Subscribe to access the full database, or Start Trial
Applicant	Tradename	Generic Name	Dosage	NDA	NDA/ANDA	Supplier	Package Code	Package	Marketing Start
Legacy Pharma	MOTOFEN	atropine sulfate; difenoxin hydrochloride	TABLET;ORAL	017744	NDA	Sebela Pharmaceuticals Inc.	54766-200-10	100 TABLET in 1 BOTTLE (54766-200-10)	2017-04-11
Legacy Pharma	MOTOFEN	atropine sulfate; difenoxin hydrochloride	TABLET;ORAL	017744	NDA	Legacy Pharma USA Inc.	83107-011-10	100 TABLET in 1 BOTTLE (83107-011-10)	2026-01-01
Legacy Pharma	MOTOFEN HALF-STRENGTH	atropine sulfate; difenoxin hydrochloride	TABLET;ORAL	017744	NDA	Sebela Pharmaceuticals Inc.	54766-200-10	100 TABLET in 1 BOTTLE (54766-200-10)	2017-04-11
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>NDA/ANDA	>Supplier	>Package Code	>Package	>Marketing Start

Last updated: February 19, 2026

This analysis identifies key suppliers for Atropine Sulfate and DifenoXin Hydrochloride, detailing their manufacturing capabilities, regulatory compliance, and market presence. The objective is to provide actionable intelligence for pharmaceutical companies assessing supply chain resilience and potential partnerships.

WHAT ARE THE PRIMARY MANUFACTURING SOURCES FOR ATROPINE SULFATE?

Atropine Sulfate, a tropane alkaloid used to treat bradycardia and as an antidote for certain pesticide poisonings, is primarily manufactured by specialized chemical and pharmaceutical ingredient producers. Production often involves extraction from plants like Atropa belladonna or chemical synthesis.

Key Manufacturers and Their Capacities:
- Jubilant Pharmova Limited: An Indian multinational pharmaceutical company. Jubilant Pharmova's Drug Discovery & Development Solutions (DDDS) segment offers API manufacturing. Their capabilities include complex APIs, and they have a track record of supplying atropine sulfate.
- Anhui Haoyuan Pharmaceutical Group Co., Ltd.: A Chinese pharmaceutical manufacturer. Haoyuan is a significant producer of active pharmaceutical ingredients (APIs), including various alkaloids. Their operations adhere to GMP standards and are subject to international regulatory oversight.
- Acacia Pharma: While more focused on finished dosage forms, Acacia Pharma may source its atropine sulfate from GMP-certified manufacturers globally. Their supply chain partners are typically vetted for quality and regulatory compliance.
- Siegfried AG: A Swiss-based company providing contract development and manufacturing organization (CDMO) services. Siegfried has broad API manufacturing expertise and can produce complex molecules like atropine sulfate under strict quality controls.
Geographic Concentration: Production of Atropine Sulfate is concentrated in regions with established fine chemical and pharmaceutical manufacturing infrastructure, notably India and China, due to cost efficiencies and specialized expertise. Europe also has significant players involved in API synthesis and purification.
Regulatory Landscape: Manufacturers supplying Atropine Sulfate must comply with Good Manufacturing Practices (GMP) as defined by regulatory bodies such as the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the World Health Organization (WHO). Certificates of Suitability to the Monographs of the European Pharmacopoeia (CEP) are often sought for European market access.

WHAT ARE THE DOMINANT SUPPLIERS OF DIFENOXIN HYDROCHLORIDE?

Difenoxin Hydrochloride, a synthetic opioid agonist structurally related to meperidine, is primarily used in combination with atropine sulfate to treat diarrhea. Its synthesis is complex, requiring specialized chemical expertise.

Leading Producers of Difenoxin Hydrochloride:
- Nectar Lifesciences Limited: An Indian pharmaceutical company that manufactures APIs. Nectar Lifesciences has diversified product portfolios and manufactures various therapeutic categories, potentially including controlled substances like difenoxin hydrochloride, subject to stringent licensing and regulatory approvals.
- Shanxi Hisun Pharmaceutical Co., Ltd.: A Chinese pharmaceutical company with a strong focus on API production. Hisun is known for its capabilities in complex organic synthesis and its adherence to international quality standards, making it a potential supplier for difenoxin hydrochloride.
- Pfizer Inc.: While Pfizer is a major pharmaceutical company with finished products containing difenoxin hydrochloride (e.g., Lomotil), they also have internal API manufacturing or secure supplies from select, highly audited partners. Their internal production is subject to rigorous quality assurance.
- Tefron Pharmaceutical Ltd.: An Israeli pharmaceutical manufacturer. Tefron specializes in APIs and intermediates, with a robust quality management system. Their expertise in pharmaceutical synthesis positions them as a potential supplier for controlled substances.
Synthesis and Sourcing Considerations: The synthesis of difenoxin hydrochloride is a multi-step process. Suppliers must demonstrate expertise in handling controlled substances, maintaining secure manufacturing environments, and meeting specific purity profiles. Sourcing often involves long-term contracts with established API manufacturers.
Controlled Substance Regulations: The production and distribution of difenoxin hydrochloride are heavily regulated due to its opioid nature. Manufacturers must possess licenses from national drug enforcement agencies (e.g., the Drug Enforcement Administration in the U.S.) and comply with international drug control treaties. Supply chains must maintain strict security protocols to prevent diversion.

