[Federal Register Volume 61, Number 87 (Friday, May 3, 1996)]
[Rules and Regulations]
[Pages 20096-20102]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 96-10961]




[[Page 20095]]


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Part VII





Department of Health and Human Services





_______________________________________________________________________



Food and Drug Administration



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21 CFR Parts 101, 201, 369 et al.



Warning Statements for Products Containing or Manufactured With 
Chlorofluorocarbons and Other Ozone-Depleting Substances; Interim Rule

Federal Register / Vol. 61, No. 87 / Friday, May 3, 1996 / Rules and 
Regulations

[[Page 20096]]



DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Parts 101, 201, 369, 501, 740, and 801

[Docket No. 93N-0442]


Warning Statements for Products Containing or Manufactured With 
Chlorofluorocarbons and Other Ozone-Depleting Substances

AGENCY: Food and Drug Administration, HHS.

ACTION: Interim rule; opportunity for comment.

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

SUMMARY: The Food and Drug Administration (FDA) is issuing interim 
regulations governing warning statements for products containing or 
manufactured with chlorofluorocarbons (CFC's) and other ozone-depleting 
substances. The amendments prescribe specific warning statements and 
additional labeling statements for physicians and patients. These 
additional statements direct patients to consult their physicians 
before discontinuing use of a prescription medical product because of 
concerns about the product's effect on the environment and public 
health. The interim rule also provides warning statements for over-the-
counter (OTC) drug and device products and directs patients to consult 
their physicians, health professional, or suppliers with questions 
about the products. In addition, the interim rule revises certain 
regulations concerning foods, cosmetics, and animal foods in a self-
pressurized container with a CFC propellant in order to be consistent 
with current statutory requirements. FDA is issuing these regulations 
as an interim rule with opportunity for public comment.

DATES: Interim rule effective May 17, 1996; comments by August 1, 1996.

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

FOR FURTHER INFORMATION CONTACT: Wayne H. Mitchell, Center for Drug 
Evaluation and Research (HFD-7), Food and Drug Administration, 7500 
Standish Pl., Rockville, MD 20855, 301-594-1049.

SUPPLEMENTARY INFORMATION:

I. Background

    On February 11, 1993 (58 FR 8136), the Environmental Protection 
Agency (EPA) issued final regulations requiring, among other things, a 
warning statement on all products containing or manufactured with 
specific ozone-depleting substances. In general, the EPA regulations 
require each container or product containing or manufactured with 
CFC's, halons, carbon tetrachloride, and methyl chloroform to bear the 
following warning statement (58 FR 8136 at 8165):

    Warning: Contains [or Manufactured with, if applicable] [insert 
name of substance], a substance which harms public health and 
environment by destroying ozone in the upper atmosphere.

    EPA issued the rule under section 611 of the Clean Air Act (42 
U.S.C. 7671(j)), which requires the warning statements on all products 
containing or manufactured with CFC's on or after May 15, 1993. In 
promulgating the rule, EPA noted that several comments had argued that 
certain prescription medical products, such as metered-dose inhalers, 
should be exempt from the labeling requirements because they are 
essential to the health of patients. The comments indicated that a 
warning statement might lead some patients to avoid their medication 
because of concerns about the product's effect on the environment or 
alarm over the words ``harms public health.'' EPA stated that it 
understood the importance of such products to patients as well as the 
need to ``tailor the labeling requirement to avoid unduly alarming 
patients,'' but also stated that it lacked the authority to exempt 
prescription medical products from the labeling requirement (see 58 FR 
8136 at 8155). Consequently, EPA indicated that the statutorily 
required warning statement could appear on supplemental printed 
material intended for physicians rather than patients, provided that 
the supplemental printed material intended for patients contain similar 
warning language without the words ``warning'' and ``harms public 
health'' (see 58 FR 8136 at 8156). EPA also indicated that 
manufacturers of prescription medical products could supplement this 
information with additional information for patients. EPA anticipated 
that FDA would provide the specific additional language (see 58 FR 8136 
at 8156). On June 29, 1993 (58 FR 34812, corrected on July 29, 1993, 58 
FR 40656), FDA published a notice in the Federal Register setting out 
alternative labeling warning language designed not to cause undue 
patient alarm. The warnings were essentially identical to the warnings 
contained in this interim rule. As part of the notice, FDA requested 
comments about CFC warning statements. These comments are summarized 
and responded to in section III of this preamble.
      
    Since 1977 (42 FR 22018, April 29, 1977), FDA has required, with a 
few exceptions, that OTC human drug and nonrestricted device products 
containing CFC propellants be labeled with a warning (21 CFR 369.21 and 
801.425). In addition, FDA established regulations in Secs. 101.17(c), 
501.17(c), and 740.11(c) (21 CFR 101.17(c), 501.17(c), and 740.11(c)) 
that required that the package of a food, animal food, or cosmetic in a 
self-pressurized container in which the propellant consists in whole or 
in part of a fully halogenated CFC bear the following warning 
statement:

    Warning: Contains a chlorofluorocarbon that may harm the public 
health and environment by reducing ozone in the upper atmosphere.

