25 TAC §§229.461-229.464
The Texas Department of Health (department) adopts new §§229.461-229.464,
concerning standards for the formulation, sale and distribution of dietary
supplements containing ephedrine from natural ephedra alkaloids and restricting
the sale and distribution of certain drug products containing ephedrine. Sections
229.461, 229.462 and 229.463 are adopted with changes to the proposed text
as published in the January 29, 1999, issue of the
Texas Register
(24 TexReg 496). Section 229.464 is adopted without
change, and therefore will not be republished.
The new sections prohibit the sale and distribution of chemically synthesized
ephedrine group alkaloids. The new sections impose mandatory labeling requirements
and set standards for advertising and promotional literature for dietary supplements
containing ephedrine from natural ephedra alkaloids and restrict the sale
and distribution of certain drug products containing ephedrine.
Section 229.461 concerns regulations restricting the sale and distribution
of dietary supplements containing ephedrine. The requirement establishing
25 milligrams of ephedrine group alkaloids per serving has been deleted in
proposed §229.461(1). Proposed §229.461(3) has been deleted in order
to eliminate the language concerning the daily intake of 100 milligrams of
ephedrine group alkaloids. With the deletion of proposed §§229.461(1)
and 229.461(3), the paragraphs had to be renumbered. Also, the 25 milligrams
of ephedrine group alkaloids per serving contained in proposed §229.461(4)
has been deleted. Proposed §229.461(4), now renumbered as §229.461(2)
is changed to clarify that each batch, rather than all products, must be analyzed
to ensure uniformity with the amount of total ephedrine alkaloids listed on
the product label. Batch analysis moots the requirement that product analysis
be performed in accordance with the methodology utilized by the U.S. Food
and Drug Administration (FDA), and this language has been deleted.
Section 229.462(e)(1) is changed to add a requirement that the product
label warn an individual to consult a physician or licensed qualified health
care professional before using the product if the individual has a family
history of the medical conditions listed in the section. Section 229.462(e)(1)
is changed to add "recurrent headaches" to the conditions for which the product
may be contraindicated. Section 229.462(e)(1) also adds dietary supplements
to the products for which an individual is advised to consult a physician
or licensed qualified health care professional before using. Section 229.462(e)(2)
is changed to clarify that the warning on the product label indicate that
exceeding recommended serving may cause serious adverse health effects, including
heart attack and stroke. Section 229.462(e)(3) is changed to clarify that
the warning on the product label indicate that an individual experiencing
certain symptoms should discontinue use and call a physician or licensed qualified
health care professional. Section 229.462(e)(4) is changed to require the
warning on the product label to indicate that individuals who consume caffeine
with the dietary supplements containing ephedrine may experience serious adverse
health effects. The language in §229.462(f) is changed to clarify that
the toll-free number that is required to be provided on the product label
must contain a telephone number that permits consumers to report serious adverse
effects to the department. The toll-free telephone number must be provided
on the product label within 60 days from the date that such number is published
in the
Texas Register
.
Proposed §229.462(g) is changed to clarify that all labeling, except
that affixed to the product container, all prerecorded or scripted radio and
television advertising and all promotional literature must include in the
warning that the product may cause serious adverse health effects. Section
229.463 concerns requirements for advertising and promotional literature for
dietary supplements containing ephedrine. Section 229.463(a) is changed to
require that all advertising and promotional literature concerning a dietary
supplement containing ephedrine be submitted to the department. Section 229.463(b)(5)
is changed to clarify that referrals about side effects be made to a physician
or licensed qualified health care professional. Section 229.463(f) is changed
to clarify that the product label must be submitted to the department prior
to any company distributing an ephedrine containing dietary supplement in
Texas.
Section 229.464 concerns the regulations to restrict the sale and distribution
of certain drug products containing ephedrine and has not been changed.
The department is making the following minor changes to correct a typographical
error and provide clarification to the section:
Change: Concerning §229.462(e)(3), the department has deleted the
word "occur" at the end of the sentence.
The following comments were received concerning the proposed sections.
Following each comment is the department's response and any resulting changes.
