Polyethylene glycols (PEGs) are small molecules that can be used for a broad range of applications from cosmetics and surfactants to wood preservation, textiles and in chemical mixtures. One major application for PEGs is the pharmaceutical industry, where PEGs have been used for more than 30 years to improve the bioavailability, stability, targeting and performance of therapeutics. These drug products span a range of treatment areas such as cancer, hepatitis, auto-immune disorders and diabetes. 

Manufacturing PEGs is challenging because the starting material, ethylene oxide, is both highly reactive and carcinogenic. Developing and manufacturing pharma-grade PEGs comes with additional challenges. The high purity required demands well-defined processes that produce extremely low levels of diol content, eliminate genotoxic impurities and a narrow range for the molecular weight distribution.  

Finding a partner with the necessary competencies to meet these purity and quality requirements can be challenging. If you are looking for a reliable development and manufacturing partner for PEGs with decades of experience handling ethylene oxide, come and talk to us! We have built up development and production know-how for PEGs – especially for medical applications – and can help you every step of the way.  

Over many years we have built up a network of sites to support all stages of production – with the exception of biologicals. We can handle ethylene oxide and other epoxides on a lab and commercial scale.  

Our network includes:  

• PEG R&D labs in Essen and Hanau, Germany 
• Production of PEGs and mPEGs in Essen and Hanau, Germany 
• Activation of PEGs and mPEGs under (non-)cGMP conditions in Hanau, Germany and Tippecanoe, USA 
• PEGylation development, production and filling capabilities in Birmingham, USA 

We also have a complete analytical setup at multiple locations.  

The use of therapeutic proteins is increasing rapidly, and these active ingredients have the potential to bring about significant medical advances. However, therapeutic proteins often degrade quickly in the human body before they can release their full therapeutic effect. PEGs can extend the retention time of active ingredients.  

PEGylation is a process in which polyethylene glycols (PEGs) form a covalent attachment to pharmaceutical molecules. The long PEG chains make the active ingredient more voluminous and prevent it from being filtered out of the blood plasma and then broken down in the kidneys. The hydrophilicity of PEGs also makes PEGylated drugs more soluble in water. Other key advantages include shielding the protein component against enzymes and the immune system.   

PEGs and their derivatives have a strong clinical record for safety and functional versatility. They are used across a wide range of drug classes including proteins and peptides, bioresorbable polymeric excipients like PLG and also advanced drug delivery systems like micelles and nanoparticles.  

Protein drugs have been shown to have improved stability and blood half-life through PEGylation. Other benefits also include better water solubility, reduced immunogenicity and extended stability in the body. For a therapeutic this can mean fewer injections are required with fewer side effects and ultimately a safer product.  

Evonik has operated a specialized plant to produce PEGs for pharmaceutical applications in Hanau since 2017. This plant focuses on process development and pilot scale manufacturing. Services include in-house development and the production of multi-kilogram batches under non-GMP conditions.

The pilot plant can address the stringent process control and manufacturing requirements sought by pharmaceutical companies for the synthesis of highly pure PEGs and mPEGs including a PDI of less than 1.05 and diol contents less than 1.0 %.

We have experience functionalizing and activating PEGs in volumes up to hundreds of kilograms. Processes and reactions that have been done under ISO and GMP include oxidations, hydrogenations and the preparation of amino-active PEG esters.

Our dedicated special technologies group in the Hanau R&D team works on crystallization and chromatography techniques for PEGs on a kilogram scale.

High purity requirements

• Polydispersity (PDI) (Mw/Mn): ≤ 1.05
• Diol content (mPEG) < 1.0 %
• Average molecular weight: + / - 5 %
• Reactors: 1 L, 10 L and 50 L
• Target batch site: 1 kg and 5 kg
• Production under ISO
• Workup in R&D lab or GMP pilot plant 

Our facilities offer a complete analytical setup for PEGs and mPEGs. This includes the following capabilities:

• Average molecular weight per SEC/GPC and/or MALDI-TOF
• Polydispersity (PDI) per SEC/GPC
• Assay and purity determined per NMR and/or HPLC (CAD, ELSD)
• Diol content (for substituted PEGs) per HPLC (CAD, ELSD)
• GC for residual solvents
• X-Ray Powder Diffraction (XRPD)
• Thermal: DSC, TGA, TG-IR, bomb calorimetry

Evonik combines decades of expertise handling ethylene oxide with experience in contract manufacturing of APIs and intermediates, and as a CDMO for complex parenteral drug products. This enables us to provide highly pure PEGs and mPEGs that meet the highest pharmaceutical standards.

Alongside in-house production of PEGs and mPEGs, Evonik can also support you across the value chain with PEGylated APIs. This could include activation, API synthesis, conjugation and analytical setup. At our FDA-inspected facility in Birmingham, Alabama, we can also support the development, manufacturing and aseptic filling of PEGylated drug products.

Get in touch with us for further information on our services for PEGs and PEGylated drug products.