80 FR 38212 - Unapproved and Misbranded Otic Prescription Drug Products; Enforcement Action Dates

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Federal Register Volume 80, Issue 127 (July 2, 2015)

The Food and Drug Administration (FDA or Agency) is announcing its intention to take enforcement action against unapproved and misbranded otic drug products labeled for prescription use and containing benzocaine; benzocaine and antipyrine; benzocaine, antipyrine, and zinc acetate; benzocaine, chloroxylenol, and hydrocortisone; chloroxylenol and pramoxine; or chloroxylenol, pramoxine, and hydrocortisone; and against persons who manufacture or cause the manufacture or distribution of such products in interstate commerce. These unapproved and misbranded prescription drug products are marketed without evidence of safety and effectiveness; may present safety concerns; and pose a direct challenge to the new drug approval system and, in some cases, the over-the-counter (OTC) drug monograph system.

[Federal Register Volume 80, Number 127 (Thursday, July 2, 2015)]
[Notices]
[Pages 38212-38216]
From the Federal Register Online  [www.thefederalregister.org]
[FR Doc No: 2015-16360]


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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2015-N-2008]


Unapproved and Misbranded Otic Prescription Drug Products; 
Enforcement Action Dates

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing 
its intention to take enforcement action against unapproved and 
misbranded otic drug products labeled for prescription use and 
containing benzocaine; benzocaine and antipyrine; benzocaine, 
antipyrine, and zinc acetate; benzocaine, chloroxylenol, and 
hydrocortisone; chloroxylenol and pramoxine; or chloroxylenol, 
pramoxine, and hydrocortisone; and against persons who manufacture or 
cause the manufacture or distribution of such products in interstate 
commerce. These unapproved and misbranded prescription drug products 
are marketed without evidence of safety and effectiveness; may present 
safety concerns; and pose a direct challenge to the new drug approval 
system and, in some cases, the over-the-counter (OTC) drug monograph 
system.

DATES: This notice is effective July 2, 2015. For information about 
enforcement dates, see SUPPLEMENTARY INFORMATION, section IV.

ADDRESSES: For all communications in response to this notice, identify 
with Docket No. FDA-2015-N-2008 and direct to the appropriate office 
listed in this ADDRESSES section as follows:
    Applications under section 505(b) of the Federal Food, Drug, and 
Cosmetic Act (the FD&C Act) (21 U.S.C. 355(b)): Division of Anesthesia, 
Analgesia, and Addiction Products (for drug products with analgesic and 
anti-inflammatory indications), or Division of Anti-Infective Drug 
Products (for drug products with anti-infective indications), Office of 
New Drugs, Center for Drug Evaluation and Research, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 22, Silver Spring, MD 
20993-0002.
    Applications under section 505(j) of the FD&C Act: Office of 
Generic Drugs, Center for Drug Evaluation and Research, Food and Drug 
Administration, 10903 New Hampshire Ave., Bldg. 75, Silver Spring, MD 
20993-0002.
    All other communications about this action should be directed to: 
Kathleen Joyce, Division of Prescription Drugs, Office of Unapproved 
Drugs and Labeling Compliance, Center for Drug Evaluation and Research, 
Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 51, Rm. 
5236, Silver Spring, MD 20993-0002; 301-796-3329 or email: 
[email protected].

FOR FURTHER INFORMATION CONTACT: Kathleen Joyce, Division of 
Prescription Drugs, Office of Unapproved Drugs and Labeling Compliance, 
Center for Drug Evaluation and Research, Food and Drug Administration, 
10903 New Hampshire Ave., Bldg. 51, rm. 5236, Silver Spring, MD 20993-
0002; 301-796-3329 or email: [email protected].

