List of Excipients in Branded Drug ALFENTANIL

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Company	Tradename	Ingredient	NDC	Excipient	Potential Generic Entry
Akorn	ALFENTANIL	alfentanil hydrochloride	17478-841	SODIUM CHLORIDE
Akorn	ALFENTANIL	alfentanil hydrochloride	17478-841	WATER
Akorn	ALFENTANIL HYDROCHLORIDE	alfentanil hydrochloride	17478-067	SODIUM CHLORIDE
Akorn	ALFENTANIL HYDROCHLORIDE	alfentanil hydrochloride	17478-067	WATER

Generic Drugs Containing ALFENTANIL

Company	Ingredient	NDC	Excipient
Hospira Inc	alfentanil hydrochloride	0409-2266	SODIUM CHLORIDE
Hospira Inc	alfentanil hydrochloride	0409-2266	WATER

What are the Most Frequently-Used Excipients in ALFENTANIL?

# Of NDCs	Excipient

Alfentanil Excipient Strategy and Commercial Opportunities

Last updated: October 2, 2026

Alfentanil is an injectable, ultra-short-acting opioid anesthetic with limited remaining patent protection and a narrow but commercially relevant hospital market. The strongest opportunities are formulation-led: ready-to-use syringes, standardized anesthesia concentrations, preservative-free presentations, and products designed to reduce preparation errors and controlled-substance waste. A conventional generic injection faces low patent barriers but intense competition from fentanyl, remifentanil, and established hospital suppliers.

What is the current FDA and commercial status of alfentanil?

Alfentanil hydrochloride is a synthetic opioid used intravenously for induction and maintenance of general anesthesia, supplementation of regional anesthesia, and administration by infusion. The original U.S. reference product was Alfenta, manufactured by Janssen. The drug is administered in hospital and procedural settings rather than through retail pharmacy channels.

The commercial product is an aqueous injection containing alfentanil hydrochloride equivalent to alfentanil. U.S. labeling has historically described a concentration of 500 micrograms per milliliter, with an acidic formulation adjusted using hydrochloric acid or sodium hydroxide. The product is intended for intravenous use and is supplied in single-dose containers.[1]

Attribute	Alfentanil
Active ingredient	Alfentanil hydrochloride
Drug class	Synthetic opioid analgesic
Primary use	General anesthesia and procedural anesthesia
Route	Intravenous
Typical commercial concentration	500 micrograms/mL
U.S. controlled-substance status	Schedule II
FDA regulatory pathway for a conventional generic	ANDA under section 505(j)
Biosimilar exposure	None
Main competitors	Fentanyl, remifentanil, sufentanil
Principal commercial channel	Hospital, ambulatory surgery, anesthesia supply

Alfentanil has a rapid onset and short duration. Those characteristics can be useful when anesthetic depth must be adjusted quickly, but they also limit routine use because other opioids have stronger purchasing scale and broader familiarity.

What excipients are used in alfentanil injection?

The core excipient strategy for alfentanil is simple: an aqueous, sterile, low-complexity formulation that maintains solubility, chemical stability, and compatibility with infusion equipment.

The reference formulation has used:

• Water for injection as the vehicle.
• Sodium chloride for isotonicity.
• Hydrochloric acid and sodium hydroxide for pH adjustment.
• No functional preservative in the conventional single-dose injectable presentation.

The exact excipient composition must be confirmed against the applicable reference label and FDA inactive-ingredient records before regulatory filing. Excipient selection can differ between reference, generic, and premixed presentations.

Why is an acidic pH important?

Alfentanil is a weakly basic, water-soluble opioid supplied as a hydrochloride salt. An acidic pH supports the protonated, soluble form of the drug and reduces the risk of precipitation after dilution. A formulation program should establish:

• pH range at release and through shelf life.
• Assay and degradation-product limits.
• Compatibility after dilution in 0.9% sodium chloride and 5% dextrose.
• Stability in syringes, bags, and infusion lines.
• Adsorption to polymeric containers and tubing.
• Light sensitivity and oxygen-related degradation.
• Extractables and leachables from the final container.

The formulation should avoid unnecessary buffers if they create compatibility, toxicity, or regulatory complexity. A low-excipient composition is commercially attractive because it reduces raw-material cost and simplifies parenteral qualification.

Which excipients should be evaluated for a differentiated product?

