[Federal Register Volume 60, Number 144 (Thursday, July 27, 1995)]
[Proposed Rules]
[Pages 38643-38647]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 95-18448]




Federal Register / Vol. 60, No. 144 / Thursday, July 27, 1995 / 
Proposed Rules

[[Page 38643]]


DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 310 and 341

[Docket No. 95N-0205]
RIN 0905-AA06


Cold, Cough, Allergy, Bronchodilator, and Antiasthmatic Drug 
Products for Over-the-Counter Human Use; Proposed Amendment of 
Monograph for OTC Bronchodilator Drug Products

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice of proposed rulemaking.

-----------------------------------------------------------------------

SUMMARY: The Food and Drug Administration (FDA) is proposing to amend 
the final monograph for over-the-counter (OTC) bronchodilator drug 
products to remove the ingredients ephedrine, ephedrine hydrochloride, 
ephedrine sulfate, and racephedrine hydrochloride and to classify these 
ingredients as not generally recognized as safe and effective for OTC 
use. This action is being taken in response to a request from the U.S. 
Department of Justice, Drug Enforcement Administration (DEA) to 
restrict OTC availability of ephedrine because of its illicit use as 
the primary precursor utilized in the synthesis of the controlled 
substances methamphetamine and methcathinone. This action is also based 
on new information that shows that the misuse and abuse of OTC 
ephedrine drug products has the potential for causing harm and on 
comments made by FDA's Pulmonary-Allergy Drugs Advisory Committee and 
the Nonprescription Drugs Advisory Committee on November 14, 1994. This 
proposal is part of the ongoing review of OTC drug products conducted 
by FDA.

DATES: Written comments or objections by August 28, 1995; written 
comments on the agency's economic impact determination by August 28, 
1995. FDA is proposing that any final rule that may issue based on this 
proposal become effective 30 days after its date of publication in the 
Federal Register.

ADDRESSES: Submit written comments or objections to the Dockets 
Management Branch (HFA-305), Food and Drug Administration, rm. 1-23, 
12420 Parklawn Dr., Rockville, MD 20857.

FOR FURTHER INFORMATION CONTACT: William E. Gilbertson, Center for Drug 
Evaluation and Research (HFD-810), Food and Drug Administration, 5600 
Fishers Lane, Rockville, MD 20857, 301-594-5000.

SUPPLEMENTARY INFORMATION:

I. Background-

    In the Federal Register of September 9, l976 (41 FR 38312), FDA 
published, under Sec. 330.10(a)(6) (21 CFR 330.10(a)(6)), an advance 
notice of proposed rulemaking to establish a monograph for OTC cold, 
cough, allergy, bronchodilator, and antiasthmatic drug products, 
together with the recommendations of the Advisory Review Panel on OTC 
Cold, Cough, Allergy, Bronchodilator, and Antiasthmatic Drug Products 
(the Panel), which was the advisory review panel responsible for 
evaluating data on the active ingredients in this drug class. The Panel 
recommended that ephedrine preparations be Category I (generally 
recognized as safe and effective) for OTC bronchodilator use (41 FR 
38312 at 38370 and 38371, September 9, 1976). The agency concurred with 
the Panel in the bronchodilator tentative final monograph (47 FR 47520 
at 47527, October 26, 1982) and included ephedrine preparations in the 
final monograph for OTC bronchodilator drug products (51 FR 35326 at 
35339, October 2, 1986).

II. Recent Developments

    Since publication of the final monograph for OTC bronchodilator 
drug products, the agency's views about OTC ephedrine-containing 
bronchodilator drug products have changed for several reasons: (1) A 
large-scale diversion of OTC ephedrine-containing drug products to 
illicit use in the manufacture of the controlled substances 
methamphetamine and methcathinone, (2) new information that ephedrine 
may be unsafe for OTC use and has the potential for causing harm as a 
result of misuse and abuse, due to widespread and easy availability as 
an OTC drug, and (3) the consensus of FDA's Pulmonary-Allergy Drugs 
Advisory Committee and the Nonprescription Drugs Advisory Committee 
(the Committee) on November 14, 1994, that the use of oral ephedrine 
drug products as an OTC bronchodilator to relieve the symptoms of 
asthma can no longer be justified when the drug's potential for illicit 
use and misuse is considered.

