Bulk Pharmaceutical API Sources for TYLENOL W/ CODEINE

Bulk Pharmaceutical API Sources for TYLENOL W/ CODEINE

Vendor	Vendor Homepage	Vendor Sku	API Url
BenchChem		B1211854
THE BioTek		bt-1549344
RR Scientific		R349760
Starshine Chemical		2023-03-15C002188

Bulk Active Pharmaceutical Ingredient (API) Sources for Tylenol with Codeine

Last updated: August 3, 2025

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Introduction

Tylenol with Codeine is a combined analgesic used for moderate to severe pain management, comprising acetaminophen (paracetamol) and codeine phosphate. As a Schedule II controlled substance in many jurisdictions, the sourcing of its active pharmaceutical ingredients (APIs)—acetaminophen and codeine—is subject to stringent regulatory controls, quality standards, and supply chain considerations. This article examines the global landscape of bulk API sources for Tylenol with Codeine, analyzing key suppliers, regulatory dynamics, and supply chain stability crucial for pharmaceutical manufacturers, distributors, and healthcare providers.

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Acetaminophen API Sources

Global Manufacturing and Supply Dynamics

Acetaminophen is one of the most widely synthesized APIs globally, with manufacturing dominated by several large, established chemical companies. The bulk of acetaminophen production occurs in China, India, and parts of Europe, reflecting cost-effective manufacturing capabilities and regulatory environments conducive to API production.

Key Suppliers and Manufacturers

• Hainan Taiyu Pharmaceutical Co., Ltd. (China): Recognized for large-scale acetaminophen production, supplying APIs to multinational pharmaceutical companies. Their GMP-compliant facilities meet international standards, ensuring high-quality APIs suitable for pharmaceutical use [1].

• Shandong Xinhua Pharmaceutical Co., Ltd. (China): A leading producer of acetaminophen with extensive export capabilities. They comply with DMF (Drug Master File) registration processes, facilitating regulatory approval processes globally [2].

• Hikal Ltd. (India): A well-established API manufacturer with facilities adhering to cGMP, offering acetaminophen APIs for global markets. Their strategic partnerships with pharma companies have expanded their supply footprint [3].

• FLL (Fukuyama Fine Chemicals, Japan): Although smaller in scale, FLL supplies high-purity acetaminophen APIs primarily to North American and European markets, emphasizing stringent quality control [4].

Regulatory and Quality Considerations

Suppliers adhering to cGMP, PIC/S, and FDA standards ensure API quality and compliance. Many APIs from China and India are registered via DMFs or Certificates of Suitability (CEP) with the EDQM, streamlining regulatory approval in key markets.

Codeine API Sources

Complexity in Production and Regulation

Codeine is an opiate alkaloid derived from morphine, often produced via semi-synthetic processes involving opium poppy derivatives or synthetic pathways. Its manufacturing is tightly regulated due to potential abuse and diversion risks, with suppliers operating under strict controls and licensing.

Major Suppliers and Countries

• Johnson Matthey (UK): A leading supplier of pharmaceutical-grade codeine, Johnson Matthey produces APIs with high purity and consistent supply, complying with global regulatory standards [5].

• Mallinckrodt Pharmaceuticals (USA): A major American manufacturer of codeine, with extensive API manufacturing capabilities. Their production complies with DEA Scheduling requirements, and they source raw materials in compliance with international controls [6].

• Hainan Ziyu Pharmaceutical Co. Ltd. (China): Produces codeine APIs primarily for Asian markets, with some exports to Europe and North America, subject to licensing and strict import controls [7].

• Honjo Pharmaceutical Co. Ltd. (Japan): Provides high-quality codeine APIs, with robust quality assurance procedures, primarily serving markets requiring rigorous regulatory compliance [8].

Opium Poppy-Derived or Synthetic Codeine

Manufacturers pool raw materials from two primary sources:

• Opium poppy derivatives: Semi-synthetic nature necessitates licensing and control measures, with cultivation and extraction often regulated by government bodies in producing countries.

• Synthetic processes: Advances in synthesis have allowed the production of codeine via chemical transformations, reducing reliance on opium-derived raw materials but still subject to phase-appropriate controls.

Regulatory Environment

Codeine APIs are classified in various jurisdictions as controlled substances—Schedule II in US, Schedule 5 in Canada, and similarly in Europe—limiting the number of qualified suppliers with appropriate licensing and compliance.