Comment: Concerning §§229.461(1), 229.461(3), and 229.461(4),
several commenters questioned the 25 mg per serving and 100 mg per day amounts
of ephedrine alkaloids specified in the rules. One commenter stated that restricting
amounts above 25 milligrams per serving and 100 milligrams per day levels
appears wholly arbitrary, was not justified by the department and cannot be
based on scientific evidence and medical studies. The commenter cited studies
showing that ephedrine is safe in amounts that exceed the limits in the proposed
rule. Two commenters suggested that the amounts are the same or greater than
that known to cause serious adverse events and death and that the rules effectively
sanction those levels as safe. One of these commenters noted that the amounts
are in direct conflict with the conclusions of the department and Texas Medical
Association medical/scientific panels convened to evaluate the department's
ephedrine docket, the FDA's Food Advisory Panel and recommended that the serving
size should be no more than 10 mg per serving total ephedrine alkaloids and
40 mg per day. Another commenter stated that the rules should prohibit ephedrine
and ephedrine alkaloids from non-prescription foods, dietary supplements,
or other over- the-counter commercial products because they are drugs, and
the quality and quantity of data is sufficient to establish that ephedrine
alkaloids are associated with serious adverse effects. Three commenters suggested
that ephedrine should be restricted to prescription because it is a dangerous
substance and has the potential for addiction and they detailed specific injuries
or deaths they attributed to consumption of ephedrine products. In lieu of
restriction to prescription only, the same and other commenters stated that
the rules should follow the FDA's June 1997 proposed rule to limit the serving
size to no more than 7 mg total ephedrine alkaloids per dose and 24 mg per
day any person. One of these commenters cited the need for manufacturers to
provide peer-based clinical studies to support claims that dietary supplements
containing ephedrine are safe for consumption. Another commenter stated that
the rules should consider a very low dosage. One commenter stated that specific
reference to a single serving size and/or a daily serving size should be removed
from the rules pending further research and that serving recommendations could
be re-evaluated and determined during a subsequent rule procedure.
Response: The department disagrees with the first commenter that medical
studies show the 25 milligrams per serving, 100 milligrams per day or greater
amounts are safe. The FDA's monograph for over-the-counter drug products restricts
ephedrine to 12.5 to 25 mg per dose and up to 150 mg per day for very limited
indications, which does not include energy or long-term use for weight loss
or bodybuilding. The department agrees with the commenter that many ephedrine-containing
dietary supplement products contain less than 25 mg ephedrine alkaloids per
individual unit (capsule, tablet, etc.). However, a majority of products recommend
a serving size that contains 20-25 mg total ephedrine alkaloids or more. The
department agrees with the commenters that ephedrine has the effect of a drug,
that serious adverse effects have been clearly associated with taking it,
and that no safe amount has been established for ephedrine alkaloids in a
food or dietary supplement. However, the department disagrees with the commenters
as to establishing FDA's proposed serving size of no more than 7 milligrams
per serving and 24 milligrams per day because it is unknown whether those
levels are safe for human consumption or too stringent. Based on the divergence
of comments from the remaining commenters and the lack of peer-reviewed clinical
studies on the long term effects of dietary supplements containing ephedrine
group alkaloids, the department is deleting the requirement establishing 25
milligrams per serving in proposed §§229.461(1), and 229.461(4)
and 100 milligrams recommended daily intake from proposed §229.461(3).
The department may address this issue in the future should data from such
studies become available.
Comment: Concerning §229.461(2), now renumbered as §229.461(1),
one commenter objected to the prohibition of chemically synthesized ephedrine
group alkaloids contained in §229.461(2) on the basis that there is no
difference between the effects of natural and synthetic ephedrine and without
synthesization, manufacturers would be unable to ensure uniformity of potency
in the finished product.
Response: The department disagrees with the commenter because synthetic
ephedrine is classified by the U.S. Drug Enforcement Administration as a restricted
chemical and a drug. Ephedrine may only be sold in over-the-counter products
when combined with therapeutic amounts of another pharmacologically active
agent. No change was made as a result of this comment.
Comment: Concerning §229.461(4), now renumbered as §229.461(2),
several commenters stated that each batch be analyzed to ensure consistency
of ephedrine alkaloid content in the product.
Response: The department agrees with the commenters and §229.461(2)
is changed to require each batch to be analyzed to ensure it contains the
amount of total ephedrine alkaloid content listed on the product label as
required in §229.462(a). Since the requirement of analysis has shifted
from "all products" to each particular batch, the department believes that
proper analysis on each batch may be achieved in accordance with other effective
methodologies. Batch analysis moots the requirement that product analysis
be performed in accordance with the methodology utilized by the U.S. Food
and Drug Administration (FDA), and this language has been deleted.
Comment: Concerning §229.461(4), now renumbered as §229.461(2),
one commenter questioned whether the analysis for ephedrine alkaloid content
would be confirmed by self certification or a commercial laboratory surprise
inspection system. Another commenter suggested that the department, at the
expense of the manufacturer, should conduct the analysis.
Response: The department will consider scientifically accepted methods
of analysis. The department disagrees that the department should conduct the
analysis because it lacks the staff and facilities to collect samples and
conduct the quantity of analysis that would be required for all products manufactured
nationally and internationally. No change was made as a result of this comment.
