List of Excipients in Branded Drug ULTIVA

Company	Tradename	Ingredient	NDC	Excipient	Potential Generic Entry
Mylan Institutional LLC	ULTIVA	remifentanil hydrochloride	67457-198	GLYCINE
Mylan Institutional LLC	ULTIVA	remifentanil hydrochloride	67457-198	HYDROCHLORIC ACID
Mylan Institutional LLC	ULTIVA	remifentanil hydrochloride	67457-912	GLYCINE
Mylan Institutional LLC	ULTIVA	remifentanil hydrochloride	67457-912	HYDROCHLORIC ACID
Mylan Institutional LLC	ULTIVA	remifentanil hydrochloride	72078-034	GLYCINE

ULTIVA Excipient Strategy and Commercial Opportunities for Remifentanil Injection

Last updated: September 24, 2026

ULTIVA is a sterile, preservative-free, lyophilized formulation of remifentanil hydrochloride for intravenous administration. Its excipient platform is deliberately minimal: glycine is the principal bulking agent, while hydrochloric acid is used for pH adjustment. The formulation’s commercial value comes less from excipient complexity than from rapid onset, rapid offset, controlled infusion, and compatibility with operating-room and intensive-care workflows.

The strongest commercial opportunities are generic remifentanil injection, ready-to-use presentations, pharmacy-compounded infusion solutions, anesthesia-specific delivery systems, and improved handling formats that reduce preparation errors without changing the active ingredient.

What is ULTIVA and how is remifentanil formulated?

ULTIVA contains remifentanil hydrochloride, an ultra-short-acting synthetic opioid administered by continuous intravenous infusion. The product is supplied as a sterile, nonpyrogenic, preservative-free powder for reconstitution.

Product attribute	ULTIVA specification
Active ingredient	Remifentanil hydrochloride
Therapeutic class	Opioid analgesic; general anesthetic adjunct
Dosage form	Lyophilized powder for injection
Administration	Intravenous infusion only
Vial strengths	1 mg, 2 mg, and 5 mg
Principal excipient	Glycine
pH adjuster	Hydrochloric acid
Preservatives	None
Reconstitution	Sterile diluent before administration
Typical use	Induction and maintenance of general anesthesia; monitored anesthesia care
Key pharmacology	Rapid onset and rapid offset because of ester metabolism

Each vial contains remifentanil hydrochloride equivalent to the labeled amount of remifentanil and glycine at approximately 15 mg per 1 mg of remifentanil equivalent. Hydrochloric acid adjusts formulation pH, generally within the acidic range specified in the prescribing information.[1]

The formulation does not use antimicrobial preservatives, surfactants, complex carbohydrates, or a multi-excipient stabilizer system. That simplicity reduces excipient-related toxicity and narrows the principal development risks to pH, moisture control, reconstitution performance, container closure integrity, and post-reconstitution stability.

What excipients protect ULTIVA and generic remifentanil products?

Glycine is the principal functional excipient in ULTIVA. Its likely formulation roles include providing bulk for the lyophilized cake and supporting the physical characteristics of the powder during manufacture and reconstitution. Hydrochloric acid controls pH and contributes to chemical stability.

The excipient system creates several development advantages:

1. A short inactive-ingredient list simplifies regulatory review.
2. The absence of preservatives supports use in controlled hospital environments.
3. The lyophilized format improves shipping and storage compared with a ready-to-use aqueous product.
4. The formulation is comparatively easy to reproduce for an abbreviated new drug application, provided the generic matches relevant quality attributes.

The same simplicity limits opportunities to differentiate through conventional excipient substitution. A generic manufacturer is unlikely to obtain meaningful commercial protection merely by replacing glycine with another bulking agent. The principal value lies in manufacturing efficiency, container format, stability, reconstitution time, and workflow integration.

Why glycine matters in the formulation

Glycine is not the source of remifentanil’s analgesic effect. It is an inactive formulation component. Its commercial relevance arises from the lyophilized dosage form, where a suitable bulking agent must produce a robust cake, support uniform vial filling, and permit rapid dissolution.

