List of Excipients in Branded Drug FRAGMIN

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Company	Tradename	Ingredient	NDC	Excipient	Potential Generic Entry
Pfizer Laboratories Div Pfizer Inc	FRAGMIN	dalteparin sodium	0069-0195	SODIUM CHLORIDE	1969-12-31
Pfizer Laboratories Div Pfizer Inc	FRAGMIN	dalteparin sodium	0069-0195	WATER	1969-12-31

FRAGMIN Excipient Strategy and Commercial Opportunities

Last updated: August 31, 2026

FRAGMIN, the branded dalteparin sodium injection from Pfizer, has limited excipient differentiation in its current U.S. presentations. Its commercial opportunity lies primarily in preservative-free packaging, ready-to-administer delivery systems, dose flexibility, pediatric suitability, container-closure performance, and manufacturing control rather than in a novel excipient platform.

What is the FRAGMIN formulation and which excipients does it contain?

FRAGMIN is a sterile injectable preparation of dalteparin sodium, a low-molecular-weight heparin derived from porcine intestinal mucosa. The U.S. product is supplied in single-dose prefilled syringes and multidose vials.

FRAGMIN presentation	Active ingredient	Key formulation characteristic	Commercial relevance
Single-dose prefilled syringe	Dalteparin sodium	Aqueous, preservative-free presentation	Supports outpatient use and reduces preservative exposure
Multidose vial	Dalteparin sodium, 25,000 IU/mL	Contains benzyl alcohol preservative	Supports repeated withdrawals and institutional use
Common syringe strengths	2,500 IU, 5,000 IU, 7,500 IU, 10,000 IU, 12,500 IU, 15,000 IU and 18,000 IU	Multiple fixed-dose volumes	Reduces bedside calculation and preparation requirements

The FRAGMIN prescribing information identifies water for injection as the vehicle for the single-dose presentations. The multidose vial contains benzyl alcohol at 14 mg/mL as a preservative. The label describes the injection as a clear, colorless to yellow solution with a pH range of approximately 5.0 to 7.5 (Pfizer, 2023).

The product’s excipient profile is therefore simple. The main formulation variables are preservative selection, solution stability, container closure, syringe materials, extractables and leachables, and the interaction between dalteparin and the delivery device.

How does the FRAGMIN excipient strategy compare with competing anticoagulants?

FRAGMIN competes with other low-molecular-weight heparins, including enoxaparin sodium and tinzaparin sodium, as well as unfractionated heparin and oral anticoagulants.

Product class	Representative product	Typical administration	Excipient and packaging opportunity
Low-molecular-weight heparin	FRAGMIN, dalteparin	Subcutaneous injection	Prefilled syringes, preservative-free formats and dose-volume accuracy
Low-molecular-weight heparin	Lovenox, enoxaparin	Subcutaneous injection	Preassembled syringes, graduated doses and safety devices
Unfractionated heparin	Multiple hospital products	Intravenous or subcutaneous	Multidose vial preservation, infusion-bag compatibility and adsorption control
Direct oral anticoagulant	Apixaban, rivaroxaban	Oral	Tablet excipients, solid-state stability and packaging moisture protection
Vitamin K antagonist	Warfarin	Oral	Dose flexibility, tablet scoring and solid-dose manufacturing

Compared with oral anticoagulants, FRAGMIN has a more constrained excipient strategy because injectable administration limits the acceptable range of preservatives, surfactants, buffers and tonicity agents. Compared with enoxaparin, the product opportunity is similar but technically complicated by differences in molecular-weight distribution, sulfation pattern, anti-factor Xa activity, anti-factor IIa activity and impurity profile.

A generic or follow-on dalteparin product cannot rely only on matching nominal concentration. It must demonstrate consistent physicochemical and biological characteristics, including anticoagulant potency and molecular attributes relevant to low-molecular-weight heparin products (U.S. Food and Drug Administration, 2019).

Which excipients offer the strongest commercial opportunity for FRAGMIN?

The strongest opportunities are not broad substitution of inactive ingredients. They are targeted formulation and packaging improvements that address clinical use, safety, stability or manufacturing cost.

Preservative-free multidose systems

Benzyl alcohol enables repeated withdrawal from the multidose vial, but it creates a clear product-positioning issue for neonatal, pediatric and other sensitive populations. A preservative-free multidose presentation could use a validated container-closure system, a restricted-use vial, a sterile transfer device or a prefilled cartridge.

The technical burden is substantial. A preservative-free multidose product would need validated antimicrobial control through container design, manufacturing controls and in-use stability studies. A new multidose format could also require a new drug application supplement or a separate abbreviated application, depending on the sponsor’s regulatory strategy.

