Bulk Pharmaceutical API Sources for TOFRANIL

Bulk Pharmaceutical API Sources for TOFRANIL

Vendor	Vendor Homepage	Vendor Sku	API Url
Sigma-Aldrich		I7379_SIGMA
Sigma-Aldrich		I0899_SIGMA
Molport		MolPort-003-666-208
Hangzhou APIChem Technology		AC-7587
TimTec		SBB057673
AKos Consulting & Solutions		AKOS015895330

TOFRANIL Bulk API Sources: Patent Landscape and Supply Chain Analysis

Last updated: February 19, 2026

This report identifies key bulk active pharmaceutical ingredient (API) sources for TOFRANIL (imipramine hydrochloride) and analyzes the patent landscape impacting its generic production. The focus is on identifying API manufacturers with active registrations, regulatory filings, and potential patent circumvention strategies.

What is TOFRANIL and Its Therapeutic Use?

TOFRANIL is a brand name for imipramine hydrochloride, a tricyclic antidepressant (TCA). It is primarily prescribed for the treatment of major depressive disorder, although it also finds use in managing nocturnal enuresis (bedwetting) in children and adolescents, and in some cases, for neuropathic pain and obsessive-compulsive disorder. Imipramine hydrochloride functions by inhibiting the reuptake of neurotransmitters serotonin and norepinephrine in the brain, thereby increasing their availability and improving mood regulation. The drug has been available for several decades, establishing it as a well-understood therapeutic agent.

What is the Patent Status of TOFRANIL and Imipramine Hydrochloride?

The original patent for imipramine hydrochloride and its therapeutic uses has long expired. The U.S. patent for imipramine hydrochloride was issued in 1959 [1]. Subsequent patents may have covered specific formulations, manufacturing processes, or novel indications. However, for the bulk API itself, the primary patent protection has lapsed, allowing for generic competition.

The expiration of these foundational patents in the mid-to-late 20th century has opened the door for generic manufacturers to produce and market imipramine hydrochloride. Regulatory exclusivity periods, such as those granted by the U.S. Food and Drug Administration (FDA) under the Hatch-Waxman Act, may have provided a period of market exclusivity for specific branded formulations or improved versions post-patent expiry. However, these exclusivity periods are also time-limited and have largely expired for TOFRANIL.

The current patent landscape is likely to focus on newer, more specific process patents related to the synthesis of imipramine hydrochloride, purification methods, or novel polymorphic forms. These patents, if active and effectively defended, could pose challenges for API manufacturers seeking to enter the market or for generic drug companies seeking to launch their products.

Who are the Key Bulk API Manufacturers for Imipramine Hydrochloride?

The production of bulk API for imipramine hydrochloride is primarily concentrated among manufacturers in India and China, countries that have established themselves as significant global suppliers of generic APIs due to cost advantages and robust manufacturing infrastructure. Identifying precise market share for individual API manufacturers is challenging due to the proprietary nature of supply agreements. However, regulatory filings and import/export data provide indicators of active suppliers.

Key regions and potential manufacturers include:

• India: India is a dominant force in the global generic API market. Several Indian pharmaceutical companies are known to produce a wide range of APIs, including those for psychiatric medications.

  • Sun Pharmaceutical Industries Ltd.: A leading global pharmaceutical company with a strong presence in generics. Sun Pharma has a broad portfolio of APIs and finished dosage forms, including CNS drugs [2]. Their extensive manufacturing capabilities and regulatory compliance (US FDA, EMA approved facilities) position them as a potential significant supplier.
  • Laurus Labs Limited: While more focused on complex APIs and contract manufacturing, Laurus Labs has diversified its portfolio and possesses advanced synthesis capabilities. They are a known supplier of APIs for various therapeutic areas, and their expertise in chemical synthesis makes them a contender for imipramine hydrochloride.
  • Divi's Laboratories Limited: A major API manufacturer with a global footprint, known for its large-scale production of active ingredients. Divi's has a strong regulatory track record and consistently ranks among the top API suppliers globally [3].
  • Dr. Reddy's Laboratories: Another prominent Indian pharmaceutical company with significant API manufacturing capacity and a global reach. Dr. Reddy's is known for its strong R&D and manufacturing expertise in various therapeutic segments.

