United States Pharmacopeia (USP) <232> and <233> elemental impurities testing, screening and quantification of toxic metals in pharmaceutical products
United States Pharmacopeia (USP) chapters <232> Elemental Impurities-Limits and <233> Elemental Impurities-Procedures specify limits and procedures for elemental impurities in drug products.
Elemental impurity analysis plays an important role in pharmaceutical development and manufacturing, particularly due to the known toxicity and the potential for contamination by lead (Pb), mercury (Hg), arsenic (As) and cadmium (Cd).
It is vital to demonstrate compliance to the USP <232> elemental impurities specified levels where impurities such as Pb, Hg, As and Cd are known to be present or could potentially be introduced during manufacture via raw materials, reagents or processing equipment. These levels can, in certain cases, be extremely low.
Harmonization of USP <232>/<233> with ICH Q3D Guideline for Elemental Impurities
The United States Pharmacopeia (USP) has published in the Pharmacopeial Forum, (PF 42(2) [Mar.-Apr. 2016]) a proposed revision to the USP General Chapter <232>, Elemental Impurities – Limits. In the introduction to the revised chapter, it states “This chapter is being revised to address comments received and to further align this chapter with ICH Q3D. The USP’s Elemental Impurities Expert Panel approved a recommendation to the General Chapters - Chemical Analysis Expert Committee that this chapter be revised to align with the ICH Q3D Step 4 document to the greatest extent possible.” The USP has added elements not previously listed in chapter <232> and adjusted its Permitted Daily Exposure in order to match those found in the Q3D guidance.
New USP Chapter 232/233 Becomes a Requirement on January 1, 2018
The deadline is quickly approaching for companies to comply with both the USP 232 and USP 233 standards for elemental impurity limits and procedures which will serve as the overarching standards for elemental impurity testing for pharmaceutical products for the US market. Now is the time for developers and manufacturers to conduct elemental impurities testing to ensure a fast and efficient path to market for their products.
We offer elemental impurity analysis services according to USP General Chapter <232> and USP Chapter <233> which are Good Manufacturing Practice (GMP) compliant and are conducted in accordance with these USP chapters to support your raw materials quality control testing, reference materials certification, stability testing and GMP batch release testing. Additionally, our experts have in depth knowledge in the implementation of ICH 3QD Guideline for Elemental Impurities and can provide combined toxicological risk assessment and testing compliance services in order to meet all your regulatory requirements.
Our experts have established a strategic approach, which includes options for semi-quantitative screening, method development and validation (as either a limit test or a quantitative test as dictated by the client’s analytical needs) and routine analysis. Our expertise in sample preparation ensures that we meet the challenges of difficult samples which have poor solubility enabling very low levels of detection (i.e. at toxicologically relevant levels, such as parts per billion or lower in solution). Our GMP facilities are equipped with both inductively coupled plasma – mass spectrometry (ICP-MS) or inductively coupled plasma – optical emission spectroscopy (ICP-OES) technologies.
With over 20 years of elemental impurity analysis experience and centers of excellence located in North America and Europe, our scientists apply the right approaches for your samples through cost effective and efficient services. With the latest technology for sample preparation and pharmaceutical impurity analysis, we can effectively overcome any challenge presented by sample type and sample matrices.
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