How India Exports Valsartan to the World

In the United States, valsartan is approved through Abbreviated New Drug Applications (ANDAs), as listed in the FDA's Orange Book. The FDA has granted numerous ANDAs for valsartan, indicating a competitive generic market. Notably, in March 2024, the FDA approved ANDA 213748 for Sacubitril and Valsartan Tablets, submitted by MSN Pharmaceuticals Inc., a U.S. agent for India's MSN Laboratories Private Limited. This approval underscores the active participation of Indian manufacturers in the U.S. pharmaceutical market.

The substantial number of Indian exporters (259) reflects a robust supply chain catering to the U.S. demand for valsartan. However, manufacturers must adhere to stringent FDA regulations, including compliance with Current Good Manufacturing Practices (cGMP) and prompt reporting of any adverse events or quality issues.

In the European Union, valsartan-containing medicines require marketing authorization from the European Medicines Agency (EMA). For instance, Exforge, a combination of amlodipine and valsartan, received EU-wide approval on January 17, 2007. (ema.europa.eu) Similarly, the UK's Medicines and Healthcare products Regulatory Agency (MHRA) oversees the authorization of valsartan products within the UK.

Manufacturers exporting to the EU and UK must comply with Good Manufacturing Practice (GMP) standards, ensuring product quality and safety. Notably, in September 2018, an EU inspection found Zhejiang Huahai's site in China non-compliant with GMP in the manufacture of valsartan, leading to the suspension of its certificate of compliance. (ema.europa.eu) This incident highlights the critical importance of maintaining GMP compliance to avoid market disruptions.

Valsartan is included in the World Health Organization's (WHO) Model List of Essential Medicines, underscoring its significance in global health. The WHO Prequalification Programme also evaluates valsartan products to ensure they meet international quality standards, facilitating their procurement by UN agencies and other organizations.

Pharmacopoeial standards for valsartan are established in major compendia, including the United States Pharmacopeia (USP), British Pharmacopoeia (BP), European Pharmacopoeia (EP), and Indian Pharmacopoeia (IP). Compliance with these standards is essential for market acceptance and regulatory approval across different regions.

In India, valsartan is classified under Schedule H of the Drugs and Cosmetics Act, indicating that it is a prescription-only medication. The National Pharmaceutical Pricing Authority (NPPA) regulates the pricing of essential medicines, including valsartan, to ensure affordability. Manufacturers intending to export valsartan must obtain a No Objection Certificate (NOC) from the Directorate General of Foreign Trade (DGFT), ensuring compliance with export regulations.

The primary patents for valsartan have expired, leading to increased generic competition globally. This has resulted in a more competitive market landscape, with multiple manufacturers producing and exporting valsartan, particularly from countries like India.

In March 2024, the FDA approved ANDA 213748 for Sacubitril and Valsartan Tablets, submitted by MSN Pharmaceuticals Inc., highlighting the ongoing entry of Indian manufacturers into the U.S. market.

In September 2018, an EU inspection found Zhejiang Huahai's site in China non-compliant with GMP in the manufacture of valsartan, leading to the suspension of its certificate of compliance. (ema.europa.eu)

These developments underscore the dynamic nature of the valsartan market, influenced by regulatory actions, market approvals, and manufacturing compliance issues.

India is a leading producer of Active Pharmaceutical Ingredients (APIs), including valsartan. However, the production of these APIs is heavily reliant on Key Starting Materials (KSMs) sourced from China. According to the U.S. Pharmacopeia (USP), 41% of KSMs used in U.S.-approved APIs are solely sourced from China, while 16% are from India. This dependency poses a significant risk, as any disruption in the supply chain from China can directly impact API production in India.

The reliance on Chinese KSMs has previously led to quality concerns. In July 2018, the World Health Organization (WHO) reported the detection of N-nitrosodimethylamine (NDMA), a probable human carcinogen, in valsartan produced by Zhejiang Huahai Pharmaceuticals in China. This discovery prompted global recalls and highlighted the vulnerabilities associated with concentrated sourcing of critical raw materials. (who.int)

The export market for valsartan from India is highly concentrated. Our proprietary trade data indicates that the top five exporters—Mylan Laboratories Limited, Macleods Pharmaceuticals Ltd, Sandoz Private Limited, Alembic Pharmaceuticals Limited, and Dr. Reddy's Laboratories Ltd—account for 75.5% of total exports. Notably, Mylan Laboratories Limited alone holds a 37.1% share. This concentration increases the risk of supply disruptions, as issues affecting a major supplier can have widespread implications.

To mitigate such risks, the Indian government has implemented the Production Linked Incentive (PLI) scheme, aiming to boost domestic manufacturing of APIs and reduce dependency on imports. While this initiative is a positive step, its effectiveness in diversifying the supplier base for valsartan remains to be fully realized.

Global shipping routes, including the Red Sea and the Strait of Hormuz, are critical for the transportation of pharmaceutical products. Any geopolitical tensions or conflicts in these regions can lead to delays and increased costs. Additionally, ongoing U.S.-China trade tensions have the potential to disrupt the supply of KSMs, further impacting valsartan production in India.

The U.S. Food and Drug Administration (FDA) has previously issued alerts regarding valsartan shortages. For instance, in July 2018, the FDA announced a voluntary nationwide recall of valsartan due to the detection of NDMA impurities. Such incidents underscore the importance of a resilient supply chain to ensure uninterrupted availability of essential medications.

• Diversify KSM Sourcing: Encourage Indian API manufacturers to source KSMs from multiple countries to reduce dependency on China.

• Strengthen Domestic Production: Enhance the effectiveness of the PLI scheme to promote local manufacturing of KSMs and APIs.

• Supplier Base Expansion: Support the growth of smaller pharmaceutical companies to reduce market concentration and single-source risks.

• Supply Chain Monitoring: Implement robust systems to monitor geopolitical developments and shipping routes to anticipate and mitigate potential disruptions.

• Quality Assurance: Establish stringent quality control measures to prevent contamination and ensure compliance with international standards.

RISK_LEVEL: HIGH