Tofacitinib Citrate 540737-29-9 — China API Manufacturer | USP/EP R&D to Production

China Manufacturing Landscape for Tofacitinib Citrate

Tofacitinib Citrate (CAS 540737-29-9) is a Janus kinase (JAK) inhibitor used in the treatment of rheumatoid arthritis, psoriatic arthritis, ulcerative colitis, and other autoimmune and inflammatory conditions. As patent expirations have opened the global market for generic Tofacitinib formulations, Chinese API manufacturers have established reliable synthesis capabilities for this structurally complex pyrrolopyrimidine derivative. Our production facility is a recognized supplier of pharmaceutical-grade Tofacitinib Citrate to generic drug companies undertaking ANDA, ANDA-equivalent, and emerging market registrations worldwide.

China’s advanced organic chemistry synthesis capabilities, honed through decades of producing complex heterocyclic pharmaceutical intermediates and APIs, provide the ideal manufacturing platform for Tofacitinib Citrate. Our investment in chiral synthesis technology, including asymmetric catalysis and chiral resolution infrastructure, enables efficient production of this single-enantiomer API with the stereochemical precision that regulatory authorities and downstream formulators demand.

Manufacturing Process & Facility

Tofacitinib Citrate synthesis follows a convergent route involving construction of the 3H-pyrrolo[3,2-d]pyrimidine heterocyclic core from appropriately functionalized pyrrole and pyrimidine precursors, introduction of the piperidine ring system bearing the required (R)-3-aminopiperidinyl stereocenter, and N-cyanoacetylation to install the cyano group. The chiral center is established either through asymmetric synthesis using chiral auxiliaries or through classical resolution of racemic intermediates, with chiral HPLC verification at multiple process stages ensuring stereochemical integrity throughout.

Citrate salt formation is conducted under controlled crystallization conditions optimized for the target polymorphic form, with polymorph identity confirmed by XRPD for every batch. The manufacturing facility features glass-lined reactors (200 L to 3,000 L), low-temperature reaction capability (down to -78°C), hydrogenation equipment for catalytic reduction steps, and automated process control systems. The facility operates under NMPA certification with annual production capacity of 5 metric tons of Tofacitinib Citrate API.

Quality Standards & Multi-Pharmacopeial Compliance

Tofacitinib Citrate from our facility meets USP and EP pharmacopeial specifications. HPLC purity consistently exceeds 99.5%, with chiral purity (R-enantiomer content) above 99.8% by chiral HPLC. Individual specified impurities are controlled below 0.10%, with total impurities below 0.50%. Polymorphic form consistency is verified by XRPD comparison against qualified reference patterns, ensuring reproducible dissolution behavior in finished dosage forms.

Complete quality testing includes HPLC assay and related substances profiling, chiral purity analysis, polymorphic form by XRPD, citrate content verification by titration, residual solvents by headspace GC, elemental impurities by ICP-MS per ICH Q3D, water content, sulfated ash, particle size distribution, and microbial limits testing. Genotoxic impurity assessment per ICH M7 with validated trace-level analytical methods is performed for all identified potentially mutagenic process impurities. ICH Q1A stability data supports a 36-month retest period.

Regulatory Documentation

Our Tofacitinib Citrate regulatory package includes US FDA Type II Drug Master File, EU ASMF documentation, and CTD Module 3.2.S packages for additional regulatory jurisdictions. Documentation completely covers manufacturing process description with critical process parameters, starting material specifications and supplier qualification, control strategy with in-process controls and release testing, impurity fate analysis with purge factor calculations, and ICH M7-compliant genotoxic impurity assessment. Nitrosamine risk evaluation documentation per current regulatory guidance is included. quality certificates and recent inspection history are available upon request.

Packaging & Logistics

Tofacitinib Citrate API is packaged in double PE bag-lined HDPE drums or fiber drums, with standard pack sizes of 1 kg, 5 kg, and 10 kg. The product is stable at controlled room temperature (15-25°C) and does not require cold chain handling. International shipments are arranged via air freight (5-10 business days) for development and commercial quantities, with sea freight available for large bulk orders. Complete export documentation including CoA, MSDS, quality certificate copies, and customs classification guidance is provided as standard. We support FOB, CIF, and DDP Incoterms to accommodate varying customer logistics requirements.

Competitive Pricing & Supply Reliability

Direct manufacturer pricing for Tofacitinib Citrate is structured to support customers at all stages of product development, from initial R&D evaluation through commercial-scale supply. Volume-tiered pricing offers meaningful savings for annual commitments exceeding 500 kg. Standard production lead times are 4-6 weeks for orders against validated campaigns, with expedited turnaround of 2-3 weeks available for urgent requirements from maintained intermediate stock. Our supply reliability track record demonstrates 100% on-time delivery performance for contracted orders over the past 36 months, reflecting the priority we place on meeting customer commitments.

Tofacitinib Citrate Specifications