Somatostatin API CAS 38916-34-6

Somatostatin API CAS 38916-34-6 | Growth Inhibitor Acetate cGMP production | Peptide API | Science-Peptide

Somatostatin API CAS 38916-34-6 - Peptide API for the treatment of acute esophageal variceal bleeding, pancreatitis, etc. Science-Peptide provides Growth Inhibitor Acetate in accordance with cGMP standard, with mature process, clear impurity profiles, support for China, USA and Europe declarations, and can be authorized for DMF. welcome to contact us.

Somatostatin has a very stable position in gastroenterology and emergency medicine - acute esophageal variceal bleeding, acute severe pancreatitis, pancreatic fistula, intestinal fistula, these scenarios, it is the first-line drug. It's not a "breakout" product, but demand has been steady and global use is not insignificant.

 

Its mechanism of action is quite specific: it inhibits the release of a variety of hormones, including growth hormone, insulin, glucagon, gastrin, pancreatin, etc. It also reduces visceral blood flow and lowers portal venous pressure. It also reduces visceral blood flow and lowers the pressure in the portal vein. In the case of bleeding esophageal varices, it is the mainstay of vasoactive drugs, as is terlipressin.

 

Science-Peptide has been making peptide APIs for more than 20 years, and growth inhibitor is one of the species that we have entered into early. This peptide is a 14 amino acid cyclic peptide with a pair of disulfide bonds, and we have been running the synthesis process for more than 10 years. At present, we can stably supply growth inhibitor acetate APIs from grams to 100 kilograms, and have completed the FDA DMF filing, and support China, the United States and Europe to declare. The impurity profile is clear, and there are mature control strategies for key impurities such as disulfide bond mismatch, oxidized impurities and missing peptides.

Acute esophageal variceal hemorrhage: Combined with endoscopic ligation, it reduces visceral blood flow, lowers portal pressure, and has a definite hemostatic effect. Guidelines recommend continuous infusion for 2-5 days.
Acute severe pancreatitis: inhibit pancreatic enzyme secretion, reduce pancreatic inflammatory reaction. Although it is not a specific drug, it can be used as an adjunctive treatment to minimize complications.
Adjuvant therapy for pancreatic and intestinal fistulas: reduces secretion of digestive juices and promotes healing of fistulas.
Acromegaly (long-acting form): inhibits growth hormone secretion, but that's the home of octreotide and lanreotide, and growth inhibitors are used less because of their short half-life.

From the perspective of APIs, growth inhibitors are characterized by a certain threshold process - 14 peptides, cyclization, the sequence of a number of hydrophobic amino acids, synthesis and purification are more complex than short peptides. However, because of the threshold, suppliers are stable and will not be overwhelmed by low prices. The experience we have accumulated in this species allows us to achieve a high degree of consistency in impurity profiles with the original researchers.

1. Craft has been running for over a decade and amplification is not a concern
The difficulty in the synthesis of growth inhibitors lies in the precise cyclization of disulfide bonds and the purification of multiple hydrophobic amino acids in the sequence. We used the route of "solid-phase synthesis of linear precursors + liquid-phase cyclization":

• Linear precursor: Fmoc solid-phase synthesis, optimized coupling conditions for hydrophobic region, stable yield of crude peptide.
• Cyclization: Mild oxidation in liquid phase, precise formation of 3-14 disulfide bonds, cyclization efficiency is controlled above 95%, and the content of mismatch isomers is very low.
• Purification: A multi-step HPLC was performed to separate the missing peptides, oxidized impurities, dimers, and mismatched isomers one by one.
• Freeze-drying packaging: clean area operation, double-layer aseptic bag.

We have run this process from a few tens of grams of small trials all the way to hundreds of kilograms of commercialized batches. The process validation data showed that the purity was stable at over 99% with highly overlapping impurity profiles in several batches. The release profiles are consistent from batch to batch.

