Contains Nonbinding Recommendations
General Considerations for Animal 
Studies Intended to Evaluate Medical 
Devices
______________________________________________________________________________
Guidance for Industry and
Food and Drug Administration Staff
Document issued on March 28, 2023.
The draft of this document was issued on October 14, 2015.
This document supersedes Guidance for Industry and FDA Staff: General 
Considerations for Animal Studies for Cardiovascular Devices issued July 
29, 2010.
For questions about this document, contact CDRHanimalstudies@fda.hhs.gov.
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Devices and Radiological Health Contains Nonbinding Recommendations
Preface
Public Comment
You may submit electronic comments and suggestions at any time for Agency consideration to 
https://www.regulations.gov. Submit written comments to the Dockets Management Staff, Food 
and Drug Administration, 5630 Fishers Lane, Room 1061, (HFA-305), Rockville, MD 20852. 
Identify all comments with the docket number FDA-2015-D-3419. Comments may not be acted 
upon by the Agency until the document is next revised or updated.
Additional Copies
Additional copies are available from the Internet. You may also send an email request to CDRH-
Guidance@fda.hhs.gov to receive a copy of the guidance. Please include the document number 
1802 and complete title of the guidance in the request. Contains Nonbinding Recommendations
Table of Contents
I.  Introduction ............................................................................................................................. 1
II.  Overview ................................................................................................................................. 1
III.  Scope .................................................................................................................................... 3
IV.  Considerations When Determining the Need  to Conduct an Animal Safety Study ........... 4
V.  Personnel ................................................................................................................................. 5
VI.  Study Planning and Conduct ................................................................................................ 6
Study Design .................................................................................................................... 6 
(1) Study Objectives ........................................................................................................... 7 
(2) Selecting an Animal Model .......................................................................................... 8 
(3) Sample Size and Groupings .......................................................................................... 8 
  Test System Monitoring ................................................................................................... 9 
(1) Intra-Procedural Monitoring ....................................................................................... 10 
(2) Post-Procedural Recovery and Monitoring ................................................................ 10 
(3) In-Life Monitoring ...................................................................................................... 10 
(4) Unexpected Morbidity and Mortality ......................................................................... 11 
  Post-Mortem Assessment Methods ................................................................................ 11 
(1)  Post Mortem Imaging ................................................................................................. 12 
(2) Necropsy and Gross Tissue Evaluation ...................................................................... 12 
(3) Histologic Evaluation ................................................................................................. 12 
  Test and Control Article Characterization ..................................................................... 13 
VII.  Testing Facility Selection .................................................................................................. 13
VIII.  Animal Housing ............................................................................................................. 14
Animal Quarantine and Conditioning ............................................................................ 15 
  Food, Water, and Basic Husbandry ................................................................................ 15 
IX. Records and Reports .......................................................................................................... 15 
X.  Preparation of Animal Study Reports for Medical Device Premarket Submissions ............ 16 
  Executive Summary ....................................................................................................... 17 
  Final Study Report ......................................................................................................... 17 
(1) In-Life Veterinarian Report ........................................................................................ 18 
(2) Pathology Report ........................................................................................................ 18 
(3) Other Reports/Forms .................................................................................................. 19 
Appendix A - Example Organization of Animal Study Final Report ........................................... 20 Contains Nonbinding Recommendations
General Considerations for Animal 
Studies Intended to Evaluate Medical  
Devices
______________________________________________________________________________
Guidance for Industry and
Food and Drug Administration Staff
This guidance represents 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 
or Office responsible for this guidance as listed on the title page.
I. Introduction 
FDA developed this guidance document to assist medical device sponsors, testing facilities, and 
other persons involved in designing, conducting, and reporting the results of animal studies 
intended to assess the safety of medical devices to support premarket submissions. These animal 
studies typically provide initial evidence of device safety, which may include device 
performance and handling, and the biological effects of the device when used in a living system. 
The recommendations in this guidance reflect current review practices and are intended to 
promote consistency and facilitate efficient review of medical device submissions that include 
animal study data.
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. Overview 
The in vivo setting generally provides an initial assessment of how a medical device interacts 
with biological systems, including physiological, pathological, and toxicological effects of the 
device, and how the biological system may affect the device. Animal studies are often conducted 
to support medical device premarket submissions. Nonclinical laboratory studies, including 
1 Contains Nonbinding Recommendations
animal studies,1 intended to support premarket submissions must comply with the Good 
Laboratory Practice for Nonclinical Laboratory Studies (GLP) Regulations.2 The GLP 
Regulations are intended to ensure the quality and integrity of the safety data submitted as part of 
a premarket submission to FDA.3
A primary purpose of an animal study submitted in support of a premarket submission is for the 
submitter to provide evidence of safety, which could include performance and handling4, of a 
medical device. Note that in many cases, the performance and handling of a particular device is 
intricately linked to its safety, including but not limited to implantable devices or interventional 
devices. FDA acknowledges that an animal study can have multiple purposes beyond the 
assessment of safety. For example, a secondary objective for conducting an animal study can be 
to evaluate the effectiveness of the device or to demonstrate proof of concept and principle of 
operation. Manufacturers could also conduct an animal study to help meet design verification 
and validation requirements.5
Animal studies submitted to the Agency to support the safety of a medical device must comply 
with the GLP Regulations. However, the intent of this guidance is not to comprehensively 
describe when compliance with the GLP Regulations is required for an animal study. The 
applicability of the GLP Regulations to a specific animal study may be dependent on individual 
facts and circumstances. If you have specific questions on aspects of your animal study or your 
studys compliance with the GLP Regulations, we recommend that you seek feedback from FDA 
through the Q-Submission process.6
This guidance outlines the general considerations for certain animal studies used to support 
device premarket submissions, when a suitable alternative to an animal study is not available. 