    These regulations also provided requirements for placement and 
conspicuousness of the warning statement. The required warning 
statement applied only to self-pressurized containers that use CFC as a 
propellant. For example, for foods, the use of the warning statement 
was not required when the CFC was used as a stabilizer in food toppings 
and spreads (Sec. 101.17(c)(3)).
    Since 1978 (43 FR 11301, March 17, 1978), FDA has prohibited the 
use of CFC propellants in most products it regulates (21 CFR 189.191, 
300.100, 500.49, 700.23, and 801.417), except those listed as essential 
uses of CFC's in Sec. 2.125 (21 CFR 2.125). Nonessential uses, which 
were prohibited by the 1978 final rule, included CFC use as a 
propellant in self-pressurized containers for foods and cosmetics. The 
prohibitions against nonessential uses of CFC's, set out in 
Sec. 2.125(c), provide that ``any food, drug, device, or cosmetic in a 
self-pressurized container that contains a chlorofluorocarbon 
propellant is adulterated and/or misbranded in violation of the act * * 
*.'' Section 2.125(e) exempts certain essential uses of CFC's from the 
adulteration and misbranding provisions of Sec. 2.125(c). Further, 
Sec. 2.125(f) specifically provides for the filing of a petition in 
accordance with 21 CFR part 10 to provide for the listing of additional 
essential uses so as not to subject the new use to the adulteration and 
misbranding provisions in Sec. 2.125(c).
    FDA notes that all of the essential uses of CFC's exempted from the 
adulteration and misbranding provisions of Sec. 2.125 that are listed 
in Sec. 2.125(e) apply to drug products. No

[[Page 20097]]

essential uses of CFC's for foods, cosmetics, or animal foods in self-
pressurized containers have been identified.

II. Description of the Interim Rule

    This interim rule describes the warning statements that should 
accompany human prescription drug, biologic, and device products, and 
restricted device products (hereafter referred to as ``prescription 
human medical products''), OTC drug and device products, and animal 
drug products that contain or are manufactured with CFC's, halons, 
carbon tetrachloride, methyl chloroform, and any other class I ozone-
depleting substance designated by the EPA Administrator. (A list of 
class I ozone-depleting substances can be found in 40 CFR part 82, 
appendix A to subpart A, and any later EPA rulemaking adding other 
ozone-depleting substances.)
    The interim rule provides two options for labeling prescription 
human medical products and OTC drugs and devices. The first option is 
EPA's warning statement:

    Warning: Contains [or Manufactured with, if applicable] [insert 
name of substance], a substance which harms public health and 
environment by destroying ozone in the upper atmosphere.

    The second option for prescription human medical products contains 
FDA's additional language for the alternative warning statements. These 
warning statements are intended for physician labeling and patient 
labeling.
    The warning for the physician package insert would be used in 
conjunction with an alternative warning statement that would appear on 
patient labeling as stated in the EPA final regulation (58 FR 8136 at 
8166). These alternative warning statements would be written so that 
patients do not cease using their medications because of concerns over 
the products' effect on the environment or alarm over the words ``harms 
public health'' without first consulting their physicians. Instead, 
patients would be able to discuss their concerns with their physicians 
or, in the case of OTC drug or device products, another health 
professional or suppliers, and, if they wish, consider the use of 
alternative treatments. Also, physicians would be alerted to products 
that contain ozone-depleting substances. FDA believes that these 
warning statements will enable patients, physicians, pharmacists, other 
health professionals, and suppliers (in the case of devices) to make 
informed decisions.
    Animal drug products manufactured with CFC's or other ozone-
depleting products are required to use EPA's warning statement because 
the optimal alternative labeling statement is restricted to human 
medical products.

A. Prescription Human Medical Products

    For prescription human drug products, new Sec. 201.320 (21 CFR 
201.320) provides both the EPA warning statement and FDA's alternative 
warning statements. New Sec. 801.443 (21 CFR 801.443) provides the same 
two options for prescription and restricted devices. A biological 
product regulated as a drug or a device would use whichever labeling 
applies to the particular biological product. Under new Secs. 201.320 
and 801.443, all prescription drug and device products and restricted 
devices containing or manufactured with CFC's, halons, carbon 
tetrachloride, methyl chloroform, or any other class I ozone-depleting 
substance designated by the EPA Administrator shall use the EPA warning 
statement or specified alternative warning statements. For the first 
option for a warning statement, new Secs. 201.320(a) and 801.443(a) 
provide the EPA warning statement quoted earlier in this preamble.
    Under new Secs. 201.320(a)(2) and 801.443(a)(2), the warning 
statement shall be clearly legible and conspicuous on the product, its 
immediate container, its outer packaging, or other labeling, and appear 
with such prominence and conspicuousness as to render it likely to be 
read and understood by consumers under normal conditions of purchase.
    For the second option, new Secs. 201.320(b)(1) and 801.443(b)(1) 
provide FDA's alternative warning statements for supplemental printed 
materials intended for physicians and for patients. For patient 
labeling, the warning statement would appear on the product, its 
packaging, or supplemental printed material intended for the patient 
and would read as follows:

    Note: The indented statement below is required by the Federal 
government's Clean Air Act for all products containing or 
manufactured with chlorofluorocarbons (CFC's) [or name of other 
class I substance, if applicable].

