List of Excipients in Branded Drug SEMGLEE

SEMGLEE Excipient Strategy and Commercial Opportunities

Last updated: August 7, 2026

SEMGLEE (insulin glargine-yfgn) uses a conventional insulin-glargine excipient system built around glycerol for tonicity, m-cresol for antimicrobial preservation, zinc for insulin stabilization, and polysorbate 20 for interfacial protection. The formulation is commercially attractive because it supports a 100 units/mL product in both vial and prefilled-pen presentations while relying on widely available pharmaceutical excipients. The main opportunities are supply-chain optimization, device compatibility, lifecycle management, and differentiated insulin delivery rather than wholesale reformulation.

SEMGLEE is a U.S. Food and Drug Administration-approved biosimilar to Lantus (insulin glargine), and it became the first interchangeable insulin biosimilar in the United States in July 2021.[1,2] Its commercial position is shaped by payer substitution, pharmacy-channel access, pen-device economics, and competition from Basaglar and Rezvoglar.

What excipients are used in SEMGLEE?

SEMGLEE contains insulin glargine-yfgn at 100 units/mL and uses the following inactive ingredients:

Excipient	Function	Label concentration or role
Glycerol	Tonicity and formulation-volume control	20 mg/mL
m-Cresol	Antimicrobial preservative for multidose use	2.7 mg/mL
Zinc oxide	Zinc source for insulin stabilization and self-association	30 micrograms/mL
Polysorbate 20	Interfacial stabilizer that limits adsorption and aggregation	0.01 mg/mL
Hydrochloric acid and sodium hydroxide	pH adjustment	Adjust formulation to approximately pH 4
Water for injection	Vehicle	Balance

The formulation is acidic, with a target pH near 4. Insulin glargine remains soluble in the acidic vial formulation and forms a depot after subcutaneous injection as the formulation approaches physiological pH. This pH-dependent precipitation is central to the product’s prolonged pharmacokinetic profile.[1]

The excipient profile is materially similar to the reference insulin-glargine formulation. That similarity reduces formulation-related biosimilar risk because the sponsor can focus development on analytical similarity, biological activity, pharmacokinetic comparability, immunogenicity, and device performance rather than introducing a new delivery mechanism.

How does SEMGLEE’s excipient strategy support commercial manufacturing?

SEMGLEE’s formulation uses established, low-cost excipients with extensive pharmaceutical precedent. The strategy has four commercial advantages.

First, the excipients are available from multiple qualified suppliers. Glycerol, m-cresol, zinc compounds, polysorbate 20, hydrochloric acid, sodium hydroxide, and water for injection are not unique raw materials. Supplier redundancy lowers the risk of a single-source disruption.

Second, the excipient concentrations are low relative to the active biologic load. Zinc oxide is used at microgram-per-milliliter levels, while polysorbate 20 is used at a very low concentration. This limits per-unit excipient cost. The principal manufacturing costs are more likely to arise from recombinant insulin production, purification, aseptic filling, analytical release testing, cold-chain distribution, and device assembly.

Third, the formulation supports both vial and prefilled-pen presentations. A shared bulk formulation can serve two channels, reducing formulation complexity and allowing commercial segmentation through packaging, device design, volume, and reimbursement.

Fourth, the excipient system is compatible with the established insulin-glargine quality profile. Any change must preserve potency, purity, aggregation profile, subvisible particles, pH, zinc content, preservative effectiveness, extractables and leachables, and container-closure integrity.

What technical functions do SEMGLEE excipients perform?

Why does SEMGLEE use glycerol?

Glycerol controls tonicity and contributes to the product’s osmolality. It also affects protein hydration and solution properties. An incorrect glycerol level can change injection tolerability, solution density, and insulin behavior during storage.

Glycerol is commercially uncomplicated, but the sponsor still must control bioburden, endotoxin, grade, water content, and supplier-change impact. Pharmaceutical-grade glycerol also requires controls for contamination risks, including diethylene glycol and ethylene glycol.

Why does SEMGLEE use m-cresol?

m-Cresol is the preservative used to support multidose vial sterility after repeated withdrawals. It is a familiar excipient in insulin products and is relevant to both microbiological protection and patient tolerability.

