Terlipressin API CAS 1884420-36-3

Terlipressin API | Terlipressin acetate cGMP production | Liver and kidney function improvement API | Science-Peptide

Terlipressin API CAS 1884420-36-3 - Peptide API for Hepatorenal Syndrome(HRS-AKI) treatment.Science-Peptide provides cGMP compliant Terlipressin Acetate with mature process, clear impurity profile, support for China, USA and Europe declarations, and has passed the relevant DMF filing of FDA. Welcome to contact us.

Terlipressin, a synthetic vasopressin analog, is widely used globally for the treatment of hepatorenal syndrome-acute kidney injury (HRS-AKI).The 2016 American College of Gastroenterology Guidelines and the formal FDA approval in 2021 established it as central to the treatment of HRS-AKI.

 

Its mechanism of action is unique: by acting on the V1a receptor of visceral circulation, it selectively constricts the dilated splanchnic and visceral blood vessels, reduces the visceral blood flow, and increases the effective arterial blood volume and mean arterial pressure, so as to increase renal perfusion and improve renal function. Clinical data show that after terlipressin combined with albumin treatment, about 40%-45% of patients' renal function was significantly improved.

 

Science-Peptide has accumulated over 20 years of experience in the field of peptide APIs. Terlipressin is one of the species that we have completed process development and commercialized earlier. We have adopted a mature solid-phase synthesis and fragment condensation route, with a robust process and clear impurity profile. We have passed the relevant DMF filing with the FDA, and are able to support our customers in the registration of preparations in major markets such as China, the United States, Europe, and so on.

Terlipressin (Terlipressin Acetate) is a cyclic peptide consisting of 12 amino acids that form a cyclized structure through a disulfide bond between the 1-position and 6-position cysteines. Its first three glycines are enzymatically cleaved in vivo to slowly release the active metabolite, lysopressin, which results in a long-lasting effect.

Major clinical applications of terlipressin include:

Hepatorenal Syndrome-Acute Kidney Injury (HRS-AKI): This is currently the leading indication. By constricting dilated visceral blood vessels and improving the effective circulating blood volume, functional renal injury can be reversed.
Bleeding from esophageal varices: as a vasoactive drug, used in combination with endoscopic ligation to control acute bleeding.
Other Uses: Refractory ascites, infectious shock, etc. (use beyond instructions).
From a market perspective, terlipressin is a classic generic drug. With the opening of the U.S. market after FDA approval and the persistent demand for treatment of cirrhosis-related kidney injury worldwide, the demand for its API has been relatively stable.

1. Proven experience in process routing and scale-up

The difficulties in the synthesis of terlipressin lie in the precise formation of disulfide bonds and the efficiency of cyclization. We adopt a combined strategy of "fragment condensation + liquid phase cyclization":

• The full-length sequence was split into 2-3 fragments synthesized separately in solid phase
• Cyclization of disulfide bonds in the liquid phase under mild conditions and with few side reactions
• fragment assembly followed by multi-step preparative HPLC purification

We have been running this process for more than ten years, from laboratory trial to commercial production of 100 kilograms. The crude peptide yield is stable, the cyclization efficiency can reach over 95%, and the purity of the final product is stable at over 99%. Our process validation batch data show that the impurity profiles are highly reproducible in successive batches.

2. Strict quality control, in accordance with cGMP standards

We produce Terlipressin API CAS 1884420-36-3 according to cGMP requirements, each batch is strictly tested:

• Release testing: content (97.0%-102.0% by anhydrous and solvent-free), purity (HPLC, ≥99.0%), related substances (singletons ≤0.15%), moisture, residual solvents, bacterial endotoxins, microbial limit
• Impurity profile control: comprehensive identification of process impurities and degradation products. Critical impurities such as disulfide bond mismatch isomers, oxidized impurities, missing peptides, etc. were controlled within acceptable limits
• Stability studies: long-term, accelerated stability data to support a 24-36 month retest period, in accordance with ICH Q1
• Method validation: All analytical methods were validated in accordance with ICH Q2.