This guidance provides recommendations for various elements of animal studies, including the 
credentials for personnel conducting an animal study, and the study planning and conduct 
process, including but not limited to selecting an appropriate animal model, study monitoring, 
and study evaluation. This guidance also provides recommendations on testing facility7 selection, 
animal housing, records and reports, and how to prepare an animal study report for premarket 
submissions to FDA. 
1This guidance contemplates animal studies that meet the definition of nonclinical laboratory studies, and does not 
include field trials in animals. See 21 CFR 58.3(d).
2See 21 CFR Part 58 which outlines the requirements for Good Laboratory Practice for Nonclinical Laboratory 
Studies. For the purposes of this guidance document, 21 CFR Part 58 will be referenced as the GLP Regulation.
3See 21 CFR 58.1(a). 
4For the purposes of this guidance document, handling is defined as the way the device or device system responds 
to the demands of the operator, such as ease of insertion/deployment, radiopacity, tracking, maneuvering, and 
retrieval. 
521 CFR 820.30 outlines the requirements for design verification and validation.
6For more information, see Requests for Feedback and Meetings for Medical Device Submissions: The Q-
Submission Program, Guidance for Industry and Food and Drug Administration Staff, available at
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/requests-feedback-and-meetings-
medical-device-submissions-q-submission-program.
7See 21 CFR 58.3(g) for definition of a testing facility.
2 Contains Nonbinding Recommendations
FDA supports the principles of the 3Rs, to replace, reduce, and/or refine animal testing 8,9,10, 
animal use in testing when feasible. FDA encourages sponsors to consult with the Agency 
through the Q-Submission process if you wish to use a non-animal testing method that is 
suitable, adequate, validated, and feasible. Through the Q-Submission process, FDA will 
consider if a proposed alternative testing method could be assessed for equivalency to an animal 
test method.11 FDA also encourages the use of the Q-Submission process to obtain feedback on 
the design of an animal study if an animal study is warranted. Additionally, it is important to 
consider the adequacy of controls, timing and route of intervention, and methods to minimize 
bias (i.e., blinding, randomization, use of controls, sample size based on expected magnitude of 
the biological response, reporting missing data, and clearly stated statistical considerations) when 
designing an animal study.12 FDA recommends that sponsors submit a Pre-Submission (a type of 
Q-Submission) for clarification regarding elements of the animal study to support a premarket 
submission.
FDA acknowledges that there are other relevant statutes, regulations, and policies that govern 
laboratory animal care.13,14,15,16,17,18 FDA maintains a memorandum of understanding (MOU) 
with the Animal and Plant Health Inspection Service (APHIS) in the United States (U.S.) 
Department of Agriculture (USDA) and the National Institutes of Health (NIH) that sets forth a 
framework for reciprocal cooperation, which will assist each agency in meeting its 
responsibilities in promoting proper laboratory animal care and welfare in the U.S.19
III. Scope 
The recommendations in this guidance refer to devices, as defined in section 201(h) of the 
Federal Food, Drug, and Cosmetic Act (FD&C Act), intended for human use. This guidance is 
applicable to animal studies intended to provide evidence of device safety, which may include 
8Advancing New Alternative Methodologies at FDA, available athttps://www.fda.gov/media/144891/download.
9Russell WMS, Burch, RL. The Principles of Humane Experimental Technique. London: Methuen & Co.; 1959. 
Special edition published by Universities Federation for Animal Welfare, 1992, available at 
http://altweb.jhsph.edu/pubs/books/humane_exp/het-toc.  
10 Animal Use Alternatives (3Rs), available at https://www.nal.usda.gov/animal-health-and-welfare/animal-use-
alternatives#:~:text=The%20%E2%80%9C3Rs%20alternatives%E2%80%9D%20refers%20to,Principles%20of%20
Humane%20Experimental%20Technique%22. 
11 See FDA webpage for Medical Device Development Tools (MDDT) (https://www.fda.gov/medical-
devices/science-and-research-medical-devices/medical-device-development-tools-mddt) for potential alternatives to 
animal studies. 
12 See 21 CFR 58.120.  
13 See 7 U.S.C.  213159. 
14See 9 CFR Parts 14. 