Comment: Concerning §229.462, one commenter stated that this section
attempts to limit the information that can be placed on a dietary supplement's
label in a patently excessive and unreasonable way. The commenter states that
the labeling restrictions are not warranted because the Texas Health and Safety
Code, Chapter 431.021 already provides adequate consumer protection. The commenter
states that safety or labeling concerns can be mitigated with a disclaimer
such as: "Consume this product in strict accordance with directions for use.
Report any adverse reaction to a physician for appropriate diagnosis and treatment."
Response: The department disagrees with the commenter. Section 229.462
is intended to ensure that consumers are informed about the risks associated
with the products, that they are aware of contraindications, and that they
are instructed to contact a physician when appropriate. No change was made
as a result of this comment.
Comment: Concerning §229.462(c), two commenters stated that the rules
should not allow any dietary supplement product to contain sources of caffeine
and/or other stimulants in combination with ephedrine because of the increased
risk of adverse reactions and abuse potential. One commenter stated that this
combination was banned by FDA in 1983 for over-the-counter drug products and
the rules should prohibit the combination in dietary supplement products.
The same commenter stated it makes no sense that the rules require ephedrine
over-the-counter drug products to be combined with a minimum level of guiafenesin
to address abuse potential, but allow pharmacologically identical "natural
products" to be marketed in combination with other stimulants.
Response: The department agrees that the safety of combinations containing
ephedrine with multiple herbs and other ingredients (i.e., laxatives, diuretics),
is not known. The department also agrees that ephedrine combined with caffeine
and other stimulants have been shown in clinical trials to increase the number
and severity of adverse events compared to use of either ingredient alone.
The department agrees that combining ephedrine with other stimulants carry
increased risks of side effects. For this reason, consumers should be informed
about the presence and amounts of added stimulants as required by §229.462(c).
The department believes that stricter label warnings and mandatory training
requirements for distributors of dietary supplements containing ephedrine
required by these rules address the safety concerns associated with these
products. No change was made as a result of these comments.
Comment: Concerning §§229.462(d) and 229.462(e), one commenter
stated that the department has not disclosed sufficient rationale or justification
for the various warnings the rules require. The commenter further states that
the proposed warnings are based on safety concerns raised by FDA and the department
in the federal ephedrine rulemaking proceedings. The commenter states that
FDA's concerns are unwarranted because they are based on the adverse events
reports. The commenter states the adverse event reports are not scientific,
not complete, they fail to account for substance or supplement abuse, they
do not provide insight into the actual cause of the adverse event, and cannot
be used as a basis for this rulemaking.
Response: The department disagrees with the comment that the rules fail
to account for abuse of dietary supplements containing ephedrine as a cause
of the adverse events, since investigations of the reported adverse events
revealed that eighty per cent of individuals stated they took the product
as directed by the manufacturer on the product label. The department disagrees
with the commenter that the warning statements were based solely on the adverse
event reports. Both the department and FDA proposed the warnings based on
the known physiological and pharmacological effects of ephedrine alkaloids
found in pharmacology texts and the scientific literature, controlled clinical
trials using ephedrine in the treatment of obesity, and the published literature
concerning the traditional use of ephedrine-containing botanical products.
No change was made as a result of this comment.
Comment: Concerning the warning statement contained in §229.462(e),
three commenters stated that the rules fail to address the types of adverse
events (e.g., dependence and cardiomyopathy) that are related to the duration
of use of ephedrine alkaloids. The commenters suggested that the product warnings
include the statement, "Do not use for more than seven days."
Response: The department disagrees with the commenters because of the lack
of peer-reviewed clinical studies on the effects of dietary supplements containing
ephedrine to establish an appropriate time limit for usage. No change was
made as a result of this comment.
Comment: Concerning §229.462(e)(1), one commenter stated that the
warning label should be amended to read: "WARNING: Not for use by children
under the age of 18. Consult an appropriately qualified health care professional
before using this product if you are pregnant or nursing: have, think you
may have, or have a family history of the following medical conditions:..."
Another commenter requested that the product label contain language stating:
"Anyone that is taking or considering taking this drug should consult their
doctor."
Response: The department disagrees with the recommendation to replace "individuals"
with "children" since "children" is reserved for individuals under thirteen
in over the counter drug labeling. The department disagrees that "do not use
if pregnant or nursing" be preceded with the instructions to consult a health
care professional before using the product because the more prohibitive language
contained in the current rule is warranted. The department agrees with the
commenters as to consulting a doctor or a qualified health care professional
prior to use and has changed the language in §229.462(e)(1) to clarify
that the product label warn an individual to consult either a "physician or
licensed qualified health care professional." Additionally, references to
"health care professional" or "health care practitioner" contained in §§229.462(e)(3)
and 229.463(b)(5) respectively, have been changed to "physician or licensed
qualified health care professional" to provide clarification and consistency
to the sections. The department disagrees with the suggested language "think
you may have" because the wording may be confusing to the consumer. The department
agrees with the commenter that the consumer would make a more informed decision
if the individual considered family history prior to use therefore, §229.462(e)(1)
is changed to clarify that the warning on the product label must include such
language.
