Proteins & Peptides Residual Solvent and Volatile Impurity Analysis

Residual solvents are considered impurities that are not removed during product purification and are a class of impurities derived from downstream processing of protein/peptide biopharmaceuticals. These impurities can be harmful to human health and the environment, so it is important to ensure that they are not present in the product or are present only below the recommended acceptable levels. Based on the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use ICH Q3C (R8) residual solvents guidance and United States Pharmacopeia (USP) <467>, CD Formulation provides professional residual solvent determination services to ensure that your drug meets all quality standards before obtaining strict regulatory approval.

Sources of Residual Solvents in Protein/Peptide Biopharmaceuticals

Residual solvents in pharmaceuticals, also known as organic volatile impurities (OVIs), are chemicals used or generated during the manufacturing of small molecule active pharmaceutical ingredients (APIs), excipients, and drug products. Residual solvent analysis is generally not required for protein-based drugs produced by cultured cell lines that don't introduce solvents.

However, the following are exceptions:

• Organic solvents (e.g., N, N-dimethylacetamide (DMA), N, N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), or propylene glycol (PG)) used to dissolve hydrophobic small molecule drugs for binding to proteins during the production of antibody-drug conjugates and other protein conjugates, where drugs or other molecules are covalently bound to proteins.
• Residual solvents in chromatographic media used during purification.
• Reaction solvents are used during peptide cleavage.
• OVIs are introduced during packaging, warehouse storage, and/or transportation.

Fig. 1 Potential sources of residual solvent impurities in protein/peptide biopharmaceuticals. (CD Formulation)

Explore Our Proteins & Peptides Residual Solvent and Volatile Impurity Analysis

At CD Formulation, our scientists are experts in identifying and analyzing any residual solvents in protein and peptide biopharmaceuticals. With expertise gained from decades of analytical experience, we utilize a range of powerful analytical tools to monitor OVI in your protein/peptide biopharmaceuticals.

To address residual solvents introduced during the protein/peptide drug manufacturing process and residues from the chromatography media used during purification, such as residual solvents (e.g., DMF, DMSO) and other organic volatile impurities (OVI) introduced during packaging and shipping. Our residual solvent analysis team performs standard residual solvent analysis testing services based on methods described in the European Pharmacopoeia (EP) and United States Pharmacopoeia (USP) <467> and Japanese Pharmacopoeia General Chapters, and in compliance with the ICH Q3C (R8) residual solvents guideline, ensuring that residual solvents in drug substances as well as finished products are controlled.

However, all of our analytical testing services are customizable, and we are able to develop customized methods suitable for your specific samples based on the characteristics of your samples.

Our residual solvent analysis services include but are not limited to the following:

• Residual solvent analysis method development and optimization.
• Residual solvent analysis method validation and transfer.
• Residual solvent determination (such as DMSO, NMP, ether).
• Specificity testing.
• Recovery testing.
• Solution Stability testing.
• Batch release testing support.
• Process validation support.

How Do We Detect Residual Solvent and Volatile Impurity?

Our cGMP laboratories perform residual solvent testing according to pharmacopoeial methods, particularly USP <467> and the European Pharmacopoeia. In addition, we are able to develop and validate custom methods to meet your specific needs using a range of chromatographic techniques such as headspace gas chromatography or gas chromatography-mass spectrometry (GC-MS).

Our residual solvent analysis experts perform residual solvent method validation in accordance with the ICH Q2 guidelines for the validation of analytical procedures. The accurate and reliable data generated for residual solvents can help you make appropriate risk assessments for your finished products.

Residual Solvent Analysis Based on USP <467>

The United States Pharmacopeia (USP) method is a worldwide quality control method that follows the ICH Q3C guidelines. The method consists of three analytical steps for identification and quantification.

• Step 1: Identification and limit testing. G43 stationary phase (624 column) is used.
• Step 2: Determine if the concentration of the identified solvent exceeds the specified limit. G16 stationary phase (WAX column) is used.
• Step 3: Quantitative testing. The choice of stationary phase (G43 or G16) depends on which stationary phase produces fewer coeluting substances.

Residual Solvent Analysis by Headspace Gas Chromatography (GC)

• Static headspace GC residual solvent analysis is a mature technology that is often used in pharmaceutical quality control and research. The method is based on the distribution coefficient of the detected substance between the mobile phase and the stationary phase with high detection sensitivity and selectivity. According to the boiling point of the solvent, GC methods are divided into direct injection and headspace injection. Generally speaking, headspace injection is suitable for solvents with lower boiling points and temperature sensitivity, while direct injection is suitable for high boiling point solvents.
• Our residual solvent analysis team custom develops GC methods suitable for your samples to ensure accurate and reliable detection of residual solvent content.

In addition to residual solvent analysis based on the USP <467> and GC. Our scientists also use other technologies such as gas chromatography/mass spectrometry, liquid chromatography/mass spectrometry, etc., to support residual solvent impurity testing services.

Why Choose Us for Residual Solvent and Volatile Impurity Analysis?

• We have hundreds of residual solvent and volatile impurity analysis achievements, supporting proteins/peptides biopharmaceutical development.
• Our team of analytical chemists has extensive experience in residual solvent and volatile impurity analysis, ensuring accurate and reliable results.
• We utilize cutting-edge instrumentation and technology to perform our analysis, guaranteeing high-quality data.
• We adhere to strict regulatory requirements and guidelines, providing you with confidence in the validity of our results..
• We offer flexible testing options to meet the needs of your different projects.

Publication

CD Formulation's impurity analysis team offers expert residual solvent and volatile impurity services, which are performed in our GMP-compliant laboratories. Please feel free to contact us if you are interested in our services or have further questions. We look forward to working with you.

How It Works

STEP 1

Submit a service request describing your specific research or development need.

STEP 2

We'll email you to provide your quote and confirm order details if applicable.

STEP 3

Execute the project with real-time communication, and deliver the final report promptly.