III. Illicit Use of OTC Ephedrine Drug Products

    FDA has received correspondence and inquiries from consumers, U.S. 
Senators, DEA, and others (Ref. 1) concerning the need for additional 
controls on the distribution of OTC ephedrine-containing drug products. 
The ``Domestic Chemical Diversion Control Act of 1993, Pub. L. 103-
200'' was signed into law on December 17, 1993, to control the 
diversion of certain chemicals (e.g., ephedrine) used in the illicit 
production of controlled substances such as methcathinone and 
methamphetamine. The law became effective on April 16, 1994, and 
removed the exemption from the definition of a ``regulated 
transaction'' that had existed for single entity ephedrine drug 
products legally marketed under the Federal Food, Drug, and Cosmetic 
Act (the act). Thus, drugs that were previously marketed lawfully under 
the act are no longer exempt from chemical precursor controls. The new 
law was intended to close this loophole and help eliminate the 
availability of ephedrine as a raw material source in the clandestine 
synthesis of methamphetamine and methcathinone.-
    In the Federal Register of October 11, 1994 (59 FR 51365), DEA 
issued a final rule eliminating the threshold for ephedrine and 
subjecting all transactions involving bulk ephedrine and single entity 
ephedrine drug products to the applicable provisions of the Controlled 
Substances Act (21 U.S.C. 801). The final rule eliminated the threshold 
(an amount of a listed chemical that determines if a transaction such 
as receipt or sale of the chemical is a regulated transaction under 
part 1310 (21 CFR part 1310)) for single entity ephedrine drug 
products. The final rule established that all transactions involving 
ephedrine, regardless of size, are subject to recordkeeping and 
reporting requirements set forth in part 1310 and the notification 
provisions of part 1310 (21 CFR part 1313). However, the final rule did 
not apply to combination drug products containing ephedrine.
    At the Committee meeting on November 14, 1994, the Committees 
discussed OTC bronchodilator drug products. DEA had submitted a comment 
(Ref. 2) to the Committee expressing its concern that, although the 
recent legislation and proposed regulations (59 FR 12562, March 17, 
1994) (now final regulations (59 FR 51365)) adequately address the 
ability to control single ingredient ephedrine products, DEA is aware 
that laboratories may turn to combination drug products containing 
ephedrine and guaifenesin that would be exempt from the final rule.
    The comment stated that the illicit use of OTC ephedrine drug 
products is contributing to a serious public health problem that is an 
extremely critical 

[[Page 38644]]
issue requiring further action at the Federal level. The comment added 
that the OTC marketing status and broad distribution of these products 
is hindering efforts to prevent this illicit use of ephedrine and urged 
the Committees to restrict the OTC availability of this ingredient.
    The agency has also received comments from county, State, and 
Federal Government organizations; pharmacists' associations; and 
consumers who object to the continued marketing of OTC ephedrine drug 
products because some manufacturers are promoting these products for 
misuse as stimulant, weight control, and muscle enhancement products 
(Ref. 3). The comments contended that this promotion has resulted in 
extensive and extremely dangerous misuse and abuse of such products, 
particularly in teenaged children.