The preservative concentration must remain effective throughout the labeled in-use period. Preservative effectiveness testing, container-closure studies, and repeated-dose simulations are important for the vial presentation. The pen presentation also requires compatibility testing because repeated needle penetration and device exposure can alter preservative demand.

Why does SEMGLEE use zinc?

Zinc supports insulin hexamer formation and influences the physical behavior of insulin glargine. Zinc concentration affects aggregation, precipitation, stability, and the product’s in vivo depot behavior.

Zinc oxide is used as a zinc source. Control of zinc content is important because small changes can affect product quality attributes. The sponsor must also manage elemental impurities, raw-material particle characteristics, dissolution behavior, and batch-to-batch assay consistency.

Why does SEMGLEE use polysorbate 20?

Polysorbate 20 reduces adsorption of insulin to manufacturing equipment, filters, vials, cartridges, and delivery-device surfaces. It also helps limit interfacial aggregation caused by agitation, pumping, filling, and shipping.

At the low concentration used in SEMGLEE, polysorbate 20 requires sensitive analytical control. Oxidation and hydrolysis can generate degradation products, including free fatty acids and peroxides. These products can affect protein stability and particulate formation. The sponsor should monitor polysorbate quality by lot and evaluate supplier changes through stability and comparability protocols.

What formulation risks matter most for SEMGLEE?

The principal formulation risks are aggregation, precipitation variability, preservative loss, adsorption, particulate formation, and device interaction.

Risk	Relevant excipient or interface	Commercial consequence
Protein aggregation	Polysorbate 20, zinc, pH, agitation	Potential potency or immunogenicity concern
Inconsistent depot formation	Zinc, pH, insulin concentration	Pharmacokinetic and clinical comparability risk
Microbial growth after opening	m-Cresol, container closure	Vial shelf-life and patient-safety risk
Surface adsorption	Polysorbate 20, container and device materials	Potency loss and dose-delivery variability
Oxidative degradation	Polysorbate 20 and trace impurities	Increased particulates or altered purity
Extractables and leachables	Pen, cartridge, stopper, adhesive	Device approval and postmarket risk
Freeze-thaw damage	Protein and excipient matrix	Distribution and excursion risk

For a biosimilar, an excipient change is commercially significant even when the active ingredient is unchanged. A new excipient system can create a new analytical comparability package, alter immunogenicity risk, require additional clinical evidence, and complicate interchangeability positioning.

What formulation patents protect SEMGLEE and insulin glargine products?

SEMGLEE is a biologic, so its U.S. regulatory and patent framework differs from that of a conventional small-molecule generic.

SEMGLEE does not have an Orange Book listing because the Orange Book covers approved drug products submitted under the Federal Food, Drug, and Cosmetic Act, while SEMGLEE was approved under the Public Health Service Act’s 351(k) biosimilar pathway. Biologic reference products and biosimilars are tracked through FDA’s Purple Book.[3]

A competitor cannot file a conventional ANDA Paragraph IV certification against SEMGLEE. A biosimilar sponsor uses the patent-exchange process under the Biologics Price Competition and Innovation Act, commonly called the patent dance, subject to the statutory and litigation framework in Section 351(l) of the Public Health Service Act.[4]

The practical patent estate for insulin glargine products normally includes:

• insulin sequence and molecular-structure claims;
• recombinant production and purification claims;
• formulation claims involving zinc, preservatives, tonicity agents, and pH;
• cartridge, vial, and prefilled-pen claims;
• dose-delivery and injection-device claims;
• manufacturing-process claims;
• method-of-use claims for diabetes treatment.

The original insulin-glargine composition is mature, which limits the commercial leverage of basic active-ingredient claims. The stronger remaining barriers are usually formulation, device, process, and market-access protections. Claim scope must be evaluated against the specific presentation, concentration, manufacturing route, and device architecture.

When does SEMGLEE lose exclusivity?

SEMGLEE’s regulatory exclusivity is not the same as patent exclusivity.

