Status of Certain Additional Over-the-Counter Drug Category II Active Ingredients, 34895-34902 [E8-13826]

Agencies

• Food and Drug Administration
• DEPARTMENT OF HEALTH AND HUMAN SERVICES

[Federal Register Volume 73, Number 119 (Thursday, June 19, 2008)]
[Proposed Rules]
[Pages 34895-34902]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E8-13826]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

21 CFR Part 310

[Docket No. FDA-2008-N-0297]
RIN 0910-AF95


Status of Certain Additional Over-the-Counter Drug Category II 
Active Ingredients

AGENCY: Food and Drug Administration, HHS.

ACTION: Proposed rule.

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[[Page 34896]]

SUMMARY: The Food and Drug Administration (FDA) is proposing that 
certain ingredients in over-the-counter (OTC) drug products are not 
generally recognized as safe and effective (GRASE) or are misbranded. 
FDA is issuing this proposed rule because we did not receive any data 
and information on these ingredients in response to our request on 
December 31, 2003 (68 FR 75585). This proposed rule is part of FDA's 
ongoing review of OTC drug products.

DATES: Submit written or electronic comments on the proposed rule and 
on FDA's economic impact determination by September 17, 2008. Please 
see section IV of this document for the proposed effective date of any 
final rule that may publish based on this proposal.

ADDRESSES: You may submit comments, identified by Docket No. FDA-2008-
N-0297 and RIN number 0910-AF95, by any of the following methods:
Electronic Submissions
    Submit electronic comments in the following ways:
     Federal eRulemaking Portal: https://www.regulations.gov. 
Follow the instructions for submitting comments.
Written Submissions
    Submit written submissions in the following ways:
     FAX: 301-827-6870.
     Mail/Hand delivery/Courier [For paper, disk, or CD-ROM 
submissions]: Division of Dockets Management (HFA-305), Food and Drug 
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
    To ensure more timely processing of comments, FDA is no longer 
accepting comments submitted to the agency by e-mail. FDA encourages 
you to continue to submit electronic comments by using the Federal 
eRulemaking Portal, as described previously, in the ADDRESSES portion 
of this document under Electronic Submissions.
    Instructions: All submissions received must include the agency 
name, docket number, and Regulatory Information Number (RIN) for this 
rulemaking and may be accompanied by a supporting memorandum or brief. 
All comments received may be posted without change to https://
www.regulations.gov, including any personal information provided.
    Docket: For access to the docket to read background documents or 
comments received, go to https://www.regulations.gov and insert the 
docket number, found in brackets in the heading of this document, into 
the ``Search'' box and follow the prompts and/or go to the Division of 
Dockets Management, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852, 
between 9 a.m. and 4 p.m., Monday through Friday.

FOR FURTHER INFORMATION CONTACT: William E. Gilbertson or Gerald M. 
Rachanow, Center for Drug Evaluation and Research, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 22, MS5411, Silver 
Spring, MD 20993, 301-796-2090.

SUPPLEMENTARY INFORMATION:

Table of Contents

I. What is the Purpose of This Document?
II. What Past FDA Actions Are Relevant to This Proposed Rule?
    A. What Categories of Products Were Included in the Call-for-Data 
Notice?
    B. What Data Were Submitted in Response to the Call-for-Data 
Notice?
III. What Is the Regulatory Process When No Data Are Submitted to 
Support Ingredients?
IV. What is FDA's Proposed Effective Date?
V. Analysis of Impacts
    A. What Are the Costs and Benefits Associated With This Proposed 
Rule?
    B. What Regulatory Alternatives Has FDA Considered?
    C. What Is the Small Business Impact?
VI. Paperwork Reduction Act of 1995
VII. Environmental Impact
VIII. Federalism