    This product contains [or is manufactured with, if applicable] 
[insert name of substance], a substance which harms the environment 
by destroying ozone in the upper atmosphere.
    Your physician has determined that this product is likely to 
help your personal health. USE THIS PRODUCT AS DIRECTED, UNLESS 
INSTRUCTED TO DO OTHERWISE BY YOUR PHYSICIAN. If you have any 
questions about alternatives, consult with your physician.

    These statements are designed to explain that the Clean Air Act 
requires the warning statement, but that patients should continue to 
use the prescription medical product unless instructed otherwise by 
their physicians. The labeling for the physician would be placed on the 
physician package insert after the ``How supplied'' section on the 
label describing the special handling and storage conditions.
    For the package insert for the physician, the warning statement 
would state that:

    Note: The indented statement below is required by the Federal 
government's Clean Air Act for all products containing or 
manufactured with chlorofluorocarbons (CFC's) [or name of other 
class I substance, if applicable].

    Warning: Contains [or Manufactured with, if applicable] [insert 
name of substance], a substance which harms public health and 
environment by destroying ozone in the upper atmosphere.

    A notice similar to the above WARNING has been placed in the 
information for the patient [or patient information leaflet, if 
applicable] of this product under Environmental Protection Agency 
(EPA) regulations. The patient's warning states that the patient 
should consult his or her physician if there are questions about 
alternatives.

    For the second option, for the alternative placement on 
supplemental printed material described in new Secs. 201.320(b) and 
801.443(b), the interim rule specifies a particular location for the 
warning statement intended for the physician; provided, however, that a 
person places the statement intended for the patient on the product, 
its packaging, or supplemental printed material for the patient. The 
warning label shall be clearly legible and conspicuous on the product, 
its immediate container, or other labeling as to render it likely to be 
read and understood by consumers under normal conditions of purchase. 
FDA further advises all parties that new Secs. 201.320 and 801.443 do 
not replace or relieve a party from the requirements under 40 CFR part 
82.
    FDA notes that EPA's regulations (58 FR 8136 at 8166 (40 CFR 
82.108(c))) state that, for prescription human medical products that 
FDA finds to be essential for patient health, the warning statement may 
be placed in supplemental printed material intended to be read by the 
prescribing physician, as long as the alternative statement is placed 
on the product, its packaging, or supplemental printed material 
intended to be read by the patient at time of purchase. The agency 
believes that new Secs. 201.320 and 801.443 are consistent

[[Page 20098]]

with these EPA requirements. However, FDA declines at this time to 
determine which products are essential for public health. The Clean Air 
Act requires that the warning labels be on all products containing or 
manufactured with CFC's on or after May 15, 1993. FDA believes it would 
be impractical and unnecessary to engage in case-by-case determinations 
of which medical products are essential to public health before 
permitting alternative warning statements. Thus, until FDA can 
establish criteria and make individualized determinations as to whether 
a drug is essential to public health, the most prudent course of action 
is to presume, for purpose of the warning statement, that all 
prescription human medical products are essential to public health.

B. OTC Drug and Device Products

    This interim rule also removes the existing CFC warning statement 
for OTC drug products at 21 CFR 369.21 in favor of revised warning 
statements at new Sec. 201.320 (a) and (c). This interim rule also 
removes the existing warning statement at 21 CFR 801.425 for 
nonrestricted devices in favor of a revised warning statement at new 
Sec. 801.63 (21 CFR 801.63). Under new Secs. 201.320 and 801.63, an OTC 
drug or device product that contains or is manufactured with CFC's or 
other class I substances may use the EPA warning statement or, as an 
alternative, state:

    Note: The indented statement below is required by the Federal 
government's Clean Air Act for all products containing or 
manufactured with chlorofluorocarbons (CFC's) [or other class I 
substance, if applicable]:

    Warning: Contains [or Manufactured with, if applicable] [insert 
name of substance], a substance which harms public health and 
environment by destroying ozone in the upper atmosphere.

    CONSULT WITH YOUR PHYSICIAN OR HEALTH PROFESSIONAL IF YOU HAVE 
ANY QUESTION ABOUT THE USE OF THIS PRODUCT.

    For OTC devices, the sentence of the label shall state:

    CONSULT WITH YOUR PHYSICIAN, HEALTH PROFESSIONAL, OR SUPPLIER IF 
YOU HAVE ANY QUESTION ABOUT THE USE OF THIS PRODUCT.

    The warning statement shall appear on the product, its immediate 
container, its packaging, or other labeling on or within the package 
from which the drug is dispensed, and must also be prominent and 
conspicuous so as to render it likely to be read and understood by 
consumers under normal conditions of purchase. This statement also must 
be consistent with EPA's regulations at 40 CFR part 82.
    The agency believes that these warning statements for OTC drug and 
device products, like those for prescription human medical products, 
enable patients, physicians, and other health professionals to 
appreciate environmental concerns and will also avoid unduly alarming 
patients.

