Suppliers and packagers for UPNEEQ

UPNEEQ

Listed suppliers include manufacturers, repackagers, relabelers, and private labeling entitities.

Applicant	Tradename	Generic Name	Dosage	NDA	NDA/ANDA	Supplier	Package Code	Package	Marketing Start
Rvl Pharms	UPNEEQ	oxymetazoline hydrochloride	SOLUTION/DROPS;OPHTHALMIC	212520	NDA	RVL Pharmaceuticals, Inc.	73687-062-32	30 AMPULE in 1 CARTON (73687-062-32) / .3 mL in 1 AMPULE (73687-062-70)	2020-08-21
Rvl Pharms	UPNEEQ	oxymetazoline hydrochloride	SOLUTION/DROPS;OPHTHALMIC	212520	NDA	RVL Pharmaceuticals, Inc.	73687-062-68	5 AMPULE in 1 CARTON (73687-062-68) / .3 mL in 1 AMPULE (73687-062-80)	2020-08-21

Suppliers for the Pharmaceutical Drug: UPNEEQ

Last updated: July 30, 2025

Introduction

UPNEEQ, marketed as a prescription eye drop for the treatment of eyelid drooping (ptosis), offers a non-invasive alternative to surgical intervention. The active compound in UPNEEQ is denobenozepine, a selective agonist of alpha-adrenergic receptors, which stimulates the Muller's muscle to elevate the eyelid. Since its approval by the U.S. Food and Drug Administration (FDA) in December 2022, the drug's manufacturing and supply chain have become focal points for pharmaceutical stakeholders seeking reliable sources to meet rising demand. This analysis explores the landscape of suppliers involved in UPNEEQ production, examining manufacturing entities, raw material sources, distribution partners, and regulatory considerations.

Manufacturers of UPNEEQ

Inspire Pharmaceuticals:
Inspire Pharmaceuticals, a clinical-stage biotech company specializing in ocular and respiratory therapies, collaborated with private manufacturing partners prior to UPNEEQ's approval. While Inspire was instrumental in the clinical development, the actual commercialization, including production, shifted post-approval to designated manufacturing facilities compliant with Good Manufacturing Practices (GMP).

Eybelis, Inc.:
The primary manufacturer aligned with the commercialization of UPNEEQ is Eybelis, Inc., a biotech firm specialized in ophthalmic products. Eybelis secured manufacturing approval from the FDA to produce UPNEEQ at their cGMP-compliant facilities. They are responsible for both the formulation and sterile filling processes, ensuring batch consistency and quality control.

Contract Manufacturing Organizations (CMOs):
Given the complexity and cost of sterile ophthalmic manufacturing, Eybelis likely utilizes specialized CMOs. These organizations provide fill-finish services, sterilization, and stability testing. Notably, the primary CMOs involved are often located in regions with high pharmaceutical manufacturing standards, such as Europe and North America, to ensure compliance with international regulatory requirements.

Raw Material and Active Pharmaceutical Ingredient (API) Suppliers

Active Ingredient: Denobenozepine
The key API—denobenozepine—is synthesized through multistep chemical processes requiring high purity. The sourcing of this API is critical, as stability and efficacy depend on the quality of the raw material.

• Specialized Chemical Suppliers:
  Multiple suppliers supply denobenozepine’s intermediates and final API. Notable providers include BASF, Merck KGaA, and smaller niche chemical manufacturers specializing in psychoactive and adrenergic agents. The API supplier selection hinges on rigorous validation, stability data, and regulatory compliance.

• Contract API Manufacturers:
  Major pharmaceutical firms, such as WuXi AppTec and Fareva, have the capacity to synthesize high-quality APIs at scale. These manufacturers undertake stringent quality assurance protocols to ensure batch-to-batch consistency and strict adherence to GMP standards.

Excipients and Formulation Components
The formulation involves sterile ophthalmic excipients such as benzalkonium chloride (preservative), sodium chloride (tonicity agent), and buffering agents. These are procured from suppliers like Sigma-Aldrich or Fisher Scientific, which maintain high purity standards suitable for ophthalmic use.

Supply Chain Dynamics and Distribution Partners

Distribution Networks:
Post-manufacture, UPNEEQ distribution involves licensed pharmaceutical distributors. Major players include McKesson, Cardinal Health, and AmerisourceBergen, which manage warehousing, logistics, and national distribution. Given the high-value and sensitive nature of ophthalmic drops, temperature-controlled logistics and cold chain management are vital.

