FDA Should Consider New Lead Level Tests, Label Requirements – Advisers

Drug and dietary supplement manufacturers may need to include lead information on labels and use more sensitive test methods for lead levels in products if FDA follows the suggestions of the Advisory Committee for Pharmaceutical Science and Clinical Pharmacology.

The Center for Drug Evaluation and Research advisory committee met July 22 to review and suggest improvements for FDA's current process for evaluating and regulating lead in pharmaceutical products and supplements.

The committee recommends FDA require manufacturers include lead levels and information about lead exposure on drug and supplement labels.

FDA currently does not require lead level information on labels nor does it have any lead related guidance, an FDA spokesperson said.

However, committee member Marvin Meyer said he did not agree with that recommendation.

Meyer, professor emeritus for the Pharmaceutical Sciences Department at the University of Tennessee College of Pharmacy in Memphis, said while he understands the concern, labeling requirements might "add a lot of variables."

The committee, U.S. Pharmacopeia and FDA should "just focus on what we can handle fairly expeditiously" in terms of "getting something moving," he added.

The committee recognizes FDA "has a handle on what needs to be done and they are going about it in a noble and rational way," Meyer said, but added FDA needs to work more quickly with USP to update current lead testing methods so they are more sensitive and then set "acceptable limits" on lead.

Darrell Abernethy, USP's chief science officer, said the current method for testing lead levels is "out of the dark ages."

He told the committee that USP's current testing method uses sulfide ion precipitation that changes colors when it detects heavy metals.

However, he referred to a 1995 study that revealed "approximately 50 percent of the metals may be lost during the ash process" in the current test, and as a result "the validity of test results obtained with the current USP, JP and EP general test procedures is questionable."

Abernethy also pointed to a 2000 study that found "methods based on the intensity of the color of sulfide precipitation are non-specific, insensitive, time-consuming, labor intensive and more often than hoped, yield low recoveries or no recoveries at all."

FDA allows manufacturers to use different lead level tests as long as they are equivalent to or exceed the current USP tests. As a result, many manufacturers already use more sophisticated assays than the "antiquated" USP method that FDA is legally required to follow, Abernethy said.

With that in mind, the advisory committee encouraged USP and FDA to learn what tests manufacturers are using to determine lead levels and then compare the statistical efficacy of those methods to the tests USP recommends for future use, such as inductively-coupled plasma or atomic absorption spectroscopy.

"Once we know that we are getting reliable data, we need to have some toxicologist group tell us what those levels should be for safe" consumption, said committee member Arthur Kibbe, pharmaceutical sciences chair at the Nesbitt School of Pharmacy at Wilkes (Pa.) University.

Kibbe added that FDA should consider the safety levels of lead for different demographics since smaller amounts will affect children and people with end stage renal disease more adversely than healthy adults.

Some panel members added that lead limits should be updated and set for finished drug products, and not just for some of the direct product components, as is currently done.

When setting the lead limits for different drugs and supplements, a GlaxoSmithKline representative urged the committee, and by extension USP and FDA, to remember that naturally occurring lead in mined calcium may be higher than in other products, but that calcium blocks the body's absorption of lead.

- Elizabeth Crawford ([email protected])