SUPPLEMENTARY INFORMATION: 

I. Background

    FDA is announcing its intention to take enforcement action against 
certain unapproved and misbranded otic drug products labeled for 
prescription use. These marketed unapproved and misbranded otic drug 
products are labeled for, among other things, the temporary relief of 
pain associated with ear infections or inflammation, including acute 
otitis media (middle ear infection), otitis media with effusion (fluid 
in the ear, but without infection), and acute otitis externa (infection 
in the outer ear or ``swimmer's ear''). Other indications for these 
unapproved drug products include anti-infective and anti-inflammatory 
claims, as well as claims for the removal of cerumen (earwax).
    This notice covers the following marketed unapproved prescription 
otic drug products: (1) Single-ingredient otic drug products containing 
benzocaine; (2) fixed-dose combination otic drug products containing 
benzocaine and antipyrine; (3) fixed-dose combination otic drug 
products containing benzocaine, antipyrine, and zinc

[[Page 38213]]

acetate; (4) fixed-dose combination otic drug products containing 
benzocaine, chloroxylenol, and hydrocortisone; (5) fixed-dose 
combination otic drug products containing chloroxylenol and pramoxine; 
and (6) fixed-dose combination otic drug products containing 
chloroxylenol, pramoxine, and hydrocortisone. These drug products are 
marketed without evidence of safety and effectiveness, present safety 
concerns, and pose a direct challenge to the new drug approval system 
and, in some cases, the OTC drug monograph system.
    For example, FDA is aware of many unapproved and misbranded 
prescription fixed-dose combination drug products containing benzocaine 
and antipyrine that are labeled for use for the prompt relief of pain 
and reduction of inflammation in the congestive and serous stages of 
acute otitis media and for adjuvant therapy during systemic antibiotic 
administration for resolution of acute otitis media. These products 
have also been labeled to facilitate the removal of excessive or 
impacted cerumen. FDA has received at least five adverse event reports 
of allergic reactions to these drug products, including angioedema of 
the ear, eye, face, neck, and/or mouth. We are also aware of at least 
one case of methemoglobinemia associated with the administration of an 
otic product containing benzocaine in an infant, which resulted in 
death (Ref. 1). Methemoglobinemia is a serious blood disorder in which 
an abnormal amount of methemoglobin (a form of hemoglobin) is produced 
(Ref. 2). Other less serious adverse reactions associated with these 
products include contact hypersensitivity, pruritus, stinging, burning, 
and irritation.
    FDA is also aware of at least one unapproved and misbranded 
prescription single-ingredient otic drug product containing benzocaine 
that is labeled for use as a topical anesthetic in the external 
auditory canal to relieve ear pain, and for the treatment of acute 
otitis media, acute swimmer's ear, and other forms of otitis externa. 
Potential adverse reactions include methemoglobinemia, local burning, 
stinging, tenderness or edema, and hypersensitivity reactions.
    FDA is aware of an unapproved and misbranded prescription fixed-
dose combination drug product containing benzocaine, antipyrine, and 
zinc acetate that is labeled with an indication to relieve pain, 
congestion, and swelling caused by middle ear inflammation (acute 
otitis media), and to help remove earwax. Potential adverse reactions 
include methemoglobinemia and contact hypersensitivity, pruritus, 
stinging, burning, and irritation.
    FDA is also aware of an unapproved and misbranded prescription 
fixed-dose combination drug product containing benzocaine, 
chloroxylenol, and hydrocortisone that is labeled for the treatment of 
superficial infections of the external auditory canal complicated by 
inflammation caused by organisms susceptible to the action of the 
antimicrobial, and to control itching in the auditory canal. Unapproved 
and misbranded prescription fixed-dose combination products containing 
chloroxylenol and pramoxine are also on the market and labeled for 
treating superficial external ear infections and the associated 
itching. Potential adverse reactions for these fixed-dose combination 
products include contact hypersensitivity, pruritus, stinging, burning, 
and irritation.
    In addition, FDA is aware of various unapproved and misbranded 
prescription fixed-dose combination drug products containing 
chloroxylenol, pramoxine, and hydrocortisone that are labeled with 
analgesic, anti-inflammatory and anti-infective indications. The 
chloroxylenol, pramoxine, and hydrocortisone drug products are labeled 
for the treatment of superficial infections of the outer ear, 
inflammation, and itching. Potential adverse reactions include 
pruritus, stinging, burning, and irritation.
    In addition to the safety concerns listed previously, these drugs 
present direct challenges to the FDA drug approval system and, in some 
cases, the OTC monograph system. These drugs directly challenge the new 
drug approval system by competing with approved otic drug products 
appropriately labeled for anti-inflammatory uses and the treatment of 
otitis externa. The unapproved and misbranded drug products covered by 
this notice also pose a direct challenge to the OTC drug monograph 
system because they compete with legally marketed OTC products labeled 
for cerumen removal and ear drying aid indications under an OTC drug 
monograph (part 344 (21 CFR part 344)).
    For the reasons described in sections II and III, among others, 
FDA's drug approval process is critical to protecting the public 
health. Drugs are evaluated by FDA before being marketed to ensure that 
they are safe and effective for their intended uses and are only 
approved for marketing after a careful risk-benefit analysis. The drug 
approval process is designed to avoid the risks associated with 
potentially unsafe, ineffective, and fraudulent drugs.\1\
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    \1\ See ``Marketed Unapproved Drugs--Compliance Policy Guide'' 
(Marketed Unapproved Drugs CPG) at 5, available at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070290.pdf.
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II. Safety and Effectiveness Concerns With Unapproved New Drugs

    The new drug approval process affords FDA the opportunity to review 
and evaluate a drug before it is marketed to ensure safety, efficacy, 
and quality. This includes reviewing the processes used to manufacture 
the active pharmaceutical ingredient(s) and the finished drug product, 
and the labeling of the drug product. Because marketed unapproved new 
drug products have not undergone FDA's rigorous premarket review and 
approval process, they may present safety risks. This is particularly 
true because FDA has not reviewed and approved the label for unapproved 
new drugs, so some unapproved drug labeling omits or modifies safety 
warnings or other information that is important to ensure safe use, 
such as drug interactions or potential adverse experiences.
    With respect to the otic drug products subject to this notice, FDA 
is particularly concerned about pediatric labeling because these drug 
products are often prescribed for young children, a population most 
susceptible to ear infections (Ref 3). FDA has not assessed the 
scientific support, if any, for the use of these drug products in 
pediatric populations. In other words, none of these products have been 
shown to be safe for use in any population, including children or 
infants. In fact, as described in section I, FDA has received at least 
five adverse events reports associated with unapproved prescription 
otic products. There is also the potential for rare, but serious 
adverse events to occur, including methemoglobinemia, a dangerous blood 
disorder. Not all of these adverse events are included in the labeling 
for these unapproved drug products.
    FDA also has concerns regarding the manufacturing processes for 
unapproved new drugs. When new drugs are marketed without FDA approval, 
FDA does not have an opportunity, prior to product marketing, to 
determine whether the manufacturing processes for the drugs are 
adequate to ensure that they are of suitable quality.
    For example, the Agency scrutinizes the chemistry, manufacturing, 
and controls involved in producing the active pharmaceutical ingredient 
(API or drug substance) and finished dosage

[[Page 38214]]

form or drug product.\2\ With respect to the drug substance, FDA's 
examination includes the following: (1) Physical and chemical 
characteristics and stability of the drug substance; (2) the process 
controls used in manufacturing and packaging; and (3) specifications 
necessary to ensure the identity, strength, quality, and purity of the 
drug substance. For the drug product, FDA's review includes the 
following: (1) The specifications for the components used in the 
manufacture of the drug product; (2) manufacturing and packaging 
procedures and process controls; and (3) the specifications necessary 
to ensure the identity, strength, quality, and purity of the drug 
product. Unapproved drug products do not undergo this review process, 
and therefore the quality of the finished drug product is uncertain.
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    \2\ See, generally, Sec.  314.50(d) (21 CFR 314.50(d)). See also 
section 505(d)(3) of the FD&C Act requiring FDA to determine whether 
the methods used in, and the facilities and controls used for, the 
manufacture, processing, and packing of such a drug are adequate to 
preserve its identity, strength, quality, and purity.
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    Because unapproved new drugs have not been subject to FDA's 
premarket review and approval process, FDA cannot be sure that 
unapproved drugs are effective. Section 505(d) of the FD&C Act requires 
``substantial evidence'' of safety and effectiveness. ``Substantial 
evidence'' is evidence consisting of adequate and well-controlled 
investigations, including clinical investigations, by experts qualified 
by scientific training and experience to evaluate the effectiveness of 
the drug involved, on the basis of which it could fairly and 
responsibly be concluded by such experts that the drug will have the 
effect it purports or is represented to have under the conditions of 
use prescribed, recommended, or suggested in the labeling or proposed 
labeling thereof (section 505(d)(7) of the FD&C Act).
    Among other characteristics, an adequate and well-controlled study 
must use a design that permits a valid comparison with a control to 
provide a quantitative assessment of the pertinent drug effects (Sec.  
314.126(b)(2)) (21 CFR 314.126(b)(2)). The method of selection of 
subjects must assure that those subjects have the disease or condition 
being studied (Sec.  314.126(b)(3)) .
    A review of the current literature suggests that the efficacy of 
unapproved prescription otic drugs in managing pain associated with ear 
infections is uncertain (Ref. 4). Use of unapproved products of 
uncertain efficacy may delay treatment with products that have been 
proven to be effective, leading to undue prolonged pain and discomfort.
    In conclusion, these drug products are marketed without evidence of 
safety and effectiveness; present actual and potential safety concerns; 
and pose a direct challenge to the new drug approval system. In some 
cases, they may directly challenge the OTC drug monograph system.

III. Legal Status of Products Identified in This Notice

    FDA has reviewed the publicly available scientific literature for 
the following unapproved prescription drug products: (1) Single-
ingredient otic drug products containing benzocaine; (2) fixed-dose 
combination otic drug products containing benzocaine and antipyrine; 
(3) fixed-dose combination otic drug products containing benzocaine, 
antipyrine, and zinc acetate; (4) fixed-dose combination otic drug 
products containing benzocaine, chloroxylenol, and hydrocortisone; (5) 
fixed-dose combination otic drug products containing chloroxylenol and 
pramoxine; and (6) fixed-dose combination otic drug products containing 
chloroxylenol, pramoxine, and hydrocortisone. In no case did FDA find 
literature sufficient to support a determination that any of these 
prescription products are generally recognized as safe and effective. 
Therefore, these prescription drug products are ``new drugs'' within 
the meaning of section 201(p) of the FD&C Act (21 U.S.C. 321(p)), and 
they require approved new drug applications (NDAs) or abbreviated new 
drug applications (ANDAs) to be legally marketed.
    The unapproved drug products covered by this notice are labeled for 
prescription use. Prescription drugs are defined under section 
503(b)(1)(A) of the FD&C Act (21 U.S.C. 353(b)(1)(A)) as drugs that, 
because of toxicity or other potentially harmful effect, are not safe 
to use except under the supervision of a practitioner licensed by law 
to administer such drugs. If an unapproved drug product covered by this 
notice meets the definition of ``prescription drug'' in section 
503(b)(1)(A) of the FD&C Act, adequate directions cannot be written for 
it so that a layman can use the product safely for its intended uses 
(21 CFR 201.5). Consequently, it is misbranded under section 502(f)(1) 
of the FD&C Act (21 U.S.C. 352(f)(1)) in that it fails to bear adequate 
directions for use. A prescription drug is exempt from the requirement 
in section 502(f)(1) of the FD&C Act that it bear adequate directions 
for use if, among other things, it bears the FDA-approved labeling (21 
CFR 201.100(c)(2) and 201.115). Because the prescription drug products 
subject to this notice do not have approved applications with approved 
labeling, they fail to qualify for the exemptions to the requirement 
that they bear ``adequate directions for use,'' and are misbranded 
under section 502(f)(1) of the FD&C Act.
    If a drug covered by this notice is labeled as a prescription drug 
but does not meet the definition of ``prescription drug'' under section 
503(b)(1)(A) of the FD&C Act, the drug is misbranded under section 
503(b)(4)(B).
    The final OTC drug monograph in part 344, ``Topical Otic Drug 
Products for Over-the Counter Human Use'' (Topical Otic Drug 
monograph), permits the use of carbamide peroxide 6.5 percent 
formulated in an anhydrous glycerin vehicle as an active ingredient for 
earwax removal, in the amounts and under the conditions specified in 
the final Topical Otic Drug monograph (see Sec.  344.10). The final OTC 
drug monograph also permits the use of isopropyl alcohol 95 percent in 
an anhydrous glycerin 5 percent base as an ear drying aid in the 
amounts and under the conditions specified in the final Topical Otic 
Drug monograph (see Sec.  344.12).
    The final Topical Otic Drug monograph is the only monograph that 
specifies the requirements for marketing an OTC drug for cerumen 
removal. Unless a product included in this notice was reformulated and 
labeled to meet all the requirements of the final Topical Otic Drug 
monograph, the product would require an approved NDA or ANDA to be 
legally marketed.\3\
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    \3\ In addition to any other applicable requirements, firms that 
manufacture OTC drugs must comply with the labeling requirements in 
21 CFR 201.66.
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IV. Notice of Intent To Take Enforcement Action

    Although not required to do so by the Administrative Procedure Act, 
by the FD&C Act (or any rules issued under its authority), or for any 
other legal reason, FDA is providing this notice to persons \4\ who are 
marketing the following unapproved and misbranded drugs labeled for 
prescription use: (1) Single-ingredient otic drug products containing 
benzocaine; (2) fixed-dose combination otic drug products containing 
benzocaine and antipyrine; (3) fixed-dose combination otic drug 
products containing benzocaine, antipyrine, and zinc acetate; (4) 
fixed-dose combination otic drug products containing benzocaine, 
chloroxylenol, and

[[Page 38215]]

hydrocortisone; (5) fixed-dose combination otic drug products 
containing chloroxylenol and pramoxine; and (6) fixed-dose combination 
otic drug products containing chloroxylenol, pramoxine, and 
hydrocortisone. The Agency intends to take enforcement action against 
such products and those who manufacture them or cause them to be 
manufactured or shipped in interstate commerce.
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    \4\ The term ``person'' includes individuals, partnerships, 
corporations, and associations (21 U.S.C. 321(e)).
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    Manufacturing or shipping the drug products covered by this notice 
can result in enforcement action, including seizure, injunction, or 
other judicial or administrative proceeding.\5\ Consistent with 
policies described in the Agency's Marketed Unapproved Drugs CPG 
(available at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070290.pdf), the 
Agency does not expect to issue a warning letter or any other further 
warning to firms marketing drug products covered by this notice before 
taking enforcement action. The Agency also reminds firms that, as 
stated in the Marketed Unapproved Drugs CPG, any unapproved drug 
marketed without a required approved application is subject to Agency 
enforcement action at any time. The issuance of this notice does not in 
any way obligate the Agency to issue similar notices (or any notice) in 
the future regarding marketed unapproved drugs (see Marketed Unapproved 
Drugs CPG at 5).
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    \5\ In fact, U.S. Marshals seized $16.5 million of Auralgan Otic 
Solution (which contains antipyrine and benzocaine) after Deston 
continued to market the unapproved new drug following an FDA warning 
letter. See http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm243638.htm.
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    As described in the Marketed Unapproved Drugs CPG, the Agency may, 
at its discretion, identify a period of time (i.e., a grace period) 
during which the Agency does not intend to initiate an enforcement 
action against a currently marketed unapproved drug solely on the 
grounds that the drug lacks an approved application under section 505 
of the FD&C Act. In deciding whether to allow such a grace period, the 
Agency considers several factors, which are described in the Marketed 
Unapproved Drugs CPG. With respect to drug products covered by this 
notice, the Agency intends to exercise its enforcement discretion for 
only a limited period of time, because there are readily available 
legally marketed alternatives. Therefore, the Agency intends to 
implement this notice as follows.
    For the effective date of this notice, see the DATES section of 
this document. Any drug product covered by this notice that a company 
(including a manufacturer or distributor) began marketing after 
September 19, 2011, is subject to immediate enforcement action. For 
products covered by this notice that a company (including a 
manufacturer or distributor) began marketing on or before September 19, 
2011, FDA intends to take enforcement action against any such product 
that is not listed with the Agency in full compliance with section 510 
of the FD&C Act (21 U.S.C. 360) before July 1, 2015, and is 
manufactured, shipped, or otherwise introduced or delivered for 
introduction into interstate commerce by any person on or after July 1, 
2015. FDA also intends to take enforcement action against any drug 
product covered by this notice that is listed with FDA in full 
compliance with section 510 of the FD&C Act but is not being 
commercially used or sold \6\ in the United States before July 1, 2015, 
and that is manufactured, shipped, or otherwise introduced or delivered 
for introduction into interstate commerce by any person on or after 
July 2, 2015.
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    \6\ For the purpose of this notice, the phrase ``commercially 
used or sold'' means that the product has been used in a business or 
activity involving retail or wholesale marketing and/or sale.
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    However, for drug products covered by this notice that a company 
(including a manufacturer or distributor): (1) Began marketing in the 
United States on or before September 19, 2011; (2) are listed with FDA 
in full compliance with section 510 of the FD&C Act before July 1, 2015 
(``currently marketed and listed''); and (3) are manufactured, shipped, 
or otherwise introduced or delivered for introduction into interstate 
commerce by any person on or after July 2, 2015, the Agency intends to 
exercise its enforcement discretion as follows: FDA intends to initiate 
enforcement action regarding any such currently marketed and listed 
product that is manufactured on or after August 17, 2015, or that is 
shipped on or after September 30, 2015. Furthermore, FDA intends to 
take enforcement action against any person who manufactures or ships 
such products after these dates. The purpose of these enforcement 
timeframes is to allow manufacturers and distributors to deplete their 
current inventory and ensure a smooth transition for consumers. Any 
person who has submitted or submits an application for a drug product 
covered by this notice but has not received approval must comply with 
this notice.
    The Agency, however, does not intend to exercise its enforcement 
discretion as outlined previously if either of the following applies: 
(1) A manufacturer or distributor of drug products covered by this 
notice is violating other provisions of the FD&C Act, including, but 
not limited to, violations related to FDA's current good manufacturing 
practices, adverse drug event reporting, labeling, or misbranding 
requirements other than those identified in this notice or (2) it 
appears that a firm, in response to this notice, increases its 
manufacture or interstate shipment of drug products covered by this 
notice above its usual volume during these periods.\7\
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    \7\ If FDA decides to take enforcement action against a product 
covered by this notice, the Agency may simultaneously take action 
relating to defendant's other violations of the FD&C Act. See, e.g., 
United States v. Sage Pharmaceuticals, 210 F. 3d 475, 479-480 (5th 
Cir. 2000) (permitting the Agency to combine all violations of the 
FD&C Act in one proceeding, rather than taking action against 
multiple violations of the FD&C Act in ``piecemeal fashion'').
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    Nothing in this notice, including FDA's intent to exercise its 
enforcement discretion, alters any person's liability or obligations in 
any other enforcement action, or precludes the Agency from initiating 
or proceeding with enforcement action in connection with any other 
alleged violation of the FD&C Act, whether or not related to a drug 
product covered by this notice. Similarly, a person who is or becomes 
enjoined from marketing unapproved or misbranded drugs may not resume 
marketing of such products based on FDA's exercise of enforcement 
discretion as described in this notice.
    Drug manufacturers and distributors should be aware that the Agency 
is exercising its enforcement discretion as described previously only 
in regard to drug products covered by this notice that are marketed 
under a National Drug Code (NDC) number listed with the Agency in full 
compliance with section 510 of the FD&C Act before July 1, 2015. As 
previously stated, drug products covered by this notice that are 
currently marketed but not listed with the Agency on the date of this 
notice must, as of the effective date of this notice, have approved 
applications before their shipment in interstate commerce. Moreover, 
any person or firm that has submitted or submits an application but has 
yet to receive approval for such products is still responsible for full 
compliance with this notice.