Low-adsorption syringe materials

Dalteparin is a highly sulfated polysaccharide with substantial charge density. Interactions with glass, elastomer closures, silicone oil and polymer syringe surfaces require evaluation. A low-adsorption syringe system could reduce dose variability and support a differentiated device claim, particularly for low-volume presentations.

Commercially relevant materials include:

• Cyclic olefin polymer or cyclic olefin copolymer syringes
• Low-silicone or silicone-free barrel systems
• Fluoropolymer-coated elastomer stoppers
• Low-extractable needle shields
• Reduced-dead-space syringe geometries

These materials are more likely to create a defensible product advantage than a conventional replacement of water for injection with another vehicle.

Ready-to-administer dose formats

A ready-to-administer format can reduce hospital preparation, medication errors and sharps handling. Opportunities include:

• Graduated prefilled syringes
• Unit-dose cartridges
• Needle-safety systems
• Autoinjector-compatible formats
• Dose-band presentations for weight-based regimens
• Packaging that separates prophylactic and therapeutic strengths

The commercial value depends on whether the device reduces administration time or enables home treatment. Device differentiation may also support contracting with hospitals and specialty pharmacies after the core composition patents have expired.

Pediatric and neonatal formulations

Dalteparin is used in pediatric settings under specialized dosing protocols. A preservative-free presentation with smaller dose increments could address a clinically relevant gap. A pediatric opportunity would require more than a new excipient. It would require dose accuracy at low volumes, compatibility with pediatric syringes, stability after withdrawal and a labeling strategy supported by clinical and pharmacokinetic data.

Benzyl alcohol exposure is a central consideration in pediatric product design. The current multidose vial’s preservative makes it less attractive for populations in which preservative exposure is restricted or avoided (Pfizer, 2023).

Container-closure and cold-chain optimization

An improved container-closure system could reduce breakage, particulate risk, extractables and shipping losses. Because FRAGMIN is a refrigerated product in many markets, packaging that tolerates temperature excursions without compromising syringe performance could have commercial value.

A formulation sponsor should evaluate:

• Freeze-thaw sensitivity
• Agitation during transport
• Syringe plunger movement
• Needle-shield integrity
• Light exposure
• In-use stability
• Container-closure integrity
• Subvisible particles
• Potency after temperature excursion

The opportunity is strongest where packaging can reduce total cost of ownership rather than merely change the appearance of the product.

What formulation patents could protect a FRAGMIN follow-on product?

Formulation patents could protect a specific combination of dalteparin sodium, excipients, concentration range, pH range, container material, delivery device or storage condition. The strongest claims would usually require a measurable technical effect, such as improved stability, reduced adsorption, lower particulate formation or enhanced dose delivery.

Potential claim categories include:

Claim category	Possible protected subject matter	Relative strength
Composition	Dalteparin with a defined buffer, preservative, stabilizer or tonicity system	Moderate if linked to unexpected stability
Concentration	Defined IU/mL range or dose-volume relationship	Low to moderate unless clinically useful
Container closure	Specific syringe, stopper, coating or polymer combination	Moderate
Device	Safety syringe, autoinjector or low-dead-space system	Moderate to strong if device-specific
Manufacturing process	Purification, depyrogenation, filling or control of molecular attributes	Strong if difficult to design around
Method of use	Specific prophylaxis or treatment regimen	Variable and jurisdiction-dependent
Stability	Storage condition or shelf-life claim	Stronger when supported by comparative data

A patent directed only to water for injection, benzyl alcohol or a conventional isotonic solution would generally have limited defensive value. A patent combining a specific dalteparin profile with a defined container system and demonstrated stability improvement would be more commercially meaningful.

When does FRAGMIN lose exclusivity and what is the generic-entry risk?

FRAGMIN’s original product exclusivity and core patent protection are no longer the principal barriers to competition in the United States. The product has been marketed for decades, and the principal commercial risk now comes from generic or follow-on dalteparin products, manufacturing complexity and purchasing-channel access.

The relevant exclusivity framework includes:

Protection type	Relevance to FRAGMIN
New chemical entity exclusivity	Not a current barrier for this mature product
New clinical investigation exclusivity	May apply only to qualifying later approvals
Orphan-drug exclusivity	Indication-specific and not a general FRAGMIN barrier
Orange Book patents	Must be assessed against the current listed product and indications
Formulation or device patents	May protect later presentations rather than the original product
Trade secrets	Important for dalteparin source material, process controls and release testing

The Orange Book remains the relevant U.S. source for listed patents and regulatory exclusivity associated with an approved drug application (U.S. Food and Drug Administration, 2024). A potential entrant must evaluate listed patents, pediatric extensions, litigation history, product-specific guidance and any regulatory exclusivity attached to later supplements.

What Paragraph IV challenges and litigation affect FRAGMIN?

