Thymalfasin API CAS 62304-98-7

Thymalfasin API CAS 62304-98-7 | Thymofaxine acetate cGMP production | Immunomodulators API | Science-Peptide

Thymalfasin API CAS 62304-98-7- Peptide API for the adjuvant treatment of chronic hepatitis B, immunodeficiency, etc. Science-Peptide provides Thymofaxine Acetate according to cGMP standard, 28 peptide process is mature, oxidized/deamidated impurities can be controlled, support the filing of China, USA, Europe, and can authorize DMF. welcome to contact us.

Thymalfasin (also known as Thymopeptide alpha 1) has been used in the field of immunomodulation for more than two decades. It has been used in the adjuvant treatment of chronic hepatitis B, immunodeficiency, infection, and immune recovery after tumor radiotherapy. It is not the kind of product that is on the hot search every day, but the amount of use has been very stable, and domestic and foreign pharmaceutical companies have not stopped producing it.

 

This peptide is 28 amino acids, linear, and has no disulfide bonds. The difficulty of synthesis is medium to high - the length is there, missing peptides, oxidized impurities, deamidation impurities have to be watched closely. We have been working on this product for more than ten years, and have been able to pass from small trials to commercialized batches. Now thymofaxine acetate API, grams to hundred kilograms can be supplied, FDA DMF has been filed, support for the United States, Europe and China to declare.

Thymofaxine is a natural peptide produced by thymic epithelial cells, which can promote T-cell differentiation and enhance Th1 response when administered.

Mainly used in these areas:

• Chronic hepatitis B: combined with interferon or nucleoside analogs to improve viral clearance and e antigen conversion. It has been used for many years in domestic hepatology departments.
• Immunodeficiency diseases: congenital immunodeficiency, HIV, etc., adjunctive therapy.
• Serious infections: sepsis, severe pneumonia, improvement of immunosuppression.
• After radiotherapy for tumors: reducing immunosuppression and improving quality of life.

From the API point of view, the impurity profile of 28 peptides is more complex than that of short peptides. There are three major categories: missing peptides (synthesis of a missing amino acid), oxidized impurities (methionine at position 5), and deamidation impurities (asparagine at positions 14 and 25). We have put a lot of effort into these pieces.

Synthesis is not a matter of chance
Long linear peptides, the coupling efficiency tends to fall off the further you go. We used Fmoc solid-phase synthesis, but adjusted it for the long chain:
The resin is selected based on the first amino acid at the C-terminal end to ensure starting efficiency.
For Ser and Asp, which are easy to be detached, or for the middle and posterior sites, double coupling was performed to minimize the deletion.
The purification was performed by multi-step preparative HPLC.28 The difference in polarity of the missing peptides was very small, and we repeatedly adjusted the pH and gradient to separate the common ones that were missing the 10th position and the 20th position.
The process has been running for more than ten years, and the crude peptide yield is stable, and the purity after purification is more than 99%. The validation batches showed that the impurity profiles of several consecutive batches were highly overlapping.

Oxidizing and deamidating. Keep an eye on it
Each batch is released for testing according to cGMP, covering USP/EP, but there are a few impurities that we pay special attention to:
Methionine oxidation (Met→sulfoxide at position 5): oxidized impurities usually <0.10% when purification pH and storage conditions are controlled.
Deamidation (14th and 25th Asn): After deamidation, the molecular weight difference was only 1, and it was not easy to be separated by HPLC. We optimized the chromatographic conditions and confirmed it by mass spectrometry, and controlled it below 0.15%.
Missing peptides: Controls were available at common sites, and the sum of missing peptides was <0.5%.
Endotoxin:<0.25 EU/mg, standard for injection.
Stability was done long term and accelerated, with a retest period of 24-36 months. Methods were validated.

Documentation is available, DMF is ready
The filing information can be used directly: process development report, validation protocol and report, analytical method validation, stability data, impurity profiling (structure confirmation of oxidized/deamidated/deficient peptides), structure confirmation (NMR, MS, IR), and batch production records. We also cooperate with on-site audits.
DMF has been filed with the US FDA and is authorized for use in China, the US and Europe.

The supply chain is pre-planned
There are 28 kinds of amino acids, and there are a few special materials with large dosage and long purchasing cycle. We have made a safety stock, at least two suppliers of key materials, will not stop production because of a supply shortage.

• Preparation production: direct feeding, good solubility, aseptic filling.
• Generic filing:Provide DMF authorization and validation data.
• Consistency evaluation:Provide comparative data on API and impurity profiles consistent with the original study.
• Pilot R&D: small quantities, a few grams to tens of grams.
• our facilities
• Manufacturing facility 10 acres,cGMP standards,FDA/EMA/NMPA compliance,ISO 9001:2015.
• Synthesis plant: automated solid-phase synthesis, 100 kg capacity
• Purification workshop: multiple sets of preparative HPLC, suitable for long peptide separation
• Freeze-drying workshop: 30 square meters +, industrial freeze-drying machine
• Clean area: ISO class 7/8
• QC Lab: HPLC, UPLC, LC-MS, GC, ICP-MS, etc
• Quality System: Change Control, Deviation Management, CAPA, Supplier Audit, Annual Quality Review. Cooperated with FDA, EMA, NMPA on-site audits.

Domestic pharmaceutical company:Doing consistency evaluation of thymofaxine injection. The oxidized impurities of the raw material used before fluctuated greatly (0.05%-0.25%). We gave three validation batches, and the oxidized impurity was stabilized at about 0.08%, and we also provided the control and structure confirmation of oxidized impurity. They passed the evaluation successfully, and now they are purchasing steadily every month.

Southeast Asian pharmaceutical company: local registration requires EP-compliant thymofaxine. We supplied four batches in a row, and the purity was above 99.2%, and the impurity profile of the missing peptide was consistent. They got the approval for local registration.

We have been working on Thymofaxine for more than 10 years, and we have understood the synthesis, purification and impurity control of 28 peptides. If you are developing thymofaxine preparation and need API, please feel free to contact us.