Comment: Concerning §229.462(e), one commenter requested that a disclaimer
be added to the warning label that the safety of the products have not been
established.
Response: The department agrees that safety has not been established for
ephedrine-containing dietary supplement products; however, the department
believes that the warning label required in §229.462(e) will provide
sufficient information to consumers regarding the side effects and contraindications
associated with ephedrine use and when to consult a physician or licensed
qualified health care professional. No change was made as a result of this
comment.
Comment: Concerning §§229.462(e)(1) and 229.462(e)(2), one commenter
stated that the rules fail to provide explicit warnings in each section of
the label of the adverse consequences associated with ephedrine use and abuse
including stroke, severe hypertension, irregular heat beat, chest pain, heart
attack, seizure, psychosis and death. The commenter stated that the label
should include a stronger statement because "may cause serious adverse health
effects" does not accurately convey the seriousness of potential adverse events
associated with ephedrine. Another commenter stated that not stating the actual
adverse consequences of the drug provides an illusion of safety.
Response: The department disagrees with the commenters as to §229.462(e)(1)
because the department believes that the warning provides sufficient information
to consumers who may otherwise misuse the product and exceed the recommended
serving. The department declines to include a stronger statement but changes
§229.462(e)(1) to require that recurrent headaches be included as a contraindication
listed on the warning on the product label. The department agrees with the
commenters as to the need to provide examples of "serious adverse health effects"
and §229.462(e)(2) is changed to add "heart attack and stroke".
Comment: Concerning §229.462(e)(1), one commenter stated that the
warning statement include asthma and kidney disease to the medical conditions
for which the consumer should consult a health care professional and bodybuilding
products and other dietary supplements to the product categories in the parentheses
in the last sentence.
Response: The department disagrees with the commenters because the statement
required on the label already warns a person using ingredients found in certain
asthma products to consult a health care professional before using the product.
Additionally, the department declines to include kidney disease to the label
because it is not listed in either FDA's over-the-counter monograph or as
a pre-existing condition in FDA's proposed rule of June 7, 1997. The department
agrees with the commenter that an individual using dietary supplements should
consult a health care professional before using another dietary supplement
containing ephedrine product. Accordingly, §229.462(e)(1) is changed
to provide such warning. The department disagrees with the commenter as to
including individuals using bodybuilding products to consult a health care
professional because such products are included in the addition of dietary
supplements.
Comment: Concerning §229.462(e)(4), one commenter stated that the
warning statement concerning caffeine consumption was weak. A commenter stated
that this subsection should read: "Consuming caffeine with this product may
increase the risk of serious side effects." Another commenter said the subsection
should say consuming caffeine, including caffeine-containing food and drinks,
with this product may increase the frequency and severity of side effects.
Response: The department agrees with the commenters and §229.462(e)(4)
is changed to require that the warning on the product label contain a statement
that serious adverse health effects may be experienced by individuals who
consume caffeine with dietary supplements containing ephedrine. This provision
is consistent with the warning in §229.462(e)(2).
Comment: Concerning §229.462(f), four commenters stated that the toll-free
number be required to be connected to a national registry, public entity or
recognized Poison Control Center to collect information and provide advice.
One commenter stated that the rules do not specify actions to be taken by
the manufacturer in response to adverse effects reports to the toll free number.
All of the commenters stated that the rules should require the manufacturer
to forward the complaint to the department and the FDA and that the adverse
event reports should be maintained in a publicly accessible database such
as a website to keep consumers informed about past and future adverse events.
Response: The department agrees with the commenters that requiring a toll-free
number back to the manufacturer does not provide an adequate reporting system
for adverse events and §229.462(f) is changed to clarify that the warning
on the product label must contain a toll-free number for consumers to report
adverse effects to the department. Additionally, the toll-free number must
be included on the warning within 60 days of the date the department publishes
such number in the
Texas Register
.
Comment: Concerning §229.462(f), one commenter stated that a toll
free number be provided for people to call in and report how well the products
worked for them.
Response: The department disagrees with the commenter because the rules
do not prohibit the manufacturer from providing such a toll-free number. No
change was made as a result of this comment.
Comment: Concerning §229.462(g), two commenters stated that the warning
statements required for product labels in §229.462(e) should also be
required to appear on advertising and promotional materials. One commenter
stated that stronger advertising reporting requirements were necessary than
what the section proposed.