IV. Misuse and Abuse of OTC Ephedrine Drug Products-

    The agency has received a number of reports (Ref. 4) of young 
people abusing OTC ephedrine drug products. In one case, nine junior 
high school students took three to eight ephedrine 25 milligram (mg) 
tablets for added energy and experienced rapid heart beats. One female 
who took eight tablets had 200 heart beats per minute 2 hours after 
taking the tablets. The student was able to purchase the ephedrine 
tablets from a product display at a local convenience store without 
being questioned about the reason for its use. Another report (Ref. 5) 
indicated that three 15-year-old girls had consumed 24 to 33 tablets of 
ephedrine-containing OTC drugs for ``kicks.''
    The agency is aware of numerous other reports involving young 
people who have overdosed by using OTC ephedrine products promoted as a 
stimulant or for weight control, or by using such products for 
recreational purposes in high doses and on a regular basis. One report 
(Ref. 5) involved a 17-year-old male who died after ingesting a toxic 
or lethal amount of ephedrine. The youth apparently took the ephedrine 
to increase alertness, strength, and physical stamina. In another case 
(Ref. 4), a 21-year-old female developed respiratory problems (trouble 
breathing) after taking three to four 25 mg ephedrine tablets, 
purchased OTC, every other hour (and then every hour) over an 8-hour 
period and consuming alcoholic beverages. Hospitalization resulted from 
this recreational use of ephedrine.
    In another case (Ref. 4), a 22-year-old female took OTC ephedrine 
tablets because her friends had told her they would act as ``uppers.'' 
The woman's job required her to work long hours, and she felt she 
needed a chemical pick-up to get through the day. She presented to a 
hospital emergency room with headache, nausea, anxiety, and blood 
pressure of 170/110 millimeters mercury. She was treated, with no 
permanent adverse effects.
    FDA's Spontaneous Reporting System also contains a number of 
reports of ephedrine misuse and abuse (Ref. 4), some of which have 
resulted in death due to an overdose of ephedrine. In one case, a 52-
year-old male took 10 to 15 ephedrine tablets (believed to be 50 mg) 
over the previous 24 hours. In another case, a 24-year-old male who 
died of an overdose had a blood level of ephedrine over 30 times the 
usual therapeutic range. In another overdose case, the reporting 
pharmacist commented that ``ephedrine is becoming a drug for abuse--
would recommend to withdraw OTC status.'' In another case, the 
reporting hospital pharmacist noted that the ephedrine overdose (in a 
19-year-old female) was the second incident observed this year for 
these ephedrine/caffeine products sold at convenience markets and ``not 
FDA regulated.''
    Interested consumers and state regulatory officials (e.g., health 
departments, boards of pharmacy) have expressed concern about OTC 
ephedrine drug products being sold under brand names that reflect a use 
other than as a bronchodilator (e.g., use as a stimulant or for weight 
control); about products being readily available at convenience stores, 
truck stops, gas stations, and mini-marts with little, or no, 
restriction on their sale; and about products being purchased and used 
by children and adolescents, on an ever increasing basis, with a 
continuing increase in the number of reported adverse events.
    One director of an addictions program informed FDA (Ref. 6) that 
his locality (in Indiana) is experiencing a surge of adverse responses 
or reactions to the use of OTC ephedrine being abused for its stimulant 
effect. He reported that a number of people abusing ephedrine have 
demonstrated stimulant dependence characterized by compulsion, 
obsession, or preoccupation, and that ephedrine abuse has induced or 
worsened mental disorders such as depressive anxiety and different 
thought disorders. He stated that people are obtaining the drug OTC as 
ephedrine (not in combination with other drugs) under different brand 
names, some of which are advertised as an ``energizer.'' He mentioned 
that the age group abusing ephedrine ranges from teenagers to people 
who are in their 40's.
    A nurse reported her daughter's adverse experience with an OTC 
ephedrine product (Ref. 4) and mentioned that within the last year the 
child's pediatrician had treated several adolescents who had overdosed 
on ephedrine. The nurse added that many emergency room physicians are 
seeing behavior similar to schizophrenia occurring in young adults as a 
result of ephedrine obtained OTC. The nurse questioned why this drug 
was readily purchasable by unsuspecting teenagers.
    The agency concludes that these reports show that OTC ephedrine 
drug products are marketed in ways that are misleading, that promote 
misuse and abuse, and that can be dangerous. The agency believes that 
these reports represent only a small percentage of the actual number of 
adverse events that have occurred and that ephedrine misuse and abuse 
are a widespread problem in the United States.
    According to one source (Ref. 7), at least 14 states have placed 
additional controls and restrictions on ephedrine to address the abuse 
problem. These controls include, in at least five states (Florida, 
Idaho, New Mexico, Oregon, and Washington), switching the products to 
prescription only status. In Michigan, possession of more than 4 grams 
of ephedrine requires a prescription. Six states (Arizona, Missouri, 
Nevada, Ohio, Oklahoma, and Wisconsin) have scheduled ephedrine as a 
controlled substance. The agency is aware that Kentucky, Massachusetts, 
and Virginia have introduced bills to tighten ephedrine controls and 
that other states are also considering similar actions.
    The agency concludes that the misuse and abuse of OTC ephedrine 
drug products have the potential for causing harm as shown by the many 
reports submitted to the agency. FDA has determined that action is 
needed to eliminate this misuse/abuse potential. FDA's proposed action, 
when finalized, will eliminate the need for future action by individual 
states.