Global API Supply Chain Challenges

Regulatory Compliance

Manufacturers must navigate complex, region-specific regulations such as US FDA, EMA, and international standards. API suppliers are required to maintain rigorous cGMP compliance, and their licenses are subject to periodic audits.

Supply Chain Disruptions

Recent disruptions due to geopolitical instability, COVID-19 pandemic effects, and stricter regulatory scrutiny have impacted API availability, leading to increased procurement costs and supply delays. Chinese and Indian suppliers have faced specific challenges including export restrictions, quality concerns, and logistical disruptions.

Quality and Certification

Ensuring APIs meet pharmacopoeial standards (USP, EP, JP) and possess appropriate Certificates of Analysis (CoA), Certificates of Suitability (CEP), or Drug Master Files (DMF) is critical to ensure regulatory approval and patient safety.

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Strategic Sourcing Considerations

Diversification of Suppliers

Pharmaceutical companies are increasingly diversifying their API sources across regions and manufacturers to mitigate supply risks. Establishing relationships with multiple qualified API producers ensures continuity, especially for critical APIs like acetaminophen and codeine.

Vertical Integration and In-house Production

Some large pharma companies invest in vertical integration, establishing in-house API manufacturing or long-term supply agreements with trusted, GMP-compliant API producers to safeguard quality and supply.

Regulatory Track Record

Prioritizing suppliers with clear regulatory histories, validated manufacturing processes, and proven compliance reduces audit risks and expedites registration processes globally.

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Conclusion

The sourcing landscape for Tylenol with Codeine APIs remains concentrated yet globally diverse. Acetaminophen APIs are primarily sourced from China, India, and Europe, with high compliance standards ensuring quality. Codeine APIs originate mainly from the UK, USA, China, and Japan, with stringent regulation shaping supply options.

In this highly regulated environment, pharmaceutical manufacturers must engage with reputable suppliers maintaining robust quality standards and regulatory compliance. The ongoing geopolitical and supply chain uncertainties necessitate strategic diversification and compliance vigilance to ensure uninterrupted production and market supply.

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Key Takeaways

• Global API sourcing is concentrated in China, India, and select Western countries, with compliance standards such as cGMP, CEP, and DMF essential for regulatory acceptance.
• Codeine API supply is highly regulated due to its classification as a controlled substance, limiting the pool of qualified suppliers.
• Supply chain disruptions have intensified reliance on diversified sourcing strategies, emphasizing supplier qualification and regulatory validation.
• Quality assurance remains paramount, with pharmaceutical companies prioritizing suppliers with proven GMP certification, regulatory approval, and transparent documentation.
• Vertical integration and long-term supply agreements are increasingly adopted strategies to mitigate market volatility and ensure API availability.

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FAQs

1. What are the primary regions for sourcing acetaminophen APIs?
China, India, and Europe lead in acetaminophen production, offering cost-effective and high-quality APIs, with suppliers adhering to international GMP standards.

2. How does the regulation of codeine APIs impact sourcing strategies?
Due to strict controls and scheduling, only a limited number of licensed manufacturers—primarily in the UK, USA, China, and Japan—can produce certified codeine APIs for pharmaceutical use.

3. Are synthetic routes to produce codeine feasible?
Yes, advances in chemical synthesis have enabled production of codeine via synthetic pathways, but regulated manufacturing and licensing remain mandatory due to its narcotic classification.

4. How do supply chain challenges influence API procurement?
Disruptions from geopolitical, pandemic, or regulatory factors have increased sourcing risks, prompting companies to diversify suppliers and reinforce supply chain resilience.

5. What should manufacturers prioritize when selecting API suppliers for Tylenol with Codeine?
Stringent compliance with GMP/regulatory standards, proven quality control processes, reliable supply capacity, and transparent documentation are critical in supplier selection.

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References

1. Hainan Taiyu Pharmaceutical Co., Ltd. [Company Profile].
2. Shandong Xinhua Pharmaceutical Co., Ltd. DMF overview.
3. Hikal Ltd. Quality standards for APIs.
4. Fukuyama Fine Chemicals (FLL). High-purity API offerings.
5. Johnson Matthey, Pharmaceutical APIs.
6. Mallinckrodt Pharmaceuticals, Codeine API sourcing.
7. Hainan Ziyu Pharmaceutical Co., Ltd. Licensure and supply data.
8. Honjo Pharmaceutical Co. Ltd. API compliance documentation.