Response: The department disagrees with the two commenters because the
purpose of the statement in the subsection is to instruct the consumer to
read and follow the label instructions. The department agrees with the commenter
that §229.462(g) needs to clarify requirements for advertising. Section
229.462(g) is changed to add the language "all prerecorded or scripted radio
and television advertising" to clarify the specific advertising that is the
target of the warning required by the subsection. Additionally, §229.462(g)
is changed to be consistent with §229.462(e)(2) by deleting "may not
be appropriate for everyone" and requiring the warning on all labeling, all
prerecorded or scripted radio and television advertising and all promotional
literature to state that the product may cause serious adverse health effects.
Comment: Concerning §229.463, one commenter stated that the rules
should restrict radio, TV and magazine advertisements for ephedrine products
similar to cigarette advertising.
Response: The department disagrees with the commenter because it does not
have the authority to restrict advertising in this manner. No change was made
as a result of this comment.
Comment: Concerning §229.463, one commenter specified the following
additional language: "All advertising and promotional literature must contain
a list of possible adverse health effects, a list of contraindications to
use, and toll-free numbers for the FDA Office of Consumer Affairs and the
Texas Department of Health."
Response: The department disagrees with the commenter because the warning
on the product label required in §§229.462(e)(1) and 229.462(f)
already requires information concerning possible adverse health effects, a
list of contraindications and a toll-free number for consumers to contact
the department. No change was made as a result of this comment.
Comment: Concerning §229.463(a), one commenter states that the rules
are unconstitutional under the Fourteenth Amendment of the U.S. Constitution
due to vagueness. The commenter stated that the rules do not define a standard
for "review and approval" of labeling, making compliance impossible and the
manufacturer exposed to a violation of the rules. The commenter states that
the failure to define key terms necessary for compliance constitutes an unwarranted
exercise of agency discretion. Another commenter stated that the language,
"...to ensure compliance with these regulations" be added to the end of the
subsection.
Response: The department disagrees with the commenter that the rules are
unconstitutional under the Fourteenth Amendment for vagueness because the
department believes that the rules clearly establish requirements, prohibitions
and restrictions on manufacturers and on companies that engage in direct marketing
of dietary supplements containing ephedrine products in the State of Texas.
The department also disagrees with the commenter's suggestion to add language
because such language is unnecessary. No change was made as a result of this
comment.
Comment: Concerning §229.463(b)(2), one commenter stated that the
term "medical claims" is too vague and must be defined further.
Response: The department disagrees because the term "medical claims" is
commonly understood. No change was made as a result of this comment.
Comment: Concerning §229.463(b)(3), one commenter suggested requiring
distributors, franchisees, and/or independent contractors to direct the consumer
to read the product label prior to purchase of the product only and not prior
to consumption.
Response: The department disagrees with the commenter because the product
label will contain the warning required by §229.462(e) of the health
risks associated with the product to the consumer. No change was made as a
result of this comment.
Comment: Concerning §229.463(c), one commenter states that the rules
fail to define or describe the actions required to "effectively respond" to
unauthorized labeling and literature. Another commenter stated that the word
"monitor" replace "respond to" in the subsection. The commenter also suggested
adding the language "to ensure compliance with these regulations" before "to
prevent the distribution of unauthorized literature."
Response: The department disagrees with the commenters and believes that
the rule is adequate to support enforcement of its provisions. No change was
made as a result of this comment.
Comment: Concerning §229.463(c), one commenter stated that compliance
to the subsection is impossible because the manufacturer will not be able
to control the actions of others, especially when title to the product has
passed to the independent distributor and/or retailer.
Response: The department disagrees since the manufacturer can enter into
legal agreements with distributors that may be terminated by the manufacturer
for noncompliance. No change was made as a result of this comment.
Comment: Concerning §229.463(c), one commenter stated that a person
who makes a complaint about side effects be referred to the FDA and the department.
Response: The department disagrees with the commenter because the rules
require distributors, franchisees and/or independent contractors to direct
injured consumers to a licensed health care practitioner. Practitioners are
informed about the FDA's MedWatch system and the department will evaluate
their participation in reporting adverse events for possible future rulemaking.
No change was made as a result of this comment.
Comment: Concerning §229.463(d), one commenter stated that the following
sentence be added to the end of the subsection: "The companies shall also
ensure that all distributors, franchisees and/or independent contractors are
fully informed of the possible adverse health effects and contraindications
to use of dietary supplements containing ephedrine products."
Response: The department disagrees with the commenter since the product
warning label required by §229.462(e) would provide that information.
No change was made as a result of this comment.
