Suppliers and packagers for generic pharmaceutical drug: TREPROSTINIL

TREPROSTINIL

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

Applicant	Tradename	Generic Name	Dosage	NDA	NDA/ANDA	Supplier	Package Code	Package	Marketing Start
United Therap	REMODULIN	treprostinil	INJECTABLE;INTRAVENOUS, SUBCUTANEOUS	021272	NDA	United Therapeutics Corporation	66302-101-01	1 VIAL in 1 BOX (66302-101-01) / 20 mL in 1 VIAL	2002-05-22
United Therap	REMODULIN	treprostinil	INJECTABLE;INTRAVENOUS, SUBCUTANEOUS	021272	NDA	United Therapeutics Corporation	66302-102-01	1 VIAL in 1 BOX (66302-102-01) / 20 mL in 1 VIAL	2002-05-22
United Therap	REMODULIN	treprostinil	INJECTABLE;INTRAVENOUS, SUBCUTANEOUS	021272	NDA	United Therapeutics Corporation	66302-105-01	1 VIAL in 1 BOX (66302-105-01) / 20 mL in 1 VIAL	2002-05-22

Global Supplier Landscape and Regulatory Considerations for Treprostinil in Pulmonary Hypertension Treatment

Last updated: April 19, 2025

Treprostinil remains a critical therapeutic agent for pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with interstitial lung disease (PH-ILD), with a complex global supply chain involving over 20 active pharmaceutical ingredient (API) manufacturers and specialty distributors. The market is dominated by synthetic prostacyclin analogs produced under stringent Good Manufacturing Practices (GMP), with key players such as United Therapeutics, Dr. Reddy’s Laboratories, and EuroAPI supporting both branded and generic formulations. Recent developments include a major recall affecting intravenous formulations, expanded distribution partnerships for inhalation therapies, and emerging Asian manufacturers challenging traditional supply hierarchies through cost-competitive production.

---

Pharmaceutical Profile and Therapeutic Significance of Treprostinil

Molecular Characteristics and Mechanism of Action

Treprostinil ((C{23}H{34}O_4)) is a stable synthetic analog of prostacyclin (PGI2) that binds to IP receptors on vascular smooth muscle cells, inducing vasodilation through cyclic AMP-mediated signaling[5][12]. Unlike epoprostenol, its longer half-life ((4.4) hours) allows for subcutaneous, intravenous, inhalational, and oral administration[5][12]. The drug’s bifunctional activity—combining vasodilation with antiplatelet effects—makes it uniquely suited for managing PAH-related right heart strain[2][12].

Clinical Applications and Formulation Diversity

Approved indications include:

• WHO Group 1 PAH: Continuous IV/SC infusion (Remodulin®) or inhalation (Tyvaso®) to improve exercise capacity[5][12].
• PH-ILD: Inhaled treprostinil demonstrated a (27\%) reduction in clinical worsening in the INCREASE trial[4][14].
• Transition therapy: Substituted for epoprostenol in patients with catheter-related complications[5][7].

Novel applications under investigation include idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF), with Phase 3 trials ongoing[14].

---

Global API Manufacturing Ecosystem

Major API Suppliers by Region

Indian Manufacturers (Cost-Leadership Segment)

• Dr. Reddy’s Laboratories: Supplies treprostinil API with USDMF, EU-WC, and Israel DMF filings[2][6]. Their Hyderabad facility specializes in complex synthetics, achieving (99.8\%) purity through chiral chromatography[2].
• Msn Laboratories: Produces SC-grade API at ₹4.2 million/kg, targeting generic injectables[1][12].
• Emcure Pharmaceuticals: Exports to Argentina and Malta at $36–$42/g, leveraging TRIPS flexibilities[3][12].

Western Manufacturers (Premium Segment)

• LGM Pharma (USA): Charges $5,400–$12,000/vial for GMP-certified API, focusing on inhaled formulations[3][8].
• EuroAPI (France): Provides lyophilized API for freeze-dried injectables at €10,000–€12,000/batch[1][12].

East Asian Specialists

• Chirogate International (Taiwan): Dominates prostaglandin intermediate supply, offering treprostinil at $2.5k/g with JDMF certification[1][3].
• Yonsung Fine Chemicals (South Korea): Supplies PPF-grade API to Phase 3 trials under FDA’s CAMD program[14].

---

Regulatory Compliance and Quality Assurance

Dossier Requirements by Market

Region	Key Filings	Stability Data	Impurity Profile
US FDA	USDMF Type II (eCTD)	24-month ICH Q1A	≤0.15% total
EU EMA	CEP No. 2018-072-Rev01	18-month	EP 2.2.58
Japan PMDA	JDMF 24600AMZ10260110	12-month	JP XVII

Recent FDA enforcement actions include Par Pharmaceutical’s March 2024 recall of Lot 57014 due to silicone particulate contamination in 20 mg/mL vials[7]. The incident underscored vulnerabilities in secondary packaging processes, with CAPA requiring inline microscopy for particulate screening[7].

