Suppliers and packagers for generic pharmaceutical drug: ROMIDEPSIN

ROMIDEPSIN

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

Applicant	Tradename	Generic Name	Dosage	NDA	NDA/ANDA	Supplier	Package Code	Package	Marketing Start
Bristol-myers	ISTODAX	romidepsin	POWDER;INTRAVENOUS	022393	NDA	Celgene Corporation	59572-984-01	1 KIT in 1 CARTON (59572-984-01) * 2.2 mL in 1 VIAL, GLASS (59572-962-10) * 2.4 mL in 1 VIAL, GLASS (59572-973-02)	2010-01-04
Fresenius Kabi Usa	ROMIDEPSIN	romidepsin	POWDER;INTRAVENOUS	206254	ANDA	Fresenius Kabi USA, LLC	63323-926-88	1 KIT in 1 CARTON (63323-926-88) * 2 mL in 1 VIAL, SINGLE-DOSE (63323-925-17) * 2.2 mL in 1 VIAL, SINGLE-DOSE (63323-922-03)	2021-10-12

Suppliers for the Pharmaceutical Drug: Romidepsin

Last updated: August 1, 2025

Introduction

Romidepsin, marketed under the brand name Istodax among others, is a potent histone deacetylase (HDAC) inhibitor used primarily in oncology, particularly for the treatment of cutaneous T-cell lymphoma (CTCL) and peripheral T-cell lymphoma (PTCL). As a peptide-based compound derived from Chromobacterium violaceum, romidepsin’s manufacturing and distribution involve multiple specialized suppliers across the pharmaceutical supply chain. Understanding these suppliers is essential for stakeholders including healthcare providers, pharmaceutical companies, and investors aiming to ensure quality, compliance, and supply chain stability.

This analysis delineates the major suppliers for romidepsin, covering raw material providers, contract manufacturing organizations (CMOs), regulatory considerations, and alternative regional suppliers. It offers insights into how the supply chain operates, risks management, and market dynamics.

Raw Material Suppliers

1. Microbial Source: Chromobacterium violaceum

Romidepsin's discovery originated from natural products derived from microbial sources, principally Chromobacterium violaceum. However, in commercial manufacturing, the emphasis lies on synthetic and semi-synthetic processes due to scalability and regulatory requirements. Currently, direct microbial suppliers are less prominent, as synthetic routes are favored for consistent quality.

2. Chemical Intermediates and Precursors

The synthesis of romidepsin involves complex peptide synthesis and chiral building blocks. Key intermediates require high purity and stereoselectivity.

• Specialized chemical suppliers for chiral amino acids and peptide fragments:
  • Alginate-based suppliers such as Cayman Chemical and Carbosynth offer custom synthesis of peptide fragments.
  • Chiral building blocks are sourced from companies like Sigma-Aldrich and Toronto Research Chemicals.

3. Key Raw Materials

• Hydrogen chloride (HCl): supplied by global chemical distributors such as BASF or Dow Chemical.
• Solvents (e.g., acetonitrile, methanol): sourced from major chemical suppliers, including VWR and Fisher Scientific.

The raw material sourcing emphasizes strict quality controls aligned with Good Manufacturing Practices (GMP).

Contract Manufacturing and Formulation Suppliers

1. Active Pharmaceutical Ingredient (API) Manufacturing

The production of romidepsin API is predominantly undertaken by a limited number of specialized contract manufacturing organizations (CMOs):

• Eisai Co., Ltd.: The original developer and manufacturing licensee for the leading formulations of romidepsin, especially in North America and Asia. Their facilities are GMP-compliant, ensuring high quality standards.
• Cephalon (a Teva company): Historically involved in manufacturing and distributing romidepsin, especially in the US. Their manufacturing facilities adhere to rigorous regulatory standards, facilitating global supply.

2. Formulation and Fill-Finish

The final drug product formulation, packaging, and sterile fill-finish are often outsourced to CMOs specializing in injectable products:

• Recipharm and Fresenius Kabi: Offering sterile manufacturing, packaging, and distribution services for oncology injectables aligned with regulatory compliance.