C. Foods, Cosmetics, and Animal Foods

    As noted above, no essential uses of CFC's for foods, cosmetics, or 
animal foods have been identified. Any uses of CFC's or of other class 
I substances deemed to be appropriate in the manufacture of foods, 
cosmetics, and animal foods, or the indirect use of such substances as 
additives in the manufacture of packaging materials intended to be used 
for foods and animal foods, will subject the foods, cosmetics, and 
food-packaging materials to the labeling requirements established by 
EPA in 40 CFR part 82. Such EPA warning statement, as cited above in 
the discussion on prescription and OTC medical products, must be 
prominent and conspicuous so as to render it easily read and understood 
by consumers under ordinary conditions of purchase.
    Because the EPA warning statement is applicable to all products 
``manufactured with'' or ``that contain CFC's or other class I 
substances,'' the current exemption for CFC's used as a stabilizer in 
food toppings and spreads is no longer appropriate and such foods must 
comply with the applicable labeling requirements set forth in 40 CFR 
part 82. Thus, FDA is removing the specific requirement for the CFC 
warning statement for foods, cosmetics, and animal foods in 
Secs. 101.17(c), 740.11(c), and 501.17 and the exemption for toppings 
and spreads in Sec. 101.17(c)(3). In addition, FDA is revising these 
sections to reference the EPA labeling requirements designated for 
CFC's and other class I substances in 40 CFR part 82.

III. Comments

    In the Federal Register of June 29, 1993 (58 FR 34812), FDA 
published a notice setting out alternative labeling warnings, designed 
not to cause undue patient alarm, that comply with the EPA regulation, 
and that are acceptable to FDA. As part of the notice, FDA requested 
comments about the labeling warning statements, which were nearly 
identical to the warnings contained in this interim rule. These 
comments are summarized and addressed below.
    1. One comment suggested that use of the FDA alternative warnings 
be made mandatory. The comment stated that if manufacturers did not opt 
for the FDA alternative warning, and used the EPA warning instead, this 
could cause undue concern and result in patients stopping medication.
    FDA believes that manufacturers should have the option of using the 
warning statement that best meets their particular needs. FDA does not 
believe that a manufacturer will use the EPA warning if there is any 
real likelihood that the warning's use will cause its customers to 
cease using the manufacturer's product.
    2. Two comments said that, due to the small size of some containers 
for products with CFC's, any labeling rule should allow for alternative 
placement of the warning on outer packaging or other labeling.
    FDA considered these concerns during the drafting of this interim 
rule, and the interim rule does allow such alternative placement.
    3. One comment suggested that the phrase in the patient warning on 
prescription drug labeling ``[i]f you have any questions about 
alternatives please consult with your physician'' was too succinct and 
that the warning should indicate that alternative delivery systems for 
the drug product may be available and that an alternative therapy may 
not be necessary.
    FDA believes that patients will understand that the alternatives 
available may include alternative delivery systems for the same drug 
substance and that any need for additional clarity is outweighed by the 
necessity of keeping this general warning concise.
    4. Another comment suggested that the patient warning statement was 
not sufficiently inclusive in directing patients to contact their 
physician or pharmacist. The comment suggested that labeling refer to 
``physician or health professional'' so as to refer to other health 
care professionals, such as physician's assistants or nurses, who can 
and do provide patients with information on drug products and medical 
devices.
    FDA agrees with this comment in regard to OTC products. Health care 
professionals, other than physicians and pharmacists, are competent to 
advise patients on OTC therapies. However, in regard to prescription 
products, FDA believes that, in such a brief warning, the modification 
may cause confusion and may cause consumers to direct questions to 
health care professionals other than the prescribing physician (or 
other authorized prescribing practitioner) and dispensing pharmacist. 
In such event, the patient could receive inadequate or inappropriate 
advice.
    5. Several comments stated that the physician package insert does 
not alert

[[Page 20099]]

the physician to the fact that patients have been instructed to consult 
with their physician about possible alternatives. Two comments 
suggested that the warning on the physician package insert contain the 
following additional sentence: ``The patient has been instructed to 
consult with you if they have questions about alternatives.''
    FDA agrees with the comment and has reworded the warning in the 
physician package insert with language to that effect.
    Another comment suggested that the proposed OTC drug product 
warning was unduly worrisome to consumers and that a warning similar to 
the alternative warning contained in patient labeling for prescription 
products be allowed for OTC drug products.
    EPA's regulations allow an exception to the general rule of 
requiring the EPA warning only on patient labeling for prescription 
products when the EPA warning is contained in the physician labeling 
for the product. No similar exception is provided for OTC drug 
products; therefore, the warning suggested in the comment would not be 
in compliance with EPA regulations.