15 Health Research Extension Act of 1985, Public Law 99158, 99 Stat. 820 (Nov. 20, 1985).
16U.S. Department of Health and Human Services, National Institutes of Health, Office of Laboratory Animal 
Welfare (2015). Public health service policy on humane care and use of laboratory animals. Retrieved from 
https://grants.nih.gov/grants/olaw/references/phspolicylabanimals.pdf.
17National Research Council of the National Academies (2011). Guide for the care and use of laboratory animals 
(8th ed.). Retrieved from https://grants.nih.gov/grants/olaw/guide-for-the-care-and-use-of-laboratory-animals.pdf.
18FDA Guidance for Industry (2007). Good Laboratory Practices - Questions and Answers. Available at 
https://www.fda.gov/media/75866/download
19FDA MOU 225-16-010. Available at https://www.fda.gov/about-fda/domestic-mous/mou-225-16-010.
3 Contains Nonbinding Recommendations
performance and handling, in premarket submissions to FDA.20 These types of submissions 
include investigational device exemption (IDE) applications, premarket approval applications 
(PMA), premarket notification (510(k)), humanitarian device exemption (HDE) applications, or 
De Novo classification requests. This guidance is not intended to alter or supersede any device-
specific final guidance but is intended to augment the recommendations in device-specific 
guidance.   
This guidance also does not apply to basic exploratory studies conducted to determine whether a 
device has any potential utility or preliminary assessments of physical or chemical characteristics 
of a device. In addition, this guidance does not apply to, nor changes any regulatory requirements 
relevant to, animal studies conducted under the Animal Rule.21 Finally, this guidance is not 
intended to address the regulations and policies of other agencies.
IV. Considerations When Determining the Need  to 
Conduct an Animal Safety Study 
Below outlines general considerations a sponsor may find helpful when determining whether an 
animal safety study should be conducted to support a premarket submission.
 A risk analysis22 that considers all sources of relevant information, including known 
failure modes and previously identified risks for the device, risks commonly 
attributed to this general device type, and postmarket information for similar 
marketed devices. Postmarket information can be searched using the published 
literature and the Manufacturer and User Facility Device Experience (MAUDE) 
database.23
 Testing the evaluable risks on the benchtop to the extent feasible using the device in 
its final finished form (a device in its final finished form includes all manufacturing 
processes for the to be marketed device including packaging and sterilization, if 
applicable). Before considering an animal study to support a premarket submission, 
FDA recommends completion of nonclinical benchtop performance testing with the 
device in its final finished form to evaluate potential harm(s) identified during the risk 
analysis.
 Consider conducting an animal study when the risk analysis suggests that such a 
study is necessary to further assess potential safety concerns that cannot be 
adequately addressed through alternative methods. When sponsors are uncertain 
about whether they should conduct an animal study, FDA recommends utilizing the 
Q-Submission process to request FDA feedback on the overall nonclinical testing 
approach.
20For ease of reference, this guidance will refer to these studies as animal safety studies.
21See 67 FR 37988 (May 31, 2002). Those animal studies submitted for premarket review of drug and biologic 
products are also specifically outside the scope of this guidance.
22For example, ISO 14971: Medical devices  Application of risk management to medical devices.
23FDA MAUDE Database. Available online at:
https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfMAUDE/search.CFM.
4 Contains Nonbinding Recommendations
 When there is no established animal model for the type of device (i.e., one that has 
been described in the literature or used to support the clearance or approval of a 
similar device), as applicable, we recommend that sponsors:
 Assess the anatomy and physiology (e.g., angiographic, radiographic, 
computed tomography (CT) screening) of commonly used laboratory 
animal species for intended use, allometric scaling, and procedural 
approach features.
 Consult an experienced laboratory animal veterinarian to determine the 
availability and utility of common laboratory species.
 Engage with the Agency using the Q-Submission process to discuss 
significant challenges that preclude the use of a reasonable animal model 
for all or some of the animal studies recommended by the risk analysis and 
potential alternative approaches for collecting information to support 
device safety before clinical use in humans. As part of this discussion, 
sponsors should include any available information that demonstrates that 
animal studies would not be feasible and propose alternative solutions, 
including any available simulations, cadaveric studies, and clinical 
information. Although FDA generally does not consider cost as sufficient 
justification for not conducting animal studies, we apply least burdensome 
principles to premarket regulatory activities.24
FDA recommends that sponsors submit a Pre-Submission if how to structure or conduct the 
animal study is unclear. FDA recommends the Pre-Submission include a detailed proposal for 
the animal study design that includes specific questions for which they would like FDA input. 
V. Personnel 
FDA believes that a carefully planned and executed animal study is more likely to provide useful 
data in support of a device premarket submission. In this regard, animal studies should be 
planned and conducted by a team with appropriate credentials and training. Under the GLP 
Regulations, a study director25 with relevant education, training and experience must be 
designated before initiation of a nonclinical laboratory study26 to provide direct oversight of the 
technical conduct of the study, among other responsibilities.27
Further, the GLP Regulations also require the use of a Quality Assurance Unit (QAU). QAU 
personnel are independent from the personnel engaged in the direction and conduct of the 
study.28 The QAU for an animal study could be an independent contractor or employed 
elsewhere within the testing facility organization.