Potential formulation risks include:

• Cake collapse during freeze-drying.
• Incomplete or slow dissolution.
• Variability in reconstitution volume.
• Moisture uptake during storage.
• Particulate formation.
• Differences in pH or osmolality after dilution.
• Interaction with vial stopper or container materials.

A manufacturer that achieves faster reconstitution, lower particulate burden, or improved resistance to temperature excursions could create operational value even without changing the active pharmaceutical ingredient.

What FDA regulatory status applies to ULTIVA?

ULTIVA was approved in the United States as a prescription intravenous remifentanil product. Remifentanil is a Schedule II controlled substance under the federal Controlled Substances Act, which affects procurement, inventory control, distribution, waste management, and hospital handling.[2]

The FDA-approved product is supplied as a powder requiring reconstitution and dilution before infusion. The labeling specifies acceptable diluents and provides preparation instructions for anesthesia and monitored-care settings.[1]

Regulatory and operational requirements include:

• Compliance with controlled-substance security and recordkeeping rules.
• Sterility assurance for a parenteral product.
• Demonstration of drug-product stability.
• Validation of reconstitution and dilution procedures.
• Compatibility testing with infusion systems.
• Container closure integrity testing.
• Labeling that clearly separates reconstitution from subsequent dilution.
• Risk controls for accidental bolus administration and respiratory depression.

The product’s preservative-free status is commercially useful but increases dependence on aseptic preparation and controlled handling. A ready-to-use presentation would need to manage microbiological risk without undermining the clinical preference for preservative-free administration.

What patents protect ULTIVA and remifentanil injection?

ULTIVA’s original commercial protection was based primarily on historical compound, formulation, and regulatory exclusivity rather than a currently differentiated excipient estate. Remifentanil has been available through generic versions in multiple markets, reducing the practical value of legacy brand exclusivity.

A current commercial assessment should distinguish among four categories:

Protection category	Relevance to remifentanil
Active-ingredient patents	Primarily historical for the original compound
Lyophilized formulation patents	Potentially relevant to specific excipient ratios or manufacturing conditions
Method-of-use patents	Possible coverage for anesthesia protocols, but generally limited by established clinical use
Device or presentation patents	Potential protection for prefilled syringes, infusion cartridges, or closed systems

The U.S. Orange Book must be reviewed for current listed patents and exclusivity associated with the specific reference product. A remifentanil generic entrant also must evaluate Paragraph IV exposure, patent certification requirements, and any litigation involving the reference product or later-developed presentations.[3]

Because the formulation uses common excipients and an established injectable route, broad composition-of-matter protection is unlikely to provide a durable barrier for new entrants. Defensible intellectual property is more likely to arise from:

• Specific lyophilization cycles.
• Improved stability after reconstitution.
• Novel ready-to-use concentrations.
• Device integration.
• Automated dose preparation.
• Closed-system transfer technology.
• Packaging that improves controlled-substance accountability.
• Use in a defined patient population or procedural setting.

When does ULTIVA lose exclusivity and what generic entry risks exist?

The original exclusivity period for ULTIVA has elapsed in the United States, and generic remifentanil products have entered the market. The commercial question is therefore not whether generic entry is possible, but how manufacturers can capture share in a mature hospital injectable category.

Generic-entry risks include:

• Price erosion in standard vial presentations.
• Hospital preference for established suppliers.
• Contracting pressure from group purchasing organizations.
• Controlled-substance supply-chain requirements.
• Manufacturing-site qualification.
• Shortages caused by limited sterile-injectable capacity.
• Substitution restrictions in hospital formularies.
• Procurement preference for suppliers offering multiple vial sizes.
• Product liability exposure associated with opioid handling.

An ANDA applicant generally benefits from the reference product’s straightforward excipient profile. The development burden remains significant because sterile injectable products require robust process validation, container closure controls, particulate testing, and supply continuity.

Paragraph IV litigation risk is likely to be more relevant for newly developed delivery systems than for the basic lyophilized vial. A conventional generic may face limited patent friction where the original product’s primary intellectual-property rights have expired, but a manufacturer pursuing a novel prefilled or integrated system could encounter active device or formulation claims.

What formulation patents could protect improved remifentanil products?

The most commercially relevant patent opportunities involve improvements that solve hospital workflow problems rather than merely alter inactive ingredients.

