List of Excipients in Branded Drug BIVALIRUDIN IN 0.9% SODIUM CHLORIDE

« Back to Dashboard

Company	Tradename	Ingredient	NDC	Excipient	Potential Generic Entry
Baxter Healthcare Corporation	BIVALIRUDIN IN 0.9% SODIUM CHLORIDE	bivalirudin in 0.9% sodium chloride injection	0338-9572	HYDROCHLORIC ACID
Baxter Healthcare Corporation	BIVALIRUDIN IN 0.9% SODIUM CHLORIDE	bivalirudin in 0.9% sodium chloride injection	0338-9572	SODIUM CHLORIDE
Baxter Healthcare Corporation	BIVALIRUDIN IN 0.9% SODIUM CHLORIDE	bivalirudin in 0.9% sodium chloride injection	0338-9572	SODIUM HYDROXIDE
Baxter Healthcare Corporation	BIVALIRUDIN IN 0.9% SODIUM CHLORIDE	bivalirudin in 0.9% sodium chloride injection	0338-9572	WATER

Bivalirudin in 0.9% Sodium Chloride: Excipient Strategy, Patent Position, and Commercial Opportunities

Last updated: October 2, 2026

Bivalirudin in 0.9% sodium chloride is primarily a ready-to-use hospital formulation opportunity, not a conventional new-molecule patent opportunity. The commercial value comes from reducing reconstitution steps, preparation time, dosing errors, vial waste, and pharmacy workload in percutaneous coronary intervention and other anticoagulation settings. The active ingredient is an established synthetic direct thrombin inhibitor, while the formulation uses a minimal excipient system centered on sodium chloride injection.

The core bivalirudin patent estate has expired. Competitive protection is more likely to depend on formulation execution, container-closure performance, stability, manufacturing reliability, regulatory pathway selection, hospital contracting, and supply continuity than on broad composition-of-matter claims.

What is bivalirudin in 0.9% sodium chloride?

Bivalirudin is a 20-amino-acid synthetic direct thrombin inhibitor. It binds thrombin directly and inhibits both circulating and clot-bound thrombin. The product was originally marketed as Angiomax and received FDA approval for use during percutaneous coronary intervention (PCI) [1].

A ready-to-use formulation in 0.9% sodium chloride generally consists of:

Component	Function
Bivalirudin	Active anticoagulant
Sodium chloride injection	Isotonic vehicle and diluent
Water for injection	Solvent component of the aqueous vehicle
Container-closure system	Maintains sterility and stability

The formulation does not require a complex excipient platform. Its differentiation depends on concentration, pH control, sterility assurance, stability, adsorption control, packaging, and administration convenience.

The established injectable presentation is a lyophilized 250-mg vial requiring reconstitution and further dilution before administration. FDA labeling identifies 0.9% sodium chloride, 5% dextrose, and other compatible infusion solutions as dilution vehicles for bivalirudin preparations [2].

What excipients are used in bivalirudin 0.9% sodium chloride formulations?

The principal excipient is sodium chloride. A formulation designed as a ready-to-use infusion can avoid bulking agents, preservatives, surfactants, and complex buffer systems if the active ingredient remains stable at the selected concentration and pH.

Sodium chloride as the primary excipient

0.9% sodium chloride injection contains approximately 9 mg/mL sodium chloride and is widely used for intravenous administration. The vehicle is familiar to hospitals, compatible with existing infusion infrastructure, and generally accepted by pharmacy and nursing operations.

Its commercial advantages include:

• Established regulatory and clinical familiarity.
• Broad availability of bags and flexible containers.
• Standard compounding and administration procedures.
• Low excipient complexity.
• Reduced risk of excipient-related tolerability concerns.

The principal technical concern is that sodium chloride is a vehicle rather than a stabilizing system. It does not inherently prevent peptide oxidation, aggregation, adsorption, hydrolysis, or other degradation pathways.

Buffer selection and pH control

A bivalirudin premix may require pH adjustment or buffering depending on the stability profile of the drug substance and final formulation. A buffer can improve stability but may create new risks:

• Increased osmolality.
• Greater incompatibility with infusion materials.
• More complex extractables and leachables assessment.
• Potential precipitation or degradation during sterilization.
• A larger formulation patent footprint but also greater regulatory burden.

A minimal formulation using sodium chloride alone may be commercially preferable if it provides adequate shelf life and in-use stability. A buffered formulation may be justified where stability data show a meaningful benefit.

Preservative-free design

Bivalirudin infusion products are expected to be preservative-free and supplied for single-patient, single-use administration. Preservatives would add limited commercial value in an intravenous hospital product and could create tolerability, compatibility, and regulatory complications.