A conventional generic should initially target the reference formulation or a qualitatively and quantitatively comparable composition. A differentiated product may evaluate:

Formulation objective	Potential excipient or material strategy	Commercial purpose
pH control	Hydrochloric acid and sodium hydroxide; selected low-capacity buffer only if justified	Maintain solubility and stability
Isotonicity	Sodium chloride or equivalent tonicity adjustment	Improve intravenous tolerability
Oxidation control	Low-oxygen headspace, nitrogen overlay, oxygen-barrier container	Reduce oxidative degradation
Container compatibility	Type I glass or qualified cyclic olefin polymer	Support prefilled syringe or cartridge delivery
Dose-concentration control	Sterile dilution into a ready-to-use vehicle	Reduce bedside compounding
Microbial control	Sterile single-dose packaging	Avoid preservative-related risk

Preservatives should not be added solely to extend commercial flexibility. In anesthesia products, preservative-free single-dose presentations are more compatible with hospital safety expectations, neonatal and pediatric use, and intravascular administration.

What formulation patents protect alfentanil?

Alfentanil was developed decades ago, and the principal composition and use patents associated with the original drug are expected to be expired in major markets. The commercially relevant intellectual-property position is therefore more likely to involve:

• Container and closure systems.
• Prefilled syringe configurations.
• Automated anesthesia delivery systems.
• Stable premixed solutions.
• Manufacturing controls and aseptic processing.
• Combination products or procedure-specific delivery systems.

A new alfentanil molecule patent is unlikely to create meaningful exclusivity. A patent strategy would need to claim a technically defensible formulation or delivery configuration, such as improved stability in a polymeric syringe, a defined low-sorption container system, or a ready-to-use concentration with validated in-use stability.

Broad claims covering alfentanil in water, sodium chloride, or a conventional acidic injectable would face substantial validity and obviousness risk because the reference product and standard parenteral practices are longstanding.

What is the Orange Book status of alfentanil?

A conventional alfentanil injection may be eligible for ANDA approval if an FDA reference listed drug remains available and the proposed product meets pharmaceutical-equivalence and bioequivalence requirements. Orange Book status should be checked at the time of filing because reference-listed-drug availability, discontinued-product classifications, and active listing status can change.[2]

For a standard injectable, the key Orange Book issues are:

1. Whether the reference product is listed as a reference standard.
2. Whether any unexpired patents or regulatory exclusivities are listed.
3. Whether the applicant must make Paragraph I, II, III, or IV certifications.
4. Whether the proposed product has the same strength, dosage form, route, and active ingredient.
5. Whether a suitability petition or 505(b)(2) application is required for a meaningful formulation difference.

Given the age of alfentanil, regulatory exclusivity is unlikely to be a material barrier. Any active patent listing would require product-specific review rather than reliance on the drug's historic development timeline.

When does alfentanil lose exclusivity?

Alfentanil's principal small-molecule and original-product exclusivity periods have expired. The commercial opportunity is therefore generic and formulation-driven rather than dependent on new-molecular-entity exclusivity.

Exclusivity category	Alfentanil position
New chemical entity exclusivity	Expired
Original compound patent estate	Expected to be expired
Pediatric exclusivity	No current commercial significance identified
Orphan-drug exclusivity	Not a principal market protection
Biosimilar exclusivity	Not applicable
Potential new-product exclusivity	Possible only for a qualifying new formulation or delivery product

A manufacturer launching a conventional injection should assume that market access depends on ANDA readiness, sterile manufacturing capacity, controlled-substance compliance, supply reliability, and contracting rather than patent exclusivity.

Are there Paragraph IV challenges involving alfentanil?

Paragraph IV litigation is generally less likely for an old injectable with an expired primary patent estate than for a recently approved oral, long-acting, or combination product. A Paragraph IV certification would matter only if the relevant Orange Book patent list contained an unexpired patent covering the proposed product or method of use.

For alfentanil, the more likely scenarios are:

• No Paragraph IV certification because no relevant unexpired patent is listed.
• Paragraph III certification if a listed patent remains active.
• A conventional ANDA filing based on expired patent protection.
• A 505(b)(2) application for a materially different dosage form or delivery system.

There is no biosimilar pathway because alfentanil is a chemically synthesized small molecule, not a biologic. Generic competition, not biosimilar competition, defines the regulatory landscape.

What commercial opportunities exist for alfentanil formulations?

Ready-to-use prefilled syringes

A prefilled syringe is the most practical formulation-led opportunity. It can reduce dilution steps, preparation time, calculation errors, and controlled-substance wastage. The product could be offered in standardized anesthesia doses or concentrations, subject to dose flexibility and hospital protocols.

The development program must address:

• Syringe material compatibility.
• Drug adsorption to the barrel, plunger, and needle.
• Sterility over the labeled shelf life.
• Delivery accuracy at low fill volumes.
• Extractables and leachables.
• Tamper evidence and controlled-substance security.
• Human-factors validation.