Comment: Concerning §229.463(e)(3), one commenter stated that distributors,
franchisees, and/or independent contractors be added to the advertising and
promotional materials considered by the department to determine compliance
with the subsection.
Response: The department disagrees with the commenter because the subsection
is intended to include all promotional materials and advertisements. No change
was made as a result of this comment.
Comment: Concerning §229.463(f), one commenter suggested that companies
be required to submit all advertising and promotional literature to the Texas
Poison Center Coordinating Committee.
Response: The department agrees with the commenter in part that the advertising
and promotional literature should be filed with the department and §229.463(a)
is changed to require that this information be submitted to the department's
Division of Drugs and Medical Devices. In addition, §229.463(f) is clarified
to require the submission of the product label to the department's Texas Poison
Center Coordinating Committee prior to distribution.
Comment: Concerning §229.464, one commenter recommended restricting
caffeine from any drug product that contains ephedrine.
Response: The department disagrees since the combination with caffeine
is already prohibited for ephedrine containing drug products by FDA. No change
was made as a result of this comment.
Comment: Concerning §229.464(d)(1), one commenter stated that formulations
containing 25 milligrams ephedrine combined with at least 400 milligrams guiafenesin
be removed from the exception subsection.
Response: The department disagrees since this formulation is approved by
the FDA for treatment of mild diagnosed asthma. In addition, the department
has no evidence that products with this formulation are abused and misused
compared to other formulations. No change was made as a result of this comment.
Comment: Concerning §229.464(d)(5), one commenter questioned whether
ephedrine containing drug products that are marketed pursuant to an approved
new drug application under the federal Food, Drug, and Cosmetic Act should
be exempted from the designation as dangerous drugs and the dispensing restrictions
of the section.
Response: The department disagrees with the commenter and notes that products
submitted for an approved new drug application undergo much more required
testing and marketing prior to introduction on the market. No change was made
as a result of this comment.
Comment: Concerning the rules in general, a commenter opposed the rules
because they are arbitrary and capricious in violation of Texas Government
Code, Chapter 2001.
Response: The department disagrees with the commenter. A work group of
department employees and industry representatives developed these rules and
they have been proposed in accordance with Texas Government Code, Chapter
2001.
Comment: Concerning the rules in general, a commenter stated that the rules
are contrary to law in violation of Texas Government Code Section 483.
Response: The department disagrees with the commenter and believes that
the commenter was referencing Health and Safety Code, Chapter 483. The rules
propose to classify ephedrine as a prescription drug in formulations not exempted
by §229.464(d). No change was made as a result of this comment.
Comment: Concerning the rules in general, a commenter stated that the rules
are unnecessary because Texas law allows for enforcement against companies
that sell unsafe or misbranded products.
Response: The department disagrees because the label requirements, (i.e.,
warning statements, ephedrine content disclosure requirements) are not specified
in Texas law and are necessary to inform consumers about the specific health
risks associated with ephedrine containing products. No change was made as
a result of this comment.
Comment: Concerning the rules in general, a commenter stated that the rules
are premature and a waste of government resources in light of rules proposed
by the FDA. The commenter stated that the department's rules as proposed conflict
with the FDA rules that, when adopted, would address the same subjects and
that the rules will interfere with the national regulation of ephedrine alkaloids
because it fails to account for interstate issues. The commenter stated that
the department should withhold action on its proposed rules until the FDA
completes its rulemaking process.
Response: The department disagrees. The FDA proposed regulations to remove
ephedrine from over-the-counter drug products in July 1995 and to severely
restrict ephedrine alkaloid levels in dietary supplements in June 1997. Neither
of the proposed regulations have been finalized. The department believes the
rules are necessary to address the immediate health risks these products pose.
After the FDA rules are finalized, the Texas Board of Health may elect to
retain any more stringent requirements or amend or repeal the Texas rules
to address any conflicts between the two rules. No change was made as a result
of this comment.
Comment: Concerning the rules in general, one commenter stated that the
department does not explain the reasons for proposing the new requirements
and no administrative record is provided. The administrative record does not
include the evidentiary basis for administrative findings, inferences and
conclusions, and therefore constitute an abuse of discretion and an arbitrary
and capricious act. As a result, the commenter states that the proposed rules
are invalid.
Response: The department disagrees with the commenter because the purpose
of the proposed rules, as stated in the preamble, is to assist consumers with
understanding the possible side effects of taking dietary supplements containing
ephedrine from natural ephedra alkaloids and to require over-the-counter drugs
to follow specific formulations. No change was made as a result of this comment.
Comment: Concerning the rules in general, one commenter states that scientific
research has established the safety and efficacy of ephedrine alkaloids for
weight loss as well as other therapeutic advantages and the studies demonstrate
only minor side effects. The commenter states that studies support the finding
that ephedrine alkaloids pose the same health risks, both in severity and
likelihood, as caffeine and that the department should regulate ephedrine
alkaloids as it currently regulates caffeine.