Surfactants and protein-style excipients

Bivalirudin is a peptide, but it is not generally managed like a monoclonal antibody formulation. Surfactants such as polysorbates may reduce interfacial adsorption in some peptide products, yet their inclusion is not automatically desirable. They can introduce peroxide-related degradation pathways, container interactions, and additional analytical controls.

The preferred development sequence is to test a sodium chloride-only system first, followed by targeted use of a buffer or surfactant only when forced by stability data.

What concentration and presentation create the strongest commercial opportunity?

A 0.5 mg/mL ready-to-use concentration is commercially attractive because it aligns with common dilution practices for bivalirudin infusion. A product could be packaged in several container sizes:

Example presentation	Bivalirudin content	Commercial use
50 mL bag	25 mg	Limited or specialized dosing
100 mL bag	50 mg	Supplemental or short-duration use
250 mL bag	125 mg	Lower-volume administration
500 mL bag	250 mg	Standard vial-equivalent supply
1,000 mL bag	500 mg	Longer PCI or high-dose use

Actual commercial presentations must be matched to labeled concentration, dose, stability, and hospital purchasing practices.

For a patient weighing 80 kg, the standard PCI regimen of a 0.75 mg/kg bolus followed by 1.75 mg/kg/hour produces a 60-mg bolus and a 140-mg hourly infusion before any procedural adjustment [2]. A 250-mg equivalent presentation may therefore be more practical than a small-volume bag for procedures lasting several hours.

The strongest hospital value proposition is a formulation that eliminates the sequence of:

1. Reconstituting a lyophilized vial.
2. Inspecting the solution.
3. Transferring the solution into a diluent.
4. Calculating the final concentration.
5. Labeling the compounded container.
6. Discarding unused product.

How does a ready-to-use formulation compare with the lyophilized vial?

Attribute	Lyophilized bivalirudin vial	Bivalirudin in 0.9% sodium chloride
Preparation	Requires reconstitution and dilution	Ready for administration after standard handling
Pharmacy labor	Higher	Lower
Dose-preparation steps	Multiple	Reduced
Packaging cost	Lower per active unit	Higher container and fill-finish cost
Waste risk	Unused vial and preparation waste	Potentially lower if bag size matches dose
Shelf-life complexity	Powder stability plus in-use stability	Liquid stability throughout shelf life
Manufacturing complexity	Lyophilization	Sterile liquid fill-finish
Hospital differentiation	Limited	High if workflow savings are demonstrated
Patent scope	Core product patents expired	Potentially narrow formulation and process claims

The liquid premix shifts technical risk from reconstitution performance to long-term liquid stability. That tradeoff is commercially acceptable where the product can demonstrate a meaningful shelf life and lower preparation burden.

What patents protect bivalirudin and its sodium chloride formulation?

The original bivalirudin composition-of-matter and product patent estate is no longer a meaningful barrier to generic entry. The historical Angiomax patent estate included U.S. Patent No. 5,196,404, which was associated with the bivalirudin product and expired in the 2010s after applicable term adjustments and extensions [3].

Current protection for a new bivalirudin-in-sodium-chloride product would more likely arise from:

• Specific concentration ranges.
• Defined pH ranges.
• Stability claims.
• Low-degradation impurity profiles.
• Container and bag materials.
• Oxygen-control or nitrogen-overlay processes.
• Sterile filtration and aseptic-fill processes.
• Administration systems.
• Premixed dosing kits.
• Method-of-use claims tied to a defined patient population or procedure.

These claims would generally be narrower and more vulnerable to invalidity or design-around challenges than the original active-ingredient patent.

Formulation patent strength

A formulation patent is strongest when it claims a non-obvious relationship between composition and performance. Useful claim elements could include:

• A specific bivalirudin concentration in 0.9% sodium chloride.
• A defined pH range that suppresses a known degradation pathway.
• A specified impurity threshold after accelerated storage.
• A particular polymer bag that minimizes adsorption.
• A combination of oxygen content, headspace control, and storage temperature.
• Stability for a commercially meaningful period that was not predictable from prior art.

A claim that merely recites bivalirudin in normal saline may face substantial novelty and obviousness challenges if the prior art already discloses bivalirudin dilution in 0.9% sodium chloride.

What is the Orange Book status of bivalirudin?

The Orange Book is relevant to FDA-approved bivalirudin drug products and their listed patents, but it does not capture every formulation, manufacturing, trade-secret, or contractual right. The original Angiomax patent protection has expired, and generic bivalirudin products have entered the U.S. market through abbreviated approval pathways [3,4].

For a new premixed sodium chloride product, the central regulatory question is whether the product can qualify for an abbreviated new drug application or whether its differences from the reference product require a 505(b)(2) application.