I. What is the Purpose of This Document?

    In this rule, FDA proposes to add to Sec.  310.545 (21 CFR 310.545) 
certain ingredients and categories of OTC drug products that are not 
GRASE and are misbranded in the absence of an approved new drug 
application (NDA):
Ingredients
     Any external analgesic drug products containing aloe vera 
or urea
     Any topical antimicrobial drug products containing aloe 
vera
     Any drug products containing urea for any labeled claims
     Ammonia as a reflex stimulant
Drug Categories
     All skin protectant blister guard drug products
     Any skin protectant drug products labeled with claims or 
directions for use as a nipple protectant (previously referred to as 
breast creams for use when nursing), except lanolin
     Any drug products formulated as a wet dressing other than 
skin protectant and astringent drug products formulated and labeled in 
accordance with 21 CFR part 347
     Any drug products labeled with claims or directions for 
the following uses:
      Bed-wetting deterrent
      Blemish remedy other than topical acne drug products 
formulated and labeled in accordance with 21 CFR part 333, subpart D
      Bunion remedy
      Drawing salve (for drawing or removing splinters, 
slivers, or similar items), except ichthammol
      Foot balm, bath, or other topical dosage forms for any 
``foot'' claims (including relieving foot muscle strains and soreness 
from working out), other than topical antifungal drug products 
formulated and labeled in accordance with 21 CFR part 333, subpart C 
and external analgesic drug products formulated and labeled in 
accordance with the tentative final monograph (proposed 21 CFR part 
348) published on February 8, 1983 (48 FR 5852)
      Impotency cure
      Medicated bath preparation
      Nonantimicrobial skin wound cleanser (previously listed 
as ``detergents'' in call-for-data notices
      Topical products for treatment or prevention of male 
urethral problems
      Treatment or prevention of prickly heat
      Urinary acidifier
      Urinary alkalinizer
      Weight control drug products with ingredients formulated 
as an impregnated body wrap
      Wound wash saline
    FDA notes that the names of several active ingredients have changed 
from the way they appeared in the December 31, 2003, call-for-data 
notice. FDA is using the new names in the proposed amendments to Sec.  
310.545. Table 1 lists the old and new ingredient names:

                                 Table 1.--Active Ingredients With Name Changes
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              Old name                            Current name                            Category
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Aromatic spirits of ammonia           Ammonia spirit, aromatic              Ammonia as a reflex stimulant
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[[Page 34897]]

 
Benzophenone-3                        Oxybenzone                            Medicated bath
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Carbolic acid                         Phenol                                Foot balm, bath
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Formalin                              Formaldehyde solution                 Foot balm, bath
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Natural pine needle oil               Pine needle oil                       Foot balm, bath
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Oil of eucalyptus                     Eucalyptus oil                        Foot balm, bath
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Oil of peppermint                     Peppermint oil                        Foot balm, bath
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Peru balsam                           Peruvian balsam                       Medicated bath
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Phenol sodium                         Phenolate sodium                      Nonantimicrobial skin wound cleanser
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Trisodium phosphate                   Sodium phosphate, tribasic            Foot balm, bath
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    FDA is proposing that any OTC drug product containing any of these 
ingredients that are not considered GRASE for the uses discussed in 
this document must first be the subject of an approved NDA before it 
may be initially introduced (or initially delivered for introduction) 
into interstate commerce.
    The following product categories, for which data were submitted in 
response to the December 31, 2003, call-for-data notice, will be 
discussed in future issues of the Federal Register: Lubricants and 
vaginal moisturizers, nasal moisturizers, urinary analgesics/
antiseptics, wrinkle removers, lanolin as a nipple protectant, and 
ichthammol as a drawing salve. FDA is not discussing those product 
categories, or specific active ingredients in those categories, in this 
document.

II. What Past FDA Actions Are Relevant to This Proposed Rule?

A. What Categories of Products Were Included in the Call-for-Data 
Notice?

    In the Federal Register of December 31, 2003, FDA published a call 
for data for certain categories of ingredients in OTC drug products 
that FDA had not reviewed to date. We listed the following 22 
categories (68 FR 75585 at 75589 to 75590): Ammonia as a reflex 
stimulant; bed-wetting deterrents; blemish remedies (excluding topical 
acne active ingredients in Sec.  310.545(a)(1) and Sec.  333.310 (21 
CFR 333.310)); breast creams (for use when nursing) (now called 
``nipple protectants''); bunion remedies; drawing salves (excluding 
products labeled for the treatment of boils in 21 CFR 310.531 and 
including products labeled for the drawing or removal of splinters, 
slivers, or similar items); foot balms, baths, and creams (excluding 
topical antifungal active ingredients in Sec.  310.545(a)(22) and Sec.  
333.210 (21 CFR 333.210) and including claims for relieving foot muscle 
strains and soreness from working out); impotency cures; impregnated 
body wraps for weight reduction; lubricants and vaginal moisturizers; 
medicated bath preparations; nasal moisturizers; nonantimicrobial skin 
wound cleansers; prickly heat products; skin protectant blister guard; 
urethral creams for males; urinary acidifiers; urinary alkalinizers; 
urinary analgesics/antiseptics; wet dressings (excluding astringent 
active ingredients in Sec.  310.545(a)(18)(ii) and Sec.  347.10 (21 CFR 
347.10)); wound wash saline; and wrinkle removers. Most categories 
identified in the call for data included a list of specific active 
ingredients for review.
    FDA also requested the submission of data and information (68 FR 
75585 at 75588) on:
     Aloe vera as an active ingredient in OTC topical 
antimicrobial and external analgesic drug products
     Urea as an active ingredient in OTC external analgesic 
drug products, or for any other OTC drug use
    FDA invited interested persons to submit data and information on 
these categories and ingredients by June 28, 2004.