IV. Implementation Scheme

    FDA advises applicants who have an approved new drug application 
(NDA) and whose products contain or are manufactured with CFC's or 
other ozone-depleting substances to use the existing procedures in 21 
CFR 314.70(c) (supplements for changes that may be made before FDA 
approval) to notify the agency of any labeling changes to add a CFC 
warning statement. Applicants who have an approved abbreviated new drug 
application (ANDA) should follow the same procedures (see 21 CFR 
314.97).
    Applicants who have submitted either an NDA or ANDA but have not 
received approval should, if necessary, amend their applications to 
notify FDA about the warning statement(s) they intend to use. 
Applicants should submit such amendments in accordance with 21 CFR 
314.60 or 314.96, whichever is appropriate.
    Applicants who hold an approved product license application (PLA) 
and whose products contain or are manufactured with CFC's or other 
ozone-depleting substances are to follow the guidance offered in this 
interim rule. Revision of labeling to accommodate this warning 
statement may be implemented without preclearance from the Center for 
Biologics Evaluation and Research (CBER) and submitted to the file as 
final printed labeling provided that the placement of such information 
does not interfere with or render less prominent any information 
required by biologics labeling regulations (21 CFR 610.60 through 
610.65)).
    Applicants who have submitted a PLA but have not yet received 
approval should, if necessary, amend their applications to notify CBER 
about inclusion of the required warning statement(s) they intend to 
use. Such amendments should be submitted under the applicable reference 
number.
    Applicants who have submitted premarket approval applications 
(PMA's) for medical devices but have not received approval should, if 
necessary, amend their applications to notify FDA about the warning 
statement(s) they intend to use. Applicants should submit such 
amendments in accordance with 21 CFR 814.37. With respect to approved 
PMA's, applicants should use the procedures in 21 CFR 814.39 to notify 
the agency of any labeling changes to add a CFC warning. Applicants who 
have received premarket clearance pursuant to 21 U.S.C. 360(k) 
(``510(k) clearance'') do not need to file a new 510(k) submission 
requesting new clearance if this rule only results in the addition of 
the warning statement to the labeling.
    FDA advises applicants who have an approved new animal drug 
application (NADA) and whose products contain or are manufactured with 
CFC's or other ozone-depleting products to use the existing procedures 
as identified in 21 CFR 514.8(e) (supplements for changes which may be 
made before FDA approval) to notify the agency of any labeling changes 
made to add the CFC warning statement. FDA advises applicants who have 
submitted an NADA but have not received approval should, if necessary, 
amend their applications to reflect the required label warning. No 
notification to the agency is necessary for foods, cosmetics, or animal 
foods.
    Manufacturers who amended their labeling to conform with the June 
29, 1993, notice and who have an approved marketing application for 
their product should submit a supplemental application to bring their 
labeling into compliance with this interim rule. Such manufacturers may 
continue to use their current stocks of labeling that comply with the 
June 29, 1993, notice until those stocks are exhausted.

V. Effective Date and Opportunity for Public Comment

    For the reasons described in this section, FDA is issuing these 
requirements as an interim rule with an opportunity for public comment. 
In view of the May 15, 1993, statutory warning label requirement, the 
agency is issuing these requirements at this time, but FDA will 
consider modifications to the regulations based on issues raised during 
the comment period and experience gained under the interim rule.
    The Administrative Procedure Act provides an exception to notice 
and comment rulemaking when an agency, for good cause, finds that the 
notice and comment procedures are impracticable, unnecessary, or 
contrary to the public interest (see 5 U.S.C. 553(b)(B)). For this 
interim rule, FDA finds that notice and comment procedures would be 
impracticable for a CFC warning statement requirement because the Clean 
Air Act requires such warning statements to be placed on products 
containing or manufactured with CFC's or other ozone-depleting 
substances by May 15, 1993.
    FDA also finds that notice and comment rulemaking to be unnecessary 
and contrary to the public interest. The interim rule permits parties 
to use the EPA warning statement or an alternative FDA statement. FDA 
has no authority to change or modify the warning statements established 
in EPA's regulations, and, in this interim rule, offers, but does not 
require, the use of an alternative statement. Consequently, because one 
warning statement is established by another agency and because the 
alternative warning statement is optional, FDA believes that notice and 
comment procedures are unnecessary. Furthermore, FDA believes that, 
without the availability of the alternative warning statement, patients 
who are concerned about a medical product's impact on the environment 
and public health might inappropriately refrain from taking their 
medication. This interim rule provides an alternative warning statement 
that encourages patients to continue taking their medication and to 
consult their physicians, pharmacists, other health professionals, or, 
in the case of devices, their suppliers, concerning the product's 
effect on the environment or public health. It would, therefore, be 
contrary to the public interest to delay the implementation of this 
rule pending notice and comment rulemaking.
    FDA believes, however, that it should invite and consider public 
comment on its practices and procedures for these CFC warning 
statements. Interested persons may, on or before August 1, 1996, submit 
to the Dockets Management Branch (address above) comments regarding 
this interim rule. Two copies of any comments are to be submitted, 
except that individuals may submit one copy. Comments are to be 
identified with the docket number

[[Page 20100]]

found in brackets in the heading of this document. Received comments 
may be seen in the office above between 9 a.m. and 4 p.m., Monday 
through Friday.

