April 7, 2003

The Dockets Management Branch

(HFA -- 305)

Food and Drug Administration

5630 Fishers Lane, Room 1061

Rockville, MD 20852

**Re: Dietary Supplements Containing Ephedrine Alkaloids;**

**Reopening of the Comment Period (95N-0304)**

To Whom It May Concern:

The Office of Advocacy respectfully submits the following comments on
the Food and Drug Administration's (FDA) proposed rule entitled,
"Dietary Supplements Containing Ephedrine Alkaloids; Reopening of the
Comment Period" which was published in the *Federal Register* on March
5, 2003.[^1] Because the Office of Advocacy is an independent entity
within the U.S. Small Business Administration (SBA), the views expressed
by the Chief Counsel do not necessarily reflect the views of the SBA, or
the Administration. The Chief Counsel for Advocacy participates in
rulemakings and other agency actions when he deems it necessary to
ensure proper representation of small business interests. In addition to
these responsibilities, the Chief Counsel monitors agencies' compliance
with the Regulatory Flexibility Act (RFA), and works with Federal
agencies to ensure that their rulemakings demonstrate an analysis of the
impacts that their decisions will have on small businesses.[^2]

## Introduction

One of the Administration's goals has been to lessen the regulatory
burden on small businesses. U.S. Department of Health and Human Services
Secretary, Tommy Thompson, has taken up this issue by voicing his
support for reducing regulatory burden in his agency's rulemakings. The
Office of Management and Budget has also supported reducing the impact
of regulatory burden on small businesses through various mechanisms,
including the use of a science-based approach to measuring a rule's
impact on small entities.

Advocacy appreciates the FDA's effort to educate consumers on the
potential risks of using dietary supplements containing ephedrine
alkaloids. Advocacy's comments are not critical of the public policy
behind the regulation. Rather, Advocacy requests that the FDA balance
the need for the regulation with its likely effect on small businesses
through the use of a science-based regulatory approach. This request is
warranted because the majority of the industry is comprised of small
businesses and the science behind the regulation continues to be
unsettled. Advocacy commends the FDA for its continued efforts to obtain
scientific evidence on the health risks associated with the use of
dietary supplements containing ephedrine alkaloids. Advocacy welcomes
the opportunity to help the FDA assess potential impacts of the proposed
rule on small businesses and is confident that the FDA will take steps
prior to finalizing the rule to minimize adverse affects on small
businesses.

[On February 3, 1998, Advocacy filed comments based on the FDA's Notice
of Proposed Rulemaking (NPRM)]{.underline}[^3] [on this issue and many
of Advocacy's concerns remain valid today.]{.underline}

A.  **In the June 1997 NPRM, the FDA concluded that the proposed rule
    would have a significant impact on a substantial number of small
    entities.**

In its June 1997 NPRM, the FDA concluded that the proposed rule would
have a significant impact on a substantial number of small entities.
Pursuant to the RFA, the FDA appropriately prepared an Initial
Regulatory Flexibility Analysis (IRFA). At the time, Advocacy faulted
the adequacy of the IRFA because, among other things, it failed to
properly assess the rule's affect on small businesses and it relied on
questionable scientific evidence.

Advocacy recommends that the FDA revisit the issue of small business
impact as it undergoes the current rulemaking process. If the regulation
of dietary supplements was likely to have a significant effect on a
substantial number of small entities in 1997, the same situation is
likely to exist today. Pursuant to the RFA, in order to determine the
impact of a regulation, an agency must make a reasonable effort to
identify the type and number of entities likely to be affected by the
regulation. This is especially important in this instance as the
rulemaking will not only affect the manufacturers of the ephedrine
alkaloid products, but the distributors and retailers as well.

The FDA will not be able to obtain meaningful public input on the rule's
impact on the industry by reopening the comment period for only thirty
(30) days. Further, the March 5, 2003, proposed rule narrowly seeks
input on the FDA's authority to regulate products containing ephedrine
alkaloids, the appropriateness of the proposed warning label, and any
new evidence on the health risks associated with ingesting products
containing ephedrine alkaloids. Why not obtain the information necessary
to ascertain the economic impact of the rule at the same time? Advocacy
believes that the FDA can obtain useful information on the number of
entities affected by opening a dialogue with industry associations and
others through greater use of agency outreach. This will help to foster
small business participation in the rulemaking and minimize the
potential for judicial review based on RFA issues.

Advocacy also recommends that the FDA consider reasonable alternatives
to the rule in an effort to reduce the burden on small businesses. This
will provide small businesses with the flexibility necessary to minimize
the economic impact of the rule. For example, the FDA may consider
lengthening the time required for small businesses to comply with the
regulation or extending the time for any recordkeeping or reporting
mandates required by the rule.

B.  **The warning label suggested by the FDA in the proposed rule may
    adversely impact small businesses.**

It should be noted that Advocacy has discussed the proposed warning
label with various small businesses. The small business representatives
agree that there is a need for a warning label on products that contain
ephedrine alkaloids. However, the proposed rule provides that a warning
label will appear on the principal display panel of the product.
Advocacy is concerned that such a prominently displayed warning label
may result in a significant economic impact on small businesses. Small
business representatives question whether the warning is too large to
fit on the principal display pane. Further, the warning label
specifically warns the consumer that heart attack, stroke, seizure and
death have been reported after consumption of the product. Advocacy is
concerned that the warning label as described by the FDA may be
construed as misleading because there is ongoing scientific debate as to
any causal relationship between the use of ephedrine alkaloids and the
medical outcomes described on the label. Further, the FDA's White Paper
concludes on page 3 that the agency does, "not have definitive evidence
that ephedra has caused serious injury and deaths."

In light of the likely negative economic impact on small businesses,
Advocacy requests any warning label promoted by the FDA be
science-based. The small business representatives also support an
over-the-counter regulatory model for the warning label, which would
include indications for use, and dosage limits. Small business
representatives also believe this can be adequately achieved with a back
panel warning label. Lastly, Advocacy encourages the FDA to consider
other less burdensome alternatives with respect to the warning label
that may serve to minimize the economic impact on the industry.

**[Conclusion]{.underline}**

In conclusion, the proposed rule presents a number of significant issues
for small businesses in the dietary supplement business, the majority of
which are small. Advocacy is not suggesting that the industry does need
to be regulated, as the industry itself appears to be agreement that
regulation is appropriate. However, Advocacy wants to persuade the FDA
to better consider small business in the rulemaking through analysis,
the use of public comment and greater agency outreach. Advocacy also
asks the FDA to

consider meaningful alternatives to the rule that will serve to minimize
the rule's impact on small businesses. Lastly, Advocacy commends the FDA
on its continued resolve to study the effects of the use of ephedrine
alkaloids by the public and encourages the agency to incorporate their
findings as it drafts the final rule.

> Sincerely,
>
> Thomas M. Sullivan
>
> Chief Counsel for Advocacy
>
> Linwood L. Rayford, III
>
> Assistant Chief Counsel for Advocacy

[^1]: 68 Fed. Reg. 10417 (March 5, 2003).

[^2]: Pub. L. No. 96-354, 94 Stat. 1164 (1981). (Codified as amended at
    5 U.S.C. §§ 601-612).

[^3]: 62 Fed. Reg. 30,678 (June 4, 1997).