Elemental Impurities USP 232/233 & ICH Q3D Guidelines
Contaminants, impurities, and residuals can be introduced into pharmaceutical and biopharmaceutical products at almost any stage of drug development and manufacturing. The screening and quantitation of elemental impurities in raw materials, APIs, excipients, drug products, and packaging materials is significant to safely optimizing both pharmaceutical development and manufacturing. Left unchecked, elemental impurities can derail even the most robust path-to-market, as drug products will fail to comply with key regulations – including those set forth by the United States Pharmacopeia Convention (USP 232 and 233) and the International Council for Harmonisation (ICH Q3D guidelines). As noted by the FDA, these impurities may be present in drug products from a variety of sources, including elements intentionally added (e.g., catalysts) during drug product component synthesis, those present in the ingredients used in the preparation of the drug product, and those that leach from container closure systems or manufacturing equipment (Figure 1).
Figure 1: Sources of Elemental Impurities
As of January 1, 2018, manufacturers are required to comply with new provisions outlined in USP 232/233, which call for pharmaceutical and biopharmaceutical manufacturers to ensure that their manufacturing processes are kept free from toxic metals. USP 232 sets limits on the amounts of specific class 1, 2A, 2B, and 3 elements allowed in drug products, while USP 233 defines the appropriate analytical methods for measuring elemental impurities. The USP 232 and 233 chapters are globally harmonized with the ICH Q3D guidelines, which promote a risk-based approach to evaluating elemental impurities in drug products. In order to comply with these guidelines, detailed risk assessments of materials must be completed.
This is where a trusted analytical partner with deep regulatory expertise makes a difference. Avomeen’s elemental impurity identification scientists have decades of combined chemical analysis and regulatory expertise and take a customized approach to method development. We use advanced analytical techniques that provide the most accurate results for your project, informed by decades of experience in element-specific protocols, advanced analytical method development, and validation.
Expertise in drug substance and drug product specific protocols, method development, and validation along with flexible customized elemental impurities protocols and study designs that provide the most accurate results down to necessary trace level detection.
Dedicated, trained, and experienced pharmaceutical scientists employ a variety of advanced techniques to identify impurities in pharma products, including ICP-MS coupled with individualized sample preparation techniques.
Microwave digestion methods which allow for digestion of even the most complex matrices, guaranteeing reliable and reproducible limit and quantitative results for submission and release testing.
Elemental Impurities Testing Capabilities
With the unrivaled knowledge, advanced equipment, and scientific expertise available at Avomeen’s laboratory, our scientists can perform qualitative screening and quantitative assays on everything from raw materials to finished drug products. The team at Avomeen will help you develop quality control checks such as batch-to-batch testing, refined development methods, and analysis of substances from raw material suppliers that will monitor and support the control of elemental impurities in your product and production processes.
- 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
Sample preparation techniques:
- Microwave digestion
- Wet chemical digestion
- Solvent extraction
- Reflux extraction
- Agilent Inductively Coupled Plasma Mass Spectrometer (ICP-MS)
- Milestone Scientific Microwave digestion system
Comprehensive Risk Assessment Program Support
Ongoing risk assessment helps define and refine processes for controlling and preventing elemental impurities. The FDA also mandates that applications for new products are accompanied by a risk assessment summary for elemental impurities. To remain in compliance with the mandate, previously approved pharmaceutical products must also be submitted with documentation on changes in controls. Even if no changes take place, the FDA still encourages manufacturers to deliver an annual risk assessment summary. The Avomeen team is well-versed in risk-based approaches for compliance with elemental impurities regulations, and our expertise in both testing and consulting can help you maximize the effectiveness of your risk assessments. If the finished product ingredients are individually not qualified for elemental impurities control, our experts can make recommendations on other options allowed in the guidelines, such as drug product control of elemental impurities.
Experience our Tailored Approach to Elemental Impurities Testing
Every project for elemental impurities testing is different. Before kicking off your project, our project managers and scientists will meet with you to ensure they have a concrete understanding of the needs and complexities of your project. From there, Avomeen takes a customized approach to method development, using analytical techniques that provide the most accurate results down to trace levels.
Our scientists have deep expertise in element-specific protocols, method development, and validation, but above all else, Avomeen is a partner. Not only do we test key products, but we also strive to transfer knowledge to pharmaceutical companies on how to implement a smooth production process with strategies that prevent future elemental impurities complications.