A Paragraph IV challenge would target an Orange Book-listed patent as invalid, unenforceable or not infringed. The commercial significance depends on whether the challenged patent covers the active ingredient, a formulation, a method of use, a device or a later presentation.

For FRAGMIN, the most important litigation questions are:

1. Whether current listed patents cover the commercial product or only discontinued or modified presentations.
2. Whether a generic applicant can use a section viii statement to omit patented indications.
3. Whether a device or container patent creates a separate launch barrier.
4. Whether the reference-listed drug has an applicable regulatory exclusivity period.
5. Whether a settlement includes a licensed entry date, authorized generic provision or manufacturing restriction.

No single excipient patent should be assumed to block generic dalteparin entry. The more material barriers are likely to be regulatory comparability, source-material qualification, manufacturing validation and commercial supply reliability.

Is FRAGMIN exposed to biosimilar competition?

FRAGMIN is not a conventional biologic and is not normally treated as a biosimilar reference product under the U.S. Public Health Service Act. Dalteparin is a complex low-molecular-weight heparin drug substance rather than a recombinant protein or monoclonal antibody.

Competition is more likely to occur through an abbreviated drug application or another drug-specific pathway than through a conventional biosimilar application. The regulatory challenge is still substantial because low-molecular-weight heparins are heterogeneous mixtures. FDA guidance for enoxaparin illustrates the agency’s focus on detailed structural, physicochemical and biological characterization for complex heparin products (U.S. Food and Drug Administration, 2018).

For investors and licensing teams, the practical conclusion is that “biosimilar risk” is low as a legal category but “complex generic risk” is material.

How strong is the FRAGMIN patent estate?

The original FRAGMIN estate should be viewed as mature rather than expansionary. Composition-of-matter protection for dalteparin is not a credible long-term barrier. Commercial protection is more likely to reside in:

• Later formulation patents
• Prefilled syringe and safety-device patents
• Manufacturing know-how
• Source-material controls
• Analytical methods
• Regulatory dossiers
• Supply contracts
• Brand recognition and institutional purchasing arrangements

A strong follow-on estate would combine a formulation patent with a device patent and manufacturing know-how. A weak estate would rely on conventional injectable excipients with no demonstrated technical effect.

Patent strength should be scored against design-around options. A claim covering a broad aqueous dalteparin injection is likely to face design-around pressure. A claim covering a specific low-adsorption syringe, sterilization method and stability profile may be more durable.

What manufacturing and IP barriers affect commercial entry?

The largest barriers are upstream and analytical rather than excipient-related.

Dalteparin manufacturing requires controlled depolymerization of heparin starting material and tight control of molecular-weight distribution, sulfation, potency and impurity levels. The product’s biological activity cannot be established through a simple chemical assay alone. Release testing typically requires multiple orthogonal methods, including anti-factor Xa and anti-factor IIa activity assays, molecular-weight characterization and identity testing.

Key manufacturing risks include:

• Variability in porcine intestinal mucosal heparin
• Control of depolymerization chemistry
• Residual reagents and process impurities
• Batch-to-batch molecular-weight distribution
• Endotoxin and bioburden control
• Sterile filling at low dose volumes
• Syringe and elastomer compatibility
• Long-term stability and in-use data

These barriers can delay entry even when patent exposure is limited. They also create licensing opportunities for companies with qualified heparin supply, validated analytical methods or established sterile injectable capacity.

What licensing deals could create value around FRAGMIN?

The most attractive licensing structures are likely to involve enabling technology rather than a new inactive ingredient alone.

High-value licensing targets

A commercial partner could license:

• A preservative-free multidose platform
• A low-adsorption prefilled syringe
• A pediatric dose-delivery system
• A validated autoinjector
• A dalteparin manufacturing process
• A heparin-source supply agreement
• Analytical methods for molecular-weight and potency comparability
• A regional sterile-fill network

Lower-value licensing targets

Less defensible opportunities include:

• Commodity water-for-injection supply
• Conventional benzyl alcohol preservation
• Generic syringe components without exclusivity
• Broad claims to aqueous dalteparin solutions
• Excipients lacking comparative stability data

A licensing agreement should allocate responsibility for device human factors, stability studies, regulatory submissions, pharmacovigilance and supply continuity. The party controlling the reference product or a qualified dalteparin drug substance has greater negotiating leverage than an excipient supplier with no differentiated data package.

What is the FDA regulatory status of FRAGMIN?

FRAGMIN is an FDA-approved prescription anticoagulant indicated for several venous thromboembolism-related uses, including prophylaxis in surgical settings, treatment of unstable angina and non-Q-wave myocardial infarction in combination with aspirin, and extended treatment of symptomatic venous thromboembolism in patients with cancer (Pfizer, 2023).