V. Advisory Committee Comments

    At a meeting of FDA's Pulmonary-Allergy Drugs Advisory Committee 
and Nonprescription Drugs Advisory Committee (the Committee) held on 
November 14, 1994, the Committee members heard presentations from 
private citizens and state officials concerning the misuse and abuse of 
OTC ephedrine drug products (Ref. 8). The Committee members expressed 
concern about the reports of abuse and illicit diversion of ephedrine. 
One Committee member mentioned that removal of ephedrine from the OTC 

[[Page 38645]]
marketplace by FDA or DEA regulatory action would cause no harm and, 
indeed, would do some amount of good. Although the Committee did not 
hear from manufacturers of OTC ephedrine drug products and was not 
asked the specific question whether these products should be removed 
from the OTC market, there was a consensus that the benefit of OTC 
ephedrine does not justify its continued use as an OTC bronchodilator 
active ingredient when the potential for illicit use and misuse is 
considered (Ref. 9).
    FDA received comments from manufacturers in response to the notice 
for the Committee meeting (59 FR 34847, July 7, 1994). Two 
manufacturers opposed the marketing of any OTC bronchodilator drug 
product (Ref. 10). One manufacturer submitted a ``Profile of Asthma 
Sufferers and Users of Nonprescription Epinephrine (Mist) and Ephedrine 
Combination (Tablets)'' in support of its position these drug products 
remain available OTC (Ref. 11). Another manufacturer supported the 
continued marketing of legitimate OTC ephedrine-containing 
bronchodilator drug products (Ref. 12). This manufacturer briefly 
discussed the abuse potential for single ingredient ephedrine-
containing products, particularly those that are deliberately labeled 
to imply nonmonographed usage. The manufacturer stated that the extent 
of any abuse is unclear and potentially exaggerated by a small number 
of highly publicized abuse instances. The comment noted that a number 
of states have enacted legislation to discourage abuse, in response to 
this situation. The comment mentioned that most states have generally 
made provisions to ensure continued OTC availability of legitimate 
combination asthma products, such as its product containing ephedrine 
sulfate and guaifenesin, an expectorant.-
    The agency has considered the manufacturers' views in developing 
this proposal. As discussed above, the agency believes that the misuse/
abuse problem is widespread and much broader than one manufacturer 
suggested. Continued OTC availability of combination products 
containing ephedrine and guaifenesin would not alleviate this problem. 
Large quantities of guaifenesin are generally safe, and the combination 
product would not stop people from taking large amounts for the effects 
of the ephedrine. Further, DEA has informed FDA that it is aware that 
ephedrine can readily be isolated from such combinations for illicit 
manufacture (Ref. 13). Accordingly, FDA concludes that the best 
resolution for this misuse/abuse problem is for ephedrine, singly or in 
combination products, not to be available OTC.

VI. References-

    The following references are on display in the Dockets Management 
Branch (address above) and may be seen by interested persons between 9 
a.m. and 4 p.m., Monday through Friday.

