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With decades of combined chemical analysis and regulatory expertise, we deliver industry-leading, highly accurate element-specific protocols, advanced analytical method development, and validation in accordance with USP <232>/<233> and ICH Q3D guidelines for elemental impurities testing in drug products, down to necessary trace level limits of detection.

At almost any stage of drug development and manufacturing, impurities, contaminants, and residuals can be introduced into pharmaceutical and biopharmaceutical products. The presence of elemental impurities in raw materials, active pharmaceutical ingredients (APIs), drug product, and packaging materials can cause significant disruption to even the most robust path-to-market, as drug products will not comply with necessary regulations, including those set by The International Council for Harmonization () and The United States Pharmacopeial Convention (USP <232> and <233>). 

Effective January 1, 2018, manufacturers of small and large molecule drugs are required to meet the specifications outlined in and elemental impurities testing guidance, which has been globally harmonized with ICH Q3D guidelines. The USP and ICH elemental impurities testing guidance promote a risk-based approach for the evaluation and control of elemental impurities in drug products, or permitted daily exposures (PDE) for individual elements, to ensure manufacturing processes are free from toxic metals. All potential sources of elemental impurities should be considered, including those intentionally added during synthesis (e.g., catalysts), those potentially present in materials used to prepare drug product, and any elements that may be introduced from manufacturing equipment or container closure systems.

Elemental impurities testing capabilities

Element’s teams of dedicated and experienced scientists have a proven track record of developing and validating customized, specific elemental impurities methods, protocols, and study designs for challenging APIs and complex sample matrices with accurate trace level detection, including those with poor solubility. Our deep expertise in USP heavy metals testing and elemental impurities testing of biologics and pharmaceuticals, along with a variety of advanced techniques, including ICP-MS coupled with individualized sample preparation methods and the use of three collision gases, allow for low-level detection of elements that are typically obscured by polyatomic interferences (e.g., sulfur and silicon. Generally, detection limits are sub parts per billion (ppb) for elements such as calcium, sodium, potassium, and silicon, and sub parts per trillion (ppt) detection limits can be achieved for select elements and applications. Furthermore, with the use of advanced sample preparation techniques, our scientists can analyze challenging sample matrices, such as plastics, lubricants, and pharmaceuticals, with the use of our microwave digestion system. 

Our comprehensive suite of quality control-focused solutions support the control of elemental impurities in product and production processes, including batch-to-batch testing, raw material testing, method optimization and refinement, and production process refinement to prevent elemental impurities challenges in the future.

Expert regulatory support for elemental impurities risk assessment programs

Maximize the effectiveness of your elemental impurities risk assessment with the support of our consultative team. As your collaborative, strategic contract development and manufacturing organization (CDMO) partner throughout the entire drug development lifecycle, our knowledgeable team can provide recommendations and alternative options that meet the standards set forth in USP <232>/<233> and ICH Q3D regulatory guidance for the control of elemental impurities in drug products if finished product ingredients do not meet standards for elemental impurities control.

Elemental impurities testing services

• Elemental impurity testing
• Implementation of ICH Q3D elemental impurities guideline
• USP <232>/<233> implementation of elemental impurity screening
• Method development and validation
• Limit test validation
• Quantitative method validation
• Semi-quantitative screening
• Trace metal analysis
• Targeted metals analysis
• Monograph (compendial) testing
• Extractables and leachables studies
• API and drug substance testing
• Raw materials testing
• Finished product testing
• Stability studies
• Batch and lot release testing
• Metal speciation
• Impurity characterization

Elemental impurities sample preparation techniques

• Closed-vessel microwave digestion
• Open-vessel microwave digestion
• Wet chemical digestion
• Acid digestion
• Base digestion
• Solvent extraction
• Reflux extraction

The ÈÕ±¾avÎÞÂëadvantage

Ensure the control of elemental impurities in small and large molecule drug products with Element’s deep regulatory knowledge, consultative approach, well-equipped laboratory, and proven success in achieving optimal methods for complex and challenging samples. Our end-to-end solutions include regulatory-driven elemental impurities risk assessment support, elemental impurities USP <232>/<233> and FDA ICH Q3D testing programs, screening, batch-to-batch testing, raw material testing, method development, validation, and optimization. We offer a customized approach to method development, using analytical techniques that provide the most accurate results down to trace levels.

To learn about our customized approach to controlling elemental impurities in pharmaceuticals and biologics, or to speak with one of our experts, contact us today.