B. What Data Were Submitted in Response to the Call-for-Data Notice?

    Data were submitted for the following product categories: Nipple 
protectants (for use when nursing); drawing salves labeled for the 
drawing or removal of splinters, slivers, or similar items; lubricants 
and vaginal moisturizers; nasal moisturizers; urinary analgesics/
antiseptics; and wrinkle removers. For two of the product categories, 
FDA received data and information on only one ingredient in each 
category. In the category of nipple protectants, FDA received data on a 
product containing lanolin. FDA did not receive any data or information 
on the following ingredients that were listed for the nipple protectant 
category in the call-for-data notice: Cetyl alcohol, cocoa butter, cod 
liver oil, dimethicone, glycerin, glyceryl monostearate, hard fat, 
mineral oil, petrolatum, and white petrolatum. In the category of 
drawing salves, FDA received data on a product containing ichthammol. 
FDA did not receive any data or information on the following 
ingredients that were listed for the drawing salves category in the 
call-for-data notice: Ergot fluid extract, juniper tar (oil of cade), 
magnesium sulfate, pine tar, rosin, rosin cerate, and sulfur. Based on 
the submissions received, the following products are not included in 
this proposed rule and will be discussed in a future issue of the 
Federal Register: Lubricants and vaginal moisturizers, nasal 
moisturizers, urinary analgesics/antiseptics, wrinkle removers, lanolin 
for use as a nipple protectant, and ichthammol for use in drawing 
salves.
    FDA did not receive any data or information on products or active 
ingredients in the following product categories: Ammonia as a reflex 
stimulant; bed-wetting deterrents; blemish remedies (excluding topical 
acne active ingredients in Sec.  Sec.  310.545(a)(1) and 333.310); 
bunion remedies; foot balms, baths, and creams (excluding topical 
antifungal active ingredients in Sec.  Sec.  310.545(a)(22) and 333.210 
and including claims for relieving foot muscle strains and soreness 
from working out); impotency cures; impregnated body wraps for weight 
reduction; medicated bath preparations; nonantimicrobial skin wound 
cleansers; prickly heat products; skin protectant blister guard; 
urethral creams for males; urinary acidifiers;

[[Page 34898]]

urinary alkalinizers; wet dressings (excluding astringent active 
ingredients in Sec.  Sec.  310.545(a)(18)(ii) and 347.10); and wound 
wash saline. FDA also did not receive any data or information on aloe 
vera and urea for topical uses. Therefore, FDA has no data and 
information to review to determine if any of these products or 
ingredients are GRASE and not misbranded for OTC use.

III. What Is the Regulatory Process When No Data Are Submitted to 
Support Ingredients?

    Under the procedures for classifying OTC drugs as GRASE and not 
misbranded and for establishing OTC drug monographs (Sec.  330.10 (21 
CFR 330.10)):
     An advisory review panel reviews the data and information 
submitted in response to a call for data and then submits a report with 
its recommendations to the Commissioner of Food and Drugs (the 
Commissioner) (Sec.  330.10(a)(2), (a)(3), and (a)(5)).
     After reviewing the advisory review panel's report and 
recommendations, the Commissioner publishes a proposed order with the 
panel's report and a monograph listing proposed GRASE conditions and a 
statement of the proposed nonmonograph conditions (Sec.  330.10(a)(6)).
     After reviewing comments and new data submitted in 
response to the publication of the advisory review panel's report, the 
Commissioner publishes a tentative final monograph (TFM) proposing 
conditions under which a category of drugs or specific OTC drugs are 
GRASE and not misbranded (Sec.  330.10(a)(7)(i)).
     The Commissioner may also publish a separate tentative 
order, such as this document, containing a statement of those active 
ingredients reviewed and proposed to be excluded from the monograph 
because they would result in a drug product not being GRASE or would 
result in misbranding. This order may be published when FDA receives no 
substantive comments in opposition to the advisory review panel's 
report or no new data and information (Sec.  330.10(a)(7)(ii)).
     After reviewing the entire administrative record, the 
Commissioner publishes a final order containing a monograph 
establishing conditions under which a category of OTC drugs or a 
specific or specific OTC drugs are GRASE and not misbranded (Sec.  
330.10(a)(9)). If there are no GRASE conditions, the Commissioner 
includes the category or the specific OTC drugs in Sec.  310.545, which 
lists active ingredients for which the data are inadequate to establish 
GRASE status (i.e., identifies nonmonograph ingredients and uses).
    FDA did not receive any data and information on most of the 
ingredients and drug categories in the call-for-data notice for an 
advisory review panel to evaluate and upon which a panel could issue a 
report. Thus, for those ingredients and drug categories, there is no 
data or report for the Commissioner to evaluate and no basis for FDA to 
publish a TFM. Therefore, the Commissioner is publishing a tentative 
order (proposed rule) listing these ingredients and drug categories as 
nonmonograph conditions.

