Small-molecule and protein drug fill/finish formulations use glucose, galactose, sucrose, and trehalose dihydrate. These carbohydrates are essential for biopharmaceutical processes because they serve as energy sources for cell growth and glycosylation, buffer supplements to protect and stabilize molecules during purification and stabilize and bulking agents, especially for parenteral formulations.

Through years of research, the use of carbohydrates with low impurity levels within cell-culture media and parenteral formulation has become an effective tool to produce quality drugs and process efficiency. This is where low endotoxin sucrose comes into the picture, reflecting the above advantage and improving drug stability.

This article concentrates on the applications and benefits of low endotoxin sucrose.

What is low endotoxin sucrose?

The term endotoxin contrasts with exotoxin, a toxin released by bacteria into the environment. But specifically, endotoxin is synonymous with lipopolysaccharide (LPS), viz., an essential component of the outer membrane of gram-negative bacteria. 

With regards to sucrose, it is a non-reducing crystalline disaccharide made up of glucose and fructose. It is used in the biopharmaceutical industry to stabilize proteins, lipids, and carbohydrates throughout the formulation and freeze lifecycle of therapeutics. These HPLEs are also added to industrial cell culture, cell therapy, and cryopreservation media as supplements.

Advantages of low endotoxin sucrose

Sucrose’s unique chemical and physical properties, particularly in aqueous solutions, make it an outstanding stabilizer for biopharmaceutical formulations.

The robustness of the formulation in biopharmaceuticals is based on the use of excipients for biopreservation against a wide variety of stresses, despite the fact that these excipients present two significant challenges due to their limited chemical and physical stability. 

Sucrose is an effective bioprotective agent against a variety of stresses and is utilized to stabilize proteins, lipids, and carbohydrates during the formulation process and the freeze-thaw cycle of therapeutics.

Additionally, it is widely used as a cryopreservative and media supplement in numerous cell-based bioprocesses. It is preferred over trehalose in situations where solubility and/or viscosity are of paramount importance.

Applications of low endotoxin sucrose

Low endotoxin sucrose is used for–

• Monoclonal Antibody(mAbs) stabilization 
• Media Supplementation 
• Antibody Drug Conjugate (ADC) stabilization 
• Peptide stabilization 
• Stem cell preservation 
• Vaccines stabilization

Some of the above points are elaborated below.

1. High-purity low-endotoxin sugars enhance the durability and stability of protein formulations and the quality of drug products.

Utilizing well-characterized carbohydrates with consistently low impurity levels in cell-culture media and parenteral formulations is an effective method for mitigating risks to drug product quality and process efficiency. 

In its carbohydrate materials, an orthogonal purification process (Avantor) reduces endotoxin, reactive impurities, and trace metals to produce high-purity low-endotoxin (HPLE) sugars. It has been shown that these high-quality sugars with low impurity levels improve the stability of drug products.

2. HPLE sugars are used in parenteral formulations

Parenteral formulations of biopharmaceuticals employ a vast array of excipients, such as buffers, bulking agents, and lyo-protectants, as well as numerous types of carbohydrates. Even in low concentrations, endotoxins sucrose can compromise the safety and efficacy of the final product. 

Key requirements for parenteral excipients that have facilitated efforts to improve their purity and reduce to an absolute minimum the endotoxins they may introduce to the product include the following:

1. Stability: The excipient must consist of substances that prevent API degradation during freeze-drying and storage.

2. Sterility excipients must be devoid of viable microorganisms that could affect the efficacy of the drug or the health of the patient.

3. Patients can develop fevers when endotoxins and beta-glucans, which are present in pyrogen-free excipients, are present in high concentrations.

Here, HPLE sucrose plays a major role as it enhances the stability of the drug and maintains its efficacy.

3. High-purity low-endotoxin sugar enhances antibody-drug conjugate (ADC) stabilization. 

ADC is a drug delivery system that combines the benefits of the selectivity of the antibody and the potency of a cytotoxic agent. However, the interaction between the antibody, linker, and payload necessitates a stable and distinct formulation. 

HPLE sucrose is used in this case as it focuses on the ionic strength and concentrations of ADCs. 

4. HPLE sucrose is used to improve yields in mammalian cell-culture processes

Biopharmaceutical raw materials should contain the lowest possible levels of reactive impurities in order to prevent modification or degradation of the drug substance and to meet regulatory requirements for microbiological endotoxins in biopharmaceutical drug products. 

The use of carbohydrates in cell-culture media and parenteral formulations can frequently result in the introduction of impurities that negatively affect the final yield and quality of a drug product.

Final Thoughts

The use of well-characterized, high-purity HPLE sucrose can increase the yield of mammalian cell cultures and contribute to the improvement of API stability in biopharmaceutical parenteral formulations. Reducing endotoxins and trace metals in HPLE sugars with consistency from lot to lot can significantly reduce potential contamination sources that affect cell-culture yield and API stability.

MB Sugars is recognized as India’s only Low Endotoxin Sucrose Manufacturer. With in-house analytical laboratories and R&D units, MB Sugars is known to maintain the highest quality standards that enhance the efficacy and the process of the drug delivery system.

Especially for low endotoxin sucrose, MB Sugar complies with IP/BP/USP/EP/JP and holds GMP, Drug license, Kosher, and Halal certificates.