    (1) Correspondence in OTC Vol. 04BPEA, Docket No. 95N-0205, 
Dockets Management Branch.
    (2) Comment No. C6, Docket No. 94N-0232, Dockets Management 
Branch.
    (3) Comments No. C5, C6, C10, C11, C12, C17, C19, C20, APE8, 
APE10, APE13, and LET142, Docket No. 94N-0232, Dockets Management 
Branch.
    (4) Adverse reaction reports in OTC Vol. 04BPEA, Docket No. 95N-
0205, Dockets Management Branch.
    (5)-Comment No. C10, Docket No. 94N-0232, Dockets Management 
Branch.---
    (6)-Letter from B. B. Rohrer, The Addictions Program, to FDA, 
dated June 24, 1993, in OTC Vol. 04BPEA, Docket No. 95N-0205, 
Dockets Management Branch.
    (7)-National Association of Boards of Pharmacy Foundation, Inc. 
Newsletter, October 1994, pp. 2-3, in OTC Vol. 04BPEA, Docket No. 
95N-0205, Dockets Management Branch.---
    (8)-Transcript of a Joint Meeting of the Pulmonary-Allergy Drugs 
Advisory Committee and the Nonprescription Drugs Advisory Committee, 
November 14, 1994, pp. 56-84, in OTC Vol. 04BPEA, Docket No. 95N-
0205, Dockets Management Branch.---
    (9)-Transcript of a Joint Meeting of the Pulmonary-Allergy Drugs 
Advisory Committee and the Nonprescription Drugs Advisory Committee, 
November 14, 1994, pp. 235, 236, 258, 259, 264, 265, 270, 271, and 
272, in OTC Vol. 04BPEA, Docket No. 95N-0205, Dockets Management 
Branch.
    (10) Comments No. C8, APE1, and C11, Docket No. 94N-0232, 
Dockets Management Branch.
    (11) Comment No. LET144, Docket No. 94N-0232, Dockets Management 
Branch.
    (12) Comment No. C18, Docket No. 94N-0232, Dockets Management 
Branch.
    (13) Memorandum of a telephone conversation between D. Snyder, 
DEA, and G. Rachanow, FDA, dated April 20, 1994, in OTC Vol. 04BPEA, 
Docket No. 95N-0205, Dockets Management Branch.

VII. Summary of the Agency's Proposed Change

    The agency is proposing that ephedrine, ephedrine hydrochloride, 
ephedrine sulfate, and racephedrine hydrochloride should no longer be 
included in the final monograph for OTC bronchodilator drug products 
based on their extensive use in illicit drug manufacture and their 
potential for causing harm as a result of misuse and abuse due to their 
widespread and easy availability as an OTC drug. This proposed 
amendment removes the ingredients ephedrine, ephedrine hydrochloride, 
ephedrine sulfate, and racephedrine hydrochloride from the final 
monograph for OTC bronchodilator drug products (21 CFR part 341). It 
does not affect the monograph status of epinephrine-containing drug 
products when used in a hand-held rubber bulb nebulizer. Such products 
will remain in the final monograph for OTC bronchodilator drug 
products.
    This proposal would remove all oral systemically acting 
bronchodilator drug products from the OTC market. Thus, the agency is 
proposing to amend Sec. 341.16 of the final monograph for OTC 
bronchodilator drug products to remove Sec. Sec. 341.16(a), (b), (c), 
and (f) for ephedrine ingredients and to redesignate Sec. 341.16(d), 
(e), and (g) as Sec. 341.16(a), (b), and (c), respectively. Also, the 
agency is proposing to amend Sec. 341.76(c) to remove paragraph (5), to 
revise the heading for paragraph (6), and to redesignate paragraphs 
(6)(i), (6)(ii), and (6)(iii) as paragraphs (5)(i), (5)(ii), and 
(5)(iii), respectively. In addition, the agency is proposing to amend 
Sec. 341.76(d) to remove paragraph (1), to redesignate paragraph (2) as 
paragraph (1), to revise the heading in new paragraph (1), and to 
reserve paragraph (2). The agency is also proposing to amend 
Sec. 341.90 by removing paragraph (a) that pertains to ephedrine and 
redesignating paragraphs (b) through (q) as paragraphs (a) through (p), 
respectively. Furthermore, the agency is proposing to amend the list of 
ingredients that are not generally recognized as safe and effective for 
specified uses in Sec. 310.545 (21 CFR 310.545) by adding new 
paragraphs (a)(6)(iv)(D) and (d)(27) for ephedrine preparations.