Event	Date or status
FDA approval of SEMGLEE	June 2020
FDA designation as interchangeable	July 2021
Biosimilar exclusivity framework	Governed by the Public Health Service Act
Reference-product exclusivity	Applies to Lantus, not SEMGLEE, under the biosimilar statute
Orange Book status	Not listed as a conventional drug product
Purple Book status	Listed as an insulin glargine-yfgn biosimilar and interchangeable product

An interchangeable designation can provide pharmacy-level substitution advantages under applicable state law, but it does not create a permanent barrier to later biosimilars. Commercial exclusivity depends on the timing of competing biosimilar approvals, patent settlements, device rights, manufacturing capacity, payer contracts, and rebates.

The reference product’s old composition patents do not eliminate newer product-specific barriers. A subsequent insulin-glargine competitor must separately assess patents and regulatory exclusivities relating to its target presentation and manufacturing process.

Which companies compete with SEMGLEE?

SEMGLEE competes in the long-acting insulin glargine market rather than in a narrow excipient market.

Product	Sponsor or commercial company	Active ingredient	U.S. regulatory position
Lantus	Sanofi	Insulin glargine	Reference biologic
SEMGLEE	Biocon Biologics and Viatris	Insulin glargine-yfgn	Biosimilar and interchangeable biosimilar
Basaglar	Eli Lilly and Boehringer Ingelheim	Insulin glargine	Follow-on insulin product
Rezvoglar	Eli Lilly	Insulin glargine-aglr	Interchangeable biosimilar
Toujeo	Sanofi	Insulin glargine U-300	Higher-concentration insulin-glargine product

The most direct competitive threat is Rezvoglar because it also has an interchangeable insulin-glargine designation. Basaglar competes through established payer access, manufacturing scale, and pharmacy familiarity. Toujeo competes on a different concentration and dosing profile.

What commercial opportunities exist for SEMGLEE excipients?

Supply-chain qualification

Excipient suppliers can pursue value through dual sourcing, tighter impurity specifications, and documented change-control packages. A supplier that provides regulatory-ready comparability data can reduce sponsor workload during postapproval changes.

Polysorbate 20 is the most technically sensitive excipient in the formulation. Opportunities include low-peroxide grades, improved oxidation control, tighter fatty-acid distribution specifications, and packaging that reduces oxidative exposure.

Device-compatible formulation support

The pen and cartridge systems create opportunities for excipient and packaging suppliers that can demonstrate low adsorption, low particulate generation, and low extractables and leachables. Compatibility with elastomeric closures, lubricants, adhesives, and plastic components is commercially important.

A formulation that performs well in a glass vial may behave differently in a cartridge or pen. Device-specific studies can support lifecycle extensions and reduce the risk of dose-delivery deviations.

Preservative optimization

m-Cresol supply is established, but preservative performance remains important for multidose products. Opportunities include more robust preservative-effectiveness data, improved closure systems, and in-use stability packages that support longer labeled use after opening.

Replacing m-cresol would be a higher-risk strategy. It could create tolerability, immunogenicity, antimicrobial-effectiveness, and comparability issues. The commercial value of replacement is therefore greatest only where a sponsor has a clear clinical or device-related benefit.

New insulin presentations

The established SEMGLEE formulation can support incremental products such as alternative pen volumes, simplified packaging, or regional presentations. Higher-concentration insulin products require a different risk assessment because changing concentration changes dose-delivery, precipitation, device, and labeling requirements.

Excipient suppliers can also target temperature-tolerant formulations. Reduced dependence on refrigerated distribution could lower logistics costs, but such a product would require substantial stability evidence and may fall outside the established biosimilar comparability envelope.

What generic launch risks exist for SEMGLEE?

A conventional generic launch scenario does not apply. The relevant entry scenario is a later biosimilar or interchangeable biosimilar.

The principal entry risks are:

1. A competing interchangeable insulin-glargine product may obtain pharmacy substitution advantages.
2. Payers may shift formulary preference through net-price contracting.
3. Large insulin manufacturers may use bundled rebates across diabetes portfolios.
4. Device patents may delay or narrow pen-based competition.
5. Manufacturing capacity may limit a competitor’s ability to supply a national launch.
6. Excipient or container-closure changes may create comparability or stability failures.
7. State substitution rules may produce different commercial effects across jurisdictions.