Response: The department disagrees that ephedrine should be regulated the
same as caffeine. Caffeine has been subjected to rigorous scientific scrutiny
for safety and is generally recognized as safe by the FDA as a food additive
in concentrations not to exceed 0.02%, while ephedrine is not. Further, because
ephedrine was grand fathered from consideration as a "new drug" under the
current regulatory scheme, it has not undergone the extensive safety studies
currently required for new drug approval. No change was made as a result of
this comment.
Comment: Concerning the rules in general, several commenters cited data
from 1991 and 1992 emergency room visits and medical examiners' reports that
showed little evidence of ephedrine adverse reactions and abuse and stated
that this amount of evidence meant that ephedrine-containing products are
not a problem.
Response: The department disagrees with the commenters. The number and
types of dietary supplement products containing ephedrine alkaloids have increased
dramatically in the marketplace since late 1993. Claims that promote the long-term
use of ephedrine for weight loss, performance enhancement and energy have
also proliferated. These claims have not been evaluated or approved by FDA
for safety or effectiveness. Since 1993, the department has received over
1300 reports of adverse events associated with products containing ephedrine.
Many of the reports were made to Poison Control Centers from emergency room
physicians. No change was made as a result of these comments.
Comment: Concerning the rules in general, three commenters stated that
the rules lacked any language addressing the consequences of noncompliance
and that sanctions and penalties should be included.
Response: The department disagrees because violations of a rule promulgated
under the Texas Food, Drug and Cosmetic Act, Health and Safety Code, Chapter
431 are subject to the administrative, civil and criminal penalties found
in the act. No change was made as a result of these comments.
Comments regarding the proposed rules were received by the department from
Lieutenant Governor Rick Perry, Senator John J. Carona, Senator Drew Nixon,
Senator Florence Shapiro, Senator Jeff Wentworth, Representative Frank J.
Corte Jr., Representative Rick Green, Representative Paul J. Hilbert, Representative
Bill Siebert, Representative Robert E. Talton, Representative Arlene Wohlgemuth,
Representative John A. Longoria, Representative Rick Hardcastle, Academy of
Clinical Environmental Research and Informational Sciences, Acupuncture and
Aesthetics Center, Advocare International, Inc., Advocare Independent Distributors,
A&N Distributors, Biogenics doing business as E'Ola International, Inc.,
E'Ola Independent Distributors, Enrich International Inc., Dietary Supplement
Safety and Science Coalition, Halt Ephedrine Abuse Today, Thomas L. Kurt,
M.D., Metabolife Independent Distributors, National Nutritional Foods Association,
Natural Balance, Omnitrition International Inc., Phil Howry Company, Nancy
Rector, M.D., Texas Medical Association, Texas Conservative Coalition, Paul
Wellman, Ph.D., Wellness International Network and Wellness International
Independent Distributors. In addition, comments were received from consumers
of ephedrine containing dietary supplement products, concerned citizens and
department staff. Comments received during a public hearing conducted on February
25, 1999, were also received and considered. Numerous commenters were in favor
of the proposed rules in their entirety. A few commenters were against the
proposed rules in their entirety. The remaining commenters were not against
the rules in their entirety, however, they expressed concerns, asked questions,
and suggested recommendations for change as discussed in the summary of comments.
The new sections are adopted under Health and Safety Code, §431.241,
which provides the department with the authority to adopt rules for the efficient
enforcement of Chapter 431, the Texas Food, Drug and Cosmetic Act, and §431.021
which prohibits the introduction or delivery into commerce of any food or
drug that is adulterated and prohibits the dissemination of any false advertisement;
and §12.001, which provide the Texas Board of Health with authority to
adopt rules for the performance of every duty imposed by law on the Texas
Board of Health, the Texas Department of Health, and the commissioner of health.
§229.461.Regulations to Restrict the Sale and Distribution of Dietary Supplements Containing Ephedrine.
The sale or distribution of any dietary supplement containing ephedrine
group alkaloids is prohibited unless the product complies with the following
requirements:
(1)
the product contains no chemically synthesized ephedrine
group alkaloids; and
(2)
each batch shall be analyzed to ensure that it contains
the amount of total ephedrine alkaloids listed on the product label.
§229.462.Product Labels for Dietary Supplements Containing Ephedrine.
(a)
The product label must state: "This product has (insert
amount in product) milligrams concentrated ephedrine group alkaloids per serving
in the form of herbal extracts."
