Regulatory agencies around the world oversee the efficacy and safety of drugs. One of the regulatory priorities is impurities that can have toxic side effects that affect drug efficacy and expiration dates. Generic drug manufacturers must pay attention to potentially toxic and harmful contaminants in the drug product, including elemental impurities, when studying the prescription process. Elemental impurities refer to trace metals that may be present in drugs and directly or indirectly participate in various physiological and biochemical processes in the human body. Elemental impurities are not beneficial to drug efficacy and may even produce toxic reactions affecting drug activity.
The Q3D guidelines for elemental impurities published by the International Conference on Harmonization (ICH) are applicable to the risk assessment of elemental impurities in APIs and pharmaceutical products. Q3D requires control of elemental impurities introduced by synthesis, production environments, APIs, excipients, and containment systems. The quantity, type and limit requirements for elemental impurities in the United States, Europe and China are consistent with ICH Q3D guidelines.
Classification of Elemental Impurities
ICH Q3D guidelines classify elemental impurities into three categories based on their toxicity to humans and likelihood of being found in pharmaceutical products.
- Elemental impurities in Class 1 are highly toxic to the human body, including Cd, Pb, As, Hg;
- Elemental impurities in Class 2 are divided into 2A and 2B groups. Class 2A (Co, V, Ni) has a higher probability in pharmaceutical preparations. The occurrence probability of class 2B in drug preparations is low, so it is not necessary to detect, such as TI, Au, Pd, etc.
- Elemental impurities in Class 3 are less toxic to humans when administered orally, such as Li, Sb, Ba, Mo, etc.
If elemental impurities are intentionally added to the production process of APIs, excipients and drugs, they need to be detected, regardless of the type. According to ICH Q3D, the Permitted Daily Exposure (PDE) for elemental impurities in oral, injectable, and inhaled routes of administration of drugs is shown in the table below.
Our Services
Due to the introduction of excessive or toxic elemental impurities in pharmaceutical preparations, such as API and manufacturing, it can have a significant impact on patients. Thus, to ensure the quality and safety of drugs, the control threshold for elemental impurities in drug preparations should be controlled to 30% of the PDE.
Our company provides pharmaceutical manufacturers worldwide with the development and validation of elemental impurity analysis methods, as well as comprehensive elemental impurity detection solutions. Our services cover all aspects from sample pre-processing to providing compliance experimental data and inspection reports to help enterprises meet the increasingly stringent drug regulatory requirements in various countries. We can perform elemental impurity assessments of APIs and formulations in accordance with ICH Q3D and can customize elemental studies to special limits according to customer requirements.
- To develop analytical methods for elemental impurities and confirm the accuracy, repeatability, reproducibility, and system sustainability of the method.
- Based on ICH guidelines and national pharmacopoeia requirements to detect elemental impurities in API and preparations, provide qualified reports.
- Assist pharmaceutical companies to develop control strategies for elemental impurities.
Our Advantages
- Professional impurity research team
- Having a thorough knowledge of drug regulations in different countries
- Industry-leading detection instruments, such as ICP-OES, ICP-MS and AAS
- Graphite digesters and microwave digesters can be used for sample pretreatment