SEMGLEE’s interchangeable status is a commercial asset, but the designation does not guarantee substitution in every pharmacy transaction. State law, payer policy, prescriber instructions, product availability, and pharmacy inventory remain decisive.

How strong is SEMGLEE’s patent and formulation position?

SEMGLEE has a moderate formulation position from a defensive perspective. Its conventional excipient system is difficult to attack as a broad technical concept because the same excipients have long been used in insulin products. The stronger protection is likely to arise from the combination of formulation parameters, manufacturing controls, delivery device, and product-specific quality attributes.

The formulation is commercially efficient but not highly differentiated. That creates two opposing effects:

• It lowers development and supply-chain risk.
• It limits the opportunity to create durable exclusivity based solely on excipient selection.

The highest-value intellectual property opportunities are likely to involve device integration, improved stability, reduced aggregation, temperature tolerance, cartridge compatibility, and manufacturing-process control rather than basic use of glycerol, m-cresol, zinc, or polysorbate 20.

Key Takeaways

• SEMGLEE contains insulin glargine-yfgn at 100 units/mL with glycerol, m-cresol, zinc oxide, polysorbate 20, water for injection, and pH-adjusting agents.
• Glycerol controls tonicity, m-cresol preserves multidose presentations, zinc supports insulin stabilization, and polysorbate 20 limits surface adsorption and aggregation.
• The formulation uses established excipients, which supports supplier redundancy and low excipient cost.
• Polysorbate 20 quality, zinc control, preservative effectiveness, and device compatibility are the main technical priorities.
• SEMGLEE is regulated as a biosimilar and interchangeable biosimilar, not as an Orange Book-listed small-molecule generic.
• Paragraph IV litigation is not the applicable pathway. Competing biologics use the BPCIA patent framework.
• The strongest commercial opportunities are in supply-chain qualification, pen and cartridge compatibility, stability enhancement, and lifecycle management.
• The strongest competitive threats are Rezvoglar, Basaglar, payer contracting, and future interchangeable insulin-glargine products.

FAQs About SEMGLEE Excipient and Commercial Strategy

Does SEMGLEE contain polysorbate 20?

Yes. SEMGLEE contains polysorbate 20 at a low concentration to reduce adsorption and interfacial aggregation during manufacturing, storage, and device use.[1]

Is SEMGLEE the same as Lantus?

SEMGLEE is biosimilar to Lantus and has an interchangeable designation in the United States. It is not the same branded product, but FDA determined that it meets the applicable biosimilarity and interchangeability standards.[1,2]

Can an excipient supplier patent an improved SEMGLEE formulation?

Potentially. Patentable subject matter could include a new excipient combination, concentration range, stability profile, device-compatible formulation, or manufacturing process. Basic use of established SEMGLEE excipients is less likely to provide broad, durable protection.

Does SEMGLEE require cold-chain distribution?

SEMGLEE has labeled storage requirements involving refrigeration before use and controlled in-use storage after opening. Temperature excursions can affect insulin stability and must be evaluated against the approved labeling and stability data.[1]

Are insulin biosimilars subject to Paragraph IV challenges?

No. Paragraph IV certifications apply to ANDA applicants for small-molecule drugs. Insulin biosimilar applicants use the biologic patent framework under Section 351(l) of the Public Health Service Act.[4]

References

1. U.S. Food and Drug Administration. (2024). Semglee (insulin glargine-yfgn) injection, prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/214998s006lbl.pdf

2. U.S. Food and Drug Administration. (2021, July 28). FDA approves first interchangeable biosimilar insulin product. https://www.fda.gov/news-events/press-announcements/fda-approves-first-interchangeable-biosimilar-insulin-product

3. U.S. Food and Drug Administration. (n.d.). Purple Book: Database of licensed biological products. https://purplebooksearch.fda.gov/

4. U.S. Food and Drug Administration. (2023). Questions and answers on biosimilar development and the BPCI Act. https://www.fda.gov/drugs/therapeutic-biologics-applications-bla/questions-and-answers-biosimilar-development-and-bpci-act