Supplements Containing Stimulants Would Need Preapproval Under Durbin Bill

Sen. Charles Schumer (D-N.Y.) is expected to co-sponsor the "Dietary Supplement Safety Act" (S 722), which was introduced March 26 by Sen. Richard Durbin (D-Ill.).

Durbin also is trying to recruit co-sponsors from the Senate Health & Education Committee. By gaining the support of at least one committee member, the bill would be more likely to receive a prompt mark-up; the measure was referred to the panel the day it was introduced in the Senate.

Rep. Henry Waxman (D-Calif.) is drafting dietary supplement legislation as well. Although details about the measure have not been disclosed, it will likely be similar to Durbin's bill. Waxman's bill will probably be introduced in the next few weeks, according to his staff.

Among the many provisions of S 722 is the requirement that dietary supplement products containing stimulants - both those already on the market and products to be introduced in the future - be approved by HHS to avoid being classified as adulterated foods.

Before a company is allowed to "introduce...into interstate commerce a dietary supplement containing a stimulant," the bill would require that the HHS Secretary have cleared "an application for premarket approval of [that] dietary supplement."

To be approved, the application must demonstrate "the dietary supplement is safe under ordinary or frequent conditions of use," the bill continues.

The type and amount of data needed to prove that a stimulant-containing supplement is safe is not described in the bill, which may allow HHS and FDA to use their own discretion in determining the types of studies needed to confirm product safety.

After receiving "an application for premarket approval of a dietary supplement containing a stimulant," the HHS Secretary would have 180 days to either approve or reject it, the bill notes.

For supplements that contain multiple stimulants, the measure states the HHS Secretary would have to "consider the interaction of the various stimulants" in the product before approving the application.

Under the legislation, a stimulant is defined as any "dietary ingredient that has a stimulant effect on the cardiovascular system or the central nervous system of a human by any means, including speeding metabolism, increasing heart rate, constricting blood vessels or causing the body to release adrenaline."

The bill does not apply to caffeine. Language in S 722 notes it would not affect "any other law (including a regulation) applicable to caffeine used as a food or drug."

Despite the exemption, many dietary supplement firms would be affected if the bill became law, including many marketers that replaced their ephedra products with ephedra-free alternatives.

Many of the ingredients used as substitutes for ephedra - such as guarana, Citrus aurantium and yerba mate - are themselves stimulants. As a result, if the bill passed, the products' manufacturers would have to submit data showing the ingredients do not cause serious side effects when taken as directed.

The section of the bill pertaining to stimulant-containing supplements would take effect 180 days after its enactment. For "already marketed dietary supplements" that contain stimulants, the bill would take effect "two years after the date of enactment."

The bill also aims to remove what a March 26 statement from Durbin's office calls "a loophole" in the Dietary Supplement Health & Education Act that allows "steroids to be sold...as dietary supplements."

If passed, the bill would define a product that "bears" or contains "an anabolic steroid (including a substance that is chemically and pharmacologically related to testosterone but not including estrogen, progestin or corticosteroid)" as subject to regulation under the Controlled Substances Act.

The action resembles legislation introduced earlier by Reps. John Sweeney (R-N.Y.) and Tom Osborne (R-Neb.) that would list androstenedione and norandrostenedione as controlled substances (¹ (Also see "Durbin DSHEA Reform To Focus On Mandatory AERs, Labeling Accuracy" - Pink Sheet, 20 Jan, 2003.), p. 5).

The Dietary Supplement Safety Act would additionally set aside $10 mil. for "each fiscal year" to establish a mandatory adverse event reporting system for dietary supplements, which would be operated by HHS.

Supplement manufacturers, packers or distributors would be required to file a report with HHS for every serious adverse experience they receive "no later than 15 days after obtaining the information."

Firms would also be required to "promptly investigate the adverse dietary supplement experience, and if additional information is obtained," submit another report to HHS "not later than 15 days after obtaining the information."

The definition of serious adverse experiences parallels the definition of AEs caused by Rx drugs, and includes incidents resulting in "death, a life-threatening condition, inpatient hospitalization or prolongation of hospitalization [or] a persistent or significant disability or incapacity."

After receiving a report, HHS would have to "conduct a clinical evaluation" of the adverse event. The bill also directs HHS to "carry out a program to collect data on serious dietary supplement [AEs], in addition to receiving reports."

If after conducting a clinical evaluation, HHS finds that "one or more serious adverse events indicate that a dietary supplement or a dietary ingredient contained in a...supple-ment appears to present a significant or unreasonable risk of illness," the HHS Secretary may require manufacturers of supplement products to submit data "demonstrating that the dietary supplement...is safe."

After reviewing the data submitted, the HHS Secretary would make a determination as to whether "the continued marketing of the dietary supplement is approved or...disapproved." The bill explains the marketing of products could be "disapproved" if "the dietary supplement is not safe or has not been shown to be safe under ordinary or frequent conditions of use."

The provision in the bill would give HHS a more proactive role in the oversight of supplement safety. At a Feb. 28 press conference to announce the release of a proposed rule on ephedra labeling, FDA Commissioner Mark McClellan, MD/PhD, noted the agency was seeking comments on whether DSHEA provides the agency with adequate authority to remove dangerous products from the market (² (Also see "Ephedra “Black Box” Warning Considered By FDA" - Pink Sheet, 3 Mar, 2003.), p. 6).

By creating a concrete system whereby HHS can remove a supplement from the market, Durbin's bill appears to tacitly give its own answer to McClellan's inquiry.

In addition to the AER system described above, the legislation also sets forth procedures for the periodic reporting of adverse events. The bill states supplement manufacturers would have to "annually (or at shorter intervals as the [HHS] Secretary may require) submit...a report that discloses all information received with respect to adverse dietary supplement experiences not previously reported."

However, the bill also affords the HHS Secretary the right to "grant a waiver from [all of the] requirements...with respect to a dietary supplement if [he or she] determines that compliance with the requirement is not necessary to protect the public health."

One of the final provisions in the Durbin bill would grant the HHS Secretary the ability to require "a manufacturer of a dietary supplement to conduct postmarket surveillance...if the Secretary determines that there is a reasonable possibility that use or expected use of the dietary supplement...may result in serious adverse experiences."

Companies would be required to submit a post-marketing surveillance plan to HHS within 30 days of receiving an order from the department. HHS would then have 60 days to review the plan. The measure notes HHS may require "a prospective surveillance period for the manufacturer of not more than...three years; or such longer period as may be" agreed to by HHS and the manufacturer or through "a dispute resolution process established...by regulation."

Durbin introduced the legislation several months after chairing two hearings on ephedra's safety (³ (Also see "DSHEA Legislative Reform Effort Likely In 108th Congress Behind Sen. Durbin" - Pink Sheet, 14 Oct, 2002.), p. 3). The bill also was introduced about a week after the American Herbal Products Association filed a citizen petition with FDA asking the agency to make adverse event reporting mandatory for dietary supplements (see ⁴ (Also see "Mandatory Supplement AE Reporting Possible Under Current Law – AHPA" - Pink Sheet, 31 Mar, 2003.) ).

In a statement on the bill, Durbin calls DSHEA "fundamentally flawed [as it] puts manufacturer's commercial gain ahead of consumer health."

The senator notes he has written five letters to HHS Secretary Tommy Thompson since Aug. 6, 2002 asking him to remove ephedra from the market, but that "we should not have to wait for the Bush Administration, which is dragging its feet on this issue."