ANDA pathway

An ANDA may be available where the proposed product can demonstrate the required sameness to the reference listed drug, including dosage form, route, strength, active ingredient, and labeling characteristics. A materially different premixed liquid presentation may create difficulties if the reference product is a lyophilized vial.

505(b)(2) pathway

A 505(b)(2) application may be more suitable where the product relies on FDA findings for bivalirudin but introduces a distinct formulation, presentation, concentration, or administration format. The pathway can support a ready-to-use product when the formulation differences require clinical, pharmaceutical, or bridging data beyond a conventional ANDA.

The commercial advantage of 505(b)(2) is formulation differentiation. The disadvantages include higher development cost, possible reliance on clinical bridging, and the risk of a more limited market-access timetable.

When does bivalirudin lose exclusivity?

Bivalirudin has already lost core small-molecule exclusivity in the United States. FDA statutory exclusivity associated with the original reference product has also expired. The practical market barrier is therefore not molecule-level exclusivity but product-level execution.

A new premixed product could receive limited regulatory exclusivity only if it qualifies under a specific FDA pathway, such as:

• New chemical entity exclusivity, which is not available for an established active ingredient.
• New clinical investigation exclusivity based on qualifying studies.
• Orphan-drug exclusivity for a qualifying orphan indication.
• Pediatric exclusivity linked to an FDA-requested pediatric program.

Those categories are unlikely to protect a routine ready-to-use formulation by themselves. Any meaningful protection would more likely come from patents and commercial contracting.

Are Paragraph IV challenges relevant to bivalirudin?

Paragraph IV challenges remain relevant for unexpired patents listed against a reference product, but the original bivalirudin patent barriers have largely fallen away. A new formulation patent listed for a premix could generate Paragraph IV litigation if an ANDA applicant certifies that the patent is invalid, unenforceable, or not infringed.

The principal risks for a formulation patent holder are:

• A challenger uses the same active ingredient and vehicle but changes concentration.
• The challenger selects a different bag material.
• The challenger uses a different pH or buffer.
• The challenger argues that the claimed formulation is obvious.
• The patent is not eligible for Orange Book listing because it does not claim the drug substance, drug product, or approved method of use in the required manner.

The Hatch-Waxman value of a formulation patent depends heavily on whether the claim is properly listed and whether the approved product labeling supports an infringement theory.

What patent litigation and settlement risks affect the market?

The historical bivalirudin market experienced generic-entry pressure after expiry of the core patent estate. For a new premixed product, litigation risk would shift to formulation and delivery claims rather than active-ingredient claims.

A settlement agreement could address:

• The first commercial entry date.
• Authorized-generic supply.
• Patent-license terms.
• Launch restrictions.
• Product-specific manufacturing rights.
• Hospital channel allocation.

No broad market exclusivity should be assumed from a formulation patent alone. A generic manufacturer can often enter with a different presentation if the patent claims do not cover the full commercial product space.

What manufacturing and intellectual-property barriers matter most?

The main barriers are technical and operational.

Liquid stability

Bivalirudin must remain within specification through labeled shelf life. The sponsor must control degradation products, visible and subvisible particles, potency loss, pH drift, and container interaction.

Adsorption and container compatibility

Peptides can interact with glass, elastomeric closures, tubing, and polymer bags. Development should evaluate:

• Polyolefin and multilayer film bags.
• PVC exposure.
• Infusion-set compatibility.
• Low-concentration adsorption.
• Extractables and leachables.
• Light exposure.
• Headspace oxygen.

Sterile fill-finish

A ready-to-use bag requires validated aseptic processing or terminal sterilization, depending product sensitivity. The manufacturing process must control bioburden, endotoxin, particulate matter, fill volume, seal integrity, and shipping stress.

Supply continuity

Hospitals may value a premix most during periods of sterile injectable shortages. A manufacturer with redundant drug-substance sourcing, validated secondary fill-finish capacity, and dependable distribution can gain share even where the formulation is not strongly patented.

Which companies are positioned to compete?

Competition is likely to come from four groups:

1. Established generic injectable manufacturers with bivalirudin vial products.
2. Large hospital-injection suppliers with premixed bag platforms.
3. Contract development and manufacturing organizations with sterile liquid fill-finish capacity.
4. Outsourcing facilities and institutional compounders supplying procedure-specific presentations.

The most credible commercial entrants are companies that already sell sodium chloride premixes, operate hospital-focused sterile manufacturing networks, and have FDA experience with ANDA or 505(b)(2) injectable products.

The differentiating assets are not limited to the drug master file. They include national distribution, group purchasing organization access, shortage-response capability, pharmacovigilance infrastructure, and validated bag technology.

