Ever since USP released its stimuli article last fall regarding the new, pending General Chapter <231> on Heavy Metals, industry has been up in arms about the proposed changes. Pharmaceutical manufacturers are uncertain of how they are going to move from purely wet-chemistry methods to more complicated, not to mention more expensive, methods such as inductively coupled plasma-mass spectrometry (ICP-MS), graphite furnace-atomic absorption spectrometry (GF-AAS), and cold vapor AAS to test their products for metal impurities. These are some of the tests USP is proposing as part of its new heavy metals chapter. Also under revision are the limits for heavy metal impurities on as many as 31 elements, although participants at a recent USP-industry workshop seem to have come to some sort of resolution to focus the new chapter on the “Big 4” elements (lead, cadmium, inorganic arsenic, and methyl mercury).

Many believe that current analytical methods for testing for metal impurities are not specific, not sensitive enough, nor do they provide adequate recovery of the elements being tested. The proposed revision to the general chapter will eliminate the specificity issue and provide greater sensitivity down to part-per-billion (ppb) levels. But there are other issues at stake, including how much of the chapter should be revised (some say just Methods II and III in the chapter—used for substances that do not yield a colorless liquid preparation and involve heating the substance—should be updated because Method I is still effective for soluble substances). There is also confusion over the new proposed limits, some of which allow more impurities than the original monograph allowed. See the full back story. So far, the European Pharmacopoeia is not revising its heavy metals standards and doesn’t necessarily agree with the pending USP changes.

With so many industry—and regulatory—questions still on the table, it’s unclear how many more revisions the new general chapter on heavy metals will undergo. USP is expected to issue the complete revised draft chapter this fall, with a final chapter to come in 2010. Pharmaceutical Technology wants to make sure you know what’s coming and how it will affect your lab, and to prepare you more fully for the public comment period when the USP chapter is released in a few months. Hear what the experts on these issues have to say at our June 4 webinar. Register today at www.pharmtech.com/heavymetals. USP has provided us with an official statement on the revision, which will be read during the webinar. You can also check out our interactive periodic table, which shows the new proposed limits for 21 metals as well as USP Advisory Panel Comments.