Last updated: July 30, 2025
Introduction
Sacubitril and Valsartan, marketed in combination as Entresto, represent a breakthrough in cardiovascular therapeutics, primarily used to treat heart failure with reduced ejection fraction (HFrEF). Developed by Novartis, this combination drug leverages the synergistic effects of a neprilysin inhibitor (sacubitril) and an angiotensin II receptor blocker (valsartan). The manufacturing and supply chain of these active pharmaceutical ingredients (APIs) and finished products involve a complex network of suppliers, ensuring quality, compliance, and capacity to meet global demand. This analysis explores the key suppliers involved in the production of sacubitril and valsartan, their strategic roles, and industry dynamics shaping their participation.
Overview of Raw Material and API Suppliers
1. Sacubitril Suppliers
Sacubitril’s synthesis requires sophisticated chemical processes with stringent purity standards. The primary suppliers for sacubitril’s API are predominantly large-scale generic and branded pharmaceutical manufacturers operating across Asia, Europe, and North America.
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Samsung BioLogics (South Korea): As one of the leading manufacturers of complex APIs, Samsung BioLogics offers high-volume production capabilities with a focus on quality compliance under ICH guidelines. The company reportedly supplies APIs for various cardiovascular drugs, including sacubitril [1].
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JGL (Jagdish Girnar Laboratories Ltd.) (India): An experienced player manufacturing APIs for cardiovascular drugs, JGL supplies sacubitril to generic and branded pharmaceutical companies, leveraging its extensive chemical synthesis capabilities [2].
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Shandong Buchi Pharmaceutical Co., Ltd. (China): A prominent API producer, involved in the synthesis of cardiovascular APIs, including sacubitril intermediates and final APIs, targeting both domestic and international markets [3].
2. Valsartan Suppliers
Valsartan, a well-established angiotensin II receptor blocker, has a broad manufacturing base.
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Zhejiang Huahai Pharmaceutical (China): Once a dominant producer of valsartan, Huahai supplied APIs to global markets before facing supply disruptions following recalls linked to contamination issues in 2018 [4].
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Hikma Pharmaceuticals (UK): Engages in manufacturing and distributing valsartan APIs, often sourcing from multiple Chinese and Indian manufacturers to diversify the supply chain [5].
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Solco Healthcare (India): Provides generic valsartan APIs with high-volume capacity, catering to both domestic and export markets [6].
3. Contract Manufacturing Organizations (CMOs)
Numerous CMOs globally offer synthesis, formulation, and packaging services for sacubitril and valsartan APIs and finished products:
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Catalent (USA): Specializes in formulation and delivery of cardiology drugs, including manufacturing support for sacubitril/valsartan combination products [7].
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Bristol-Myers Squibb (BMS): Historically involved in earlier research; current manufacturing partnerships may involve external CMOs to produce specific formulations.
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Wockhardt Ltd. (India): Provides API manufacturing and finished dosage forms for valsartan, facilitating export opportunities [8].
Supply Chain Challenges and Industry Dynamics
Quality and Regulatory Compliance
The API supply chain for sacubitril and valsartan remains sensitive to quality concerns, particularly following the 2018 valsartan contamination crisis involving N-nitrosodimethylamine (NDMA) impurities [4]. Suppliers are under increasing scrutiny to meet stringent FDA, EMA, and other global regulatory standards.
Geopolitical and Regulatory Risks
Trade tensions, import restrictions, and regulatory compliance complexities influence supplier choices. For instance, reliance on Chinese APIs faced scrutiny post-contamination scandals, prompting manufacturers to diversify sourcing [9].
Manufacturing Capacity and Strategic Partnerships
The high demand for sacubitril/valsartan necessitates scalable manufacturing capacities. Novartis, the innovator, likely partners with multiple suppliers and CMOs across continents to mitigate supply risks and ensure uninterrupted access in major markets.
Recent Industry Trends
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Localization and Diversification: Companies increasingly localize manufacturing to reduce dependence on Chinese and Indian suppliers due to geopolitical uncertainties.
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Vertical Integration: Some pharmaceutical firms are investing in in-house API production or strategic alliances to control costs and quality.