What revenue opportunities exist for a bivalirudin premix?

Revenue potential depends on procedure volume, price per dose, and conversion from vial-based preparation. The product can capture value through:

• Premium pricing for labor-saving ready-to-use bags.
• Lower total cost of preparation.
• Reduced pharmacy compounding burden.
• Lower medication-error risk.
• Better operating-room and catheterization-laboratory workflow.
• Reduced vial and dilution waste.
• Institutional standardization.

The addressable market is narrower than the broader anticoagulant market because bivalirudin is concentrated in procedural settings. The commercial case is strongest where hospitals perform high PCI volumes and have pharmacy constraints, nursing shortages, or sterile-compounding cost pressure.

How does bivalirudin compare with competing anticoagulants?

Product	Primary setting	Formulation opportunity	Competitive issue
Bivalirudin	PCI and procedural anticoagulation	Ready-to-use infusion in sodium chloride	Generic price pressure
Unfractionated heparin	PCI, surgery, intensive care	Broad injectable supply	Low cost and extensive familiarity
Enoxaparin	Thrombosis prevention and treatment	Prefilled syringes	Different clinical use and dosing
Argatroban	HIT and procedural anticoagulation	Ready-to-use infusion	Stronger relevance in HIT
Fondaparinux	Thrombosis prevention and treatment	Prefilled injection	Limited procedural substitution

Bivalirudin’s principal competitive advantage is predictable direct thrombin inhibition with a short pharmacodynamic profile. Its principal commercial weakness is that hospitals can substitute lower-cost anticoagulants in some procedures.

What generic launch scenarios exist?

Three launch scenarios are commercially plausible:

Low-price generic vial entry

A manufacturer enters with a conventional lyophilized vial and competes primarily on acquisition cost. This strategy creates significant price pressure but does not eliminate the workflow value of a premix.

Premium ready-to-use entry

A manufacturer launches a sodium chloride premix at a price above the vial equivalent. The product must demonstrate measurable labor and waste savings to gain formulary adoption.

Dual-product strategy

A supplier markets both a low-cost vial and a premix. The vial protects price-sensitive accounts, while the premix targets high-volume procedural hospitals.

The strongest market position may come from a dual-product portfolio supported by reliable supply and hospital-specific contract pricing.

Key Takeaways

• Bivalirudin in 0.9% sodium chloride is primarily a formulation and hospital-workflow opportunity.
• Sodium chloride is the core excipient; a simple preservative-free formulation is commercially attractive if stability is adequate.
• The historical bivalirudin composition-of-matter and product patent barriers have expired.
• New protection would likely depend on narrow formulation, packaging, stability, process, or method-of-use claims.
• A premix can reduce reconstitution steps, pharmacy labor, preparation errors, and waste.
• A 505(b)(2) pathway may be more suitable than an ANDA for a materially different ready-to-use liquid presentation.
• The main technical risks are liquid stability, peptide adsorption, container compatibility, particulate control, and sterile fill-finish.
• Generic entry risk is high because the active ingredient is established and core exclusivity has expired.
• Commercial success depends on procedure volume, hospital workflow economics, supply reliability, and purchasing contracts.
• There is no biosimilar risk because bivalirudin is a synthetic peptide drug, not a biologic.

FAQs

Is bivalirudin in 0.9% sodium chloride a new drug?

No. Bivalirudin is an established active ingredient. A ready-to-use sodium chloride presentation would be a new product formulation or presentation, not a new chemical entity.

Can a bivalirudin premix receive formulation patent protection?

Yes, but protection would likely be narrow. The strongest claims would tie the formulation to demonstrated stability, impurity control, container compatibility, or manufacturing performance.

Is 0.9% sodium chloride the only compatible diluent?

FDA labeling for bivalirudin identifies multiple compatible infusion solutions, including 0.9% sodium chloride and 5% dextrose, depending on the approved product and labeling [2].

Does bivalirudin require a biosimilar development program?

No. Biosimilar regulation applies to biological products. Bivalirudin is regulated as a synthetic drug product.

What is the main commercial advantage of a bivalirudin premix?

The main advantage is operational. A premix can remove reconstitution and dilution steps and provide a standardized product for catheterization laboratories, operating rooms, and hospital pharmacies.

References

1. U.S. Food and Drug Administration. (2000). Angiomax approval history and prescribing information. FDA.

2. U.S. Food and Drug Administration. (2023). Bivalirudin for injection prescribing information. FDA-approved product labeling.

3. U.S. Food and Drug Administration. (2025). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.

4. U.S. Food and Drug Administration. (2024). Drugs@FDA: FDA-approved drug products database. FDA.