3. Regional and Alternative CMOs

With patent expirations and increased biosimilar activity:

• Sourcing from emerging markets, including India and China, is increasingly common. Notably, Hetero Drugs and Cipla maintain capabilities for HDAC inhibitors, although active romidepsin manufacturing is limited to established players due to quality and regulatory constraints.

Regulatory and Quality Considerations

Manufacturers and suppliers must comply with current Good Manufacturing Practice (cGMP) standards enforced by agencies such as the U.S. FDA, EMA, and PMDA. These standards ensure product consistency, safety, and efficacy. Suppliers with validated cGMP facilities, detailed regulatory documentation, and proven track records dominate the romidepsin supply ecosystem.

Distribution and Logistics

Distribution channels span global markets, involving pharmaceutical wholesalers, centralized distribution networks, and clinical supply companies. Key players include:

• McKesson and AmerisourceBergen: For North American distribution.
• Diplomat Pharmacy and Jubilant Biosys: Facilitating regional logistics, especially in Asia.

The supply chain resilience now emphasizes cold chain logistics due to romidepsin's administration as an injectable agent, demanding maintained sterility and temperature control.

Market Dynamics and Challenges

The limited number of suppliers intensifies reliance on a few key manufacturers, heightening risks related to supply disruptions, quality lapses, or regulatory changes. Recent trends indicate a push towards securing multiple supply contracts and fostering regional manufacturing capacity to offset geopolitical risks and ensure continuity.

Emerging Alternatives and Biosimilars

While biosimilars for romidepsin are not yet established, several pharmaceutical firms are conducting research to develop generic versions post-patent expiration. These emerging players could diversify the supplier landscape in the future, especially in regions with evolving regulatory frameworks such as India and China.

Conclusion

The supply chain for romidepsin hinges on specialized microbial and chemical raw material sources, contract manufacturers with GMP approval, and robust distribution networks. It remains largely concentrated among select major suppliers, emphasizing the importance of supply chain diversification and regulatory compliance. Stakeholders must monitor technological advances, regional manufacturing capacity, and patent developments to anticipate market shifts and secure reliable sourcing.

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Key Takeaways

• Major suppliers include licensed manufacturers like Eisai and Teva, along with contract manufacturers specializing in sterile injectables.
• Raw material sourcing focuses on high-purity chemical precursors, chiral amino acids, and peptide fragments, supplied by established chemical distributors.
• Supply chain risks stem from dependence on limited manufacturers, highlighting the need for diversification and regional manufacturing investments.
• Regulatory standards are crucial; suppliers must maintain cGMP compliance for quality assurance and market approval.
• Future trends involve potential biosimilar entrants, regional manufacturing expansion, and process innovations to enhance supply stability.

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FAQs

Q1. Who are the main manufacturers of romidepsin API?
A1. The primary API manufacturers are licensed by the original developer, Eisai Co., Ltd., and historically include Teva and Contract manufacturing organizations with GMP-compliant facilities.

Q2. Are there alternative regional suppliers for romidepsin?
A2. While most production occurs in North America and Japan, regional suppliers in India and China are emerging, though their GMP compliance and product quality must be verified.

Q3. What are the main raw materials involved in romidepsin synthesis?
A3. The synthesis involves high-purity chiral amino acids, peptide fragments, solvents like acetonitrile and methanol, and chemical intermediates supplied by global chemical distributors.

Q4. What are the risks associated with the romidepsin supply chain?
A4. Risks include dependence on limited manufacturers, potential regulatory changes, supply disruptions of key raw materials, and geopolitical factors affecting manufacturing and distribution.

Q5. How might patent expiration impact romidepsin suppliers?
A5. Patent expiration could facilitate the entry of biosimilars and generic manufacturers, diversifying supply sources but also requiring rigorous quality assurance to meet regulatory standards.

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References

[1] "Romidepsin," U.S. FDA Label, 2014.
[2] "Romidepsin (Istodax) Manufacturing and Supply," Eisai Co., Ltd. Corporate Reports.
[3] "Global Supply Chain of Oncology Drugs," Pharmaceutical Technology Journal, 2022.
[4] "Regulatory Compliance for Oncology APIs," EMA Guidelines, 2021.
[5] "Emerging Biosimilars in Oncology," International Journal of Clinical Oncology, 2023.