(b)
The product label must use standardized nomenclature for
the ephedrine ingredient such that the terms "ephedrine," "pseudoephedrine"
or other ephedrine group alkaloid name is used when referring to the active
ingredients in place of or in addition to the botanical name of the ephedrine
group alkaloid.
(c)
The product label must state the amount in milligrams
of caffeine alkaloids and other ingredients per serving that have a known
stimulant effect (eg. yohimbine).
(d)
The product label must include a warning statement for
the consumption of ephedrine group alkaloids that is conspicuously displayed
on the label information panel in distinct contrast to other printing or graphics,
and must be at least 1/16 inch type.
(e)
The warning on the product label must contain at a minimum
the following information:
(1)
WARNING: Not for use by individuals under the age of 18.
Do not use if pregnant or nursing. Consult a physician or licensed qualified
health care professional before using this product if you have, or have a
family history of, heart disease, thyroid disease, diabetes, high blood pressure,
recurrent headaches, depression or other psychiatric condition, glaucoma,
difficulty in urinating, prostate enlargement, or seizure disorder, if you
are using a monoamine oxidase inhibitor (MAOI) or any other dietary supplement,
prescription drug or over-the-counter drug containing ephedrine, pseudoephedrine
or phenylpropanolamine (ingredients found in certain allergy, asthma, cough/cold,
and weight control products).
(2)
Exceeding recommended serving may cause serious adverse
health effects including heart attack and stroke.
(3)
Discontinue use and call a physician or licensed
qualified health care professional immediately if you experience rapid heartbeat,
dizziness, severe headache, shortness of breath, or other similar symptoms.
(4)
Individuals who consume caffeine with this product
may experience serious adverse health effects.
(f)
The product label must include a toll-free number to permit
consumers to report adverse effects to the department within 60 days of the
date such number is published in the
Texas Register
.
(g)
All labeling, except that affixed to the product container,
all prerecorded or scripted radio and television advertising, and all promotional
literature must include the following warning: "This product" (optional:
may use any specific reference to product) "has ephedrine group alkaloids
in the form of herbal extracts" (optional: from ma huang or other named herb)
"and may cause serious adverse health effects." Read the label and follow
directions."
§229.463. Advertising and Promotional Literature for Dietary Supplements Containing Ephedrine.
(a)
All advertising and promotional literature must be reviewed
and approved by the company responsible for the manufacture of the ephedrine
containing dietary supplement product and must be submitted to the department
in care of Drugs and Medical Devices Division, 1100 West 49th Street, Austin,
Texas 78756.
(b)
Companies that engage in direct marketing of ephedrine
containing dietary supplement products shall incorporate into contracts with
distributors, franchisees, and/or independent contractors the following conditions:
(1)
no claims about the product which have not been approved
in writing by the company may be made;
(2)
no medical claims may be made;
(3)
distributors, franchisees, and/or independent contractors
are required to direct consumers to read the product label prior to purchase
or consumption;
(4)
distributors, franchisees, and/or independent contractors
are required to advise consumers under the care of a physician or with a chronic
condition to consult with a physician prior to purchase of the product; and
(5)
distributors, franchisees, and/or independent contractors
shall refer any person who makes a complaint about side effects to a physician
or licensed qualified health care professional.
(c)
Companies that engage in direct marketing of ephedrine
containing dietary supplement products shall effectively respond to distributors,
franchisees, and/or independent contractors to prevent the distribution of
unauthorized literature.
(d)
Distributors, franchisees, and/or independent contractors
shall be trained by companies that engage in direct marketing of ephedrine
containing dietary supplement products to refer medical questions to a physician
and will not be permitted to give medical advice.
(e)
No claims shall be made for the indication of alteration
of consciousness, euphoria, as a "legal" alternative for an illicit drug,
or for any use of the product as a drug for the diagnosis, cure, mitigation,
treatment, or prevention of any disease. To determine compliance with this
requirement, the Texas Department of Health (department) may consider the
following factors:
(1)
the product packaging;
(2)
the name and container labeling of the product; and
(3)
advertising and promotional materials created by
the company responsible for the manufacture or distribution of the product.
(f)
Prior to any company distributing an ephedrine containing
dietary supplement product in Texas, the product label shall be submitted
to the Texas Poison Center Coordinating Committee, in care of Chief, Bureau
of Epidemiology, Texas Department of Health, 1100 West 49th Street, Austin,
Texas 78756.
This agency hereby certifies that the adoption has been reviewed
by legal counsel and found to be a valid exercise of the agency's legal authority.
Filed with the Office of the Secretary of State on June
3, 1999.
TRD-9903272
Susan K. Steeg
General Counsel
Texas Department of Health
Effective date: November 1, 1999
Proposal publication date: January 29, 1999
For further information, please call: (512) 458-7236