24See The Least Burdensome Provisions: Concept and Principles: Guidance for Industry and FDA Staff, available 
at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/least-burdensome-provisions-
concept-and-principles
25Consistent with 21 CFR 58.3(m), study director means the individual responsible for the overall conduct of a 
nonclinical laboratory study.
26See 21 CFR 58.31(a).
27See 21 CFR 58.33.
28See 21 CFR 58.35.
5 Contains Nonbinding Recommendations
FDA also recommends that the animal study team include skilled clinical veterinary staff to help 
ensure humane care of study animals.29 Animal studies may also benefit from input from 
investigators with expertise in specialty fields, such as engineering, pathology, radiology, 
surgery, and laboratory animal science. For example, testing for sensorimotor function involves 
specific neurologic and/or behavioral expertise. Animal models may also involve unique surgical 
approaches or present anatomical limitations that would benefit from having trained veterinary 
surgical expertise as part of the research team.
FDA notes that appropriate training and experience of study personnel that may apply to animal 
studies are also addressed in other relevant guides, regulations, and policies.30,31,32,33,34
VI. Study Planning and Conduct 
 
Under the GLP Regulation,  animal studies shall be conducted according to a written protocol 
that clearly indicates the objectives and all methods for the conduct of the study.35 The protocol 
should provide enough description to allow FDA to reconstruct the study.
FDA recommends conducting exploratory animal studies before conducting animal safety 
studies when in vivo or in vitro information exists that shows a significant learning curve that 
would significantly increase animal response variability. This could be caused by factors, such as 
investigator training and familiarity with the device or inherent challenges in the placement or 
tolerance of the device.
Study Design 
FDA recommends that the animal study is designed to ensure that the testing environment 
simulates (to the extent possible) a clinical setting that reflects the intended use and proposed 
labeling of the device (i.e., instructions for use). Under the GLP Regulation, animal studies must 
be guided by a study protocol that is approved by the sponsor and signed and dated by the study 
director.36 If the study is conducted outside of the United States, an equivalent, signed protocol 
should be in place.37
29See 21 CFR 58.29 and 9 CFR 2.31 which requires the USDA licensed facilities to appoint an Institutional Animal 
Care and Use Committee to oversee the animal study program.
30Russell WMS, Burch, RL. The Principles of Humane Experimental Technique. London: Methuen & Co.; 1959. 
Special edition published by Universities Federation for Animal Welfare, 1992, hereafter called Russell. Available 
online at: http://altweb.jhsph.edu/pubs/books/humane_exp/het-toc. 
31 9 CFR Parts 13. 
32 U.S. Department of Health and Human Services, National Institutes of Health, Office of Laboratory Animal 
Welfare (2015). Public health service policy on humane care and use of laboratory animals. Retrieved from 
https://grants.nih.gov/grants/olaw/references/phspolicylabanimals.pdf.
33FDA MOU 225-16-010. Available at https://www.fda.gov/about-fda/domestic-mous/mou-225-16-010.
34See 21 CFR 58.29.
35See 21 CFR 58.120(a).
36See 21 CFR 58.120(a)(b).
37See 21 CFR 58.120(a).
6 Contains Nonbinding Recommendations
FDA generally recommends that sponsors use the endpoints, time points, and methods reported 
for similar devices, if available. Sponsors should consider identifying new endpoints, time 
points, and methods when there are:
 Features of the device that would suggest the need to evaluate different study time points 
and objectives from those previously used in studies for similar devices with similar 
intended use; or
 New indications that suggest the use of different or additional evaluation time points or 
methods.
The study protocol should not contain statements that limit the collection of data or the reporting 
of findings so that FDA has a more complete understanding of all data collected in the study, as 
well as the interpretation of the data. 
FDA recommends limiting study bias to help ensure the quality of the data collected during an 
animal study.38 FDA recommends incorporating principles of experimental methodology to 
minimize bias or the perception of bias and to control variation, including but not limited to:
 randomization procedures to control for animal selection and procedural bias;
 blinding/masking procedures to control for assessment bias;
 use of more than one observer to control for perception bias;
 choice of experimental design to increase precision and reduce variation (i.e., blocking, 
stratification, and/or factorial designs);
 inclusion of positive, negative, and/or sham control arms;
 ensure calibration of instruments and/or equipment to minimize measurement error; and
 minimize contributions from study personnel with financial conflicts.
(1) Study Objectives 
a.  Device/Procedure Safety Risks 
FDArecommends the study director consider the risk analysis (i.e., the identified risks 
associated with the device through bench testing, device design, exploratory studies, literature 
review) to determine the specific risks to be evaluated in the study. The study director should 
also consider the known risks of the device type for the same intended use.  
