The current standard for testing for metals in pharmaceuticals is about 100 years old. So US Pharmacopeia, the standards-setting organization, wants to replace the method and revise permissible limits that will require pharma to implement new and potentially expensive methodology and, perhaps, be held to higher standards (see Chemical & Engineering News for some technical insights into the changes). The goal is to have the new methodology finalized by early 2010, although implementation will take several years. We spoke with Darrell Abernethy, USP’s chief science officer, about the need for the revision and metals testing in foreign markets, given recent scandals emanating from Asia. This is an excerpt…

Pharmalot: Have heavy metals been a particular problem in pharmaceuticals lately?
Abernethy: It’s been on the radar, particularly, with foods and dietary supplements, and to a lesser extent, pharmaceuticals. One reason is the increasing understanding of toxicities of some metals, particularly lead and to a lesser extent, cadmium, mercury and arsenic… These partiuclar metals are present in the Earth and a variety of places that would be of some concern for some kinds of products… With the screening that’s available, it’s a sporadic sort of thing… Tin, molybedenum, nickel - they crop up because they’re present in parts of the manufacturing process… It’s coming on the radar screen thanks to improvement in methodologies over the last decades..

Many years ago, there were limited means to test for metals. As analytical methodologies improved, those means are present and are so sophisticated, that you can find any metal anywhere…I think it’s gratifying to know that when (metals) have been looked for, using appropriate methodologies, very rarely (do they show up). But on some occasions, one does come across contamination. We believe that’s the case and that leads us to the appropriate methodology question.

Pharmalot: Still, if this is not a big issue in pharmaceuticals now, why the push?
Abernethy: The current standard that exists uses quite a dated methodology that lacks appropriate sensitivity or specificity. We think, for the most part, the ethical pharmaceutical manufacturing sector looks carefully at their processes and does a very good job. And that includes keeping impurities out by using a number of techniques. You could call it luck, but we’ve been privilged to have a high quality pharmaceutical manufacturing presence in the United States and other parts of the world…But the locus of most manufacturing is shifting and has shifted quite rapidly, so we want to ensure standards. The best information is that 68 to 80 percent of our active pharmaceutical ingredients now come from India and China. That number is debatable, but that’s not too far off…

Pharmalot: How does the USP effort affect overseas markets, such as China?
Abernethy: Purchasers take on responsibility for testing. With regard to materials exported into the United States, the USP standard carries the force of law and the FDA has an enforcement role. We would hope that the presence of high quality standards would not be utilized just in the US. Having a good quality standard would influence drug supply chains in other parts of the world. But our force of law only relates to the US. We hope that the presence of quality requirements for export into the US would have some carryover effect. That’s a hope…

Pharmalot: What is USP doing specifically in those markets?
Abernethy: We have a lab in Shanghai with about 40 employees and they work with the Chinese manufacturing community in a variety of roles, primarily to make standards and standardaization processes, particularly for export to the United States. We’re also on the ground in India. Our standards are the same everywhere. The best thing we can look at would be the welcome and uptake of our activity. In China, the state Food and Drug Administration and manufacturing uptake has been quite gratifying. It’s a huge country with a huge humber of manufacturers and we’re just beginning to stratch the surface… We haven’t done marketplace surviellance within manufacturers.

We do provide reference materials.. If material fails to meet standards, they’d have to disquality the batch and fail to use it. We don’t have hard evidnce, in that we’ve not gone in the marketpalce to do screening nor have we gone directly to the companies to request internal screening documentation… The absence of proof is not the proof of absence. We want to preclude a problem rather than wait for an emergency. We hope this is a preventive activity.

Pharmalot: How long will it take to determine that?
Abernethy: My hope is that the larger and more serious manufacturers are already implementing quality standards and working on other parts of the manufacturing processes. What we’re told, using China as an example, is that it’s a very disbursed industry right now with many smaller players. There’s hope there’ll be a lot of consolidation and smaller players will tend to disappear. Those kinds of forces and increased regulatory responses, internally in China and regulatory moves outside China, will all move in the right direction and we believe USP will play a useful role in that process. I’m optimistic in a year landscape will be quite different.