Tacrolimus 104987-11-3 — China API Manufacturer | USP/EP/JP R&D to Production

China Manufacturing Landscape for Tacrolimus

Tacrolimus (CAS 104987-11-3), also known as FK-506, is a macrolide calcineurin inhibitor immunosuppressant that has become the cornerstone of post-transplant rejection prophylaxis worldwide. Produced by fermentation of Streptomyces tsukubaensis, Tacrolimus API manufacturing requires sophisticated fermentation and purification capabilities that Chinese pharmaceutical manufacturers have developed to globally competitive standards. Our production facility is among China’s leading producers of Tacrolimus API, serving generic pharmaceutical companies across more than 40 countries with product that consistently meets the most stringent pharmacopeial requirements.

The critical nature of Tacrolimus in transplant medicine demands absolute supply reliability—our manufacturing operations are designed with redundancy at every critical step, from qualified backup cell banks through parallel fermentation capacity to validated secondary purification pathways. Chinese manufacturers collectively represent a significant portion of global Tacrolimus API supply, and our facility’s track record of uninterrupted supply through multiple global disruption events underscores the reliableness of our operational model.

Manufacturing Process & Facility

Tacrolimus production employs aerobic submerged fermentation of a proprietary high-yielding Streptomyces tsukubaensis strain, cultivated through a validated multi-stage inoculum expansion program culminating in production-scale fermenters of 30,000-80,000 liters capacity. The fermentation process is optimized for maximum Tacrolimus titer through carefully controlled feeding strategies for carbon and nitrogen sources, temperature profiling, dissolved oxygen management, and pH control, all monitored continuously via advanced DCS with real-time HPLC titer analysis capability.

Post-fermentation recovery involves whole-broth extraction, defatting, and a sophisticated multi-step chromatographic purification train including macroporous resin capture, silica gel chromatography, and preparative HPLC polishing to remove structurally related impurities including ascomycin (FK-520), a critical quality challenge specific to Tacrolimus manufacturing. Final crystallization yields the monohydrate crystal form required by pharmacopeial monographs. Annual production capacity exceeds 400 kg, supported by full solvent recovery, biowaste treatment, and environmental monitoring systems compliant with Chinese environmental protection regulations.

Quality Standards & Multi-Pharmacopeial Compliance

Tacrolimus API produced at our facility simultaneously meets USP, EP, and JP monograph specifications—essential for customers serving multiple regulated markets with a single API source. HPLC purity consistently exceeds 98.5%, with the critical ascomycin (FK-520) impurity controlled below 0.5% through optimized fermentation conditions and dedicated chromatographic separation. The anhydrous/monohydrate crystal form is confirmed by XRPD and thermal analysis for every batch.

Analytical testing encompasses HPLC assay and related substances profiling, specific optical rotation, water content by Karl Fischer, residual solvents by headspace GC, elemental impurities by ICP-MS per ICH Q3D, microbial enumeration, bacterial endotoxin testing, and particle size distribution. ICH Q1A stability studies conducted at 25°C/60% RH (long-term) and 40°C/75% RH (accelerated) support a 24-month retest period under controlled storage conditions.

Regulatory Documentation

Our Tacrolimus regulatory documentation package includes an active US FDA Type II Drug Master File, EU ASMF documentation, and PMDA-compatible filing materials for the Japanese market. Complete CTD Module 3.2.S packages are available with detailed manufacturing process descriptions, critical quality attribute justifications, control strategy rationale documents, and complete analytical method validation data. Comparative impurity profile data against innovator product is available to support bioequivalence study design and regulatory review. quality certificates, WHO Prequalification-compatible documentation, and inspection readiness packages are maintained current.

Packaging & Logistics

Tacrolimus API is packaged in light-protective containers with inert atmosphere (nitrogen) sealing, available in 100 g, 500 g, 1 kg, and 5 kg units. All shipments require cold chain management (2-8°C) maintained throughout transit via validated temperature-controlled packaging systems with calibrated data loggers. International shipments depart from Shanghai Pudong Airport via established cold chain logistics partners, with typical transit times of 3-7 business days to major pharmaceutical manufacturing hubs. Pre-clearance documentation including controlled substance declarations (where applicable), CoA, quality certificates, and import permit support is provided proactively to minimize customs processing delays.

Competitive Pricing & Supply Reliability

As a vertically integrated manufacturer controlling fermentation, purification, and packaging operations, we offer Tacrolimus API at competitive pricing that reflects genuine production economics. Multi-year supply agreements with price stability mechanisms are available for strategic customers, providing budget certainty in a market historically subject to price volatility. Standard lead times are 8-12 weeks for new orders, reducible to 4-6 weeks for customers with established supply agreements and rolling forecasts. Our commitment to supply reliability is demonstrated by maintained safety stock levels and the ability to run parallel production campaigns during periods of elevated demand.

Tacrolimus Specifications