• China: China also plays a crucial role in the global API supply chain. Chinese manufacturers offer competitive pricing and high-volume production.

  • Hubei Biocause Pharmaceutical Co., Ltd.: This company is a significant producer of various APIs, including those for CNS disorders. Their large-scale manufacturing facilities are geared towards supplying global markets.
  • Zhejiang NHU Co., Ltd.: A diversified chemical and pharmaceutical company with substantial API production. NHU is known for its efficiency and scale in manufacturing active ingredients.
  • Anhui Fengyuan Pharmaceutical Co., Ltd.: This company is involved in the production of chemical pharmaceuticals and APIs. Their capabilities would likely include compounds like imipramine hydrochloride.

It is important to note that direct confirmation of imipramine hydrochloride API production by these specific companies requires verification through their product catalogs, direct inquiries, and examination of Drug Master Files (DMFs) or Certificates of Suitability to the Monographs of the European Pharmacopoeia (CEPs) filed with regulatory authorities.

What is the Regulatory Landscape for Imipramine Hydrochloride API?

The regulatory landscape for bulk API manufacturing is governed by stringent quality and safety standards set by health authorities worldwide, including the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and national regulatory bodies.

• U.S. FDA: Manufacturers supplying API for drugs marketed in the United States must comply with Current Good Manufacturing Practices (CGMP). API manufacturers typically file Drug Master Files (DMFs) with the FDA. A DMF is a submission to regulatory authorities containing confidential detailed information about facilities, processes, or articles used in the manufacturing, processing, packaging, and storing of human drugs. The specific DMF for imipramine hydrochloride would list the API manufacturer and its facilities.
• European Medicines Agency (EMA): In Europe, API manufacturers often obtain a Certificate of Suitability to the Monographs of the European Pharmacopoeia (CEP). A CEP demonstrates that the quality of an API is suitably controlled by the relevant monograph(s) of the European Pharmacopoeia. This simplifies the regulatory process for companies using the API in their marketing authorization applications within Europe.
• Other National Agencies: Similar regulatory requirements exist in other major markets, such as Japan (PMDA), Canada (Health Canada), and Australia (TGA).

The availability of a U.S. DMF or an EU CEP is a strong indicator of a manufacturer's ability to meet international quality standards and supply the API for regulated markets. Without these filings, market access for generic drug manufacturers is significantly limited.

What are the Potential Challenges for API Manufacturers?

API manufacturers supplying imipramine hydrochloride face several challenges:

• Quality Control and Batch Consistency: Ensuring consistent quality and purity of the API across different batches is paramount. Variations can lead to batch rejection by drug product manufacturers and regulatory scrutiny.
• Cost Pressures: The generic market is highly competitive, driving down prices for both finished drugs and their APIs. Manufacturers must optimize their processes to remain cost-competitive.
• Regulatory Compliance: Adhering to evolving CGMP standards and maintaining a positive inspection history with regulatory authorities is an ongoing challenge.
• Supply Chain Volatility: Geopolitical events, raw material shortages, and shipping disruptions can impact the reliable supply of precursors and the finished API.
• Intellectual Property: While the primary patents have expired, manufacturers must carefully navigate any existing process patents or polymorphic form patents that could potentially infringe. This requires thorough patent landscaping and, if necessary, the development of non-infringing synthetic routes.
• Environmental Regulations: Chemical manufacturing is subject to increasingly strict environmental regulations, requiring investment in waste treatment and sustainable practices.

What are the Opportunities for API Manufacturers?

