Elemental Impurity Test

Elemental Impurity Test

Pharmaceutical products may contain elemental impurities from a variety of sources, such as interactions with production equipment or packaging materials, or catalyst residues intentionally added during the synthesis process. It is essential to keep the level of elemental impurities in pharmaceutical products within acceptable limits. The experienced Protheragen-ING Lab is committed to providing accurate and reliable results in the detection of elemental impurities, helping pharmaceutical companies maintain the quality and safety of their products.

Limit classification of elemental impurities

According to the ICH Q3D Guideline for Elemental Impurities and USP <232> Elemental Impurities - Limits, elemental impurities are classified into four categories, each with specific limits:

  • Category 1 Elements -This category includes Arsenic (As), Cadmium (Cd), Mercury (Hg), and Lead (Pb). The use of these elements is either prohibited or restricted in pharmaceutical manufacturing.
  • Category 2 Elements - This category is considered human toxicants dependent on the route of administration. Based on their relative occurrence in drug products, they are further divided into subcategories 2A and 2B.
  • Category 3 Elements - This category has relatively low toxicity when administered orally (high PDE value, typically >500 µg/day). However, their risk assessment is still required for inhalation and injection routes. Unless intentionally added, these elements are not considered for risk assessment in oral administration.
  • Other Elements - Due to their inherently low toxicity and/or regional regulatory differences, the Permitted Daily Exposure (PDE) values for other elements have not been determined.

The classification of the elements specified in ICH Q3D and their limits are shown in the table.

Element Classification Oral PDE, µg/day Injectable PDE, µg/day Inhalant PDE, µg/day
Cd 1 5 2 2
Pb 1 5 5 5
As 1 15 15 2
Hg 1 30 3 1
Co 2A 50 5 3
V 2A 100 10 1
Ni 2A 200 20 5
Tl 2B 8 8 8
Au 2B 100 100 1
Pd 2B 100 10 1
Ir 2B 100 10 1
Os 2B 100 10 1
Rh 2B 100 10 1
Ru 2B 100 10 1
Se 2B 150 80 130
Ag 2B 150 10 7
Pt 2B 100 10 1
Li 3 550 250 25
Sb 3 1200 90 20
Ba 3 1400 700 300
Mo 3 3000 1500 10
Cu 3 3000 300 30
Sn 3 6000 600 60
Cr 3 11000 1100 3

Protheragen-ING Lab's testing services

We offer comprehensive technical services tailored to meet the regulatory requirements and specific needs of pharmaceutical elemental impurity testing. Our services include:

  • Pharmaceutical Formulation Testing

We develop and validate testing methods for elemental impurities in various pharmaceutical formulations (such as oral, injectable, and aerosol dosage forms), as well as active pharmaceutical ingredients and excipients. These methods are designed in accordance with the procedures outlined in USP <233>, utilizing techniques such as ICP-OES and ICP-MS.

  • Complex Matrix Testing

We perform method development, validation (verification), and sample testing work for the detection of elemental impurities in preparations with high daily intake and complex matrices, such as fat emulsions for parenteral nutrition.

  • High-matrix Pharmaceutical Products Testing

We perform method development, validation (verification), and sample testing for the detection of elemental impurities in drugs with high daily intake and high matrix, such as contrast agents used in medical imaging.

Elemental impurities guidelines and regulations

We refer to the following guidelines and regulations for elemental impurity testing:

  • ICH Q3D: This guideline provides principles and recommendations for the control of elemental impurities in drug products.
  • USP <232>: This standard outlines the limits for elemental impurities in pharmaceutical products.
  • USP <233>: This standard describes the procedures for testing elemental impurities in pharmaceutical products.

Contact us today to learn more about our services and how we can assist you in meeting regulatory requirements for elemental impurity control in pharmaceuticals.