---

Distribution Networks and Market Access

Key Partnerships

• Ferrer-United Therapeutics Alliance: Covers 140+ countries for Tyvaso® inhalation, excluding the US, China, and Japan[4][14]. Ferrer’s B Corp status enables tiered pricing in LMICs, with Chile and Dominican Republic approvals secured in Q1 2025[14].
• Teva Pharmaceuticals: Distributes generic treprostinil injectables through Synergen Rx’s specialty pharmacy network, offering 24/7 clinician support[8].

Pricing Dynamics

Formulation	Average Cost (USD)	Therapeutic Equivalents
IV 20 mg/mL vial	$2,500	1.0 (Remodulin®)
Inhalation solution	$3,200/month	0.85 (Tyvaso®)
Oral ER tablets	$9,800/month	0.92 (Orenitram®)

Generic competition remains limited due to synthesis complexity—a 14-step process requiring cryogenic (−70°C) conditions for diastereomer separation[2][12].

---

Emerging Challenges and Innovations

Particulate Contamination Risks

The 2024 Par Pharmaceutical recall highlighted silicone migration from syringe components, necessitating revisions to USP 〈788〉 for SC/IV formulations[7]. Mitigation strategies include:

• In-process controls: Helium-ionization GC/MS for sub-visible particulates[7].
• Packaging innovations: Cycloolefin copolymer (COC) vials replacing traditional glass[7].

Dry Powder Inhaler (DPI) Advancements

MannKind’s Technosphere® technology enables room-temperature-stable DPI formulations, potentially expanding access in tropical climates[3][14]. Phase 1 trials show (78\%) bioavailability compared to nebulized Tyvaso®[14].

---

Strategic Considerations for Procurement

Supplier Evaluation Criteria

1. Regulatory track record: Prioritize manufacturers with concurrent USDMF/CEP filings[1][9].
2. Vertical integration: Providers like Chirogate controlling prostaglandin intermediates reduce supply chain risks[1][3].
3. Post-marketing surveillance: Opt for distributors with 24/7 pharmacovigilance (e.g., Synergen Rx)[8].

Market Outlook

The treprostinil API market is projected to grow at 6.8% CAGR through 2030, driven by PH-ILD label expansions and pulmonary fibrosis trials[12][14]. However, thermostability challenges for inhalation products and heparin-like contamination risks in injectables necessitate continued quality investments.

---

Key Takeaways

• Diverse supplier base: Over 18 API manufacturers across 7 countries, with India leading in cost-competitive synthetics.
• Regulatory vigilance: Post-recall particulate screening is now industry standard for parenteral forms.
• Therapeutic expansion: Ongoing IPF/PPF trials may double treprostinil’s addressable patient population by 2027.

---

Frequently Asked Questions

1. How do I verify a treprostinil supplier’s GMP compliance?
Check concurrent USDMF (US), CEP (EU), and JDMF (Japan) filings on PharmaCompass[1][9]. Request recent EMA/FDA inspection reports.

2. What was the impact of Par Pharmaceutical’s 2024 recall?
The Class II recall affected 12,000 vials, prompting FDA guidance updates on silicone oil quantification[7].

3. Which certifications are critical for inhaled treprostinil API?
Inhalation-grade API requires USP 〈601〉 aerodynamics testing and EMEA/CVMP/199/04 impurity profiling[5][9].

4. Are there biosimilar versions of treprostinil available?
No—treprostinil is synthetically produced, but generics like Novartis’s version exist for injectables[12].

5. What market trends affect treprostinil pricing?
Expiring patents (Orenitram® in 2026), Asian API entrants, and PH-ILD label expansions drive cost fluctuations[12][14].

"The Ferrer-UTHR partnership exemplifies how strategic distribution can expand access to life-sustaining therapies in underserved markets." – Mario Rovirosa, CEO of Ferrer[4][14].

References

1. https://www.pharmacompass.com/manufacturers-suppliers-exporters/treprostinil
2. https://api.drreddys.com/product/treprostinil
3. https://pharmaoffer.com/api-excipient-supplier/vasodilators/treprostinil
4. https://www.ferrer.com/en/Ferrer-announces-distribution-agreement-with-United-Therapeutics-for-treprostinil-inhalation-solution-for-pulmonary-hypertension-associated-with-interstitial-lung-disease
5. https://tecoland.com/treprostinil-sodium/
6. https://www.manusaktteva.com/api/Treprostinil+sodium
7. https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/par-pharmaceutical-issues-voluntary-nationwide-recall-one-lot-treprostinil-injection-due-potential
8. https://phassociation.org/patients/resources/ph-pharmaceutical-and-specialty-pharmacies/
9. https://www.pharmacompass.com/active-pharmaceutical-ingredients/treprostinil
10. https://pharmaoffer.com/api-excipient-supplier/vasodilators/treprostinil/fda
11. https://api.drreddys.com/product/treprostinil-olamine
12. https://www.pipelinepharma.com/treprostinil-manufacturers
13. https://www.pipelinepharma.com/treprostinil-manufacturers/country/united-states/category/generics
14. https://www.businesswire.com/news/home/20240528462230/en/Ferrer-Obtains-the-Distribution-Rights-for-Treprostinil-Inhalation-Solution-Including-the-Potential-Indications-for-Idiopathic-Pulmonary-Fibrosis-IPF-and-Progressive-Pulmonary-Fibrosis-PPF