 
FDA recommends study objectives be designed to address the risks that have been identified for 
the device or for the type of device. Acceptance criteria should be developed with a scientific 
rationale to address each study objective. Effectiveness could be a secondary objective in these 
studies.
b. Device Performance and Handling 
FDAconsiders studying relevant performance and handling parameters essential to the 
assessment of device safety. Therefore, FDA recommends that study protocols include study 
objectives to address how device performance and device handling contribute to the overall 
safety profile of the device. For example, a study to evaluate the safety of a device that is 
intended to ablate tissue by heating, cooling, or mechanical disruption should include an 
assessment of successful ablation of the target tissue to demonstrate that the procedure can be 
38See 21 CFR 58.120(a)(6)
7 Contains Nonbinding Recommendations
performed safely. FDA recommends addressing this by ensuring that all steps to deliver, implant, 
and/or use the device be identified and assessed. For example, if the device is surgically placed, 
there should be an evaluation of all steps undertaken from the anatomic point of surgical entry to 
placement location.
When reporting study findings pertaining to device performance and handling, there should be 
enough detail to understand the outcomes and potential device safety issues. FDA recommends 
that a rating scale be created that allows semi-objective scoring of device performance and 
handling parameters, such as flexibility, pushability, visibility, torquability, kinking, bending, 
leaking, ease of use, and surgical placement. Rating criteria should encompass steps between the 
preparation of the device through device placement or use as well as withdrawal and 
redeployment, if appropriate. We recommend using a semi-quantitative method of assessment 
for each parameter (e.g., for a scale of 1-4, 1 = poor and 4 = excellent). The score used for 
acceptability (total score, by parameter, or a combination of both) should be established a priori 
and based on a scientific rationale. This information should be provided in the study protocol.
c. Local and Systemic Effects 
 Medical devices can have both local and systemic effects on a biologic system. This includes 
distal physiologic and/or tissue effects that might be caused by the device and/or delivery 
system. For example, perturbation of the vagus nerve in the cervical region can produce adverse 
effects, such as gastrointestinal distension and bradycardia. The study should include objectives 
to evaluate potential adverse effects on the structure and function of tissues locally and 
systemically, as identified in the risk assessment.
(2) Selecting an Animal Model 
The animal and its related environmental and physiologic attributes should provide a testing 
condition that offers a best attempt at simulating the clinical setting.39 There should be scientific 
information to support the appropriateness of the chosen animal model. In some cases, there may 
not be an established or accepted animal model for a specific device type. The selected animal 
model should be able to address the identified objectives of the study The sponsor should 
.
consider scientifically accepted animal models of disease when they exist. FDA feedback on the 
animal model selected can be obtained  through the Q-Submission process.40
(3) Sample Size and Groupings 
The number of animals and experimental groupings should be designed after exploratory testing 
to provide some information on reliability and outcome if other data are not available to justify 
the design of the GLP study (e.g., sample size and grouping).41 The study should use the least 
number of animals that could provide a predictive outcome and meaningful interpretation; this 
includes such measures as choosing the appropriate experimental control and consideration of 
potential experimental confounders and best observation intervals.
39Michel, K. D., Sorenmo, K., Shofer, F. S. (2004). Evaluation of body condition and weight loss in dogs presented 
to a veterinary oncology service. Journal of Veterinary Internal Medicine, 13(5), 692-5.
40For more information, see Q-Submission Guidance, available athttps://www.fda.gov/regulatory-
information/search-fda-guidance-documents/requests-feedback-and-meetings-medical-device-submissions-q-
submission-program.
41Exploratory studies provide another means to identify and estimate variability, often providing key information 
for planning the study design and adequate sample size to obtain valid results.
8 Contains Nonbinding Recommendations
Recognizing the inherent variability of animal studies, sample sizes should be sufficient  to help 
meet the objectives of the study. Low animal enrollment risks data confounders such as missing 
data, unexpected animal death, or data outliers which make interpretation of data challenging.
FDA recommends performing a sample size calculation42,43 or estimating the number of animals 
based on exploratory studies. Considerations that may assist in the calculation of the sample size 
include:
 determining the standard deviation from an exploratory study, a previous study using 
a similar device, or relevant published studies;
 using an adequate number of control animals to minimize experimental variability 
and error; 
 determining the difference between treatment and control that would be clinically  
significant; and
 using uniform animals (breed, sex, age, weight) to reduce inter- and intra-animal 
variability.
Test System Monitoring  
FDA recommends that the animal study protocol follow current veterinary standards of care 
appropriate for the device and procedure. The study director should work with veterinary staff at 
the testing facility to develop pre-specified plans to monitor for and manage anticipated adverse 
events at each phase of the study. Additionally, animal responses may be unpredictable; 
monitoring should be adequate to address all adverse events that occur. Such monitoring is 
important not only for humane reasons but also because it can help differentiate spontaneous 
conditions from device-related events.
Many animal studies involve procedures that call for anesthesia and analgesia. 
Anesthetic/analgesic protocols are used for any procedures that may cause more than momentary 
or slight pain or distress to the animals. The study director should consult with the veterinarian 
when developing anesthetic and analgesic plans,44 such that appropriate drugs and dosages for 
the species, age, and weight of the animals, as well as the type of procedure are used. It may also 
help prevent introducing potential confounders to the study data.
Pain can negatively affect many physiologic systems, including wound healing, behavior, 
metabolism, and body system functions (e.g., immunity, pulmonary, cardiac, gastrointestinal, 
and urinary).45 The type and extent of pain that an animal is likely to experience during or after a 
specific experimental procedure should be predicted. This can enable the veterinarian to devise 
42ACLAM position statement on reproducibility (2016). Journal of American Association for Laboratory Animal 
Science, 55(6), 826-828824-825.
43Snedecor, G. W. & Cochran, W. G. (1990). Statistical methods (8th ed.). Ames, IA: Iowa State University Press.
44See 9 CFR 2.31(d)(iv).
45DeMaraco G. J. & Pascoe, P. J. (2008). Anatomy, physiology, and effects of pain. In R. E. Fish, M. J. Brown, P. J. 
Danneman, & A. Z. Karas (Eds.), Anesthesia and analgesia in laboratory animals (2nd ed., pp. 3-25). Burlington, 
MA: Academic Press.
9 Contains Nonbinding Recommendations
plans that include the use of suitable analgesics, supportive therapeutic measures, and criteria for 
triggering intervention and/or humane euthanasia. Anticipation of the type(s) of pain expected 
also informs the frequency and type(s) of assessment needed to effectively manage pain.
(1) Intra-Procedural Monitoring 
Adequate physiologic monitoring during anesthesia with collection (or recording) of 
physiological parameters monitored is an important aspect of a well-conducted animal study. 
FDA recommends that tracked vital signs, such as heart rate, respiratory rate, oxygen saturation, 
end-tidal CO2, body temperature, and blood pressure, be recorded at regular intervals throughout 
an anesthetic procedure. Consider whether additional monitoring, such as imaging, measurement 
of blood gases, or assessment(s) of specific clinical pathology(ies) (e.g., lactate, glucose, 
hematocrit/hemoglobin, or activated clotting time), is warranted. All monitoring information 
should be correlated with the timing of insertion, implantation, deployment, or use of the device, 
as well as the use of contrast agents or other device-associated materials and noted on the 
anesthetic and/or operative records.
(2) Post-Procedural Recovery and Monitoring 
Sponsor should follow the current standard of care for laboratory animals during and 
immediately following an anesthetic procedure.46 Human clinical care should be replicated 
whenever possible. Animals should be monitored for pain, hypo/hyperthermia, hypovolemia, and 
changes in mentation. Preemptive standard operating procedures should be established with the 
veterinarian to address any potential complications, including thermal and/or fluid interventions 
and rescue analgesic protocols that are appropriate to the device and procedure. Multimodal 
analgesic plans are often most effective. These plans should be in place before initiating the 
study to avoid confusion during the conduct of the study. 
(3) In-Life Monitoring 
During periods when animals have fully recovered from study procedures but are to be 
monitored for device-associated risks, FDA recommends observation at least twice daily at 
feeding times when they are active. The study veterinarian should be notified promptly when 
abnormal behaviors or clinical signs are noted. A pre-specified plan should be in place to address 
any abnormal clinical finding during sub-acute and chronic periods of the study.
Important parameters to consider for daily evaluation include but are not limited to:
 general appearance;
 appetite;
 mentation;
 respiratory rate, pattern, and effort;
 posture, gait; and
 urination and defecation.
46See 9 CFR 2.31(d)(ix)
10 Contains Nonbinding Recommendations
FDA also recommends consulting the veterinarian and developing a weight monitoring plan. 
Consider inclusion of body scoring as an adjunct to periodic observations of the animals.47,48
If the study involves in-life monitoring procedures, such as wound dressing changes, imaging, 
collection of clinical pathology data, or more advanced diagnostics, the sponsor should plan the 
protocol for maximum efficiency. Grouping data collection activities requiring chemical restraint 
together may also minimize handling stress. In these cases, FDA recommends developing a 
chemical restraint protocol that does not interfere with the data. Some animals, such as dogs and 
sheep, may be conditioned to be compliant for these activities without the need for chemical 
restraint, while other animals, such as pigs, may be more difficult to condition.
Imaging methods, such as radiography, computed tomography, magnetic resonance imaging, 
and/or fluoroscopy, can be helpful in evaluating device safety (e.g., migration and structural 
integrity). In vivo device visualization data can also provide information of device stability (e.g., 
spatial positioning).
To best collect in-life study monitoring data, FDA recommends following current standards of 
record-keeping in veterinary medicine, such as the problem-oriented veterinary medical record 
(POVMR) or equivalent.49 Additionally, these records should be readily available to all key 
support personnel to optimize data entry.
(4) Unexpected Morbidity and Mortality 
FDA recommends that all animal illness and unexpected or early deaths be assessed and 
documented with regards to causation. Assessments should include any post-operative, interim, 
and terminal clinical pathology, gross pathology, and histopathology as well as any other 
indicated diagnostic methods. The supporting rationale for statements made regarding whether 
adverse events are related, directly or indirectly, to the device should be thoroughly described. 