IV. What Is FDA's Proposed Effective Date?

    FDA is proposing that any final rule that may issue based on this 
proposal be implemented 180 days after its publication in order to 
provide for safe and effective use of OTC drug products at the earliest 
possible time. Manufacturers are encouraged to comply voluntarily at 
the earliest possible date.
    FDA points out that publication of a final rule under this 
proceeding would not preclude a manufacturer from testing an ingredient 
to support future use. Where a manufacturer believes it has adequate 
data to establish that an active ingredient is GRASE when used for a 
specific indication, such data may be submitted in an appropriate 
citizen petition to amend or to establish an OTC drug monograph, as 
appropriate (see 21 CFR 10.30). Data to support safety and 
effectiveness can be developed under an investigational new drug (IND) 
application to support submission and review of an NDA. An NDA, if 
approved, would make the drug eligible for prescription or OTC 
marketing status. For ingredients subject to a final monograph, an NDA 
may be submitted for a deviation from the monograph (see 21 CFR 330.11 
describing an NDA deviation). A product cannot continue to be marketed 
legally while FDA reviews a petition or NDA.

V. Analysis of Impacts

    FDA has examined the impacts of the proposed rule under Executive 
Order 12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612), and 
the Unfunded Mandates Reform Act of 1995 (Public Law 104-4). 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 not a significant regulatory action as defined by 
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. Because few products will likely be affected and 
those effects would probably be small, FDA does not believe that this 
proposed rule would have a significant economic impact on a substantial 
number of small entities. FDA requests comment on this issue.
    Section 202(a) of the Unfunded Mandates Reform Act of 1995 requires 
that agencies prepare a written statement, which includes an assessment 
of anticipated costs and benefits, before proposing ``any rule that 
includes any Federal mandate that may result in the expenditure by 
State, local, and tribal governments, in the aggregate, or by the 
private sector, of $100,000,000 or more (adjusted annually for 
inflation) in any one year. ''The current threshold after adjustment 
for inflation is $127 million, using the most current (2006) Implicit 
Price Deflator for the Gross Domestic Product. FDA does not expect this 
proposed rule to result in any 1-year expenditure that would meet or 
exceed this amount.
    The purpose of this proposed rule is to classify OTC drug products 
containing certain active ingredients as not GRASE (i.e., nonmonograph) 
for certain uses for which FDA did not receive any safety and 
effectiveness data and information. This proposed rule amends Sec.  
310.545 to include these product categories and ingredients.
    We are not able to identify the number of products that would be 
affected by this proposed rule, but the number is probably low. Based 
on our experience, when no data are received after a Federal Register 
request, it often indicates that manufacturers have little or no 
interest in those ingredients, have phased out or are in the process of 
phasing out those ingredients, or in some cases are removing the drug 
claims at issue from the product label. Without actually reading the 
label for each and every manufacturer's product, we cannot distinguish 
the numbers of products containing the proposed nonmonograph 
ingredients from those with monograph ingredients. In addition, some of 
the affected products are sold alongside cosmetics and drug-cosmetic 
combination products and we would need to read the actual labels to 
determine their classifications.
    Many of the products affected could still be marketed as OTC drugs 
if they