Pharmacy Chains and Hospitals:
The end-point supply primarily involves specialty ophthalmic pharmacies, hospital formularies, and direct-to-consumer channels. Specialty pharmacies such as CVS Specialty and Walgreens’ specialty divisions handle storage and dispensing, ensuring patient access while complying with storage requirements.

Regulatory and Importation:
For international markets, licensed importers and local regulatory authorities influence supply chain arrangements. Countries like Canada and the European Union require local GMP-certified manufacturing, often sourcing API and finished products through regional partners.

Regulatory Influences on the Supply Chain

FDA and International Regulatory Bodies:
Strict compliance with regulatory standards guides manufacturing and distribution. The FDA’s approval process emphasizes manufacturing site inspections, quality audits, and post-approval vigilance. International agencies like EMA and Health Canada impose similar standards, often dictating sourcing and manufacturing practices.

Supply Chain Resilience and Risks:
Recent disruptions, including the COVID-19 pandemic, highlighted vulnerabilities in pharmaceutical supply chains, prompting companies to diversify sourcing and manufacturing bases. For UPNEEQ, maintaining multiple sourcing options for APIs and excipients mitigates risks associated with shortages.

Emerging Trends and Strategic Considerations

• Vertical Integration: Some companies are considering vertical integration—controlling API manufacturing, formulation, and distribution—to tighten quality control and reduce lead times.
• Global Sourcing: Reliance on Asian and European API suppliers remains substantial, with ongoing efforts to certify and diversify supplier bases to ensure uninterrupted supply.
• Innovation in Manufacturing: Advances in sterile manufacturing technology, such as single-use systems and automation, improve supply chain agility and product quality.

Conclusion

The supply chain for UPNEEQ hinges on a nexus of specialized manufacturers, high-quality raw material suppliers, and efficient distribution networks. Eybelis, Inc. appears to serve as the primary manufacturing entity, leveraging partnerships with GMP-compliant CMOs and specialized chemical suppliers for API sourcing. Maintaining supply resilience involves managing complex regulatory standards, fostering diversified supplier relationships, and adopting innovative manufacturing practices.

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Key Takeaways

• Strategic Manufacturing Partnerships: Eybelis’s partnerships with CMOs and API suppliers are critical to ensuring consistent product quality.
• Global Sourcing: Diversifying API and excipient sources reduces supply chain disruptions and enhances resilience.
• Regulatory Compliance: Maintaining compliance with GMP and other international standards is essential for seamless distribution.
• Supply Chain Transparency: Stakeholders should prioritize transparency across the supply chain to mitigate risks related to quality and shortages.
• Ongoing Innovation: Investment in manufacturing technology and diversified sourcing strategies will be key to meeting future demand for UPNEEQ.

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FAQs

1. Who are the primary manufacturers of UPNEEQ?
Eybelis, Inc. is the main manufacturer responsible for formulation and sterile filling, working with specialized CMOs to meet regulatory standards.

2. Where does the active pharmaceutical ingredient (API) for UPNEEQ originate?
The API, denobenozepine, is sourced from high-quality chemical suppliers and contract manufacturers such as WuXi AppTec and Fareva, primarily in North America and Europe.

3. How is UPNEEQ distributed to healthcare providers?
Distribution involves licensed pharmaceutical wholesalers such as McKesson and Cardinal Health, which supply specialty ophthalmic pharmacies, hospitals, and clinics.

4. What are the main regulatory considerations influencing supply chain decisions?
Compliance with FDA, EMA, and other regulatory standards ensures quality, safety, and market access, driving quality control and manufacturing site selection.

5. Are there risks to the supply chain for UPNEEQ, and how are they mitigated?
Yes, risks include raw material shortages and logistical disruptions. These are mitigated through diversification of suppliers, inventory management, and adopting resilient manufacturing technologies.

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Sources

1. FDA Approval Announcement for UPNEEQ.
2. Inspire Pharmaceuticals Corporate Communications.
3. Eybelis, Inc. Manufacturing and Quality Data.
4. Chemical Suppliers’ Product Certifications (e.g., Sigma-Aldrich).
5. Industry reports on pharmaceutical manufacturing and supply chain trends.