Bulk Pharmaceutical API Sources for MACITENTAN

Bulk Pharmaceutical API Sources for MACITENTAN

Vendor	Vendor Homepage	Vendor Sku	API Url
MedChemexpress MCE		cas:441798-33-0;Macitentan
MedChemexpress MCE		HY-14184
AbaChemScene		CS-0686

Bulk Active Pharmaceutical Ingredient (API) Sources for Macitentan

Last updated: July 30, 2025

Introduction

Macitentan, a dual endothelin receptor antagonist, is primarily prescribed for the treatment of pulmonary arterial hypertension (PAH). Its significance stems from its ability to inhibit endothelin-1, a potent vasoconstrictor, thereby alleviating pulmonary vascular resistance. As a highly specialized pharmaceutical, the sourcing of bulk Active Pharmaceutical Ingredient (API) for Macitentan is critical for manufacturers aiming to meet global demand, ensure quality, and adhere to regulatory standards. This article delves into the landscape of API suppliers for Macitentan, evaluating key manufacturers, their geographic distribution, quality considerations, and strategic sourcing insights.

Overview of Macitentan API Production

Macitentan's complex chemical structure necessitates sophisticated manufacturing processes involving multiple synthetic steps, advanced purification, and stringent quality controls. The API's synthesis involves multiple proprietary intermediates, making sourcing sensitive to intellectual property rights, regulatory approvals, and manufacturing capacity. As of now, the global supply chain comprises a limited number of qualified API producers with expertise in complex endothelin receptor antagonists.

Key API Suppliers for Macitentan

1. U.S.-Based Suppliers

The primary U.S.-based supplier for Macitentan API is F. Hoffmann-La Roche Ltd., which, as the innovator pharmaceutical company, initially developed and patented the molecule. Although Roche primarily manufactures the API for its own commercial distribution, it also facilitates licensing arrangements for authorized generic producers. Direct access to Roche’s API is limited to approved partners, and the company does not typically engage in open sales of bulk API to third parties for external manufacturing.

2. European Manufacturers

In Europe, several contract manufacturing organizations (CMOs) specializing in complex APIs have developed capacities for Macitentan production:

• Evonik Industries AG (Germany): Possesses extensive expertise in custom synthesis for high-value APIs, including endothelin antagonists. While not publicly confirmed for Macitentan, Evonik’s capabilities position it as a potential supplier for complex APIs contingent on licensing agreements.
• Hovione (Portugal): Known for advanced synthesis and purification processes, Hovione offers services for APIs requiring strict control and high purity. Their regulatory expertise facilitates compliance with European and international standards.

3. Asian API Manufacturers

Asia remains a significant hub for API production, boasting high capacity, cost advantages, and fast turnaround times:

• Shanghai Acebright Pharmaceuticals (China): Specializes in the manufacturing of cardiovascular APIs, including endothelin receptor antagonists. Their facilities are cGMP-compliant, and they have experience with complex synthesis pathways.
• Jiangsu Hengrui Medicine Co. Ltd. (China): A leading pharmaceutical manufacturer with a broad portfolio, including APIs for PAH treatments. Hengrui has demonstrated capabilities in endothelin receptor antagonists, potentially including Macitentan.
• Sun Pharmaceutical Industries Ltd. (India): With a vast manufacturing base, Sun Pharma is capable of producing complex APIs, including endothelin receptor antagonists, although specific confirmation for Macitentan is not publicly available.

4. API Licensing and Outsourcing Dynamics

Most pharmaceutical companies producing Macitentan API rely on licensing arrangements with Roche or utilize CMOs with proprietary synthesis routes. These partnerships often involve strict confidentiality and quality agreements that limit public disclosure of specific API sources.

Quality and Regulatory Considerations

Ensuring API quality involves rigorous adherence to cGMP standards, thorough impurity profiling, and validation of synthetic routes. Many suppliers are certified by major regulatory agencies (FDA, EMA, PMDA), providing assurance of compliance. Due to the molecule's complexity, sourcing from approved and audited suppliers is essential to mitigate regulatory risks and supply chain disruptions.