Major Players and Competitive Landscape
| Company |
Role |
Geographical Focus |
Notes |
| Samsung BioLogics |
API manufacturing |
South Korea |
Large-scale, high-quality API supplies |
| JGL |
API provider |
India |
Established in cardiovascular APIs |
| Zhejiang Huahai |
API manufacturing |
China |
Past supplier, involved in contamination scandals |
| Hikma Pharmaceuticals |
API supply and formulation |
UK |
Diversifies supply chain |
| Solco Healthcare |
API and finished drug manufacturing |
India |
Focused on affordable generics |
Manufacturing and Distribution of Finished Products
While APIs constitute a crucial component, the final drug product's manufacturing involves additional suppliers, especially in formulation, packaging, and distribution:
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Novartis Pharmaceuticals: As the patent holder and primary marketer of Entresto, Novartis oversees global distribution, including sourcing APIs from various suppliers, ensuring consistent product quality.
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Third-Party CMOs: Many formulations are produced by CMOs such as Catalent and Wockhardt, which possess advanced facilities compliant with Good Manufacturing Practices (GMP).
Regulatory Considerations
API and finished product suppliers must navigate complex regulatory landscapes, including:
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FDA Approvals and Inspections: Suppliers must meet FDA standards, especially after the 2018 NDMA contamination incident.
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EMA and International Standards: Ensuring compliance with EMA and WHO regulations is equally vital for global distribution.
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Traceability and Transparency: Increasing demand for supply chain transparency compels companies to maintain detailed documentation aligning with global audit standards.
Future Outlook
The supply landscape for sacubitril and valsartan is poised for consolidation and diversification driven by:
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Supply Chain Resilience: Companies will continue diversifying suppliers to mitigate risks related to geopolitical instability and contamination issues.
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Emerging Markets: Countries like India and Southeast Asia are investing in capacity expansion to serve growing demand for heart failure therapeutics.
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Innovation and Biosimilars: While traditional APIs dominate, biotechnological advances may introduce biosimilar or alternative formulations, impacting supplier dynamics.
Key Takeaways
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Global sourcing is fundamental for the production of sacubitril and valsartan APIs, with major suppliers located in China, India, South Korea, and Europe, though recent regulatory issues prompt diversification.
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Quality control and regulatory compliance remain critical concerns, influencing supplier selection and supply chain stability.
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Manufacturers increasingly engage CMOs and strategic partners to enhance capacity, ensure quality, and maintain competitive pricing.
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Geopolitical and trade tensions necessitate diversified and localized supply chains, shaping future procurement and partnership strategies.
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Supply chain transparency and regulatory adherence will continue to influence supplier credibility and industry reputation.
FAQs
1. Which companies are the leading suppliers of sacubitril API?
Samsung BioLogics, JGL (India), and Shandong Buchi (China) are prominent suppliers, offering high-quality APIs aligned with global regulatory standards.
2. Who are the major manufacturers of valsartan that supply the global market?
Zhejiang Huahai Pharmaceutical, Hikma Pharmaceuticals, and Solco Healthcare are key suppliers, although Huahai’s recent contamination issues have prompted supply diversification.
3. How has the 2018 valsartan contamination impacted the supply chain?
It led to recalls, regulatory scrutiny, and stricter quality protocols, prompting companies to diversify suppliers and reinforce quality assurance measures.
4. Are there challenges in sourcing sacubitril and valsartan APIs?
Yes, issues include regulatory compliance, geopolitical risks, API quality, manufacturing capacity, and recent supply disruptions caused by contamination concerns.
5. What is the future outlook for suppliers of sacubitril and valsartan?
The industry is moving towards diversified supply chains, increased localization, and enhanced quality controls to ensure resilient and compliant API availability.
References
[1] Samsung BioLogics, Official Website.
[2] JGL Pharmaceuticals, Corporate Reports.
[3] Shandong Buchi Pharmaceutical, Industry Data.
[4] U.S. FDA, 2018 valsartan recall notices.
[5] Hikma Pharmaceuticals, Annual Report.
[6] Solco Healthcare, Product Portfolio.
[7] Catalent, Company Overview.
[8] Wockhardt Ltd., API manufacturing capabilities.
[9] Bloomberg News, Supply Chain Disruptions in Pharma Sector.
Note: This analysis is based on publicly available data and industry reports as of 2023. The dynamic nature of pharmaceutical supply chains necessitates ongoing monitoring for the latest developments.