A prefilled product may require a 505(b)(2) pathway if the presentation differs materially from the reference product. It may also support patent claims directed to the container-drug system rather than alfentanil itself.

Ready-to-use infusion bags

Premixed alfentanil in small-volume infusion bags could target operating rooms, intensive-care units, and ambulatory surgery centers. The commercial advantage would be reduced pharmacy compounding and faster deployment during procedures.

The main risks are stability after dilution, container permeability, adsorption, microbial control, and low demand relative to the minimum manufacturing batch size. A bag product is more commercially attractive when bundled with standardized dosing protocols or an anesthesia pump.

Low-waste anesthesia presentations

Alfentanil is a controlled substance, and unused product creates disposal, reconciliation, and inventory burdens. Small-volume single-dose syringes or cartridges could improve dose matching and reduce waste.

This opportunity depends on hospital purchasing data. If most customers already prepare doses from multidose or standard vials with minimal waste, the price premium for a new presentation may not be accepted.

Pediatric and neonatal presentations

A preservative-free, low-volume presentation could address pediatric anesthesia and procedural sedation requirements. The formulation must avoid excipients that create avoidable safety concerns in vulnerable populations.

The regulatory benefit is not automatic. A pediatric presentation would need appropriate labeling, dosing support, container functionality, and clinical-use justification. A smaller fill volume alone may not support meaningful exclusivity.

Combination anesthesia kits

A commercial package combining alfentanil with compatible syringes, labels, dilution instructions, or procedure-specific accessories could improve workflow. The product would likely derive its value from hospital operations rather than from pharmacology.

A kit strategy can create additional regulatory and contractual complexity if the package includes devices or drug-delivery components. It also raises procurement questions because hospitals may purchase the drug and delivery system separately.

How does alfentanil compare with fentanyl and remifentanil?

Criterion	Alfentanil	Fentanyl	Remifentanil
Onset	Rapid	Rapid	Very rapid
Duration	Short	Longer than alfentanil in many uses	Very short
Primary differentiation	Rapid titration with short duration	Broad familiarity and low cost	Rapid offset and infusion control
Hospital adoption	Niche	Broad	Strong in selected anesthetic procedures
Formulation opportunity	Prefilled and standardized injectable	High-volume generic and ready-to-use formats	Infusion-focused formats
Competitive pressure	High	Reference benchmark	High in short-procedure anesthesia
Patent-driven pricing power	Low	Low	Product- and presentation-specific

Fentanyl has greater purchasing scale and broad clinical familiarity. Remifentanil competes where rapid offset and infusion control justify its cost. Alfentanil can compete when clinicians value rapid onset without selecting remifentanil, but the product must offer operational advantages to secure formulary placement.

What manufacturing and IP barriers affect alfentanil?

The principal barriers are operational rather than patent-based.

Sterile manufacturing

A manufacturer needs validated aseptic processing, terminal sterilization feasibility assessment, container-closure integrity testing, and controlled-substance manufacturing controls. Sterile injectable shortages can create pricing opportunities, but they also expose suppliers to elevated quality and supply-chain risk.

Controlled-substance compliance

U.S. manufacturers and distributors must manage Drug Enforcement Administration registration, quotas, security, inventory reconciliation, suspicious-order controls, and destruction procedures. These requirements increase fixed costs and complicate contract manufacturing.

Container compatibility

Alfentanil development should include a comparative screen of:

• Type I glass vials.
• Cyclic olefin polymer syringes.
• Polypropylene components.
• Elastomeric stoppers.
• Infusion bags and administration sets.

Sorption and leachables can become more important as the dose concentration decreases or the product is stored for extended periods in a syringe or infusion line.

Manufacturing process claims

Process patents may be more defensible than broad composition patents if they cover a measurable improvement, such as reduced degradation, improved aseptic yield, or a validated low-oxygen filling process. Trade secrets may provide better protection for routine process parameters that are difficult to detect from the finished product.

Which companies are likely to compete in alfentanil?

Competition is likely to come from generic injectable manufacturers, hospital-focused specialty pharmaceutical companies, contract sterile-fill operators, and anesthesia-product suppliers. The competitive field includes companies with capabilities in:

• Controlled-substance injectable production.
• ANDA development.
• Ready-to-use syringe manufacturing.
• Hospital contracting.
• Shortage-response supply.
• Anesthesia and critical-care distribution.

The most credible entrant is not necessarily the company with the lowest theoretical cost. Hospitals may favor suppliers with reliable allocation, validated delivery systems, electronic ordering support, and a history of injectable quality compliance.

What generic launch scenarios exist?

