“For over 15 years, elemental testing for contaminants arsenic, cadmium, lead and mercury (As, Cd, Hg and Pb) in nutraceuticals has been done with laboratory instruments (either Graphite Furnace Atomic Absorption Spectrometry (GFAAS) or Inductively Coupled Plasma Mass Spectrometry (ICP-MS)) to comply with California’s Prop 65,” explained Mr. Cuff. “For more than 100 years, the standard method for measuring elemental impurities in pharmaceutical products sold in the United States has been the ‘Heavy Metals Test’ described in Chapter <231> of the United States Pharmacopeia’s (USP) National Formulary (NF). Originally intended as a screening tool with results being reported as < 10 parts per million (ppm), the USP Chapter <231> Method is a precipitation test which cannot detect contaminants at concentrations low enough to comply with the requirements in Prop 65.”
In 2008 a workshop was organized by the Institute of Medicine (IOM) which concluded that Chapter 231 should be revised. IOM also wanted to ensure there was harmony across the major pharmacopeias such as the European and Japanese pharmacopeias because of the need for a set of global standards for the industry. An “Expert Committee on Elemental Purities” was formed, and in April of 2012, the USP finalized new Chapters <232> and <233>.
Chapter <232> specifies the list of elements and their toxicity limits, defined as maximum daily doses of different drug categories. Chapter <233> outlines the analytical procedure, sample preparation and instrumental method for measuring the elements, using ICP-OES or ICP-MS. Sample preparation and dilution required for many raw materials and finished products will require ICP-MS for most operations. All pharmaceutical QC departments must conform to these new chapters beginning May 1, 2014.
“The review process for a separate Chapter <2232> — ‘Elemental Contamination of Dietary Supplements’ is undergoing the USP review and comments process and will become the method used by nutraceutical manufacturers to comply with global requirements (including California’s Prop 65),” said Mr. Cuff.
He went on to explain what the new testing process will look like to compliant nutraceutical manufacturers.
“USP Chapter <2232> will provide a globally recognized method for elemental contamination in nutraceuticals, enabling manufacturers to comply with regulations anywhere, not just California,” he said, and noted that the FDA will use USP <2232> to monitor compliance.
Mr. Cuff also explained that supplement manufacturers will need to establish their own laboratory or hire an analytical testing laboratory to test their raw materials and final product, as Chapter <2232> will require closed vessel microwave digestion and ICP-MS. (It’s worth noting that ICP-MS has largely replaced graphite furnace atomic absorption spectrometry (GFAAS) because ICP-MS can run all elements in two minutes or less in comparison to GFAAS, which takes about five minutes per element).
“Samples must be converted into a clear liquid to be introduced into the ICP-MS for analysis,” he said. “For most solids, this must be accomplished by digesting a small portion in acid inside a closed vessel heated in a microwave oven specially designed for safety.
“PerkinElmer has partnered with many companies to establish this same capability to comply with the current California Prop 65 (since the early days of Prop 65),” continued Mr. Cuff. “PerkinElmer’s Microwave and ICP-MS have been designed for ease of use (with the least amount of maintenance) and come with turn-key methods.”
PerkinElmer will offer two different USP Method Preparation Clinics beginning next month. Attendees will learn details about the analysis and (in the Advanced Clinics) participate in an actual analysis of a real sample. Attendees will earn a Certificate of Completion with both clinics. For more information, contact Caryn Tyler at firstname.lastname@example.org.