Proteins & Peptides Elemental-related Impurity Analysis

To reduce the risks associated with potentially toxic and harmful elemental impurities, regulatory agencies require that elemental impurities be properly analyzed to minimize patient exposure. Based on the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Q3D Elemental Impurities Guideline, CD Formulation provides extensive elemental impurity analysis to ensure your protein/peptide biologics meet all quality standards before receiving stringent regulatory approval.

Sources of Element-related Impurities in Biopharmaceuticals

Element-related impurities are a type of impurity that is of great concern for chemical APIs. They are mainly introduced into drugs through the use of catalysts during the synthesis of APIs. However, for biopharmaceuticals such as proteins/peptides, due to the use of materials from natural sources, manufacturing equipment, and dosage container systems during the manufacturing process, especially the peptide synthesis process, the final product may also introduce a certain amount of harmful elemental impurities.

In particular, these materials that may come into contact with the final product should be inert. Metal ions may interact with or covalently bind to the molecular structure of protein/peptide drugs, replacing standard counterions, thereby endangering human health.

Fig. 1 Potential sources of element-related impurities in biopharmaceuticals. (CD Formulation)

Explore Our Proteins & Peptides Elemental-related Impurity Analysis

At CD Formulation, our scientists are experts in identifying and analyzing any elemental impurities in protein and peptide biopharmaceuticals. Benefiting from decades of analytical expertise, we utilize a range of powerful analytical tools to monitor elemental impurities in your protein/peptide biopharmaceuticals.

All of our elemental-related impurity analysis services are performed according to standard elemental impurity analysis methods described in the European Pharmacopoeia (EP) and United States Pharmacopoeia (USP) general chapters and support the 24 potential elemental analyses included in the ICH Q3D guideline.

• Ⅰ: Cd, Pb, As, Hg.
• Ⅱ2A: Co, V, Ni.
• Ⅱ2B: Tl, Au, Pd, Ir, Os, Rh, Ru, Se, Ag, Pt.
• Ⅲ: Li, Sb, Ba, Mo, Cu, Sn, Cr.
• Ⅳ: Al, B, Ca, Fe, K, Mg, Mn, Na, W, Zn.

Importantly, all of our analytical testing services are customizable to your specific project and validated for successful application in process validation, stability testing, and GMP batch release testing of drug products or drug substance batches.

In addition, our experts have in-depth knowledge of implementing the ICH 3QD elemental impurities guidance and can provide comprehensive toxicology risk assessment and testing compliance services to meet all of your regulatory requirements.

Our elemental-related impurity analysis services include:

• Elemental analysis method development and optimization.
• Elemental analysis method validation.
• Elemental analysis method transfer.
• Process validation support.
• Batch release testing support.

How Do We Detect Proteins & Peptides Elemental-related Impurity?

In our analytical laboratories, inductively coupled plasma mass spectrometry (ICP-MS) and inductively coupled plasma optical emission spectrometry (ICP-OES) are the most common techniques used for elemental impurities analysis.

Both techniques use a high-energy plasma to ionize any elements present in the sample preparation and detect them using elemental masses or elemental emission bands, with the advantage that they can detect a wide range of elemental impurities at very low concentrations.

Fig. 2 Methods for elemental analysis of proteins/peptides. (CD Formulation)

Elemental Impurity Analysis Based on ICP-MS

ICP-MS is a robust and highly sensitive method for heavy metal trace analysis. Our impurity analysis team uses ICP-MS to measure multiple elements in a single acquisition while providing high throughput capabilities, with each analysis cycle completed in 3-5 minutes. In addition, our ICP-MS analytical testing services can be performed at very low detection limits for elemental impurities in samples, ranging from 0.5 ppt to 500 ppm.

Advantages:

• Multi-element technology.
• Wide analytical range.
• Low detection limits.
• High sample throughput.
• Low sample volume.
• Simple sample preparation.
• High resolution and tandem mass spectrometry provide a high level of interference control.

Elemental Impurity Analysis Based on ICP-OES

ICP-OES works by introducing a liquid sample into a plasma through a nebulizer. The nebulizer then turns the liquid sample into an aerosol. In the plasma, the sample is heated and emits light, which is then measured. The light emitted by a specific metal has a discrete wavelength, and the intensity of this light is proportional to the concentration of the element in the solution. Using this technology, our scientists can accurately and easily determine the content of trace elements in protein/peptide pharmaceuticals.

Our ICP-OES testing service can detect more than 60 elements in the periodic table at a time, with detection limits as low as 0.01-1 ug/L, and each sample takes less than 2 minutes.

However, the analysis of elemental impurities using ICP-OES must be able to be nebulized, which means that your solid and liquid samples can't be analyzed while they are still in solid and liquid form.

Advantages:

• A multi-element technology that can identify the type and proportion of elements in complex samples.
• Wide analysis range, simultaneous detection of multiple elements.
• High sample throughput.
• Small sample volume.
• Simple sample preparation.

Elemental Impurity Analysis Based on Other Analytical Techniques

In addition to the above elemental impurity quantitative analysis methods detailed in USP Chapter 232/233, our scientists also use a range of other techniques for elemental impurity qualitative detection and quantitative analysis, including:

• Ion Chromatography (IC)
• Atomic Absorption Spectroscopy (AAS)
• Atomic Emission Spectroscopy (AES)
• Flame Atomic Absorption (FLAA) Spectroscopy
• X-ray Fluorescence (XRF)

Typical Detection Limits for Common Elemental Technologies

Why Choose Us for Proteins & Peptides Elemental-related Impurity Analysis?

• We have a team of highly skilled scientists with expertise in analyzing proteins and peptides of elemental-related impurities. Our team has years of experience in this field and is equipped with the knowledge and tools to accurately assess impurities in your samples.
• We use advanced analytical equipment and techniques to ensure accurate and precise analysis of elemental impurities in proteins and peptides. Our state-of-the-art technology allows us to detect even trace amounts of impurities in your samples.
• We adhere to strict quality control standards to ensure that our analysis methods comply with regulatory requirements. We follow industry best practices to provide you with reliable and compliant results for your proteins and peptides elemental-related impurity analysis.
• We offer flexible testing options to meet the needs of your different projects.

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With the latest sample preparation techniques and elemental impurity analysis methods, CD Formulation can effectively overcome any challenges posed by sample type and sample matrix. Please feel free to contact us if you are interested in our services or have further questions. We look forward to working with you.

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