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were reformulated with an active ingredient that is contained in a 
monograph and complied with that monograph's labeling conditions. For 
example, blemish remedies covered by this proposal could be 
reformulated to contain a topical acne active ingredient included in 
Sec.  333.310. Other products could be marketed as cosmetics, some with 
a simple label change and no reformulation. For example, some foot 
balms and baths covered by this proposal might be able to be marketed 
as cosmetic products with certain label changes (i.e., deletion of any 
drug claims). For a few of the product categories, such as bed wetting 
deterrents and impotency cures, there are currently no OTC drug 
substitute products on the market, but there are prescription drugs 
approved for the conditions.
A. What Are the Costs and Benefits Associated With This Proposed Rule?
    For products that cannot be reformulated or relabeled to remain on 
the market, the cost of the rule is the short-run loss of economic 
profits from the lost sales of those goods once they are removed from 
the market. Over the long-run, however, manufacturers will be able to 
produce alternative goods on their existing equipment to partly or 
fully offset these losses. For the products that remain on the market, 
the costs include one-time costs to reformulate or relabel the product. 
We do not know the number of manufacturers that would be affected or 
the number of products and stockkeeping units (SKUs) (individual 
products, packages, and sizes) that might need to be relabeled. Many of 
the products in these categories were probably discontinued some time 
ago but a few manufacturers will continue to market them until a final 
rule prohibits such marketing.
    The one-time costs to relabel a product include designing the new 
carton and the inventory loss of any unused current labeling. FDA 
assumes the same weighted average cost to relabel, inflated to reflect 
current (2006) dollars, that it estimated for the final rule requiring 
uniform label formats of OTC drug products (64 FR 13254 at 13279 to 
13281, March 17, 1999) (i.e., $3,600 x 1.22), $4,392 per SKU.\1\ We 
also have estimated inventory loss using data from a study of the costs 
of the uniform label format rule. With a 6-month implementation period, 
we have estimated the inventory loss to be between $610 and $3,660 per 
SKU, depending on product sales, for an estimated weighted average 
inventory loss of $1,220.\2\ For example, if there were 100 SKUs that 
needed to be relabeled, the total one-time incremental costs would be 
about $561,200 (100 x ($4,392 + $1,220)).
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    \1\ The annual Producer Price Index (PPI) for pulp, paper, and 
allied products, series Id: WPU09 (the major cost driver for 
labeling) rose by 22 percent between 1998 and 2006 (from 174.1 to 
209.8) https://data.bls.gov.
    \2\ The original values from the uniform label formats rule (64 
FR 13254), inventory loss between $500 and $3,000 and a weighted 
average of $1,000, were inflated by 22 percent. The weighting ratio 
for calculating the average was 80 percent small and private label 
firms to 20 percent large firms.
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    The cost to reformulate an OTC drug product varies greatly 
depending on the nature of the product, dosage form, availability of 
alternative active ingredients, and size of company. If there are 
monograph ingredients available in the affected product category, the 
reformulation costs for another product (such as product validation, 
stability testing, and change in master production documents) would 
range from $100,000 to $500,000.\3\ The decision to reformulate would 
depend on the manufacturer's product portfolio and projected sales for 
the reformulated product. Using the midpoint of the range, $300,000, if 
there were 50 products reformulated the total incremental costs would 
be about $15 million ($300,000 x 50).
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    \3\ Value based on previously published estimations (70 FR 75988 
at 75995, December 22, 2005 and 67 FR 78158 at 78167, December 23, 
2002).
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    We are not able to estimate the total foregone economic profit from 
the lost sale of products that would be discontinued by the 
manufacturers, but sales of the products affected by the proposed rule 
were never large relative to other OTC drug products. The loss would be 
largely a short-run loss because other products, including OTC drugs, 
cosmetics, and dietary supplements, could be manufactured on the same 
equipment as the replaced products. In addition, manufacturers could 
increase production of some of their other existing products or conduct 
contract manufacturing for other products.
    FDA cannot quantify the benefits associated with this proposed 
rule. Potential benefits include removal from the market of OTC drug 
products or ingredients that have not been shown to be safe and 
effective. For the classes of products affected by this proposed rule, 
consumers would have substitute products available, either OTC or by 
prescription. The potential benefits from the rule would result from 
those substitute products having been shown to be safe and effective.
B. What Regulatory Alternatives Has FDA Considered?
    We have few alternatives available to us when we determine there 
are no data or qualitative information available to demonstrate a 
product's safety and effectiveness. Even without evidence of harm 
caused by the use of these products, they cannot remain on the market 
because there is no evidence that they are safe and effective. The two 
most plausible regulatory alternatives to this proposed rule are a 
shorter and a longer implementation period. With a shorter 
implementation period, the products at issue would be removed from the 
market sooner, but the labeling costs for 100 SKUs would rise to 
$622,000 with a 3-month compliance period.\4\ We could allow a longer 
implementation period so manufacturers could reduce their inventory of 
cartons and labels. Costs for relabeling 100 SKUs would fall to 
$500,200 with a 12-month compliance period, but consumers would be 
exposed to these products that have not been shown to be safe and 
effective for a longer period of time. Furthermore, it is probable that 
few products will, in fact, bear substantial labeling costs. 
Manufacturers have been aware of the status of these ingredients since 
the December 31, 2003, call-for-data notice and have had sufficient 
notice and time to adjust their supply of labels to limit the impact in 
the event this rule becomes final. The 6-month implementation period 
used in the cost model probably understates the actual average time 
that manufacturers will have to change labels.
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    \4\ The weighted average inventory loss would increase to $1,830 
per SKU with a 3-month compliance period, but decrease to the 
irreducible (label inventory can never be used up entirely so 
whenever there are label changes, there is always some portion of 
inventory that is scraped) inventory loss of $610 per SKU with a 
compliance period of 12 months or longer.
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C. What is the Small Business Impact?
    The Small Business Administration defines an entity as small in the 
pharmaceutical manufacturing industry if it has fewer than 750 
employees. Over 90 percent of firms in the pharmaceutical industry are 
classified as small. We assume that 90 to 100 percent of the entities 
that would be affected by this proposed rule are also small.
    The economic impact on individual firms will vary based on the 
number of affected products they manufacture, and how they respond to 
the rule. Their response could be to withdraw, relabel, or reformulate 
the product. If a small entity withdraws the product, its production 
line could be used for alternative OTC drug, dietary supplement, and 
cosmetic products, or