V. Discontinued Products

    Some firms may have previously discontinued manufacturing or 
distributing products covered by this notice without discontinuing the 
listing as required under section 510(j) of the FD&C Act. Other firms 
may discontinue

[[Page 38216]]

manufacturing or distributing listed products in response to this 
notice. All firms are required to electronically update the listing of 
their products under section 510(j) of the FD&C Act to reflect 
discontinuation of unapproved products covered by this notice (21 CFR 
207.21(b)). Questions on electronic drug listing updates should be sent 
to [email protected]. In addition to the required update, firms can 
also notify the Agency of product discontinuation by sending a letter, 
signed by the firm's chief executive officer and fully identifying the 
discontinued product(s), including the product NDC number(s), and 
stating that the manufacturing and/or distribution of the product(s) 
have been discontinued. The letter should be sent electronically to 
Kathleen Joyce (see ADDRESSES). FDA plans to rely on its existing 
records, including its drug listing records, the results of any 
subsequent inspections, or other available information when considering 
enforcement action.

VI. Reformulated Products

    FDA cautions firms against reformulating their products into 
unapproved new drugs without benzocaine; benzocaine and antipyrine; 
benzocaine, antipyrine, and zinc acetate; benzocaine, chloroxylenol, 
and hydrocortisone; chloroxylenol and pramoxine; or chloroxylenol, 
pramoxine, and hydrocortisone and marketing them under the same name or 
substantially the same name (including a new name that contains the old 
name) in anticipation of an enforcement action based on this notice. As 
stated in the Marketed Unapproved Drugs CPG, FDA intends to give higher 
priority to enforcement actions involving unapproved drugs that are 
reformulated to evade an anticipated FDA enforcement action but have 
not been brought into compliance with the law. In addition, 
reformulated products marketed under a name previously identified with 
a different active ingredient have the potential to confuse healthcare 
practitioners and harm patients.

VIII. References

    The following references have been placed on display in the 
Division of Dockets Management (see ADDRESSES) and may be seen by 
interested persons between 9 a.m. and 4 p.m., Monday through Friday, 
and are available electronically at http://www.regulations.gov.

1. Logan, B. K. and A.M. Gordon, ``Case Report: Death of an Infant 
Involving Benzocaine,'' Journal of Forensic Sciences, vol. 50, pp. 
1486-1488, 2005.
2. Cortazzo, J. A. and A. D. Lichtman, ``Methemoglobinemia: A Review 
and Recommendations for Management.'' Journal of Cardiothoracic and 
Vascular Anesthesia, vol. 28(4), pp. 1055-1059. 2014.
3. Lieberthal, A. S., A. E. Carroll, T. Chonmaitree, et al., ``The 
Diagnosis and Management of Acute Otitis Media,'' Pediatrics, vol. 
131, pp. e964-e999, 2013.
4. Wood, D. N., N. Naas, and C. W. Gregory, ``Clinical Trials 
Assessing Ototopical Agents in the Treatment of Pain Associated with 
Acute Otitis Media in Children,'' International Journal of 
Otorhinolaryngology, vol. 76, pp. 1229-1335, 2012.

    Dated: June 26, 2015.
Leslie Kux,
Associate Commissioner for Policy.
[FR Doc. 2015-16360 Filed 7-1-15; 8:45 am]
 BILLING CODE 4164-01-P