2. Quality control, not just purity

Each batch of growth inhibitor API is released according to cGMP requirements, the test items cover the pharmacopoeia requirements at the same time, we also pay extra attention to some process impurities:

• Content:95.0%-105.0% based on anhydrous and solvent-free, in accordance with USP/EP.
• Purity: HPLC ≥99.0%, actual batch is usually 99.2%-99.5%.
• Related substances: single impurity≤0.15%, total impurity≤1.0%.
• Key impurities: disulfide bond mismatch isomers (different cyclization modes), oxidized methionine impurities (no Met in the sequence, but tryptophan is easily oxidized), missing peptides, dimers, all with controls and quantification methods.
• Safety indicators: endotoxin <0.25 EU/mg, microbiological limits in accordance with the Pharmacopoeia, residual solvents in accordance with ICH Q3C.

The stability is long-term and accelerated, supporting a 24-36 month retest period. The analytical method has been validated to meet ICH Q2 and USP/EP requirements.

3. Fully documented and DMF filed

Growth inhibitors have a well-established filing pathway, and the information we provide can be used directly for ANDA or domestic generic filing:

• Process development report (how key parameters were determined)
• Process validation programs and reports (multi-batch data) analytical method validation reports
• Stability data (long-term, accelerated, impact factors)
• Heterogeneous mass spectrometry report (with structural confirmation)
• Structural corroboration information (NMR, MS, IR)
• Batch production records (complete and traceable)
• In conjunction with on-site audits

Our Growth Inhibitor API has completed FDA DMF filing, and can be authorized to be used in China, the United States and Europe declaration. If you need European CEP, we can also cooperate with you.

4. Supply chain, we have a plan

Among the amino acid raw materials used for growth inhibitors, there are several special amino acids (e.g., Fmoc-Asn(Trt)-OH, Fmoc-Trp(Boc)-OH) that have a long procurement cycle. We have done several things:

• At least two qualified suppliers for key materials, regular factory audits.
• Long procurement lead time materials, build up safety stock, no production stoppage due to delayed sea transportation.
• Multiple production lines allow for parallel scheduling and rush orders can be inserted into the queue.

On the mode of cooperation, we can either sell API, or authorize DMF, or transfer the technology to the customer's designated site. Packing specification is according to the requirement of preparation.

• Manufacturing facility 10 acres, cGMP standard, FDA, EMA, NMPA compliant, ISO 9001:2015 certified.
• Synthesis plant: automated solid-phase synthesis, 100 kg capacity
• Purification workshop: multiple sets of HPLC preparation, flow rate covering 50mL-1000mL/min
• Freeze-drying workshop: 30 square meters +, industrial freeze-drying machine
• Clean area: ISO class 7/8
• QC Lab: HPLC, UPLC, LC-MS, GC, etc

In terms of quality system, change control, deviation management, CAPA, supplier audit, annual quality review are all routine operations. We have cooperated with FDA, EMA, NMPA on-site audits, and have a lot of experience.

Client A, a domestic pharmaceutical company, is engaged in the consistency evaluation of growth inhibitor injection. The impurity profile of the previous supplier was not stable, especially the disulfide bond mismatch isomer was high. We provided three batches of validated raw materials with a full set of impurity profile data, and the mismatch isomer was controlled below 0.05%. They used our raw materials to make preparations, which passed the evaluation successfully, and now they are purchasing steadily every month.

Client B, Southeast Asia pharmaceutical company: local registration needs growth inhibitor API which meets EP standard. We have supplied four batches in a row, and the purity of each batch is above 99.2% with the same impurity profile. They used our raw materials to make the preparation and got the local registration approval.

Growth inhibitor is not the kind of "explosive" varieties, but the clinical demand is stable, the supplier's requirements are also high - the process should be mature, impurities should be controlled, the documents should stand up to inspection. We have been working on this species for more than 10 years, and we think we have delivered a good answer. If you are doing growth inhibitor preparations, need to find API suppliers, welcome to talk.