ICH Q3D analysis laboratory
As a pharmaceutical manufacturer, you would like to carry out an ICH Q3D analysis
ICH Q3D
The ICH Q3D (International Conference on Harmonisation) guideline establishes the methodology for assessing elemental impurities in pharmaceutical products. This includes medicinal products for human use.
ICH Q3D focuses on managing the risks associated with elemental impurities. It classifies elements according to their toxicity and probability of occurrence, and defines maximum exposure limits. ICH Q3D requires manufacturers to carry out a rigorous assessment of impurities at each stage of the product life cycle, from raw material to finished product.
ICH Q3D analysis
The ICH Q3D analysis is used to detect, quantify and control the presence of elemental impurities and metallic trace elements, in accordance with the requirements of the ICH Q3D international guideline. This regulatory framework has been put in place to guarantee product safety by limiting patient exposure to elemental impurities (heavy metals).
In contrast to the previous approach based on fixed concentration limits, the ICH Q3D guideline is based on the principle of PDE (Permitted Daily Exposure), taking into account the route of administration (oral, parenteral, inhaled) and the chronic toxicity of the elements.
ICH Q3D and USP 233: two complementary standards
Our ICH Q3D laboratory specialises in carrying out this complex analysis in strict compliance with EMA and FDA requirements.
USP 233, which is often used as a complement, defines the analytical methods to be applied (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.
ICH Q3D analysis for the pharmaceutical industry
Our ICH Q3D laboratory specialises in carrying out this complex analysis in strict compliance with EMA and FDA requirements.
USP 233, which is often used as a complement, defines the analytical methods to be applied (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.
ICH Q3D analysis for the pharmaceutical industry
Pharmaceutical
Pharmaceutical companies (originator or generic drugs)
To CDMOs/manufacturers
Manufacturers of excipients
Each analysis is tailored to the matrix in question, thanks to a sample preparation and method optimised to the nature of the product.
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 is used to check that the concentrations of elemental impurities – in particular heavy metals – are correct.
An ICH Q3D analysis checks for the presence of elemental impurities. This includes the analysis of heavy metals such as lead, arsenic, cadmium and mercury, among others, as well as other elements that may present risks at certain concentrations.
Using an ich q3d analysis laboratory enables impurities in raw materials, manufacturing processes, production equipment or packaging to be detected and quantified.
FILAB carries out your analysis in compliance with the ICH Q3D guideline, using state-of-the-art analytical equipment
By carrying out a Q3D analysis in a specialised laboratory such as FILAB, industries can meet a number of objectives:
Comply with the regulatory requirements of health agencies (EMA, FDA, ANSM, etc.)
Comply with the regulatory requirements of health agencies (EMA, FDA, ANSM, etc.)
Ensuring compliance with PDE (Permitted Daily Exposure) thresholds defined according to the route of administration
Ensuring compliance with PDE (Permitted Daily Exposure) thresholds defined according to the route of administration
Identify and quantify trace elements from the manufacturing process (e.g. residual catalysts or metallic materials)
Identify and quantify trace elements from the manufacturing process (e.g. residual catalysts or metallic materials)
Preventing toxicological risks linked to chronic exposure to certain impurities
Preventing toxicological risks linked to chronic exposure to certain impurities
Anticipate the impact of changes in suppliers, processes or production sites
Anticipate the impact of changes in suppliers, processes or production sites
Harmonise quality standards at international level, within the framework of the ICH Q3D guideline
Harmonise quality standards at international level, within the framework of the ICH Q3D guideline
Technical resources used
We can carry out your Q3D analysis using spectrometry techniques:
Identification of impurities by RMN analysis
ICP-OES (Optical Emission Spectrometry) depending on the nature of the element and the matrix
ICP-MS (Inductively Coupled Plasma - Mass Spectrometry)
The regulatory framework for the ICH Q3D analysis
The ICH Q3D analysis of elemental impurities is based on an internationally harmonised regulatory framework. The main reference is the ICH Q3D guideline (R1), which defines daily exposure limits. In addition, other regulatory sources support and reinforce this requirement.
The 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)
Our services according to ICH Q3D
For over 30 years, the FILAB laboratory has been providing dozens of customers with elemental impurity analysis services in accordance with USP 233 and ICH Q3D, some of which are COFRAC ISO 17025 accredited.
Thanks to its state-of-the-art analytical equipment (12 ICP-MS and ICP-AES, 1 mercury amalgamator with autosampler, plate or microwave mineralisation techniques) and its high-level skills in elemental analysis and pharmaceutical analysis, the FILAB laboratory offers you its elemental impurity analysis services to meet the requirements of USP 233:
Analysis according to ICH Q3D
ICH Q3D requires a two-phase approach to the management of elemental impurities.
The first phase, called preliminary risk assessment, consists of identifying potential sources of impurities. This stage can be carried out on the basis of documentary data or via laboratory screening analyses. The aim is to determine which elements need to be controlled in finished products and to prioritise efforts to guarantee patient safety while complying with regulatory limits.
The second phase of ICH Q3D consists of controlling and managing the risks associated with the elementary impurities identified. This involves quantitative analysis using ICP-AES and ICP-MS, to check that levels are within set limits, as well as adjustments to manufacturing processes to minimise risks and ensure product compliance.