Ready-to-use liquid formulations

A stable aqueous remifentanil product could eliminate reconstitution and reduce preparation time. The challenge is maintaining chemical stability, sterility, concentration uniformity, and acceptable container compatibility over the labeled shelf life.

Potential claim elements include:

• Remifentanil concentration.
• pH range.
• Buffer selection.
• Oxygen control.
• Container material.
• Light protection.
• Storage temperature.
• In-use stability.
• Compatibility with infusion pumps.

Prefilled syringes and cartridges

Prefilled syringes could support anesthesia workstations, procedural sedation, and intensive-care infusion protocols. Commercial value would come from reduced preparation steps and lower risk of calculation or labeling errors.

A defensible patent could cover the combination of:

• A specified remifentanil concentration.
• A syringe or cartridge construction.
• A controlled-substance tamper-evident feature.
• An administration connector.
• A validated stability period.
• A dosing or pump interface.

Premixed infusion bags

Premixed bags could target high-volume hospital use. Their constraints include low-dose accuracy, adsorption to bag or tubing materials, stability after dilution, and the need to prevent accidental bolus delivery.

Premixed products may be particularly useful in institutions that centralize pharmacy preparation. The product must compete with the cost and flexibility of pharmacy-compounded solutions.

Alternate lyophilized formulations

A manufacturer could pursue a modified lyophilized product with faster reconstitution, improved cake appearance, reduced residual moisture, or extended storage conditions. These improvements may support formulation patents, but their commercial strength depends on measurable clinical or operational benefits.

What commercial opportunities exist for ULTIVA excipient and delivery strategies?

The largest opportunities are in product presentation and hospital workflow rather than in new excipients.

Opportunity	Customer benefit	Development barrier	Commercial potential
Generic 1 mg, 2 mg, 5 mg vials	Lower acquisition cost	Sterile manufacturing and supply reliability	High but price competitive
Ready-to-use syringe	Reduced preparation time	Stability, sterility, device qualification	High in anesthesia departments
Premixed infusion bag	Fewer compounding steps	Dilution stability and packaging compatibility	Moderate to high
Standardized pharmacy kit	Lower preparation error risk	Kit assembly and labeling controls	Moderate
Closed-system transfer format	Controlled-substance accountability	Device and workflow validation	Niche but defensible
Pediatric low-volume presentation	Dosing convenience	Small-volume accuracy and safety	Selective
Extended-stability product	Less waste and fewer replacements	Formulation and packaging studies	Moderate
Smart-pump compatible cartridge	Workflow integration	Device partnerships and validation	Potentially high

An excipient-based product should be designed around a specific operational problem. A new bulking agent without an improvement in stability, reconstitution, or manufacturing cost would have weak commercial differentiation.

How does ULTIVA compare with fentanyl and other injectable opioids?

Remifentanil competes with fentanyl, sufentanil, alfentanil, and other anesthetic opioids. Its defining commercial attribute is rapid offset, not low price.

Attribute	Remifentanil	Fentanyl
Administration	Primarily continuous IV infusion	Bolus and infusion
Offset after infusion	Very rapid	Longer and more variable
Metabolism	Esterase-mediated	Hepatic metabolism and redistribution
Formulation complexity	Often simple powder or solution	Multiple injectable formats
Workflow value	Precise titration during anesthesia	Broad anesthesia and analgesia use
Generic competition	Established	Extensive
Main clinical tradeoff	Requires infusion control	Longer residual effect

Remifentanil’s rapid clearance supports procedures requiring frequent adjustment of anesthetic depth and quick recovery. Fentanyl has broader use across perioperative, emergency, and chronic-care settings. A remifentanil product therefore needs to sell into procedure-specific value rather than compete solely on unit price.

What manufacturing and intellectual-property barriers affect commercial entry?

The main barriers are sterile manufacturing and supply reliability.

A commercial entrant must control:

• Active ingredient quality and impurity profile.
• Uniform vial filling.
• Freeze-drying cycle reproducibility.
• Residual moisture.
• Reconstitution time.
• Visible and subvisible particles.
• Endotoxin levels.
• Container closure integrity.
• Controlled-substance inventory.
• Distribution security.
• Batch release testing.