VI. Analysis of Impacts

    FDA has examined the impacts of the interim 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 interim rule is consistent with the regulatory philosophy and 
principles identified in the Executive Order. In addition, the interim 
rule is not a significant regulatory action as defined by the Executive 
Order and so is not subject to review under the Executive Order.
    The Regulatory Flexibility Act requires agencies to analyze 
regulatory options that would minimize any significant impact of a rule 
on small entities. The regulatory impact analysis (RIA) (January 1993) 
that accompanied EPA's rule that implemented section 611 of the Clean 
Air Act specifically accounted for cost increases for ``medical 
aerosols, including metered-dose inhalation devices, contraceptive 
foams, topical antibiotics, and local anesthetics'' (page 15 of the 
RIA). A copy of this RIA is available for examination under Public 
Docket No. A-91-60 at the U.S. Environmental Protection Agency, rm. M-
1500, Waterside Mall (Ground Floor), 401 M St. SW., Washington, DC 
20460. Other FDA-regulated products are accounted for under separate 
industry subgroupings. The compliance costs for these labeling changes 
have thus been accounted for, and this interim rule adds no additional 
burden or cost. Thus, the agency certifies that the interim rule does 
not constitute a major rule as defined in Executive Order 12866. The 
agency further certifies that the interim 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.

VII. Environmental Impact

    The agency has determined under 21 CFR 25.24(a)(11) 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.

List of Subjects

21 CFR Part 101

    Food labeling, Nutrition, Reporting and recordkeeping requirements.

21 CFR Part 201

    Drugs, Labeling, Reporting and recordkeeping requirements.

21 CFR Part 369

    Labeling, Medical devices, Over-the-counter drugs.

21 CFR Part 501

    Animal foods, Labeling, Packaging and containers, Reporting and 
recordkeeping requirements.

21 CFR Part 740

    Cosmetics, Labeling.

21 CFR Part 801

    Labeling, Medical devices, Reporting and recordkeeping 
requirements.

    Therefore, under the Federal Food, Drug, and Cosmetic Act, the 
Public Health Service Act, the Fair Packaging and Labeling Act, and 
under authority delegated to the Commissioner of Food and Drugs, 21 CFR 
parts 101, 201, 369, 501, 740, and 801 are amended as follows:

PART 101--FOOD LABELING

    1. The authority citation for 21 CFR part 101 continues to read as 
follows:

    Authority: Secs. 4, 5, 6 of the Fair Packaging and Labeling Act 
(15 U.S.C. 1453, 1454, 1455); secs. 201, 301, 402, 403, 409, 701 of 
the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321, 331, 342, 
343, 348, 371).

    2. Section 101.17 is amended by revising paragraph (c) to read as 
follows:


Sec. 101.17  Food labeling warning and notice statements.

* * * * *
    (c) Food containing or manufactured with a chlorofluorocarbon or 
other ozone-depleting substance. Labeling requirements for foods that 
contain or are manufactured with a chlorofluorocarbon or other ozone-
depleting substance designated by the Environmental Protection Agency 
(EPA) are set forth in 40 CFR part 82.
* * * * *

PART 201--LABELING

    3. The authority citation for 21 CFR part 201 continues to read as 
follows:
    Authority: Secs. 201, 301, 501, 502, 503, 505, 506, 507, 508, 
510, 512, 530-542, 701, 704, 721 of the Federal Food, Drug, and 
Cosmetic Act (21 U.S.C. 321, 331, 351, 352, 353, 355, 356, 357, 358, 
360, 360b, 360gg-360ss, 371, 374, 379e); secs. 215, 301, 351, 361 of 
the Public Health Service Act (42 U.S.C. 216, 241, 262, 264).

    4. New Sec. 201.320 is added to subpart G to read as follows:


Sec. 201.320  Warning statements for drug products containing or 
manufactured with chlorofluorocarbons or other ozone-depleting 
substances.

    (a)(1) All drug products containing or manufactured with 
chlorofluorocarbons, halons, carbon tetrachloride, methyl chloride, or 
any other class I substance designated by the Environmental Protection 
Agency (EPA) shall, except as provided in paragraph (b) or (c) of this 
section, bear the following warning statement:

    Warning: Contains [or Manufactured with, if applicable] [insert 
name of substance], a substance which harms public health and the 
environment by destroying ozone in the upper atmosphere.

    (2) The warning statement shall be clearly legible and conspicuous 
on the product, its immediate container, its outer packaging, or other 
labeling in accordance with the requirements of 40 CFR part 82 and 
appear with such prominence and conspicuousness as to render it likely 
to be read and understood by consumers under normal conditions of 
purchase.
    (b)(1) For prescription drug products for human use, the following 
alternative warning statement may be used:

    Note: The indented statement below is required by the Federal 
government's Clean Air Act for all products containing or 
manufactured with chlorofluorocarbons (CFC's) [or name of other 
class I substance, if applicable]:

    This product contains [or is manufactured with, if applicable] 
[insert name of substance], a substance which harms the environment by 
destroying ozone in the upper atmosphere.
    Your physician has determined that this product is likely to 
help your personal health. USE THIS PRODUCT AS DIRECTED, UNLESS 
INSTRUCTED TO DO OTHERWISE BY YOUR PHYSICIAN. If you have any 
questions about alternatives, consult with your physician.

