An Update on US Pharmacopeia’s Heavy Metals Testing
As many of you know, USP has been working for several years to replace the current General Chapter addressing heavy metals (231). The proposed new general chapters include:
- General Chapter <232> which addresses the Limits of Elemental Impurities (heavy metals).
- General Chapter <233> which addresses the Procedures to be used when analyzing the Elemental Impurities (heavy metals).
As a laboratory exclusively focused on heavy metals, we get quite a few phone calls regarding these new General Chapters. As such, we thought we’d attempt to answer some of the more frequently asked questions.
General Chapter <232> and <233> – The 5 Most Frequently Asked Questions…
The US Pharmacopeia proposed General Chapters for heavy metals (elemental impurities) in pharmaceuticals is intended to replace the current General Chapter <231>. While there are three proposed new General Chapters, most of the questions we get surround General Chapter <232> which deals with limits and General Chapter <233> which deals with procedures. Here are 5 frequently asked questions…
1. Why the new regulations?
To start off with, it is not just the pharmaceutical industry that is seeing the regulatory environment increasing for heavy metals. We are seeing more heavy metals regulations in pharmaceuticals, nutraceuticals, food and beverage, and personal care products. We feel the common denominators dictating increased regulations can be distilled down to the following three drivers.
First, as the trend in healthy living and natural care continues to grow, consumers are becoming much more aware of what they are putting in their bodies. Increasingly, they are demanding to know exactly what is in the products they are purchasing. This includes all industries mentioned above. No longer are consumers waiting for manufacturers to test and report. In many cases, consumer groups are simply purchasing products and having them tested independently.
Next, the current method for testing heavy metals in pharmaceuticals is over 100 years old. The advancement’s in heavy metals testing over the last century is significant. The methods available today are sound, robust and cost-effective.
Finally, exposure to heavy metals as a population has been a long-standing health concern. The ability to test for these metals at extremely low levels (highly-sensitive) allows consumers, manufacturers and regulators the visibility necessary to ensure products are safe.
2. What testing methods are required for the proposed General Chapter <233>
The US Pharmacopeia (USP) does not require a specific method be used in the testing of heavy metals. Instead, the method a company uses is based on performance. The performance criteria used to evaluate the performance of a given test is relatively complex and would require pages to explain.
Having said that, there are some very well documented tests that represent a good combination of accuracy and efficiency the industry seems to be trending toward. These tests are ICP/MS (Inductively Coupled Plasma – Mass Spectrometry) and typically utilize microwave digestion methods. Again, as a manufacture you can choose whatever method of testing that meets your needs and the specific performance criteria establish by the USP in their proposed General Chapter <233>.
3. Who will enforce the new General Chapters?
The USP is very specific in that they are not a regulatory agency. They are a non–governmental, official public standards–setting authority for prescription and over–the–counter medicines and other healthcare products manufactured or sold in the United States. As a result, the Food and Drug Administration is intended to be the regulatory agency responsible for the enforcement of USP’s General Chapters 232 and 233.
4. What is the timing for General Chapters <232> and <233>?
That is a great question. Several things need to happen prior to USP General Chapters <232> and <233> replace the existing General Chapter <231>. First, the final comments need to be reviewed. Based on those comments it is anticipated that the actual General Chapters will be formally published. Once the General Chapters are published there is typically a period provided for the implementation of the new standards. There are a host of variables that could either slow down or speed up this process. It appears the General Chapters will be published sometime during the first half of 2011. The subsequent implementation process is a little less clear at this point.
We try to stay in close touch with new developments regarding the proposed USP General Chapters 232 and 233. As new information becomes available we will certainly pass it along.
5. What Metals do we need to test for?
There are two categories or “classes” listed in the proposed General Chapter for Elemental Impurities. The first, Class 1 specifically addresses four different metals. They are arsenic, cadmium, lead and mercury. According to the drafts, testing for these metals “is required for all drug products, regardless of the likelihood of the presence of impurities.”
The next is Class 2. These are heavy metals (elemental impurities) that “need to be conducted only when these elements are added during the manufacture of the article.” In other words, if you add any of the elements listed in Class 2 you are required to test them. If you don’t add any of the elements listed in Class you, you need not test.