

4. U.S. Environmental Protection Agency. (2024). Protection of stratospheric ozone: Listing of substitutes under the Significant New Alternatives Policy program. https://www.epa.gov/snap/regulated-products-snap-program relocal cai?