Its principal regulatory characteristics are:

Regulatory issue	Assessment
Product type	Prescription injectable drug
Active ingredient	Dalteparin sodium
Administration	Subcutaneous injection
Reference product	FRAGMIN
Biosimilar pathway	Not the normal competitive pathway
Generic pathway	Relevant, but technically complex
Orange Book relevance	Relevant for application and patent review
Main development burden	Comparability, sterile manufacturing and complex-mixture characterization

A sponsor changing excipients, concentration, syringe type or preservative system would need to establish that the change does not adversely affect quality, safety or efficacy. The regulatory burden increases when the change alters dose delivery, in-use storage, pediatric use or the approved route of administration.

What generic launch scenarios exist for FRAGMIN?

Three launch scenarios are commercially plausible.

Scenario 1: Standard generic prefilled syringe

This approach matches the reference product’s strength, dose volume and route. It offers the simplest commercial message but faces price competition and limited differentiation.

Scenario 2: Institutional multidose competitor

A multidose vial can target hospitals and clinics seeking lower acquisition cost and reduced packaging waste. The trade-off is preservative exposure, vial-access controls and a less convenient administration format.

Scenario 3: Differentiated home-use product

A preservative-free, safety-enabled prefilled syringe or autoinjector could target oncology, post-discharge and specialty-pharmacy channels. This format may command better pricing but requires device development, human-factors work, packaging validation and a stronger reimbursement case.

The third scenario offers the best opportunity for an excipient or delivery-technology company because it creates value beyond simple active-ingredient substitution.

What is the geographic opportunity for FRAGMIN excipient and formulation technologies?

The United States is the most important market for Orange Book and abbreviated-application analysis. Europe and other regulated markets require separate assessments because product classification, reference-product rules, device requirements and patent systems differ.

Geographic opportunities include:

• North America: preservative-free presentations, specialty pharmacy and hospital contracting
• Europe: device convenience, regional manufacturing and tender competitiveness
• Japan: packaging, dose precision and local regulatory compliance
• Emerging markets: stable multidose formats and lower-cost sterile filling

A formulation that succeeds in the United States may require different preservative, container or labeling strategies elsewhere. Benzyl alcohol restrictions, pediatric requirements and multidose-container expectations vary by jurisdiction.

Key Takeaways

• FRAGMIN has a simple excipient profile centered on an aqueous dalteparin sodium injection.
• The multidose vial contains benzyl alcohol; single-dose prefilled syringes are the stronger platform for preservative-free differentiation.
• The most attractive commercial opportunities are low-adsorption syringes, safety devices, pediatric dose formats, autoinjectors and preservative-free multidose systems.
• Conventional excipient substitution is unlikely to create a strong patent position without demonstrated stability or delivery benefits.
• FRAGMIN is exposed to complex-generic competition rather than conventional biosimilar competition.
• Manufacturing, source-material control and analytical comparability are larger entry barriers than the original active-ingredient patent estate.
• A differentiated device and formulation combination offers greater licensing value than a commodity excipient.

FAQs About FRAGMIN Excipients and Commercial Strategy

Can benzyl alcohol be removed from the FRAGMIN multidose vial?

Yes, removal is technically possible, but a preservative-free multidose product would require validated antimicrobial control, container-closure integrity, in-use stability and regulatory support. The product could also be redesigned as a single-dose vial or prefilled syringe.

Is sodium chloride a core FRAGMIN excipient?

The U.S. prescribing information identifies water for injection for the single-dose product and benzyl alcohol for the multidose vial. Sodium chloride should not be treated as a universal FRAGMIN excipient across all strengths and markets without presentation-specific product documentation.

Could FRAGMIN be reformulated as an oral anticoagulant?

No practical oral reformulation strategy is apparent from the existing product. Dalteparin is a large, highly sulfated polysaccharide with poor oral absorption. Commercial reformulation opportunities are concentrated in injectable delivery and packaging.

Are prefilled syringes patentable for dalteparin products?

A generic prefilled syringe format alone may provide limited protection. Patent value increases when claims cover a specific syringe material, low-dead-space geometry, needle-safety mechanism, stability result or dose-delivery performance.

What is the best commercial entry point for an excipient supplier?

The strongest entry point is a documented platform that improves dalteparin stability, reduces adsorption or enables a preservative-free ready-to-administer presentation. Commodity water, benzyl alcohol or standard elastomers offer limited strategic differentiation.

References

Pfizer Inc. (2023). FRAGMIN (dalteparin sodium) injection prescribing information. U.S. Food and Drug Administration.

U.S. Food and Drug Administration. (2018). Draft guidance on enoxaparin sodium. Center for Drug Evaluation and Research.

U.S. Food and Drug Administration. (2019). Policy for establishing equivalence of complex drug products. Center for Drug Evaluation and Research.

U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.