Scenario 1: Conventional vial generic

This is the lowest-risk regulatory route. It requires the least formulation innovation but faces the strongest price competition. Success depends on manufacturing cost, supply reliability, and access to group purchasing organizations.

Scenario 2: Premium prefilled syringe

This route offers stronger differentiation and potentially better gross margin. It carries higher device, stability, human-factors, and regulatory costs. A 505(b)(2) pathway may be appropriate if the dosage form or administration characteristics differ from the reference product.

Scenario 3: Premixed infusion product

This could reduce pharmacy preparation but requires a reliable demand base. The product is most attractive in facilities with high procedure volumes and standardized anesthesia protocols.

Scenario 4: Shortage-oriented launch

A supplier could enter during a shortage of competing injectable opioids. This strategy may produce rapid adoption, but shortage-driven demand can decline once incumbent supply normalizes. FDA shortage databases and purchasing contracts should be monitored before capacity investment.[3]

How strong is the alfentanil patent estate?

The patent estate is weak for a conventional alfentanil injection because the drug and original product are old. The strongest potential protection would relate to:

1. A prefilled syringe with defined stability and low adsorption.
2. A specific premixed infusion concentration with extended in-use stability.
3. A container-closure system that improves shelf life.
4. A validated manufacturing process with measurable quality benefits.
5. A drug-device combination with a defined administration protocol.

Patent claims should avoid merely restating the known active ingredient, concentration, saline vehicle, and acidic pH. Those features are vulnerable to prior-art and obviousness challenges.

What is the revenue exposure and market outlook?

Alfentanil is unlikely to support blockbuster revenue as a standalone generic injectable. Revenue potential is concentrated in institutional contracts and specialty presentations. A commercial model should assess:

• Annual procedure volume.
• Average dose per procedure.
• Current use of fentanyl and remifentanil.
• Hospital pharmacy preparation costs.
• Controlled-substance waste.
• Shortage frequency.
• Willingness to pay for ready-to-use packaging.
• Contracting discounts and group purchasing fees.
• Sterile manufacturing utilization.

The most attractive business case is a portfolio approach in which alfentanil is bundled with other anesthesia injectables. A single-product strategy has limited scale unless the supplier has an existing hospital sales platform or a shortage-driven manufacturing advantage.

Key Takeaways

• Alfentanil is an old, small-molecule injectable with little expected patent protection for a conventional vial.
• The core excipient system is an aqueous acidic formulation using water for injection, sodium chloride, and pH adjustment.
• Preservative-free, ready-to-use syringes offer the clearest formulation-led opportunity.
• Premixed infusion bags may reduce pharmacy workload but require stronger demand validation.
• Fentanyl and remifentanil create substantial clinical and purchasing pressure.
• The main barriers are sterile manufacturing, controlled-substance compliance, container compatibility, and hospital contracting.
• A conventional ANDA is likely to be the simplest regulatory route, while a differentiated delivery system may require 505(b)(2) review.
• No biosimilar risk applies. Paragraph IV exposure is likely to be limited unless an active Orange Book patent is identified.
• The strongest IP strategy would focus on container-drug systems, stability, delivery devices, or manufacturing controls.
• Commercial success depends more on supply reliability and workflow savings than on alfentanil's molecule-level exclusivity.

FAQs

Is alfentanil still commercially viable as a generic injection?

Yes, but primarily as a hospital product. A standard vial is likely to face price pressure, while prefilled or premixed presentations may support better differentiation.

Can alfentanil be formulated without sodium chloride?

Yes, if osmolality, solubility, stability, and intravenous tolerability are adequately controlled. Any alternative isotonicity strategy would require comparative formulation and regulatory support.

Does alfentanil require a preservative?

A preservative is not inherently required for a sterile single-dose injectable. A preservative-free presentation is generally more compatible with hospital intravenous use and vulnerable patient populations.

Can a prefilled alfentanil syringe receive new patent protection?

Potentially. Protection would need to focus on a non-obvious container-drug system, stability profile, delivery configuration, or manufacturing feature rather than the old alfentanil composition itself.

Is alfentanil subject to biosimilar competition?

No. Alfentanil is a chemically synthesized small molecule. Competition occurs through generic-drug pathways, not the biosimilar framework.

References

1. U.S. Food and Drug Administration. (2013). Alfenta (alfentanil hydrochloride injection) prescribing information.
2. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
3. U.S. Food and Drug Administration. (2024). Drug shortages.
4. U.S. National Library of Medicine. (2024). DailyMed: Alfentanil hydrochloride injection.
5. U.S. Drug Enforcement Administration. (2024). Controlled substances act, Schedule II.