VIII. Analysis of Impacts-

    FDA has examined the impacts of the proposed rule under Executive 
Order 12866 and the Regulatory Flexibility Act (Pub. L. 96-354). 
Executive Order 12866 directs agencies to assess all costs and benefits 
of available regulatory alternatives and, when regulation is necessary, 
to select regulatory approaches that maximize net benefits (including 
potential economic, environmental, public health and safety, and other 
advantages; distributive impacts; and equity). The agency believes that 
this proposed rule is consistent with the regulatory philosophy and 
principles identified in the Executive Order. In addition, the proposed 
rule is not a significant regulatory action as defined by the Executive 
Order and, thus, is not subject to review under the Executive Order.
    The Regulatory Flexibility Act requires agencies to analyze 
regulatory 

[[Page 38646]]
options that would minimize any significant impact of a rule on small 
entities. This rule would eventually stop the marketing of OTC 
bronchodilator drug products containing ephedrine, ephedrine 
hydrochloride, ephedrine sulfate, or racephedrine hydrochloride. The 
agency has determined that legitimate drug manufacturers have little or 
no interest in single ingredient OTC ephedrine drug products. However, 
some manufacturers may have an interest in combination drug products 
containing ephedrine.
    The agency acknowledges that this proposed rule, if finalized, 
would have an impact on consumers who legitimately use OTC 
bronchodilator drug products containing ephedrine to relieve their 
bronchial asthma. They will no longer be able to purchase these 
products without a doctor's prescription. However, all OTC 
bronchodilator drug products must bear a label warning that states ``Do 
not use this product unless a diagnosis of asthma has been made by a 
doctor.'' Therefore, it is presumed that legitimate users of these 
products have seen a doctor and are under a doctor's occasional care 
for the treatment of their asthma. These consumers will be able to 
obtain an ephedrine drug product upon a doctor's prescription if the 
doctor determines that ephedrine is the drug that should be used to 
treat the condition. These consumers will also be able to purchase OTC 
epinephrine for inhalation to treat their bronchial asthma without a 
doctor's prescription. At its November 14, 1994, meeting, the Committee 
recommended that epinephrine for inhalation remain available OTC for 
self-treatment of asthma under certain conditions. The agency has 
weighed the consequences of this proposed rule as it might adversely 
impact some legitimate users of these OTC ephedrine drug products. 
However, these consumers will have access to another drug without a 
prescription and could continue to obtain ephedrine products on a 
doctor's prescription. The agency has determined that as a result of 
the widespread misuse and abuse of OTC ephedrine drug products, 
especially by many young people and people up to in their 40's, that it 
is in the best interest of all consumers (especially parents) to remove 
from the OTC market ingredients that are used extensively in the 
manufacture of illicit drugs and that have widespread misuse and abuse 
with the potential to cause harm. Further, the agency is not aware of a 
widespread marketing of legitimate OTC bronchodilator drug products 
containing ephedrine, although several manufacturers could be adversely 
affected by this proposed rule. Accordingly, the agency certifies that 
the proposed rule will not have a significant economic impact on a 
substantial number of small entities. Therefore, under the Regulatory 
Flexibility Act, no further analysis is required.
    The agency invites public comment regarding any substantial or 
significant economic impact that this rulemaking would have on OTC 
bronchodilator drug products that contain ephedrine, ephedrine 
hydrochloride, ephedrine sulfate, or racephedrine hydrochloride. 
Comments regarding the impact of this rulemaking on these drug products 
should be accompanied by appropriate documentation. A period of 30 days 
from the date of publication of this proposed rulemaking in the Federal 
Register will be provided for development and submission of comments on 
this subject. Because of the existing serious public health problem 
identified by DEA and a number of states, and the many reports of 
misuse and abuse of OTC ephedrine drug products that FDA has received, 
the Commissioner has determined that there is good cause for a 
shortened comment period. FDA will evaluate any comments and supporting 
data that are received and will reassess the economic impact of this 
rulemaking in the preamble to the final rule.

IX. Environmental Impact

    The agency has determined that under 21 CFR 25.24(c)(6) that this 
action is of a type that does not individually or cumulatively have a 
significant effect on the human environment. Therefore, neither an 
environmental assessment nor an environmental impact statement is 
required.
    Interested persons may, on or before August 28, 1995, submit to the 
Dockets Management Branch (address above) written comments or 
objections regarding this proposal. Written comments on the agency's 
economic impact determination may be submitted on or before August 28, 
1995. Three copies of all comments or objections are to be submitted, 
except that individuals may submit one copy. Comments and objections 
are to be identified with the docket number found in brackets in the 
heading of this document and may be accompanied by a supporting 
memorandum or brief. Comments and objections may be seen in the office 
above between 9 a.m. and 4 p.m., Monday through Friday.