    (2) The warning statement shall be clearly legible and conspicuous 
on the product, its immediate container, its outer packaging, or other 
labeling in accordance with the requirements of 40 CFR part 82 and 
appear with such prominence and conspicuousness as to render it likely 
to be read and understood by consumers under normal conditions of 
purchase.
    (3) If the warning statement in paragraph (b)(1) of this section is 
used, the following warning statement must

[[Page 20101]]

be placed on the package labeling intended to be read by the physician 
(physician package insert) after the ``How supplied'' section, which 
describes special handling and storage conditions on the physician 
labeling:

    Note: The indented statement below is required by the Federal 
government's Clean Air Act for all products containing or 
manufactured with chlorofluorocarbons (CFC's) [or name of other 
class I substance, if applicable]:

    Warning: Contains [or Manufactured with, if applicable] [insert 
name of substance], a substance which harms public health and the 
environment by destroying ozone in the upper atmosphere.

    A notice similar to the above WARNING has been placed in the 
information for the patient [or patient information leaflet, if 
applicable] of this product under the Environmental Protection 
Agency's (EPA's) regulations. The patient's warning states that the 
patient should consult his or her physician if there are questions 
about alternatives.

    (c)(1) For over-the-counter drug products for human use, the 
following alternative warning statement may be used:

    Note: The indented statement below is required by the Federal 
government's Clean Air Act for all products containing or 
manufactured with chlorofluorocarbons (CFC's) [or other class I 
substance, if applicable]:

    Warning: Contains [or Manufactured with, if applicable] [insert 
name of substance], a substance which harms public health and 
environment by destroying ozone in the upper atmosphere.

    CONSULT WITH YOUR PHYSICIAN OR HEALTH PROFESSIONAL IF YOU HAVE 
ANY QUESTION ABOUT THE USE OF THIS PRODUCT.

    (2) The warning statement shall be clearly legible and conspicuous 
on the product, its immediate container, its outer packaging, or other 
labeling in accordance with the requirements of 40 CFR part 82 and 
appear with such prominence and conspicuousness as to render it likely 
to be read and understood by consumers under normal conditions of 
purchase.
    (d) This section does not replace or relieve a person from any 
requirements imposed under 40 CFR part 82.

PART 369--INTERPRETATIVE STATEMENTS RE WARNINGS ON DRUGS AND 
DEVICES FOR OVER-THE-COUNTER SALE

    5. The authority citation for 21 CFR part 369 continues to read as 
follows:

    Authority: Secs. 201, 301, 501, 502, 503, 505, 506, 507, 701 of 
the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321, 331, 351, 
352, 353, 355, 356, 357, 371).


Sec. 369.21  [Amended]

    6. Section 369.21 Drugs; warning and caution statements required by 
regulations is amended in paragraph (d) in the warning section for 
``DRUGS IN DISPENSERS PRESSURIZED BY GASEOUS PROPELLANTS * * *'' by 
removing the five undesignated paragraphs after the introductory text 
of paragraph (d).

PART 501--ANIMAL FOOD LABELING

    7. The authority citation for 21 CFR part 501 continues to read as 
follows:

    Authority: Secs. 4, 5, 6 of the Fair Packaging and Labeling Act 
(15 U.S.C. 1453, 1454, 1455); secs. 201, 301, 402, 403, 409, 701 of 
the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321, 331, 342, 
343, 348, 371).

    8. Section 501.17 is amended by revising paragraph (c) to read as 
follows:


Sec. 501.17  Animal food labeling warning statements.

* * * * *
    (c) Animal food containing or manufactured with a 
chlorofluorocarbon or other ozone-depleting substance. Labeling 
requirements for animal foods that contain or are manufactured with a 
chlorofluorocarbon or other ozone-depleting substance designated by the 
Environmental Protection Agency (EPA) are set forth in 40 CFR part 82.

PART 740--COSMETIC PRODUCT WARNING STATEMENTS

    9. The authority citation for 21 CFR part 740 continues to read as 
follows:

    Authority: Secs. 201, 301, 502, 505, 601, 602, 701, 704 of the 
Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321, 331, 352, 355, 
361, 362, 371, 374).

    10. Section 740.11 is amended by revising paragraph (c) to read as 
follows:


Sec. 740.11  Cosmetics in self-pressurized containers.

* * * * *
    (c) Labeling requirements for cosmetics packaged in a self- 
pressurized container containing or manufactured with a 
chlorofluorocarbon propellant or other ozone-depleting substance 
designated by the Environmental Protection Agency (EPA) are set forth 
in 40 CFR part 82.

PART 801--LABELING

    11. The authority citation for 21 CFR part 801 continues to read as 
follows:

    Authority: Secs. 201, 301, 501, 502, 507, 519, 520, 701, 704 of 
the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321, 331, 351, 
352, 357, 360i, 360j, 371, 374).