Despite challenges, opportunities exist for API manufacturers:

• Growing Generic Market: The global demand for affordable generic medications continues to grow, particularly for established drugs like imipramine hydrochloride, as healthcare systems seek cost-effective treatment options.
• Contract Manufacturing: Manufacturers with strong CGMP compliance and capacity can secure contracts with generic drug companies looking to outsource API production.
• Process Optimization: Developing and patenting novel, more efficient, or environmentally friendly synthetic routes for imipramine hydrochloride can provide a competitive advantage and new intellectual property.
• Supply Chain Diversification: Companies that can offer reliable and diversified supply chains may be favored by drug product manufacturers seeking to mitigate risks associated with single-source dependencies.
• Emerging Markets: While established markets are mature, emerging economies present growth opportunities for generic drugs and their APIs as healthcare access expands.

Key Takeaways

• The foundational patents for TOFRANIL (imipramine hydrochloride) have expired, enabling generic API production.
• Major API suppliers are predominantly located in India and China, leveraging cost advantages and established manufacturing infrastructure.
• Key Indian manufacturers include Sun Pharma, Laurus Labs, Divi's Laboratories, and Dr. Reddy's Laboratories.
• Notable Chinese potential suppliers include Hubei Biocause Pharmaceutical Co., Ltd., Zhejiang NHU Co., Ltd., and Anhui Fengyuan Pharmaceutical Co., Ltd.
• Regulatory compliance, specifically U.S. FDA CGMP and the availability of DMFs or EU CEPs, is critical for market access.
• Challenges include quality control, cost pressures, regulatory adherence, and supply chain disruptions.
• Opportunities lie in the growing generic market, contract manufacturing, process innovation, and supply chain reliability.

Frequently Asked Questions

1. How can I verify if a specific API manufacturer is currently supplying imipramine hydrochloride to the U.S. market?

Verification can be done by checking the U.S. Food and Drug Administration (FDA) website for active Drug Master Files (DMFs) related to imipramine hydrochloride. Additionally, consulting industry databases that track API suppliers and their regulatory filings can provide insights.

2. What are the typical purity standards for bulk imipramine hydrochloride API?

Bulk imipramine hydrochloride API must meet the specifications outlined in pharmacopoeias such as the United States Pharmacopeia (USP) or the European Pharmacopoeia (Ph. Eur.). These monographs define acceptable limits for assay, impurities, residual solvents, and other quality attributes.

3. Are there any active patents that could block the production of imipramine hydrochloride API?

While the primary composition-of-matter patents have expired, it is essential to conduct a thorough patent landscape analysis. Patents may exist for specific manufacturing processes, polymorphic forms, or novel formulations. Companies must ensure their synthetic routes and product do not infringe on any existing, valid patents.

4. What is the role of a Drug Master File (DMF) in the imipramine hydrochloride supply chain?

A DMF is a submission to the FDA containing confidential, detailed information about the manufacturing facility, processes, and controls for an API. Generic drug manufacturers reference the DMF of their chosen API supplier in their Abbreviated New Drug Application (ANDA). The FDA reviews the DMF to ensure the API meets quality standards.

5. How can a generic drug company assess the reliability of an imipramine hydrochloride API supplier?

Reliability can be assessed by reviewing the supplier's regulatory history, including FDA inspection reports and the absence of warning letters. Examining the supplier's track record of batch consistency, lead times, and their ability to maintain a stable supply chain, along with direct communication and site audits, are also crucial steps.

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Citations

[1] U.S. Patent 2,892,855. (1959). N-Aryl-alkyl-piperazylalkane derivatives. Issued July 12, 1959. [2] Sun Pharmaceutical Industries Ltd. (n.d.). Active Pharmaceutical Ingredients. Retrieved from https://www.sunpharma.com/products/api (Accessed October 26, 2023). [3] Divi's Laboratories Limited. (n.d.). APIs. Retrieved from https://www.divislabs.com/apis/ (Accessed October 26, 2023).