ICH Q3D analysis laboratory
As a pharmaceutical manufacturer, you want to carry out an ICH Q3D analysis
ICH Q3D
The ICH Q3D guideline (International Conference on Harmonisation) establishes the methodology for assessing elemental impurities in pharmaceutical products.
ICH Q3D focuses on risk management related to elemental impurities. It classifies elements according to their toxicity and likelihood of occurrence, and defines maximum exposure limits.
Carry out an ICH Q3D analysis (according to the ICH Q3D guideline)
ICH Q3D analysis makes it possible to detect, quantify and control the presence of elemental impurities and trace metallic elements, in accordance with the requirements of the international ICH Q3D guideline.
ICH Q3D and USP 233: two complementary standards mastered by FILAB
Our ICH Q3D laboratory specializes in implementing this complex analysis, in strict compliance with the expectations of the EMA and the FDA.
The USP 233, often used in addition, defines the analytical methods to apply (ICP-MS, ICP-OES) to meet the requirements of ICH Q3D. While ICH Q3D sets the exposure thresholds and the risk management approach, USP 233 governs the technical aspects of the analysis.
FILAB carries out your analysis in compliance with the ICH Q3D guideline, relying on state-of-the-art analytical equipment
For more than 30 years, the FILAB laboratory has been providing dozens of clients with elemental impurity analysis services according to USP 233 and ICH Q3D, some of which under COFRAC ISO 17025 accreditation.
Thanks to its state-of-the-art analytical equipment (12 ICP-MS and ICP-AES, 1 mercury amalgamator with automatic sampler, plate digestion techniques or microwave digestion) and its high-level expertise in elemental analysis and pharmaceutical analysis, the FILAB laboratory offers its elemental impurity analysis services to meet regulatory requirements.
Technical means used
We carry out your Q3D analysis using spectrometry techniques:
The regulatory framework for ICH Q3D analysis
Elemental impurity analysis according to ICH Q3D is based on a harmonized regulatory framework at the international level. The main reference is the ICH Q3D (R1) guideline, which defines daily exposure limits. In addition, other regulatory sources govern and reinforce this requirement.
Q3D analysis is part of a set of regulatory references:
ICH Q3D (R1) – Guideline on Elemental Impurities
FDA and EMA standards
European Pharmacopoeia (chap. 5.20)
Good Manufacturing Practices (GMP)
analysis according to ICH Q3D
ICH Q3D requires a two-phase approach to managing elemental impurities.
The first phase, called preliminary risk assessment (risk assessment), consists of identifying potential sources of impurities. This step can be carried out using documentary data or laboratory screening analysis. The goal is to determine which elements must be controlled in finished products and to prioritize efforts to ensure patient safety while complying with regulatory limits.
The second phase of ICH Q3D consists of controlling and managing the risks associated with the identified elemental impurities. This involves quantitative analysis by ICP-AES and ICP-MS to verify that levels comply with the established limits, as well as adjustments to manufacturing processes to minimize risks and ensure product compliance.
Analytical development and validation
Analytical development in the laboratory by ICP
Implementation of assay methods for metallic elements by ICP (inductively coupled plasma).
ICH Q3D training
Technical and regulatory training on the requirements of ICH Q3D (metal limits in pharmaceutical substances).
Analytical validation according to USP 233 for the analysis of elemental impurities
Compliance with the elemental impurity analysis method according to the United States Pharmacopeia.
Specific analysis of compounds and impurities
Analysis of ICH Q3D elemental impurities by ICP
Mapping sources of impurities in the production chain
ICH Q3D requires a two-phase approach to managing elemental impurities.
The first phase, called preliminary risk assessment (risk assessment), consists of identifying potential sources of impurities. This step can be carried out using documentary data or through laboratory screening analysis. The objective is to determine which elements must be controlled in finished products and to prioritize efforts to ensure patient safety while complying with regulatory limits.
The second phase of ICH Q3D consists of controlling and managing risks related to the identified elemental impurities. This involves quantitative analysis by ICP-AES and ICP-MS to verify that levels comply with the established limits, as well as adjustments to manufacturing processes to minimize risks and ensure product compliance.
The methodology for analyzing elemental impurities in medicines is described in the USP 233 guideline (US Pharmacopeia No. 233: Elemental Impurities – Procedures).
This analytical methodology now uses modern analytical techniques such as ICP (ICP-AES and ICP-MS), or the mercury amalgamator.
Depending on the results and consideration of the acceptable threshold (30% of the PDE), control plans can be implemented and analytical methods validated according to the United States Pharmacopeia USP 233.
Why carry out an ICH Q3D analysis in the laboratory?
ICH Q3D analysis plays a key role in controlling the quality and safety of medicines and pharmaceutical products. It makes it possible to verify that concentrations of elemental impurities – especially heavy metals.
Indeed, during an ICH Q3D analysis, the presence of elemental impurities is monitored. This includes in particular the heavy metal analysis of lead, arsenic, cadmium, and mercury, among others, as well as other elements that may pose risks at certain concentrations.