WHAT ARE THE CRITICAL REGULATORY AND QUALITY REQUIREMENTS FOR THESE APIS?

Compliance with stringent regulatory and quality standards is paramount for both Atropine Sulfate and Difenoxin Hydrochloride to ensure patient safety and efficacy.

Good Manufacturing Practices (GMP):
- FDA cGMP: Compliance with Current Good Manufacturing Practices (21 CFR Parts 210 and 211) is mandatory for APIs intended for the U.S. market. This includes stringent controls over facilities, equipment, processes, and quality systems.
- EMA GMP: The EU GMP guidelines, as detailed in EudraLex Volume 4, are essential for API suppliers targeting European Union member states. This involves rigorous quality management, personnel training, and documentation.
- ICH Guidelines: International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines, such as ICH Q7 for APIs, provide globally recognized standards for GMP.
Pharmacopoeial Standards:
- United States Pharmacopeia (USP): Atropine Sulfate and Difenoxin Hydrochloride must meet the specifications outlined in the USP monograph, including tests for identity, purity, assay, and impurities.
- European Pharmacopoeia (Ph. Eur.): Compliance with Ph. Eur. monographs is required for APIs sold in Europe. This includes similar analytical testing requirements.
- Japanese Pharmacopoeia (JP): For markets in Japan, adherence to JP standards is necessary.
Controlled Substance Licensing and Security:
- DEA Registration (U.S.): Manufacturers, distributors, and importers of difenoxin hydrochloride must be registered with the U.S. Drug Enforcement Administration (DEA) and adhere to quota restrictions and security requirements outlined in the Controlled Substances Act.
- International Narcotics Control Board (INCB): Suppliers must comply with INCB regulations for the international trade of controlled substances.
- Supply Chain Security: Robust security measures are required to prevent theft and diversion of difenoxin hydrochloride throughout the manufacturing and distribution process. This includes secure storage, transportation, and record-keeping.
Impurity Profiling and Control:
- Manufacturers must identify, quantify, and control impurities, including process-related impurities and degradation products, to ensure the safety and stability of the API. ICH Q3A (R2) and Q3B (R2) guidelines provide frameworks for impurity control.

WHAT IS THE MARKET DYNAMIC AND FUTURE OUTLOOK FOR THESE APIS?

The market for Atropine Sulfate and Difenoxin Hydrochloride is influenced by their therapeutic applications, regulatory policies, and global pharmaceutical demand.

Atropine Sulfate Market Drivers:
- Cardiovascular Health: Continued demand for treatments for bradycardia and as a component in emergency medical kits.
- Ophthalmology: Use in eye drops for diagnostic and therapeutic purposes.
- Antidote Applications: Essential use in managing organophosphate poisoning.
- Emerging Markets: Increasing healthcare access in developing nations drives demand for essential medicines.
- Supply Chain Resilience: Recent global events have increased focus on diversifying API sources and ensuring supply chain security, potentially benefiting established, compliant manufacturers.
Difenoxin Hydrochloride Market Drivers:
- Gastrointestinal Treatments: Primary use remains in the management of diarrhea, particularly in combination products.
- Regulatory Scrutiny: Strict regulations and the potential for abuse limit market expansion and favor suppliers with robust compliance frameworks.
- Generic Competition: The market is largely driven by generic versions of combination products, emphasizing cost-effective manufacturing.
- Opioid Crisis Impact: Increased awareness and stricter controls on opioid-based medications could indirectly influence the market, though difenoxin's primary use is not for chronic pain management.
Supply Chain Risks and Mitigation:
- Geopolitical Instability: Disruptions in major manufacturing regions can impact availability.
- Regulatory Changes: New or updated regulations can necessitate process modifications or compliance investments.
- Raw Material Volatility: Fluctuations in the availability and cost of precursors can affect API pricing.
- Mitigation Strategies: Diversifying supplier bases across different geographic regions, engaging in long-term supply agreements, and conducting thorough supplier audits are critical.
Future Outlook:
- The demand for Atropine Sulfate is expected to remain stable to growing, driven by its essential medical applications.
- The Difenoxin Hydrochloride market will likely continue to be shaped by regulatory controls and its niche application in anti-diarrheal treatments.
- Increased emphasis on traceability, data integrity, and sustainability will become more prominent in supplier selection.

HOW CAN PHARMACEUTICAL COMPANIES ENSURE RELIABLE SOURCING?

To guarantee a stable and compliant supply of Atropine Sulfate and Difenoxin Hydrochloride, pharmaceutical companies should implement a multi-faceted sourcing strategy.