3. Complete documentation and registration support

Generic filing for terlipressin has clear API documentation requirements. We can provide:

• Process development report (including the process of determining key process parameters)
• Process validation program and report (with validation batch data) analytical method validation reports
• Stability study data (long-term, accelerated, impact factors)
• Heterogeneous mass spectrometry report (with structural confirmation)
• Structural corroboration information (NMR, MS, IR, etc.)
• Batch production records (complete and traceable)
• Cooperating with clients undergoing on-site audits by pharmacovigilance agencies

Our Terlipressin API has completed the FDA DMF filing, and can be authorized for customers to use in China, the United States and Europe declaration.

4. Reliable supply chain security

• Dual-source procurement: two or more qualified suppliers for key materials (amino acids, resins)
• Strategic stockpiling: establishment of safety stocks of long lead time materials
• Continuous production: multiple production lines can run in parallel to ensure on-time delivery of orders
• Batch Consistency: Proven to be produced in consecutive batches, with highly reproducible purity and impurity profiles

5. Flexible modes of cooperation

• API Sales: Provide cGMP-compliant Terlipressin APIs and support the production of formulations
• DMF authorization: provide DMF file authorization, support customers to declare generic drugs
• Technology transfer: Processes can be transferred to customer-specific production sites
• Customized packaging: according to the needs of the preparation, provide different specifications of packaging

• cGMP manufacturing site (10 acres)
• Comply with US FDA, Europe EMA, China NMPA cGMP requirements
• ISO 9001:2015 certified
• Automated solid phase synthesis plant (100 kg capacity)
• Preparative HPLC purification system (multiple sets)
• Freeze-drying workshop (more than 30 square meters)
• Clean area (ISO class 7/8)
• Complete QC laboratory: HPLC, UPLC, LC-MS, GC, and so on

Quality system

• Strict change control, deviation management, CAPA system
• Supplier audits and full traceability of materials
• Annual quality review, continuous improvement
• We have had many successful experiences in cooperating with clients and regulators in on-site audits

1. Mature technology, clear impurity profile

We have accumulated more than ten years of production experience in Terlipressin API, and the process is constantly optimized, and the impurity profile is highly consistent with that of the original research. Key impurities such as disulfide bond mismatch, oxidation products, missing peptides, etc. have mature controls and control strategies.

2. Compliance systems, which can withstand scrutiny

Our cGMP facilities and documentation system can withstand the inspection of domestic and foreign drug regulatory agencies. Terlipressin has completed the FDA DMF filing, and some customers have successfully passed the domestic consistency evaluation and ANDA filing using our API.

3. Stability of supply and non-discontinuation of stock

We have established a perfect supply chain management system, dual-source procurement of key materials and sufficient strategic reserves. We have spare suppliers for key materials such as amino acid raw materials and resin of Terlipressin, and production will not be stopped because of a supply shortage.

4. Declaring support, saving effort

We provide not only APIs, but also a complete set of data and documents to support the registration, DMF file structure is clear, complete data, and fewer reviews and remedies.

A domestic pharmaceutical company needs Terlipressin API for consistency evaluation. We provided complete process validation data and stability data, and cooperated with it to complete the declaration. The variety has now passed the consistency evaluation, and we have become its long-term supplier.
European generic company: We planned to file ANDA in Europe, and needed terlipressin API with the same quality as that of the original research. We provided DMF document authorization and cooperated with them to receive audit, and finally the product was successfully approved.

Terlipressin is the core drug in the treatment of hepatorenal syndrome, with mature market and stable demand. We have been working on Terlipressin API for more than 10 years, with mature process, stable quality, complete documents, and have completed FDA DMF filing. If you are developing Terlipressin formulations and need a compliant, stable and traceable API supplier, welcome to talk to us.