[[Page 34900]]

for contract manufacturing in those industries, thereby limiting 
economic losses. Labeling costs due to the proposed rule, as explained 
in this section, would likely be small. The largest potential cost 
would be reformulation. However, we do not know if a sufficient number 
of small entities would reformulate a large enough number of products 
to constitute a significant economic impact on a substantial number of 
small entities. FDA requests comment on this issue.

VI. Paperwork Reduction Act of 1995

    This proposed rule contains no collections of information. 
Therefore, clearance by the Office of Management and Budget under the 
Paperwork Reduction Act of 1995 is not required.

VII. Environmental Impact

    FDA has determined under 21 CFR 25.31(a) 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.

VIII. Federalism

    FDA has analyzed this proposed rule in accordance with the 
principles set forth in Executive Order 13132. FDA has determined that 
the proposed rule, if finalized as proposed, would have a preemptive 
effect on State law. Section 4(a) of the Executive order requires 
agencies to ``construe * * * a Federal statute to preempt State law 
only where the statute contains an express preemption provision or 
there is some other clear evidence that the Congress intended 
preemption of State law, or where the exercise of State authority 
conflicts with the exercise of Federal authority under the Federal 
statute.'' Section 751 of the Federal Food, Drug, and Cosmetic Act (the 
act) (21 U.S.C. 379r) is an express preemption provision. Section 
751(a) of the act (21 U.S.C. 379r(a)) provides that `` * * * no State 
or political subdivision of a State may establish or continue in effect 
any requirement-- * * * (1) that relates to the regulation of a drug 
that is not subject to the requirements of section 503(b)(1) or 
503(f)(1)(A); and (2) that is different from or in addition to, or that 
is otherwise not identical with, a requirement under this Act, the 
Poison Prevention Packaging Act of 1970 (15 U.S.C. 1471 et seq.), or 
the Fair Packaging and Labeling Act (15 U.S.C. 1451 et seq.).''
    Currently, this provision operates to preempt States from imposing 
requirements related to the regulation of nonprescription drug 
products. (See Section 751(b) through (e) of the act for the scope of 
the express preemption provision, the exemption procedures, and the 
exceptions to the provision.) This proposed rule, if finalized as 
proposed, would classify as not GRASE all of the ingredients in the 
product categories listed in the December 31, 2003, request for data 
and information for which FDA did not receive any data and information. 
Although any final rule would have a preemptive effect, in that it 
would preclude States from issuing requirements related to these OTC 
drug products that are different from or in addition to, or not 
otherwise identical with a requirement in the final rule, this 
preemptive effect is consistent with what Congress set forth in section 
751 of the act. Section 751(a) of the act displaces both State 
legislative requirements and State common law duties. We also note that 
even where the express preemption provision is not applicable, implied 
preemption may arise. See Geier v. American Honda Co., 529 US 861 
(2000).
    FDA believes that the preemptive effect of the proposed rule, if 
finalized as proposed, would be consistent with Executive Order 13132. 
Section 4(e) of the Executive order provides that ``when an agency 
proposes to act through adjudication or rulemaking to preempt State 
law, the agency shall provide all affected State and local officials 
notice and an opportunity for appropriate participation in the 
proceedings.'' FDA is providing an opportunity for State and local 
officials to comment on this rulemaking.

List of Subjects in 21 CFR Part 310

    Administrative practice and procedure, Drugs, Labeling, Medical 
devices, Reporting and recordkeeping requirements.
    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 part 310 be amended as follows:

PART 310--NEW DRUGS

    1. The authority citation for 21 CFR part 310 continues to read as 
follows:

    Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 360b-360f, 
360j, 361(a), 371, 374, 375, 379e; 42 U.S.C. 216, 241, 242(a), 262, 
263b-263n.
    2. Section 310.545 is amended by redesignating the text of 
paragraph (a)(20) as paragraph (a)(20)(i), by adding new paragraph 
(a)(20)(i) heading, by adding and reserving paragraph (a)(20)(ii), by 
adding paragraphs (a)(10)(viii), (a)(18)(vii), (a)(18)(viii), 
(a)(20)(iii), (a)(27)(iii), (a)(30) through (a)(45), and (d)(52), and 
by revising paragraph (d) introductory text and paragraph (d)(2) to 
read as follows:


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

    (a) * * *
    (10) * * *
    (viii) Aloe vera and urea drug products. Any product labeled with 
claims or directions for use as an external analgesic.
* * * * *
    (18) * * *
    (vii) Blister guard drug products--Approved as of (date 180 days 
after publication of a final rule in the Federal Register).
Beta-hydroxyquinolone
Eugenol
Pyroxylin solution
Any other ingredient labeled with claims or directions for use as a 
skin protectant blister guard
    (viii) Nipple protectant drug products (in association with breast 
feeding)--Approved as of (date 180 days after publication of a final 
rule in the Federal Register).
Cetyl alcohol
Cocoa butter
Cod liver oil
Dimethicone
Glycerin
Glyceryl monostearate
Hard fat
Mineral Oil
Petrolatum
White petrolatum
* * * * *
    (20) Weight control drug products.--(i) Ingredients--Approved as of 
February 10, 1992.
* * * * *
    (iii) Impregnated body wraps--Approved as of (date 180 days after 
publication of a final rule in the Federal Register).
Amino acids
Collagen
Magnesium sulfate
Any other ingredient labeled with claims or directions for use for 
weight control
* * * * *
    (27) * * *
    (iii) Aloe vera drug products. Any product labeled with claims or 
directions for use as a topical antimicrobial.
* * * * *

[[Page 34901]]