    12. New Sec. 801.63 is added to subpart C to read as follows:


Sec. 801.63  Medical devices; warning statements for devices containing 
or manufactured with chlorofluorocarbons and other class I ozone-
depleting substances.

    (a) All over-the-counter devices containing or manufactured with 
chlorofluorocarbons, halons, carbon tetrachloride, methyl chloride, or 
any other class I substance designated by the Environmental Protection 
Agency (EPA) shall carry one of the following warnings:
    (1) The EPA warning statement:

    Warning: Contains [or Manufactured with, if applicable] [insert 
name of substance], a substance which harms public health and 
environment by destroying ozone in the upper atmosphere.

    (2) The alternative statement:

    Note: The indented statement below is required by the Federal 
government's Clean Air Act for all products containing or 
manufactured with chlorofluorocarbons (CFC's) [or other class I 
substance, if applicable]:

    Warning: Contains [or Manufactured with, if applicable] [insert 
name of substance], a substance which harms public health and 
environment by destroying ozone in the upper atmosphere.

    CONSULT WITH YOUR PHYSICIAN, HEALTH PROFESSIONAL, OR SUPPLIER IF 
YOU HAVE ANY QUESTION ABOUT THE USE OF THIS PRODUCT.

    (b) The warning statement shall be clearly legible and conspicuous 
on the product, its immediate container, its outer packaging, or other 
labeling in accordance with the requirements of 40 CFR part 82 and 
appear with such prominence and conspicuousness as to render it likely 
to be read and understood by consumers under normal conditions of 
purchase. This provision does not replace or relieve a person from any 
requirements imposed under 40 CFR part 82.


Sec. 801.425  [Removed]

    13. Section 801.425 Nonrestricted devices in self-pressurized 
containers with chlorofluorocarbon propellants is removed from subpart 
H.
    14. New Sec. 801.433 is added to subpart H to read as follows:


Sec. 801.433  Warning statements for prescription and restricted device 
products containing or manufactured with chlorofluorocarbons or other 
ozone-depleting substances.

    (a)(1) All prescription and restricted device products containing 
or manufactured with chlorofluorocarbons, halons, carbon tetrachloride, 
methyl chloride, or any other class I substance designated by the 
Environmental

[[Page 20102]]

Protection Agency (EPA) shall, except as provided in paragraph (b) of 
this section, bear the following warning statement:

    Warning: Contains [or Manufactured with, if applicable] [insert 
name of substance], a substance which harms public health and 
environment by destroying ozone in the upper atmosphere.

    (2) The warning statement shall be clearly legible and conspicuous 
on the product, its immediate container, its outer packaging, or other 
labeling in accordance with the requirements of 40 CFR part 82 and 
appear with such prominence and conspicuousness as to render it likely 
to be read and understood by consumers under normal conditions of 
purchase.
    (b)(1) For prescription and restricted device products, the 
following alternative warning statement may be used:

    Note: The indented statement below is required by the Federal 
government's Clean Air Act for all products containing or 
manufactured with chlorofluorocarbons (CFC's) [or name of other 
class I substance, if applicable]:

    This product contains [or is manufactured with, if applicable] 
[insert name of substance], a substance which harms the environment 
by destroying ozone in the upper atmosphere.
    Your physician has determined that this product is likely to 
help your personal health. USE THIS PRODUCT AS DIRECTED, UNLESS 
INSTRUCTED TO DO OTHERWISE BY YOUR PHYSICIAN. If you have any 
questions about alternatives, consult with your physician.

    (2) The warning statement shall be clearly legible and conspicuous 
on the product, its immediate container, its outer packaging, or other 
labeling in accordance with the requirements of 40 CFR part 82 and 
appear with such prominence and conspicuousness as to render it likely 
to be read and understood by consumers under normal conditions of 
purchase.
    (3) If the warning statement in paragraph (b)(1) of this section is 
used, the following warning statement must be placed on the package 
labeling intended to be read by the physician (physician package 
insert) after the ``How supplied'' section, which describes special 
handling and storage conditions on the physician labeling:

    Note: The indented statement below is required by the Federal 
government's Clean Air Act for all products containing or 
manufactured with chlorofluorocarbons (CFC's) [or name of other 
class I substance, if applicable]:

    Warning: Contains [or Manufactured with, if applicable] [insert 
name of substance], a substance which harms public health and 
environment by destroying ozone in the upper atmosphere.

    A notice similar to the above WARNING has been placed in the 
information for the patient [or patient information leaflet, if 
applicable] of this product under Environmental Protection Agency 
(EPA) regulations. The patient's warning states that the patient 
should consult his or her physician if there are questions about 
alternatives.

    (c) This section does not replace or relieve a person from any 
requirements imposed under 40 CFR part 82.

    Dated: April 16, 1996.
William K. Hubbard,
Associate Commissioner for Policy Coordination.
[FR Doc. 96-10961 Filed 5-2-96; 8:45 am]
BILLING CODE 4160-01-P