Trace Metals Analysis

Including: Method Development and Validation to Support USP <232>/<233> and ICH Q3D Requirements

Analysis of trace heavy metals is important across many industries as elevated concentrations can present toxic effects to human’s, particularly in pharmaceutical and supplement products. In other industries, they can affect product performance, such as in the case of electronic components.  Avomeen’s ICH 17025-Compliant metals analysis laboratory supports our clients testing needs, as well support for compliance with regulations including USP 232/233 and ICH Q3D.

As the equipment and expertise needed for successful trace metals analysis are extensive, many companies lack the capabilities to perform this analysis in-house.  Whether your organization produces finished drug products, supplies raw materials, or markets single-use components for biopharmaceutical manufacturing, our chemists can help you ensure the safety and regulatory compliance of your product(s) by verifying that heavy metals have not inadvertently found their way into your manufacturing process.

Avomeen can analyze for elemental impurities in:

  • Finished Drug Products
  • Raw Materials
  • Nutritional Supplements
  • Topical Products
  • Electronics
  • Consumer Goods
 

FDA-Registered & Inspected, DEA-Licensed (Schedule I-V), GMP Compliant, GLP-Compliant and ISO 17025- Accredited


Elemental Impurities in Pharmaceutical Products

Where do these heavy metals come from?

 


New Pharmaceutical Heavy Metal Guidelines – USP <232>/<233> and ICH Q3D

Over the last several years increased knowledge concerning toxicity as well as advancements in analytical instrumentation has spurred the international pharmaceutical community to update approaches to risk assessment and quantification of metals in pharmaceutical products as well as their associated systems.  Previously utilized methods were often non-specific and relied on visual inspection via colorimetric assays, but the modern ICP-MS instrumentation is capable of detecting metal species down to the parts per trillion level.

A better understanding of the toxicological effects of metals has led to grouping metals into three classifications and furthermore considers the route of administration (oral, parenteral, and inhaled) to arrive at permissible daily exposure (PDE) limits.


Classification of Metals for Consideration under New Guidance

  • Class 1 (As, Cd, Hg, and Pb)
    • Significantly toxic across all administration routes and have limited or no use in pharmaceutical manufacturing.
  • Class 2
    • Toxicity based on administration route
      • Class 2A (Co, V, Ni):
        • Relatively high probability of toxicity based on administration route
      • Class 2B (Tl, Au, Pd, Ir, Os, Rh, Ru, Se, Ag, Pt):
        • Relatively low probability of toxicity based on administration route
  • Class 3 (Li, Sb, Ba, Mo, Cu, Sn, Cr)
    • Relatively low toxicity (high PDEs) by the oral route of administration, but may require consideration in the risk assessment for the inhalation and parenteral routes

Method Development and Validation for ICP Analysis

One of Avomeen’s core competencies is method development and validation. We will work with your team to formulate a risk-based approach to comply with the new regulations.

Method development and validation to monitor impurities will take into account:

  • Route of Administration & PDE Limits
  • Detectability
  • Precision
  • Specificity
  • Accuracy
  • Ruggedness & Robustness
  • Limit of Quantification
  • Limit of Detection (LOD)
  • Linear Range

Related Services – Avomeen’s experienced chemists can analyze for

  • Class 1 Elemental Impurities (Cd, Hg, Pb & As)
  • Class 2 Elemental Impurities (Ir, Os, Pd, Pt, Rh, Ru, Cr, Mo, Ni, V & Cu)
  • USP Method Heavy Metals Limit Test
  • 15 Elemental Impurities in USP
  • 24 Elemental Impurities in ICH
  • Qualitative Screening & Quantitative Assays
  • Analysis of Metals Limits for Permissible Daily Exposure (PDE)
  • Element-Specific Method Development & Validation
  • Procedure Validation
  • Raw Material & Final Product Testing
  • Routine Sample Analysis

 

USP <232>/<233> chapters will take effect on January 1, 2018.

You will need to be prepared when these elemental impurity regulations are fully implemented and it is important to make sure that the methods used are validated to your specific product in order to be compliant to USP Standards. Our experts will help you measure, document and comply with these new stricter standards that limit the presence of heavy metals in pharmaceutical products.  Let Avomeen’s skilled CMC experts help you meet USP requirements for elemental impurities.

Contact us for a consultation with one of our experienced chemists about USP testing or other pharmaceutical development services at: