#281 
 
Infectious Otitis Externa Drugs for 
Topical Use in Dogs 
 
 
Guidance for Industry 
 
Draft Guidance 
 
This guidance document is being distributed for comment purposes only. 
 
Submit comments on this draft guidance by the dated provided in the Federal Register notice 
announcing the availability of the draft guidance.  Submit electronic comments to 
https://www.regulations.gov.  Submit written comments to the Dockets Management Staff 
(HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD  
20852.  All comments should be identified with docket number FDA-2023-D-0606. 
 
For further information regarding this document, contact Dr. Lea Cranford, Center for Veterinary 
Medicine (HFV-118), Food and Drug Administration, 7500 Standish Place, Rockville MD 
20855, 240-402-0615, email: lea.cranford@fda.hhs.gov. 
 
Additional copies of this draft guidance document may be requested from the Policy and 
Regulations Staff (HFV-6), Center for Veterinary Medicine, Food and Drug Administration, 
7500 Standish Place, Rockville MD 20855, and may be viewed on the Internet at 
https://www.fda.gov/animal-veterinary, https://www.fda.gov/regulatory-information/search-fda-
guidance-documents, or http://www.regulations.gov. 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Veterinary Medicine (CVM) 
March 2023 Contains Nonbinding Recommendations 
Draft  Not for Implementation 
 
Table of Contents 
 
I.  Introduction ....................................................................................................................... 1 
II.  Effectiveness ...................................................................................................................... 1 
A.  Dosage Characterization ............................................................................................ 1 
1.  Pilot Field Studies ................................................................................................. 2 
2.  Published Scientific Literature ............................................................................ 2 
3.  Ear Wash/Swab Depletion Studies ...................................................................... 2 
B.  Substantial Evidence of Effectiveness ....................................................................... 4 
1.  Field Study ............................................................................................................. 4 
2.  General Considerations for Combination Products .......................................... 7 
III.  Target Animal Safety ........................................................................................................ 9 
A.  Dosing ........................................................................................................................... 9 
B.  Duration and Frequency of Administration ............................................................. 9 
C.  Control ....................................................................................................................... 10 
D.  Housing ...................................................................................................................... 10 
E.  Evaluation of Toxicity............................................................................................... 10 
IV.  Human User Safety ......................................................................................................... 10 
V.  Labeling ........................................................................................................................... 11 
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Infectious Otitis Externa Drugs for Topical Use in Dogs 
 
Draft Guidance for Industry 
 
This draft guidance, when finalized, will represent the current thinking of the Food and Drug 
Administration (FDA or Agency) on this topic.  It does not establish any rights for any person 
and is not binding on FDA or the public.  You can use an alternative approach if it satisfies the 
requirements of the applicable statutes and regulations.  To discuss an alternative approach, 
contact the FDA staff responsible for this guidance as listed on the title page. 
 
I.  Introduction  
This guidance provides recommendations to help sponsors complete the effectiveness, target 
animal safety, and labeling technical sections of a new animal drug application (NADA) for 
infectious otitis externa drugs for topical use in dogs.  
 
You may follow the guidance document or may choose alternate pathways for approval.  We 
recommend that you discuss your proposed study plans with CVM, especially if you choose 
to use an alternative pathway for approval.  We encourage you to schedule a pre-submission 
conference with CVM as you begin to make your investigational plans to ensure that you are 
completely informed about the requirements contained in the Federal Food, Drug, and 
Cosmetic Act and regulations. 
 
In general, FDAs guidance documents do not establish legally enforceable responsibilities.  
Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
as recommendations, unless specific regulatory or statutory requirements are cited.  The use of 
the word should in Agency guidances means that something is suggested or recommended, but 
not required. 
 
II.  Effectiveness 
The effectiveness development plan for topical otic products should be designed to show that 
the drug product is effective for its intended use (i.e., to treat otitis externa) and, if it is a 
combination product, each active ingredient makes a contribution to the effectiveness of the 
combination.  Effectiveness data in support of an approval for topically administered otic 
products include information to support dosage characterization and data to support substantial 
evidence of effectiveness.  The recommendations regarding effectiveness data, including 
additional considerations for combination otic products, are discussed below. 
 
A.  Dosage Characterization 
You should provide the scientific rationale supporting the dose, dosing interval, 
duration of treatment, and predicted duration of action for each component of a 
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combination drug and for the final formulation.  You should also provide a scientific 
rationale for the volume per ear dose and whether animal size will be a factor in the 
delivery of the proposed volume into the ear canal.  Dosing should be consistent with 
the mechanisms of action and local pharmacokinetics of the active ingredient(s).  
Dosage characterization is submitted under the Effectiveness technical section and a 
summary of the information provided will be included in the Freedom of Information 
(FOI) Summary. 
 
There are multiple ways to support dosage characterization including, but not limited 
to: 
 
1.  Pilot Field Studies 
Pilot field studies may help determine the appropriate dose, dosing interval, 
duration of treatment, and safety profile.  Pilot field studies may also be conducted 
to determine which pathogenic microorganisms are responsive to the drug(s). 
 
2.  Published Scientific Literature  
Published scientific literature, including individual or multiple sources, may be used 
to support a portion or all of the justification for the dosage and may significantly 
assist protocol development.  For example, literature may provide information 
integral for the selection of optimal study time points or specify study design 
parameters for protocols for novel drugs and drugs with modified-release 
characteristics or extended duration of action.  In general, sufficient scientific 
literature to reasonably support the basis for the dose characterization is acceptable; 
for example, a narrative review.  Full scoping or systematic literature reviews are not 
routinely expected.1   
 
3.  Ear Wash/Swab Depletion Studies 
CVM recommends that an ear wash/swab depletion study be conducted for all topical 
otic products to establish a final time of evaluation at which the ear can be evaluated 
for success or failure in the absence of effective drug concentrations.  This may be 
used to determine the evaluation time (final evaluation day) to support substantial 
evidence of effectiveness.  For topical otic formulations designed for a longer 
duration of activity, ear wash/swab depletion studies can be particularly helpful in 
estimating the duration of activity in the ear canal to justify the dosing interval, 
timing of evaluations, and the final evaluation day.  The optimal use of ear wash/swab 
depletion data is during dosage characterization and dosing interval development to 
help identify a day or days when the drug levels are below the minimal inhibitory 
concentrations (MICs; for antimicrobials) or completely depleted (non-
antimicrobials), so that the determination of success in the field study would be in the 
absence of drug.  Without PK or in vitro data, the identification of the final evaluation 
 
1 See CVM GFI #106, The Use of Published Literature in Support of New Animal Drug Approval 
(https://www.fda.gov/media/70056/download). 
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day may be based on clinical response from a pilot study.  The major limitation to 
choosing a final evaluation day based on clinical response in a pilot study is that the 
final evaluation could take place in the presence of therapeutic concentrations 
because the topical levels of drug are unknown.  Evaluating the clinical endpoint in 
the presence of active drug is not appropriate because the infection could be 
suppressed, rather than cured, in the presence of the drug.  Therefore, evaluation in 
the absence of drug better assesses the ability of the dosing regimen to treat the 
infection and decreases the potential for relapse.  
 
The timing of the final evaluation day is dependent on the PK and the dosing interval 
of the active ingredient.  For antimicrobials, the time of evaluation should be when 
the drug level is below the MIC90 for the pathogen of interest.  Typically, the 
pathogen in the proposed indication that has the highest MIC90 is chosen as the 
worst-case scenario.  The magnitude below the MIC90 that is chosen as a target, e.g., 
MIC90/2 or MIC90/4, is dependent on several factors, such as the drugs mechanism 
of action against the pathogen of interest, and should be supported by your data 
and/or published literature.  In the absence of a well-characterized pharmacokinetic 
and pharmacodynamic target, as is generally the case for antifungals and steroids, the 
final evaluation should be conducted when the drug(s) is depleted (below the limit of 
quantification or LOQ).  
 
Ear wash/swab depletion studies are conducted in healthy laboratory dogs or cats 
without otitis.  Evaluating the kinetics of topical otic drugs in normal, healthy ears 
may not fully represent the depletion of the drug(s) in affected ears because the 
inflammation and disrupted skin barrier due to otitis externa could increase: 1) the 
systemic absorption of drug and 2) the rate of degradation, so that the depletion of the 
active ingredients may be more rapid in affected ears.  Therefore, the ear wash/swab 
depletion study should only be used to help estimate the final evaluation day.  
 
The dosing interval of the topical otic product should be considered when designing 
the ear wash/swab depletion study.  For products that are to be administered once or 
twice daily, the sponsor should account for potential drug accumulation.  For these 
products, you could either conduct a single dose study and perform a simulation to 
model the drug exposure after repeated doses, or administer repeated doses and then 
collect ear wash/swab samples after the last dose.  
  
When designing an ear wash/swab depletion study, remember that each ear is NOT 
independent of each other and the animal should be considered the experimental unit, 
not the ear.  Because of the potential high variability in the drug concentrations, you 
should sample up to, or past, the proposed final evaluation day, so that extrapolation 
is not needed to estimate duration of activity.  Regression analyses used to model 
drug concentrations assume linear drug depletion, which may not always be the case.  
If you choose to use a regression analysis to extrapolate drug concentrations, you 
should use individual values (prediction intervals) rather than the mean values to 
maximize the inferential value from a small number of samples.  
 
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Ideally, you should conduct a pilot study to validate the study design and 
bioanalytical methods before performing the final study.  Although there is no 
requirement that the final study or bioanalytical methods be carried out in compliance 
with FDA's good laboratory practices (GLP) regulations, if such studies are not 
conducted under GLP, CVM recommends that you identify any deviations from GLP 
and address the impact of these deviations on the data.  In addition, CVM may 
request that you provide additional information, such as SOPs, to support the integrity 
of the data.  Because of the lack of accepted methods for bridging topical 
formulations, you should use the final formulation in the ear wash/swab study.  If a 
non-final formulation is used, you should identify any differences between the non-
final and final formulations and address the impact of these differences on safety and 
effectiveness.  
 
CVM recommends that you use a validated bioanalytical method to measure the free 
drug (active moiety) concentration of all the active ingredients.  If the drug has 
multiple components, then the method should be able to differentiate these 
components. 
 
B.  Substantial Evidence of Effectiveness 
1.  Field Study 
The purpose of the field study is to evaluate the safety and effectiveness of the drug in 
the target animal for the proposed indication(s) under the actual conditions of use.  
The field study should be multi-center (in geographically diverse regions within the 
USA), be randomized and double-blinded, be conducted in accordance with the 
principles of Good Clinical Practice (GCP), demonstrate safety and effectiveness, and 
use the final formulation. 
 
The following are considerations for the design and conduct of the field 
effectiveness study: 
 
a.  Endpoint 
Success criteria (i.e., clinical effectiveness) should be decided at the protocol 
stage.  The protocol should numerically define a success via the scoring of clinical 
criteria (erythema, exudate, swelling, and ulceration) as evaluated by a 
veterinarian.  The protocol should also include a clause that an animal cannot be 
classified as a success if an individual evaluation criterion received a higher score 
(worse score) on the final day as compared to the score at enrollment.  The 
addition of this clause prevents an animal from being classified as a success if the 
ear actually worsened in one or more evaluation criteria during the conduct of the 
study.  The minimum difference between enrollment and the definition of success 
should be large enough to reflect a clinical difference. 
 
The sponsor should propose and justify the number of days after the last treatment 
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for the final evaluation of effectiveness.  As discussed above, the final day of 
evaluation ideally should be determined by the ear wash/swab depletion study. 
 
b.  Treatment Groups 
Studies supporting substantial evidence of effectiveness should be well-
controlled, utilizing an appropriate control group.  Refer to 21 CFR 
514.117(b)(4) for more information about study design.  The ratio of dogs 
receiving the investigational drug versus the control article should be considered 
in the design phase of the protocol. 
 
The study should be masked appropriately to control for potential bias.  The 
potential observable drug effects and routes of administration of the 
investigational drug and the control group should also be taken into 
consideration. 
 
c.  Inclusion/Exclusion Criteria 
Field effectiveness protocols should specify inclusion and exclusion criteria.  For 
example, to be included in the study each dog at enrollment should have a 
minimum clinical score as defined by the protocol and a confirmed bacterial 
and/or yeast infection based on an ear swab culture and identification by a 
microbiological laboratory. 
 
Exclusion criteria should take into account concurrent disease, clinical course of 
otic disease (e.g., stenotic or calcified ears), use of concurrent medication, 
evidence of cranial nerve disease, and/or compliance of dog owners. 
 
d.  Patient Assessments 
Methods and timing of ear examination, sample collection and analysis for 
cytology2 and culture, bacterial/yeast identification, and ear cleaning procedures 
(and type of solution) should be standardized and clearly described in the 
protocol.  If the protocol includes instructions to clean the dogs ears prior to 
administering the product, this condition of use should be included on the final 
product labeling in the Dosing and Administration section.  Any ear cleaning 
solution used during the study should not have any antibacterial, antifungal, or 
anti-inflammatory component which would interfere with the effectiveness 
evaluation.  In cases of bilateral otitis externa where both ears meet inclusion 
criteria, to decrease bias the protocol should specify whether the right or left ear 
will be evaluable in all such cases. 
 
Clinical pathology (complete blood count, serum chemistry, and urinalysis) 
should be completed during the study to evaluate the effects of the product in the 
 
2 Ginel RJ, Lucena R, et al. A semiquantitative cytological evaluation of normal and pathological samples from the external ear 
canal of dogs and cats. Veterinary Dermatology. 13, 151-156 (2002). 
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target population.  Hearing tests should be conducted by the investigator in all 
enrolled dogs at the beginning and the end of the study.  If an aminoglycoside or 
other potentially ototoxic drug is used (as a test drug or an active control), the 
owner consent form should contain suitable language about possible deafness 
associated with products being used in the study. 
 
e.  Statistical Considerations 
The study should enroll a sufficient number of subjects to adequately power the 
primary statistical test, taking into account subject attrition, censoring, and other 
factors that can affect the efficiency of the tests.  The study should be powered 
to detect a clinically relevant effect size. 
 
f.  Microbiology 
At the initial evaluation (Day 1), pre-treatment cultures should be collected for 
isolate identification to the species level (i.e., Pseudomonas aeruginosa and not 
Pseudomonas sp.).  Sound scientific justification should be provided to include 
each organism as a pathogen in the final indication.  -hemolytic Group G 
streptococcus (i.e., Streptococcus canis) may be acceptable without further 
speciation if justified as a pathogen.  CVM considers Enterococcus faecalis as a 
potential otic pathogen, but does not consider coagulase-negative staphylococci, 
Bacillus spp., or Corynebacterium spp as potential otic pathogens. 
 
Treatment success indicates that the animals otitis externa clinically resolved.  
Microbiological treatment outcomes are generally not measured because post-
treatment cultures are generally not performed on animals classified at the final 
evaluation as a treatment success because normal flora exist in the ear and may 
provide conflicting data. 
 
For antibacterial and antifungal products, susceptibility tests should be conducted 
in accordance with standardized methods described by the Clinical and 
Laboratory Standards Institute (CLSI), or by equivalent methods.  Serial two-fold 
dilutions (usually centering on 1 g/ml, e.g., 0.5, 1, 2 g/ml) should be performed 
to determine minimum inhibitory concentrations (MICs).  Measurements of 
quality control (QC) should be taken whenever possible.  These should include 
well-characterized reference strains obtained from a recognized source (e.g., 
ATCC), for which MIC QC ranges are available.  If no QC ranges exist for one of 
the antibacterial or antifungal drugs, a different representative from the same drug 
class for which QC ranges do exist should be tested to validate the testing method.  
CVM encourages the establishment of preliminary QC ranges for the drug 
through replicate testing (e.g., >30 tests).  Favorable susceptibility test conditions 
for all pathogens proposed for the label should also be sought.  Rarely will data 
only from disk diffusion susceptibility tests suffice.  A separate antimicrobial 
susceptibility testing protocol may be submitted for evaluation or it may be 
submitted in conjunction with the field study protocol. 
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If you plan to pursue a product with two or more antimicrobials with overlapping 
spectra of activity, you should submit a justification for the inclusion of the 
additional antimicrobial(s).  The submission should discuss the clinical 
importance of the target pathogen(s), the prevalence of the target pathogen(s), and 
address whether any one of antimicrobials could eradicate/control the infection 
alone.  Following an appropriate initial justification, you should conduct a 
bactericidal study.  The bactericidal study tests anticipated in vivo free-drug 
concentrations at the site of infection to determine if the additional 
antimicrobial(s) is needed to treat all of the target pathogens.  For example, with a 
topical otic product containing gentamicin, the potential local in vivo exposure of 
free gentamicin may be ~1000 fold higher (assuming all drug is bioavailable) than 
the resistant P. aeruginosa clinical breakpoint.  Thus, due to the local in vivo free-
drug exposure likely being so high, gentamicin could kill the resistant P. 
aeruginosa alone and a second antimicrobial to target resistant P. aeruginosa 
would not be necessary. 
 
g.  Adverse Events 
To accurately document adverse events, CVM recommends that the study include 
a log for the owner to complete while their animal is enrolled.  This will provide 
information about time to resolution of symptoms and local adverse reactions. 
 
h.  Informed Consent 
In addition to the general contents of an appropriate informed consent form, the 
consent form should contain suitable language about possible ototoxicity 
associated with the use of the investigational veterinary product(s) being used in 
the field study. 
 
2.  General Considerations for Combination Products 
According to 21 CFR 514.4(c)(3), sponsors must demonstrate by substantial 
evidence ... that a combination new animal drug will have the effect it purports or is 
represented to have under the conditions of use prescribed, recommended, or 
suggested in the proposed labeling and that each active ingredient or animal drug 
contributes to the effectiveness of the combination new animal drug. 
 
For the purposes of this guidance, the requirements for a combination product are 
broken down into two elements.     
Element 1  A demonstration that the new animal drug combination is effective for 
all intended uses for which it is labeled.  
For combination otic products, Element 1 is satisfied by the field safety study(ies) 
conducted in the target animal populations.   
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Element 2  A demonstration that each individual active ingredient (AI) in the 
proposed new animal drug combination contributes to the effectiveness of the 
combination. 
For combination otic products, Element 2 may be satisfied by either: 
  a non-interference study conducted to demonstrate that each active ingredient 
contributes to the effectiveness of the combination product, or  
  a written justification that may be based on literature, the known mechanisms 
of action, and/or the chemical properties of the components. 
When considering Element 2, it is important to note that each AI or animal drug in a 
combination new animal drug is not required to contribute to the effectiveness of the 
combination in the same manner; and in some cases, a single study may be designed 
with the objective of demonstrating the contribution of more than one AI to the 
effectiveness of the combination new animal drug.  CVM recommends that sponsors 
consider the contribution of each AI separately as they develop their plan to address 
the Effectiveness technical section. 
 
a.  Specific Recommendations for Combination Otic Products with 
Antimicrobial Components3  
Studies of clinical isolates representative of the target pathogens in the 
proposed indication should be submitted to assess the susceptibility of the 
isolates to each active component and demonstrate non-interference between 
AIs.  These in vitro studies should be designed with a factorial arrangement of 
treatment groups (a checkerboard design) to attempt to show that none of the 
AIs in the new animal drug combination interfere with the activity of any of the 
other antimicrobial AIs against their target pathogen(s).  All AIs in the 
combination, including anti-inflammatory AIs, need to be included in such a 
study.  For example, there are seven possible treatment groups for a three-way 
combination (A, B, AB, AC, BC, and ABC) plus the active and negative control 
groups.4  These in vitro studies can also be used to satisfy Element 2 through 
their demonstration that each antimicrobial AI likely contributes to the 
effectiveness of the combination in vivo.  The fractional inhibitory 
concentration indices (FICI) method is acceptable for characterizing such drug 
interactions.  This method may be simplified if the final drug formulation ratio 
is known prior to initiating the FICI studies. 
 
Whenever possible in vitro susceptibility and non-interference studies should 
follow CLSI standards or other appropriate validated standards, use appropriate 
QC strains, and, in general, use a two-fold dilution scheme.  Dilution ranges for 
antimicrobials should encompass the MIC QC range of the QC strains.  As 
 
3 We recommend that sponsors contact CVM regarding study design before conducting non-interference studies.  
4 Provided the ratio of the AIs to be used in the formulation of the final combination is known before starting the studies. 
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there are currently no CLSI standards for testing antifungal agents against 
Malassezia pachydermatis, CVM recommends using the broth dilution testing 
and QC guidelines described in CLSIs M27-A3 and M27-S3 for tests on this 
pathogen. 
 
III.  Target Animal Safety 
Target animal safety (TAS) studies aim to identify the margin of safety and provide veterinarians 
with information regarding the safe use of the drug.5  Safety studies conducted in the laboratory 
should be carried out in compliance with FDA's GLP regulations in 21 CFR part 58.  This 
guidance includes recommendations specific for topical otic drug products.  
 
A.  Dosing 
Both ears should be administered the full 1X, 3X, or 5X dose.  In situations where it is 
not practical to administer the full 3X or 5X volume at one time due to ear capacity 
limitations, the dose may be divided and administered separately over a reasonable 
period of time (e.g., can be divided over 8 hours or a workday).  CVM discourages 
dividing doses over multiple days.  You should not manufacture a more concentrated 
product specifically for the 3X or 5X dose because it may alter the kinetics of the active 
ingredients.  CVM recommends the study use the final formulation of the drug product. 
 
If the product is intended to be massaged into the ear, the protocol should clearly describe 
the massage procedure (i.e., duration of massage and location of massage) after 
administration of the product to the ear.  The protocol should state that the treatment 
administrator will minimize the ability of the animal to shake their head post-
administration of the product to minimize any loss of the administered dose. 
 
B.  Duration and Frequency of Administration 
Refer to Guidance for Industry (GFI) #185 (VICH GL43), section 2.4. Dose, 
Frequency, and Duration of Administration.  You are encouraged to contact CVM 
prior to study conduct to discuss the specific drug and dosing schedule. 
 
When proposing a duration and frequency of administration, you should provide a 
justification based on the active ingredients known duration of action.  For single dose 
products, you should propose an appropriate study duration and time period between 
redosing.  CVM recommends the justification be based on PK data from your ear 
wash/swab depletion study, especially for long-acting products.  The product should be 
administered frequently enough that the previous dose is not completely depleted in the 
ear, but not soon enough that the repeat dose artificially increases the chances of adverse 
events or harm to the animal.  You should take into account long-acting products, 
excipients that improve absorption, and active ingredients that persist (e.g., terbinafine) in 
the ear when considering study duration and frequency of administration. 
 
5 See Guidance for Industry #185 (VICH GL43), Target Animal Safety for Veterinary Pharmaceutical Products 
(https://www.fda.gov/media/70438/download) for  more details. 
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C.  Control 
CVM recommends a non-toxic placebo such as saline for solutions or mineral oil for 
suspensions. 
 
D.  Housing  
Otic products tend to be lipophilic and can adhere to many surfaces for an extended 
period.  Laboratory-held animals used in TAS studies can easily come into contact with 
investigational products if animals are comingled for socialization or other purposes.  
Therefore, the protocol should clearly address the commingling of animals in the 
treatment phase to ensure animals are unable to lick/ingest product from a neighboring 
animal.  While commingling is acceptable during the acclimation phase, commingling 
during the treatment phase is discouraged.   
 
E.  Evaluation of Toxicity 
The study should be designed to capture the drug effects at the time points of maximal 
exposure and/or maximal toxicity.  
 
The method and frequency of aural, otoscopic, and hearing examinations should be 
specified in the protocol.  The study should include pre- and post-treatment 
aural/otoscopic examinations and hearing tests pre-treatment and prior to necropsy.  
 
Adrenocorticotropic hormone (ACTH) stimulation tests should be conducted for otic 
products containing corticosteroids.  The minimal acceptable number of ACTH 
stimulation tests in a TAS study is two: one pre-treatment and one prior to necropsy.  
CVM recommends adding a third ACTH stimulation test at the point of maximum 
exposure (Cmax) after the first dose.  The pharmacokinetic (PK) data may provide the 
point of maximum exposure for the corticosteroid component. 
 
Necropsy procedures should include histopathology of the middle and inner ears. 
 
IV.  Human User Safety 
Human user safety covers human exposures resulting from actual conditions of use and is part of 
the TAS technical section.  Human user safety concerns should be addressed, including potential 
exposure to the drug and the active metabolites by veterinary personnel, people handling the 
drug, and people in contact with the animal.  Informed consent for the field study(ies) is 
important to ensure that dog owners understand the risks of potential exposure to the drug and to 
the people and animals that may come in contact with the treated dog.  Investigational and 
approved drug labeling should address human user safety concerns. 
 
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V.  Labeling 
The pathogenic species listed on the package insert will be determined by the results of the field 
effectiveness study that support substantial evidence of effectiveness.  The inclusion/exclusion of 
a pathogen in the indication should be considered in consultation with a microbiologist.  CVM 
lists the number of cases for each putative otitis externa pathogen species isolated in the field 
study in the FOI Summary to help explain why a particular species was not included in the 
indication.  Generally, CVM includes all pathogens cultured during the field study in the FOI 
Summary. 
 
The following Precaution statements are generally found on the package insert for a topical otic 
product.  The Precaution statements may be changed and/or not included depending on the active 
ingredients included in the product (e.g., corticosteroid versus an NSAID). 
 
Precautions 
 
  The use of [TRADENAME] in dogs with perforated tympanic membranes has not been 
evaluated.  The integrity of the tympanic membrane should be confirmed before 
administering this product.  Reevaluate the dog if hearing loss or signs of vestibular 
dysfunction are observed during treatment. 
  Use of topical otic corticosteroids has been associated with adrenocortical suppression 
and iatrogenic hyperadrenocorticism in dogs. 
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