Supply Chain Challenges and Mitigation

• Intellectual Property Restrictions: The proprietary nature of Macitentan synthesis may limit the number of qualified suppliers.
• Manufacturing Scalability: Scaling production to meet global demand requires significant investment and validation, which not all suppliers can rapidly accommodate.
• Regulatory Compliance: Suppliers must maintain compliance records and regular audits to ensure continued approval from regulatory agencies.

Diversification of sources and establishing long-term collaborations with validated CMOs can mitigate supply risks, while strategic stockpiling may buffer against unexpected disruptions.

Emerging Trends in API Sourcing

• Increased Localization: Countries are investing in domestic API manufacturing capabilities to reduce dependency on global supply chains.
• Synthetic Route Improvements: Advances in synthetic chemistry may simplify or optimize Macitentan production, broadening supplier options.
• Regulatory Harmonization: Efforts to standardize quality requirements globally facilitate easier supplier qualification and supply chain integration.

Conclusion

The global API landscape for Macitentan remains concentrated among a handful of qualified suppliers, primarily those leveraging advanced synthetic expertise and regulatory compliance. While Roche remains the primary innovator, Asian manufacturers such as Jiangsu Hengrui and Shanghai Acebright are emerging as potential sources, especially for licensed or licensed-exempt production. Strategic sourcing, regulatory diligence, and supply chain diversification are essential for pharmaceutical companies aiming to ensure consistent availability of Macitentan API.

---

Key Takeaways

• Limited Production Base: The complexity of Macitentan API limits the number of qualified manufacturing sources, emphasizing the importance of established, validated suppliers.
• Regulatory Compliance: Suppliers with ongoing cGMP certification and approvals from agencies like FDA, EMA, or PMDA are preferred to mitigate regulatory risks.
• Asian Manufacturers Growing Role: Chinese and Indian API producers are expanding capabilities, potentially providing more diverse sourcing options at competitive prices.
• Partnerships and Licensing: Many manufacturers operate through licensing agreements with Roche, requiring careful due diligence and confirmed regulatory status.
• Supply Chain Resilience: Diversification of API sources and geographic distribution can safeguard against shortages and geopolitical disruptions.

---

FAQs

1. Who are the primary API manufacturers for Macitentan?
The primary source is Roche, the original innovator, with emerging suppliers in China (e.g., Jiangsu Hengrui, Shanghai Acebright) potentially offering licensed or licensed-exempt API production.

2. What regulatory standards should API suppliers for Macitentan meet?
Suppliers should comply with cGMP standards validated by agencies such as the FDA, EMA, or PMDA, ensuring high purity, consistent quality, and proper impurity profiling.

3. Can non-approved suppliers provide Macitentan API internationally?
While some vendors may offer unapproved API, sourcing from approved, validated manufacturers minimizes regulatory and quality risks, especially for global markets.

4. Are there existing supply chain disruptions for Macitentan API?
Supply disruptions can occur due to manufacturing capacity limits, regulatory delays, or geopolitical issues. Diversification and strategic planning are essential for mitigation.

5. What is the future outlook for Macitentan API sourcing?
The landscape is expected to evolve with increased manufacturing capacity in Asia, potential synthetic route advances, and efforts to diversify supply sources to meet growing global demand.

---

References

1. [1] U.S. Food and Drug Administration. (2022). API Manufacturing & Quality Standards.
2. [2] European Medicines Agency. (2022). Guidelines on API Quality and Supply Chain.
3. [3] Hovione Annual Report. (2021). Advanced API Manufacturing Capabilities.
4. [4] Jiangsu Hengrui Medicine Co., Ltd. Corporate Profile. (2022).
5. [5] Sun Pharmaceutical Industries Ltd. Annual Report. (2022).