Remifentanil’s low dose relative to excipient mass also creates content-uniformity and fill-weight considerations. The manufacturer must demonstrate that each vial delivers the labeled amount after reconstitution and dilution.

A company with existing sterile injectable infrastructure has a cost advantage. A company without that infrastructure may require contract manufacturing, which can create capacity, supply-continuity, and technology-transfer risks.

What is the competitive landscape for remifentanil injection?

The market includes the original ULTIVA brand, generic remifentanil hydrochloride products, hospital pharmacy-compounded solutions, and potential ready-to-use injectable presentations.

Competitive differentiation is likely to depend on:

• Contract price.
• Backorder history.
• Number of vial sizes.
• Regulatory reliability.
• Delivery consistency.
• Hospital formulary position.
• Compatibility documentation.
• Labeling clarity.
• Controlled-substance distribution capability.
• Availability of integrated anesthesia products.

Generic vial products face high substitution pressure. A supplier can improve margins by combining remifentanil with adjacent anesthesia products, offering hospital-wide contracts, or providing workflow-oriented formats.

What revenue exposure and licensing opportunities exist?

Exact current ULTIVA revenue cannot be stated reliably without current company filings or market-data access. The commercial exposure is concentrated in hospital and ambulatory surgical channels rather than retail pharmacy.

Licensing opportunities include:

• Co-development of ready-to-use remifentanil syringes.
• Contract manufacturing of lyophilized vials.
• Regional commercialization rights.
• Anesthesia-workstation integration.
• Smart-pump cartridges.
• Premixed bags for centralized hospital pharmacies.
• Packaging and controlled-substance accountability systems.

A licensee should prioritize products that create a measurable reduction in preparation time, medication error risk, or wastage. A simple formulation change without a workflow advantage is unlikely to support premium pricing.

Key Takeaways

• ULTIVA is a preservative-free lyophilized remifentanil hydrochloride injection.
• Glycine is the principal excipient; hydrochloric acid adjusts pH.
• The basic formulation is simple and relatively accessible to generic manufacturers.
• The strongest commercial barriers are sterile manufacturing, controlled-substance distribution, supply reliability, and hospital contracting.
• The best product opportunities are ready-to-use syringes, premixed bags, cartridges, and workflow-integrated delivery systems.
• Formulation patents are more likely to protect stability, packaging, reconstitution, or device combinations than glycine substitution alone.
• Remifentanil competes with fentanyl on titratability and rapid offset, not on broad indications or lowest acquisition cost.
• Any new product should be designed around a documented anesthesia-workflow benefit.

FAQs

Can glycine be replaced in a generic remifentanil formulation?

Yes, a generic manufacturer may develop a different excipient system, but it must demonstrate pharmaceutical equivalence, stability, sterility, reconstitution performance, and acceptable inactive-ingredient safety. Glycine substitution alone would provide limited commercial differentiation.

Is ULTIVA supplied as a ready-to-use liquid?

The traditional ULTIVA presentation is a lyophilized powder requiring reconstitution and dilution before intravenous infusion. Ready-to-use remifentanil products, if developed, would need separate stability, packaging, and microbiological validation.

Does remifentanil require preservative-free packaging?

Preservative-free presentation is standard for the injectable product because it is administered intravenously and used in controlled clinical environments. A manufacturer should not add preservatives without a clear safety and regulatory basis.

Can a hospital pharmacy compound remifentanil infusion solutions?

Hospital pharmacies may prepare infusion solutions under applicable sterile-compounding and controlled-substance requirements. The preparation must follow validated procedures, labeling controls, stability data, and institutional policies.

What is the strongest patent strategy for a new remifentanil product?

The strongest strategy generally combines formulation, container, and delivery-system claims. Useful targets include extended in-use stability, prefilled administration, closed-system handling, smart-pump integration, and reduced reconstitution risk.

References

1. U.S. Food and Drug Administration. (n.d.). ULTIVA (remifentanil hydrochloride) for injection prescribing information. GlaxoSmithKline.
2. U.S. Drug Enforcement Administration. (n.d.). Controlled substances act, Schedule II substances. U.S. Department of Justice.
3. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. U.S. Department of Health and Human Services.