Last updated: July 28, 2025
Introduction
Sacubitril and valsartan are pivotal components of the heart failure medication, Entresto (brand name), used globally to improve clinical outcomes for patients with heart failure with reduced ejection fraction (HFrEF). Sacubitril is a neprilysin inhibitor, while valsartan is an angiotensin II receptor blocker (ARB). Their combined formulation represents a significant advancement in cardiovascular pharmacotherapy, necessitating a reliable, high-quality supply chain. This overview explores the key suppliers, manufacturing landscape, and supply chain considerations for both active pharmaceutical ingredients (APIs).
Global Suppliers of Sacubitril
Manufacturing Profile of Sacubitril
Sacubitril is a novel, complex molecule first developed by Novartis. Its synthesis involves intricate chiral chemistry processes, requiring specific expertise and compliance with stringent quality standards.
Major Suppliers and Manufacturers
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Novartis Pharmaceuticals: As the original developer, Novartis controls primary manufacturing but often outsources to third-party API suppliers for commercial supply.
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Contract Manufacturing Organizations (CMOs):
- Hetero Labs, India: Known for synthesizing various complex APIs, including neprilysin inhibitors, Hetero is a notable supplier in the pharmaceutical supply chain. The company has capabilities aligned with the production of sacubitril, especially given India’s prominence in complex API manufacturing.
- Aurobindo Pharma: Another major Indian CMO with experience in chiral and complex synthesis, potentially involved in the sacubitril supply chain due to its extensive portfolio of cardiovascular APIs.
- Zhejiang Hisun Pharmaceutical (China): Known for scalable synthesis of specialty APIs, including neprilysin inhibitors, contributing to supply diversification.
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Emerging Suppliers: With patent protections potentially expiring, additional manufacturers, particularly in India and China, are expanding their capacities and quality standards to include sacubitril APIs, driven by generic and biosimilar markets.
Major Suppliers of Valsartan
Manufacturing Profile of Valsartan
Valsartan was originally developed by Novartis but is now produced by multiple generic manufacturers post-patent expiry in various jurisdictions. The molecule's synthesis involves multiple steps, primarily involving tetrazole ring formation, with extensive manufacturing capacity worldwide.
Leading Suppliers and Manufacturers
Supply Chain Dynamics and Regulatory Landscape
The generic manufacturing landscape has led to a diversified supply chain for valsartan, but challenges arose due to contamination issues in 2018 involving nitrosamine impurities. This prompted rigorous reformulation and stricter quality controls, emphasizing the importance of qualified suppliers with robust quality assurance systems ([2]).
Key Supply Chain Considerations
Quality and Compliance
High-quality API production is vital for regulatory approval and patient safety. Suppliers must adhere to Good Manufacturing Practices (GMP) and meet international standards set by agencies such as the FDA, EMA, and PMDA.
Capacity and Scalability
Given global demand, especially during health crises or patent expirations, the capacity of suppliers to scale production influences drug availability. Multiple sourcing and regional manufacturing hubs mitigate risks associated with supply disruptions.
Intellectual Property and Market Entry
Patent protections influence supplier choices for new or generic formulations. Sacubitril's patent status is critical in determining market entry points for manufacturers.
Supply Chain Risks
Policy changes, geopolitical tensions, and quality-related recalls (notably in the valsartan case) underscore the importance of diversified suppliers and supply chain resilience.
Future Outlook
The supply landscape for sacubitril and valsartan is poised for growth, driven by expanded indications, biosimilar development, and increasing global cardiovascular disease prevalence. India and China continue to dominate API manufacturing, supported by government initiatives to strengthen pharmaceutical manufacturing capabilities ([3]).
Emerging manufacturers aim for regulatory approvals and certifications to secure sectors such as North America and Europe, where stringent standards underpin procurement decisions. Supply chain vigilance and regulatory oversight remain paramount to ensuring uninterrupted access to these vital drugs.
Key Takeaways
- Diverse global manufacturers secure the supply of sacubitril and valsartan, with major firms in India, China, and multinational corporations involved.
- Quality assurance and compliance with GMP standards are fundamental to maintaining supply integrity and regulatory approval.
- Capacity expansion and risk mitigation are ongoing priorities, particularly for valsartan following contamination scandals.
- Patent landscapes influence market dynamics, with generics filling the supply gap post-patent expiry.
- Supply chain resilience hinges on diversification, regional manufacturing, and rigorous quality controls.
FAQs
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Who are the primary suppliers of sacubitril globally?
The original manufacturer, Novartis, leads, but numerous Indian and Chinese CMOs such as Hetero Labs, Aurobindo Pharma, and Zhejiang Hisun Pharmaceutical supply sacubitril APIs to global markets.
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Are there concerns about the quality of valsartan APIs?
Yes. The 2018 nitrosamine contamination scandal prompted increased regulatory scrutiny. Reformed manufacturing practices now emphasize stricter impurity control.
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Is the supply of sacubitril at risk due to patent issues?
Since sacubitril is protected under patent in many jurisdictions, supply chains depend onNovartis or authorized generics. Patent expirations could broaden manufacturing sources in the future.
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Which countries dominate API production for valsartan?
India and China are the primary manufacturing hubs, supplying most global demand for valsartan APIs.
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What factors are critical in selecting suppliers for sacubitril and valsartan?
Quality standards, regulatory compliance, manufacturing capacity, proven reliability, and supply chain resilience are vital factors.
References
- Novartis. “Entresto® (sacubitril/valsartan): Product Information.” 2022.
- U.S. FDA. “Valsartan Recall and Impurity Issues.” 2018.
- Pharmaceutical Technology. “Global API Manufacturing Trends 2022.”
Disclaimer: This analysis is intended for informational purposes and does not constitute an endorsement or specific recommendation for any particular supplier or product.