Retrospective testimonials and statements made by study directors, their designees, or their 
consultants that explain veterinary clinical outcomes should be supported by appropriate records 
and reports. In the event of an unscheduled death, FDA recommends that a timely (for example, 
<24 hours to minimize tissue degradation), complete necropsy be performed on the animal to 
provide information to support the cause of death. 
  PostMortem Assessment Methods 
Post-mortem assessment methods are important to characterize test and control tissue responses, 
as well as to visualize the device in situ and/or after the device is explanted. The assessment 
methods described below may not be appropriate or adequate for all studies. Planned 
assessments, including tests, analyses, and measurements, must be documented in the protocol.50 
47ACLAM position statement on reproducibility (2016). Journal of American Association for Laboratory Animal 
Science, 55(6), 826-828824-825.
48Snedecor, G. W. & Cochran, W. G. (1990). Statistical methods (8th ed.). Ames, IA: Iowa State University Press
49Saidla, J. F. (1983). Problem-oriented veterinary medical record. In S. J. Ettinger & E. C. Feldman (Eds.), 
Textbook of veterinary internal medicine: Diseases of the dog and cat (Vol. 1, 2nd ed.). Philadelphia, PA: W.B. 
Saunders Co.
50See 21 CFR 58.120(a)(9)
11 Contains Nonbinding Recommendations
(1) Post Mortem Imaging   
Imaging methods are helpful in evaluating device safety parameters, such as migration, stability 
(e.g., spatial positioning), and/or structural integrity. Before necropsy, an in situ evaluation of the 
device could assist in the evaluation of device safety and should be considered when developing 
the protocol. Imaging may also be useful to assess the structural integrity of the explanted 
device. Evaluation of surface characteristics of some medical devices (e.g., some implanted 
devices) may be an important method to assess safety. When warranted, FDA recommends the 
use of scanning electron microscopy to characterize an implant device surface after it has been 
explanted from the animal.
(2) Necropsy and Gross Tissue Evaluation  
FDA recommends that a comprehensive, systematic necropsy51 be performed by a board-
certified veterinary pathologist on all animals enrolled in the study to identify and describe any 
abnormal findings that may be a result of the device or the procedure. This can help maximize 
the information gained from each animal and helps identify confounding outcomes and attribute 
causes to certain findings. FDA recommends that a timely, complete necropsy be performed on 
the animal to provide information to support the cause of death. Deceased animals awaiting 
necropsy should be refrigerated and not frozen, to avoid changes caused by ice crystal formation.
Gross observations are necessary for appropriate tissue sampling and trimming orientation. FDA 
recommends that you describe the process and rationale for the sectioning of tissues to  help 
ensure unbiased, representative tissue sampling from each animal in the protocol. The study 
prosector should have sufficient training and experience to assure an accurate, objective process 
in the sampling of gross tissue for microscopic examination.52 High-quality color photographs 
should be taken of gross tissues, including all abnormal findings and representative 
corresponding normal tissue. All gross images should be labeled with an animal identifier (ID), 
study group ID, size marker, and date for ease of identification. It is helpful if images include 
arrows, or other identifying mark, to highlight specific observations. 
(3) Histologic Evaluation  
Proper interpretation of tissue responses to a device is critical to FDAs evaluation of safety, 
especially in the absence of clinical data. Tissues should be adequately sectioned and examined 
to enable reasonable evaluation of the tissue. FDA recommends performing histology on all 
tissues potentially affected, directly and indirectly, by the device. For example, if a device may 
form emboli (i.e., particulates or thrombi), either from the device itself or its action (e.g., ablation 
devices), then the histologist should also perform full histology on all potentially affected tissue, 
such as kidney, lung, heart, brain, and coronary bands. The histologist should include high-
resolution, labeled color microphotographs of each slide in the final study report. 
51King, J. M., Roth-Johnson, L., Dodd, D. C., & Newsom, M. E. (2013). The necropsy book: A guide for veterinary 
students, residents, clinicians, pathologists, and biological researchers. Retrieved from 
https://ecommons.cornell.edu/bitstream/handle/1813/37948/King_John_Necropsy_Book_10Mar16.pdf?sequence=5
&isAllowed=y.
52Crissman, J. W., Goodman, D. G., Hildebrandt, P. K., Maronpot, R. R., Prater, D. A., Riley, J. H., Thake, D. C. 
(2004). Best practices guideline: Toxicologic histopathology. Toxicologic Pathology, 32(1), 126-131.
