Suppliers and packagers for RAMELTEON

RAMELTEON

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

Applicant	Tradename	Generic Name	Dosage	NDA	NDA/ANDA	Supplier	Package Code	Package	Marketing Start
Actavis Labs Fl Inc	RAMELTEON	ramelteon	TABLET;ORAL	091610	ANDA	Actavis Pharma, Inc.	0591-2191-01	100 TABLET in 1 BOTTLE (0591-2191-01)	2019-07-22
Actavis Labs Fl Inc	RAMELTEON	ramelteon	TABLET;ORAL	091610	ANDA	Actavis Pharma, Inc.	0591-2191-30	30 TABLET in 1 BOTTLE (0591-2191-30)	2019-07-22
Andas 5 Holding	RAMELTEON	ramelteon	TABLET;ORAL	215435	ANDA	Westminster Pharmaceuticals, LLC	69367-356-01	100 TABLET, COATED in 1 BOTTLE (69367-356-01)	2023-09-08
Andas 5 Holding	RAMELTEON	ramelteon	TABLET;ORAL	215435	ANDA	Westminster Pharmaceuticals, LLC	69367-356-30	30 TABLET, COATED in 1 BOTTLE (69367-356-30)	2023-09-08

Ramelteon Drug Substance and Intermediate Suppliers

Last updated: February 19, 2026

Ramelteon, a melatonin receptor agonist used for insomnia, relies on a global network of suppliers for its active pharmaceutical ingredient (API) and key intermediates. Analysis of patent filings and regulatory submissions reveals a concentrated supplier base, with a notable presence in Asia. Key players operate under stringent quality controls, a necessity for Good Manufacturing Practice (GMP) compliance.

Who are the Primary Suppliers of Ramelteon API?

The primary suppliers of ramelteon API are contract development and manufacturing organizations (CDMOs) with established expertise in complex organic synthesis. These entities often hold multiple GMP certifications and have undergone rigorous audits by regulatory bodies such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

• Teva Pharmaceutical Industries Ltd.: Teva is a significant producer of generic pharmaceuticals and has been identified as a supplier of ramelteon API. Their large-scale manufacturing capabilities and global distribution network position them as a key player in the supply chain. Teva operates multiple API manufacturing sites, including facilities in Israel and India, adhering to international GMP standards.
• Sun Pharmaceutical Industries Ltd.: Sun Pharma, another Indian pharmaceutical giant, is also involved in the production of ramelteon API. Their portfolio includes a broad range of therapeutic areas, and their dedicated API division focuses on developing and manufacturing complex molecules. Sun Pharma's manufacturing sites in India are regularly inspected by global regulatory authorities.
• Mylan N.V. (now part of Viatris): Prior to its merger with Pfizer's Upjohn division to form Viatris, Mylan was a recognized supplier of ramelteon API. Viatris continues to operate a substantial API manufacturing network, emphasizing quality and regulatory compliance across its global operations.
• Hetero Drugs Limited: Hetero Drugs, a prominent Indian pharmaceutical company, is also a supplier of ramelteon API. They specialize in the development and manufacturing of active pharmaceutical ingredients and finished dosage forms, with a strong emphasis on cost-effective production and adherence to quality standards.

What are the Key Intermediates in Ramelteon Synthesis?

The synthesis of ramelteon involves several critical intermediates, the reliable supply of which is essential for uninterrupted API production. Patent literature and scientific publications detail various synthetic routes, highlighting common intermediate building blocks.

• 2-(1,6,7,8-tetrahydro-2H-indeno[1,2-b]furan-8-yl)acetonitrile: This is a crucial advanced intermediate. Its efficient synthesis and purification directly impact the overall yield and quality of ramelteon. Manufacturers producing this intermediate must have robust process controls to manage stereochemistry and minimize impurities.
• Indeno[1,2-b]furan-8-ylacetic acid derivatives: Various acid chlorides or esters of indeno[1,2-b]furan-8-ylacetic acid can serve as precursors. The precise chemical structure varies depending on the specific synthetic pathway employed by different manufacturers.
• Substituted indanones: Indanone derivatives with specific functional groups are often used in the early stages of ramelteon synthesis. The regioselectivity and enantioselectivity of reactions involving these precursors are critical.
• Propyl halides or tosylates: These are used in alkylation steps to introduce the N-propyl side chain of ramelteon. Control over reaction conditions is necessary to ensure selective alkylation and prevent over-alkylation or unwanted side reactions.

What are the Regulatory Requirements for Ramelteon Suppliers?

Ramelteon suppliers, whether for API or intermediates, must adhere to stringent global regulatory requirements. These regulations are designed to ensure the safety, efficacy, and quality of the final drug product.

• Good Manufacturing Practices (GMP): All suppliers of ramelteon API must operate under current GMP guidelines, as defined by regulatory bodies like the FDA (21 CFR Parts 210 and 211) and the EMA. This includes robust quality management systems, detailed batch records, process validation, and strict control over raw materials and finished products.
• Drug Master Files (DMFs): API manufacturers typically file DMFs with regulatory agencies. These confidential documents contain detailed information about the manufacturing process, facility, quality control, and stability of the API. Pharmaceutical companies referencing a DMF for their finished drug product can access specific sections under a Letter of Authorization (LOA).
• ICH Guidelines: Compliance with International Council for Harmonisation (ICH) guidelines, particularly ICH Q7 (Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients), is essential for global market access.
• Impurity Profiling and Control: Suppliers are required to identify, quantify, and control impurities in the API according to ICH Q3A and Q3B guidelines. This includes genotoxic impurities, which require particularly stringent control limits.
• Change Control Management: Any significant changes to the manufacturing process, facility, or analytical methods must be managed through a formal change control system and, where necessary, reported to regulatory authorities.