List of Subjects

21 CFR Part 310

    Administrative practice and procedure, Drugs, Labeling, Medical 
devices, Reporting and recordkeeping requirements.

21 CFR Part 341

    Labeling, Over-the-counter drugs.
    Therefore, under the Federal Food, Drug, and Cosmetic Act and under 
authority delegated to the Commissioner of Food and Drugs, it is 
proposed that 21 CFR parts 310 and 341 be amended as follows:

PART 310--NEW DRUGS

    1. The authority citation for 21 CFR part 310 continues to read as 
follows:
    Authority: Secs. 201, 301, 501, 502, 503, 505, 506, 507, 512-
516, 520, 601(a), 701, 704, 705, 721 of the Federal Food, Drug, and 
Cosmetic Act (21 U.S.C. 321, 331, 351, 352, 353, 355, 356, 357, 
360b-360f, 360j, 361(a), 371, 374, 375, 379e); secs. 215, 301, 
302(a), 351, 354-360F of the Public Health Service Act (42 U.S.C. 
216, 241, 242(a), 262, 263b-263n).

    2. Section 310.545 is amended by adding new paragraphs 
(a)(6)(iv)(D) and (d)(27) and by revising paragraph (d) introductory 
text to read as follows:


Sec. 310.545   Drug products containing certain active ingredients 
offered over-the-counter (OTC) for certain uses.

    (a) * * *
    (6) * * *
    (iv) Bronchodilator drug products. * * *
    (D) Approved as of August 28, 1995.
Ephedrine
Ephedrine hydrochloride
Ephedrine sulfate
Racephedrine hydrochloride
* * * * *
    (d) Any OTC drug product that is not in compliance with this 
section is subject to regulatory action if initially introduced or 
initially delivered for introduction into interstate commerce after the 
dates specified in paragraphs (d)(1) through (d)(27) of this section.
* * * * *
    (27) August 28, 1995, for products subject to paragraph 
(a)(6)(iv)(D) of this section.

PART 341--COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC 
DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE

    3. The authority citation for 21 CFR part 341 continues to read as 
follows:

    Authority: Secs. 201, 501, 502, 503, 505, 510, 701 of the 
Federal Food, Drug, and 

[[Page 38647]]
Cosmetic Act (21 U.S.C. 321, 351, 352, 353, 355, 360, 371).


Sec. 341.16   [Amended]

    4. Section 341.16 Bronchodilator active ingredients is amended by 
removing paragraphs (a), (b), (c), and (f) and by redesignating 
paragraphs (d), (e), and (g) as paragraphs (a), (b), and (c), 
respectively.
    5. Section 341.76 is amended by removing paragraph (c)(5); 
redesignating paragraph (c)(6) as paragraph (c)(5); and revising the 
heading for newly redesignated paragraph (c)(5); by removing paragraph 
(d)(1); by redesignating paragraph (d)(2) as paragraph (d)(1); by 
reserving paragraph (d)(2); and by revising the heading in newly 
redesignated paragraph (d)(1) to read as follows:


Sec. 341.76   Labeling of bronchodilator drug products.

* * * * *
    (c) * * *
    (5) For products containing epinephrine, epinephrine bitartrate, or 
racepinephrine hydrochloride identified in Sec. 341.16(a), (b), and 
(c). * * *
* * * * *
    (d) * * *
    (1) For products containing epinephrine, epinephrine bitartrate, or 
racepinephrine hydrochloride identified in Sec. 341.16(a), (b), and 
(c). * * *
    (2) [Reserved]
* * * * *


Sec. 341.90  [Amended]

    7. Section 341.90 Professional labeling is amended by removing 
paragraph (a) and redesignating paragraphs (b) through (q) as 
paragraphs (a) through (p), respectively.

    Dated: July 5, 1995.
William K. Hubbard,
Acting Deputy Commissioner for Policy.
[FR Doc. 95-18448 Filed 7-26-95; 8:45 am]
BILLING CODE 4160-01-F