    (30) Ammonia as a reflex stimulant.
Ammonia inhalants
Ammonia spirit, aromatic
Any other ammonia ingredient labeled with claims or directions for use 
as a reflex stimulant
    (31) Bed-wetting deterrents.
Belladonna
Any other ingredient labeled with claims or directions for use as a 
bed-wetting deterrent
    (32) Blemish remedies (excluding topical acne active ingredients in 
paragraph (a)(1) of this section and Sec.  333.310 of this chapter).
Allantoin
Aloe vera gel
Calamine
Ethyl alcohol
Eugenol
Menthol
Oil of eucalyptus
Oil of peppermint
Propylene glycol
Sodium alkylarylpolyether sulfonate
Titanium dioxide
Triclocarban
Triclosan
Any other ingredient labeled with claims or directions for use as a 
blemish remedy
    (33) Bunion remedies. Any ingredient(s) labeled with claims or 
directions for use to treat and/or prevent bunions.
    (34) Drawing salves (excluding products labeled for the treatment 
of boils in Sec.  310.531 of this chapter)--includes products labeled 
for the drawing or removing of splinters, slivers, or similar items.
Ergot fluid extract
Juniper tar (oil of cade)
Magnesium sulfate
Pine tar
Rosin
Rosin cerate
Sulfur
    (35) Foot balms, baths, and other topical dosage forms for any 
``foot'' claims (including relieving foot muscle strains and soreness 
from working out), excluding topical antifungal active ingredients in 
paragraph (a)(22) of this section and Sec.  333.210 of this chapter and 
excluding external analgesic active ingredients in paragraphs 
(a)(10)(i) and (a)(10)(ii) of this section and Sec. Sec.  348.10 and 
348.12 of the external analgesic drug products tentative final 
monograph published on February 8, 1983 (48 FR 5852).
Amyl salicylate
Benzalkonium chloride
Cajeput oil
Di-isobutyl phenoxy ethoxy ethyldimethyl benzyl ammonium chloride
Essential oils
Eucalyptus oil
Formaldehyde solution
Glyceryl monostearate
8-Hydroxyquinoline
Iodized botanical oil
Iron sulfate
Isopropyl alcohol
Lanolin
Lithium chloride
Magnesium sulfate
O-benzyl-p-chlorophenol
Oil of thyme
Peppermint oil
Pine needle oil
Potassium iodide
Propylene glycol
Sodium bicarbonate
Sodium chloride
Sodium hypochloride
Sodium lauryl sulfate
Sodium phosphate, tribasic
Sodium sesquicarbonate
Sodium sulfate
Talc
Tragacanth mucilage
Water soluble chlorophyllins
Witch hazel
Zinc oxide
Any other ingredient labeled with claims or directions for use as a 
foot balm, bath, or other topical dosage form for any ``foot'' claims 
(including relieving foot muscle strains and soreness from working out)
    (36) Impotency cures.
Yohimbine
Yohimbine hydrochloride
Any other ingredient labeled with claims or directions for use as an 
impotency cure
    (37) Medicated bath preparations.
Acetylated lanolin
Alkyl aryl polyether alcohol
Colloidal sulfur
Cottonseed oil
Di-isopropyl sebacate
Drometrizole
Iron sulfate
Isopropyl myristate
Isopropyl palmitate
Isostearic acid
Lanolin alcohols extract
Lanolin oil
Liquid petrolatum
Lithium chloride
Magnesium sulfate
Mineral oil
Natural and essential oils
Nonoxynol-5
Octoxynol-3
Oxybenzone
PEG-4 dilaurate
PEG-8 dioleate
PEG-40 sorbitan peroleate
PEG-200 dilaurate
Peruvian balsam
PPG-15
Pine needle oil
Potassium iodide
Stearyl ether oleth-2
Sodium bicarbonate
Sodium carbonate
Sodium chloride
Sodium hyposulfate
Sodium lauryl sulfate
Sodium sesquicarbonate
Sodium sulfate
Tar distillate
Vitamin E
Water soluble chlorophyllins
Any other ingredient labeled with claims or directions for use as a 
medicated bath preparation
    (38) Nonantimicrobial skin wound cleansers (previously listed as 
``detergents'' in call-for-data notices).
Tincture of Green Soap
Phenolate sodium
Poloxamer 188
Any other ingredient labeled with claims or directions for use as a 
nonantimicrobial skin wound cleanser
    (39) Prickly heat products.
Aluminum hydroxide gel
Zinc carbonate
Zinc oxide
Any other ingredient labeled with claims or directions for use for 
prickly heat
    (40) Urethral topical products for males. Any product labeled with 
claims or directions for use to treat and/or prevent male urethral 
problems.
    (41) Urinary acidifiers.
Ammonium chloride
Ascorbic acid
Any other ingredient labeled with claims or directions for use as an 
urinary acidifier
    (42) Urinary alkalinizers.
Sodium bicarbonate
Any other ingredient labeled with claims or directions for use as an 
urinary alkalinizer

[[Page 34902]]

    (43) Wet dressings (excluding astringent active ingredients in 
paragraph (a)(18)(ii) of this section and skin protectant and 
astringent active ingredients in Sec. Sec.  347.10 and 347.12 of this 
chapter).
Aloe vera
Calcium polysulfide
Calcium thiosulfate
Oxyquinoline sulfate
Sodium propionate
Any other ingredient labeled with claims or directions for use as a wet 
dressing
    (44) Wound wash saline.
Sodium chloride solution
Sterile sodium chloride solution
Any other ingredient labeled with claims or directions for use as wound 
wash saline
    (45) Urea. Any product containing urea for any labeled claims.
* * * * *
    (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)(52) of this section.
* * * * *
    (2) February 10, 1992, for products subject to paragraph (a)(20)(i) 
of this section.
* * * * *
    (52) [Date 180 days after date of publication of a final rule in 
the Federal Register], for products subject to paragraphs 
(a)(10)(viii), (a)(18)(vii), (a)(18)(viii), (a)(20)(iii), (a)(27)(iii), 
and (a)(30) through (a)(45) of this section.

    Dated: June 9, 2008.
Jeffrey Shuren,
Associate Commissioner for Policy and Planning.
[FR Doc. E8-13826 Filed 6-18-08; 8:45 am]
BILLING CODE 4160-01-S