How is the Ramelteon Supply Chain Monitored?

Monitoring the ramelteon supply chain involves several key activities to ensure continuity, quality, and compliance.

• Audits: Pharmaceutical companies regularly audit their key API and intermediate suppliers to assess their compliance with GMP and other quality standards. These audits can be scheduled or unannounced.
• Regulatory Inspections: API manufacturing facilities are subject to inspections by regulatory agencies. A history of successful regulatory inspections is a critical indicator of a supplier's reliability.
• Quality Agreements: Formal Quality Agreements are established between the drug product manufacturer and the API supplier. These agreements outline the responsibilities of each party regarding quality control, deviation management, change control, and issue resolution.
• Supply Chain Risk Assessments: Companies conduct risk assessments to identify potential vulnerabilities in the supply chain, such as single-source dependencies, geopolitical instability, or natural disasters, and develop mitigation strategies.
• Analytical Testing: Incoming raw materials, intermediates, and the final API undergo rigorous analytical testing by the drug product manufacturer to verify that they meet predetermined specifications.

What are the Patent Expiries Affecting Ramelteon Supply?

The patent landscape for ramelteon has significantly influenced its supply chain dynamics, particularly with the expiry of key composition of matter patents, paving the way for generic competition.

• Original Composition of Matter Patent: The primary composition of matter patent for ramelteon, held by Takeda Pharmaceutical Company, expired in the United States in October 2017. This date marked a critical turning point, enabling generic manufacturers to enter the market with their own versions of ramelteon.
• Manufacturing Process Patents: While the composition of matter patent has expired, Takeda and other entities may hold patents on specific manufacturing processes, polymorphs, or formulations of ramelteon. These process patents can still provide some market exclusivity or influence the manufacturing methods employed by generic producers. For example, patents related to specific crystalline forms of ramelteon or novel synthetic routes could present challenges or opportunities.
• Generic Entry: Following the expiry of the main composition of matter patent, several generic manufacturers have launched or prepared to launch ramelteon products. This has increased demand for ramelteon API and intermediates, potentially leading to increased competition among suppliers and pressure on pricing.
• Data Exclusivity: In some jurisdictions, market exclusivity may extend beyond patent expiry due to regulatory data protection. However, for ramelteon, the primary market entry for generics has been driven by patent expiry.

Key Takeaways

• The ramelteon API supply chain is dominated by a few key global manufacturers, primarily located in India and Israel.
• Key intermediates in ramelteon synthesis require specialized chemical expertise and stringent quality control to ensure API purity and yield.
• Suppliers must adhere to strict GMP regulations and maintain robust quality management systems to meet global pharmaceutical standards.
• Patent expiry, notably the 2017 expiry of the composition of matter patent, has opened the market to generic competition, influencing supplier demand and market dynamics.
• Continuous monitoring through audits, regulatory inspections, and quality agreements is crucial for maintaining supply chain integrity.

FAQs

1. What is the typical lead time for sourcing ramelteon API from a new supplier? The typical lead time for sourcing ramelteon API from a new supplier can range from 3 to 9 months. This period accounts for supplier qualification, site audits, initial batch production, analytical testing, and the filing of necessary regulatory documentation (e.g., DMF amendments).

2. Are there any known single-source intermediates critical for ramelteon synthesis? While specific supply chain details are often proprietary, historical reliance on certain complex intermediates could pose single-source risks. Pharmaceutical companies actively work to qualify at least two suppliers for critical intermediates to mitigate such risks.

3. What are the primary quality concerns associated with ramelteon API? Primary quality concerns include the control of related substances (impurities), particularly those that are potentially genotoxic, and ensuring consistent polymorphic form. Stereochemical purity is also critical, as ramelteon exists as a racemate.

4. How has the growth of generic ramelteon affected supplier pricing? The increased competition from generic manufacturers has generally led to downward pressure on ramelteon API pricing. Suppliers have responded by optimizing manufacturing processes for cost efficiency and securing competitive raw material sourcing.

5. What is the significance of regulatory inspections for ramelteon API manufacturers? Successful regulatory inspections (e.g., FDA, EMA) are essential for market access. A history of significant findings or import alerts can prevent a supplier from providing API to regulated markets, directly impacting the availability of finished ramelteon products.

Citations

[1] U.S. Food and Drug Administration. (n.d.). Code of Federal Regulations Title 21. Retrieved from [https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/ CFRSearch.cfm?CFRPart=210](https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/ CFRSearch.cfm?CFRPart=210) [2] European Medicines Agency. (n.d.). Good Manufacturing Practice (GMP). Retrieved from https://www.ema.europa.eu/en/human-regulatory/research-development/compliance-regulation/good-manufacturing-practice [3] International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. (1999). ICH Harmonised Tripartite Guideline: Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients Q7. [4] Takeda Pharmaceutical Company Limited. (2005). US Patent 6,956,041. Ramelteon and related compounds. [5] U.S. Food and Drug Administration. (n.d.). Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. Retrieved from https://www.fda.gov/drugs/therapeutic-equivalence-drug-products/orange-book-approved-drug-products-therapeutic-equivalence-evaluations