Using an ich q3d analysis laboratory makes it possible to detect and quantify impurities originating from raw materials, manufacturing processes, production equipment, or packaging.
Details of analysis according to ICH Q3D
Tailor-made support
FILAB supports you at every stage:
Development or transfer of Q3D analytical method
Validation and GMP application
Risk studies related to elemental impurities
Writing reports compliant with regulatory requirements
ICH Q3D analysis for the pharmaceutical industry
Pharmaceutical
For pharmaceutical laboratories (innovator or generic medicines)
For CDMOs / contract manufacturers
For excipient manufacturers
our other ICH services
VICH analysis
analysis carried out according to VICH guidelines for veterinary medicines, often focused on metal impurities and stability.
Stability study according to ICH
Stability testing as part of the development or marketing of healthcare products.
FAQ
Depending on the client's needs, FILAB offers several analytical validation approaches.
The most comprehensive validation will follow the requirements of the selected reference standard (ICH Q2 or USP 233) and will be performed on one matrix.
The ICH Q3D guidelines apply to the quantification and control of elemental impurities in all types of pharmaceutical products, including:
- medicines for human use,
- veterinary medicines,
- and biological products.
These guidelines are designed to help medicine manufacturers assess the health risks associated with the levels of elemental impurities present in pharmaceutical products, and to put control measures in place to ensure these levels are safe.
The ICH Q3D guidelines also apply to:
- raw materials
- excipients used in the manufacture of medicines,
- as well as finished products.
They cover the 24 chemical elements considered the most concerning in terms of potential toxicity to patients, including lead, cadmium, mercury, arsenic, etc.
To verify compliance with ICH Q3D, pharmaceutical companies must follow several key steps, integrating a systematic and rigorous approach to the assessment and control of elemental impurities in their products.
These steps can be carried out by an expert laboratory in ICH Q3D analysis :
- Identification of potential sources of elemental impurities in products, including raw materials and manufacturing processes.
- Identification of the elements to be analyzed based on their toxicity and likelihood of presence, in accordance with ICH Q3D.
- Development and validation of analytical methods to measure impurities, in line with USP 233 recommendations.
- Analysis of products and batches to compare impurity levels against the acceptable limits of ICH Q3D.
- Management and correction of processes, if necessary, to reduce impurities.
This methodical approach ensures the safety of pharmaceutical products by controlling elemental impurity levels.
The main difference between USP 233 and ICH Q3D lies in their scope and application in the control of elemental impurities in pharmaceutical products.
USP 233 focuses specifically on the methodology (233) and the limits for the quantification of elemental impurities (232), providing detailed guidance on analytical techniques, such as mass spectrometry or atomic absorption spectroscopy, to measure these impurities.
On the other hand, ICH Q3D takes a more comprehensive approach, providing a framework for the identification, assessment, and risk management of elemental impurities throughout the lifecycle of a pharmaceutical product. This encompasses not only analytical methods, but also toxicological considerations to define safety limits for patients, and applies internationally (such as in Europe, the United States, and Japan).
In addition to ICH Q3D and USP 232/233, other standards and guidelines for elemental impurities exist: the European Pharmacopoeia, the European Medicines Agency guidelines, the U.S. Food and Drug Administration guidance, and the World Health Organization guidelines. These standards are designed to ensure the safety of pharmaceutical products by controlling elemental impurity levels, with specific requirements that may vary depending on the country and organization. Contact the FILAB laboratory for advice.
FILAB combines the requirements of USP <233> and ICH Q3D standards to provide a comprehensive analysis of elemental impurities in pharmaceutical products. USP <233> provides specific guidance on sample preparation and analytical methods, focusing on the quantification of impurities in pharmaceutical samples. FILAB uses these methods in parallel with the requirements of ICH Q3D, which focuses on assessing the risks associated with trace elements in products. This harmonized approach ensures both patient safety and regulatory compliance.
In the event of non-compliance, FILAB works closely with manufacturers to identify the source of the problem. This may include reassessing manufacturing processes, modifying formulations, or putting additional controls in place. FILAB can also offer revalidation services or additional analysis to ensure that products meet regulatory requirements.
ICP techniques, especially ICP-MS, are extremely sensitive. This high sensitivity is essential to ensure that pharmaceutical products comply with the strict limits imposed by ICH Q3D.
Even though ICH Q3D is not regulatory applicable to the cosmetics sector, its logic can inspire a risk-control approach :
The European cosmetics regulation (EC 1223/2009) requires that each cosmetic product be subject to a safety report, including the assessment of potential contaminants.
Heavy metals (lead, arsenic, mercury, cadmium, antimony, etc.) are contaminants often tested for in cosmetics, especially in pigments, plant extracts, or natural raw materials.
Thus, as part of a voluntary quality or enhanced safety approach, some cosmetics manufacturers choose to partially apply the ICH Q3D logic to:
Identify potential sources of contamination
Assess exposure levels
Define internal thresholds (often stricter than regulatory requirements)