Analytical development and validation
Laboratory analytical development using ICP
Establishment of assay methods for metallic elements using ICP (inductively coupled plasma).
ICH Q3D training
Technical and regulatory training on ICH Q3D requirements (metal limits in pharmaceutical substances).
USP 233 analytical validation for elemental impurity analysis
Compliance with the US Pharmacopoeia method of analysis for elemental impurities.
Specific analysis of compounds and impurities
Heavy metal analysis
Assessment of impurities in raw materials, active ingredients and excipients
Mapping sources of impurities in the production chain
ICH Q3D requires a two-phase approach to the management of elemental impurities.
The first phase, called preliminary risk assessment, consists of identifying potential sources of impurities. This stage can be carried out on the basis of documentary data or via laboratory screening analyses. The aim is to determine which elements need to be controlled in finished products and to prioritise efforts to guarantee patient safety while complying with regulatory limits.
The second phase of ICH Q3D consists of controlling and managing the risks associated with the elementary impurities identified. This involves quantitative analyses using ICP-AES and ICP-MS, to check that levels are within set limits, as well as adjustments to manufacturing processes to minimise risks and ensure product compliance.
The methodology for analysing elemental impurities in medicinal products is described in USP guideline 233 (US Pharmacopoeia no. 233: Elemental Impurities - Procedures).
This analysis 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 put in place and the analytical methods validated in accordance with USP 233.
Details of analysis according to ICH Q3D
Tailor-made support
FILAB is with you every step of the way:
Development or transfer of Q3D analytical methods
Validation and GMP application
ICH Q3D analysis training
Risk studies linked to elemental impurities
Drafting of reports in accordance with regulatory requirements
FAQ
Depending on the client's needs, FILAB offers several analytical validation approaches.
The most complete validation will follow the requirements of the chosen standard (ICH Q2 or USP 233) and will be based on a matrix.
For a complete validation, it takes between 6 and 8 weeks. For routine assays, analysis times are between 5 and 10 working days.
The ICH Q3D guidelines apply to the quantification and control of elemental impurities in all types of pharmaceutical products, including :
human medicinal products,
veterinary medicinal products,
and biological products.
These guidelines are designed to help drug manufacturers assess the health risks associated with the levels of elemental impurities present in pharmaceutical products, and to put in place control measures to ensure that these levels are safe.
The ICH Q3D guidelines also apply to
raw materials
excipients used in the manufacture of medicinal products
as well as to finished products.
They cover the 24 chemical elements considered to be of greatest concern in terms of potential toxicity to patients, including lead, cadmium, mercury, arsenic, etc.
To verify compliance with ICH Q3D, pharmaceutical companies need to follow several key steps, incorporating a systematic and rigorous approach to the assessment and control of elemental impurities in their products.
These steps can be carried out by a laboratory with expertise in ICH Q3D analysis:
Identification of potential sources of elemental impurities in products, including raw materials and manufacturing processes.
Identification of elements to be analysed based on their toxicity and probability of presence, in accordance with ICH Q3D.
Development and validation of analytical methods to measure impurities, in accordance with USP 233 recommendations.
Analysis of products and batches to compare impurity levels with the acceptable limits of ICH Q3D.
Management and correction, if necessary, of processes to reduce impurities.
This methodical approach ensures the safety of pharmaceutical products by controlling the levels of elementary impurities.
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 methodology (233) and limits for the quantification of elemental impurities (232), providing detailed guidance on analytical techniques, such as mass spectrometry or atomic absorption spectroscopy, for measuring these impurities.
On the other hand, ICH Q3D takes a more holistic approach, providing a framework for the identification, assessment, and risk management of elemental impurities throughout the life cycle 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 Europe, the USA and Japan).
In addition to ICH Q3D and USP 232/233, other standards and guidelines for elemental impurities exist: the European Pharmacopoeia, European Medicines Agency guidelines, US Food and Drug Administration guidelines, and World Health Organization guidelines. These standards aim to guarantee the safety of pharmaceutical products by controlling the levels of elementary impurities, with specificities that may vary from country to country and from organisation to organisation. Contact the FILAB laboratory for advice.
FILAB combines the requirements of USP <233> and ICH Q3D to offer comprehensive analysis of elemental impurities in pharmaceutical products. USP <233> provides specific guidance on 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 the risk assessment of trace elements in products. This harmonised 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 re-evaluating manufacturing processes, modifying formulations, or implementing additional controls. FILAB can also provide revalidation services or additional analysis to ensure that products meet regulatory requirements.
ICP techniques, particularly ICP-MS, are extremely sensitive. This high sensitivity is essential to ensure that pharmaceutical products comply with the strict limits imposed by ICH Q3D.
Although the ICH Q3D is not applicable to the cosmetics sector by regulation, its logic can inspire a risk management approach:
- European cosmetics regulations (EC 1223/2009) require each cosmetic product to be the subject of a safety report, including an assessment of potential contaminants.
- Heavy metals (lead, arsenic, mercury, cadmium, antimony, etc.) are contaminants often found in cosmetics, particularly in pigments, plant extracts or natural materials.
So, as part of a voluntary approach to quality or enhanced safety, some cosmetics manufacturers are choosing to partially apply the ICH Q3D logic in order to :
- Identify potential sources of contamination
- Assess exposure levels
- Define internal thresholds (often stricter than regulatory requirements)