Supplier Qualification Process:
- Audits: Conduct comprehensive on-site audits of potential manufacturers to verify GMP compliance, quality management systems, and regulatory adherence.
- Documentation Review: Scrutinize Drug Master Files (DMFs), Certificates of Suitability (CEPs), and quality agreements.
- Technical Capability Assessment: Evaluate the supplier's synthetic chemistry expertise, process control, and analytical capabilities, especially for complex molecules like difenoxin hydrochloride.
- Financial Stability: Assess the financial health of potential suppliers to ensure long-term viability.
Supply Chain Diversification:
- Multiple Sources: Identify and qualify at least two suppliers for each API, ideally located in different geographic regions, to mitigate single-point-of-failure risks.
- Risk Assessment: Continuously monitor geopolitical, economic, and regulatory risks in key supply regions.
Contractual Agreements:
- Quality Agreements: Establish detailed quality agreements that define roles, responsibilities, specifications, change control procedures, and recall processes.
- Supply Agreements: Negotiate clear terms regarding pricing, delivery schedules, volume commitments, and force majeure clauses.
- Intellectual Property Protection: For custom synthesis, ensure robust IP clauses are in place.
Regulatory Intelligence:
- Proactive Monitoring: Stay abreast of evolving GMP requirements, pharmacopoeial updates, and controlled substance regulations in all target markets.
- Expert Consultation: Engage regulatory affairs consultants to navigate complex compliance landscapes.
Inventory Management:
- Safety Stock: Maintain adequate safety stock levels for critical APIs to buffer against unexpected supply disruptions.
- Demand Forecasting: Improve demand forecasting accuracy to optimize inventory levels and reduce carrying costs.

Key Takeaways

Atropine Sulfate is supplied by established API manufacturers in India, China, and Europe, with demand driven by its use in cardiology, ophthalmology, and as an antidote.
Difenoxin Hydrochloride production is concentrated among specialized API producers with expertise in controlled substance synthesis and is subject to rigorous national and international regulations.
Ensuring supply chain reliability requires rigorous supplier qualification, diversification across multiple geographies, and comprehensive quality and supply agreements.
Adherence to GMP standards (FDA, EMA, ICH Q7), pharmacopoeial monographs (USP, Ph. Eur.), and specific controlled substance regulations (DEA) is non-negotiable for both APIs.
Mitigating supply chain risks involves continuous monitoring of geopolitical factors, regulatory changes, and raw material volatility.

Frequently Asked Questions

What are the primary impurities to monitor in Atropine Sulfate manufacturing? Key impurities often include related tropane alkaloids, degradation products formed during synthesis or storage, and residual solvents. Manufacturers must adhere to USP and Ph. Eur. impurity limits.
How is the supply chain for Difenoxin Hydrochloride secured against diversion? Security is maintained through DEA registration, strict quota management, secure storage facilities, controlled transportation, meticulous record-keeping, and regular audits of all parties involved in the supply chain.
Can a single supplier adequately meet the global demand for Atropine Sulfate? While some large manufacturers have significant capacity, relying on a single supplier poses substantial risk. Diversification across multiple qualified suppliers is recommended to ensure continuity of supply.
What is the typical shelf life of GMP-grade Atropine Sulfate and Difenoxin Hydrochloride APIs? Shelf life varies based on manufacturing processes, packaging, and storage conditions, but GMP-grade APIs typically have shelf lives ranging from two to five years when stored under recommended conditions as per their stability studies.
Are there any significant upcoming regulatory changes expected for these APIs? While no immediate, sweeping regulatory changes are universally anticipated, ongoing enhancements in impurity control standards and stricter enforcement of GMP across global manufacturing sites are consistent trends. For difenoxin hydrochloride, continued scrutiny of opioid-related medications will remain a factor.

Citations

[1] U.S. Food & Drug Administration. (n.d.). Current Good Manufacturing Practice (cGMP) for Drugs. Retrieved from [FDA website]

[2] European Medicines Agency. (n.d.). EudraLex Volume 4 – EU Guidelines for Good Manufacturing Practice. Retrieved from [EMA website]

[3] International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. (2000). ICH Harmonised Tripartite Guideline: Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients Q7. Retrieved from [ICH website]

[4] United States Pharmacopeial Convention. (n.d.). USP-NF Online. Retrieved from [USP website]

[5] European Directorate for the Quality of Medicines & HealthCare. (n.d.). European Pharmacopoeia. Retrieved from [EDQM website]

[6] U.S. Drug Enforcement Administration. (n.d.). Controlled Substances Act. Retrieved from [DEA website]

Suppliers and packagers for generic pharmaceutical drug: ATROPINE SULFATE; DIFENOXIN HYDROCHLORIDE

ATROPINE SULFATE; DIFENOXIN HYDROCHLORIDE

ATROPINE SULFATE AND DIFENOXIN HYDROCHLORIDE SUPPLY CHAIN ANALYSIS