12 Contains Nonbinding Recommendations
The testing facility should seek the expertise of an experienced, board-certified veterinarian 
and/or physician pathologist when developing and executing methods for preparing tissues for 
histologic analysis. FDA also recommends developing pre-specified objective methods for 
scoring and analyzing observations of tissue reaction. Specific assessments, such as 
inflammation, vascularization, calcification, proteoglycan/collagen, and fibrin/thrombus should 
be considered in the evaluation as appropriate. The use of pathology keys that further detail the 
histology grading system may be useful in this regard.53,54
Test and Control Article Characterization 
FDA recognizes that a medical device is often modified multiple times during the development 
process before an IDE or marketing authorization is requested from the Agency. FDA 
recommends that the animal study use the device in its final (or finished) form whenever 
possible. This ensures that study data can be best interpreted for evaluation of safety of the final 
device. If the final device design was not used in the animal study, the sponsor should identify all 
differences between the tested device and the final device design and explain why these 
differences would not be expected to affect study outcomes. Additionally, the sponsor should 
justify why the final clinical device design presents no new risks as compared to the design 
evaluated in the animal study.
If the device is intended to be used in conjunction with any accessories, the sponsor should 
describe these in the study protocol. The protocol should clearly state which, if any, accessories 
used in the animal study are intended to be provided separate from the medical device under 
study (i.e., commercially available) versus accessories that are expected to be marketed together 
with the device (i.e., a device system). FDA recommends the any test accessories used in the 
animal study also be in their final finished form.
Medical devices should be packaged, sterilized, and shipped to the testing facility in the same 
manner as the device in its final finished form. The sponsor should develop and follow a method 
for tracking the test and control devices from their manufacture or procurement to final use.55
VII. Testing Facility Selection 
Testing facilities can significantly affect the outcome of animal studies. The sponsor should 
ensure that the selected facility complies with all applicable regulations related to housing, care, 
and transport of research animals.56,57,58 FDA recommends that the sponsor consult published 
guidelines involving the well-being of research animals to minimize experimental confounding 
53ANSI/AAMI/ISO 10993-6: Biological Evaluation of Medical Devices, Part 6: Tests for Local Effects after 
Implantation.
54Gibson-Corley, K. N., Olivier, A. K., & Meyerholz, D. K. (2013). Principles for valid histopathologic scoring in 
research. Veterinary Pathology, 50(6), 1007-1015.
55See 21 CFR 58.107.
56Russell WMS, Burch, RL. The Principles of Humane Experimental Technique. London: Methuen & Co.; 1959. 
Special edition published by Universities Federation for Animal Welfare, 1992, available 
athttp://altweb.jhsph.edu/pubs/books/humane_exp/het-toc. 
57 FDA MOU 225-16-010. Available at https://www.fda.gov/about-fda/domestic-mous/mou-225-16-010. 
58 National Research Council Institute of the National Academies (2006). Guidelines for the humane transportation 
of laboratory animals. Washington, DC: National Academies Press. Retrieved from 
http://www.nap.edu/openbook.php?record_id=11557&page=R1
13 Contains Nonbinding Recommendations
factors that could adversely affect the study results.59,60 The referenced guidelines address 
recommendations for minimum housing, husbandry standards, social and environmental 
enrichment, and the development of standard operating procedures that address timely and 
adequate veterinary medical care.
In addition, FDA recommends that the sponsor carefully consider the animal study design when 
selecting the testing facility. If the proposed animal study design is complex, use of facilities and 
staffing equivalent to the human clinical setting may be warranted to facilitate high quality study 
outcomes. Sponsors should ensure that testing facilities have appropriate equipment, supplies, 
and adequate staff with appropriate training, including training with the  medical device, to 
perform the study. For example, some animal studies may benefit from advanced imaging and 
intensive care procedures. Sophisticated post-procedural monitoring and care may also be 
warranted, including 24/7 staffing similar to the clinical care patients receive in an intensive care 
unit.
FDA does not license or certify testing facilities with respect to compliance with the GLP 
Regulations. A testing facility conducting a GLP animal study must comply with all applicable 
requirements under 21 CFR Part 58, and other applicable requirements. Consistent with 21 CFR 
58.15, a testing facility must also permit an authorized FDA employee, at reasonable times and 
in a reasonable manner, to inspect the facility and to inspect all records and specimens required 
to be maintained for a GLP animal study.
VIII. Animal Housing 
Testing facilities are required to have enough animal enclosures to assure proper separation of 
species, quarantined animals, and test systems.61 The sponsor may determine that animal study 
procedure(s) warrant more intensive care during certain predicted sub-acute periods. In these 
cases, FDA recommends that the testing facility also include access to recovery rooms or 
enclosures that allow for individual animal monitoring and treatment as appropriate.
Outside of the post-procedural monitoring period, FDA recommends housing social animals in 
conspecific groups whenever possible to reduce stress. However, the environmental conditions 
should not interfere with the assessment of the study. Group-housed animals should be 
monitored for bullying and territorial stress to minimize weight loss that can result from the 
inadvertent peer-induced decreased access to food and water. All animals should have sufficient 
access to resources, such as food and water receptacles, species-appropriate resting surfaces, and 
species-specific enrichment devices (toys and treats). FDA notes that adequate play and exercise 
are increasingly recognized as important to animal well-being.62,63
59Reinhart, V. & Reinhart A. (2002). Comfortable quarters for laboratory animals (10th ed.). Washington, D.C.: 
Animal Welfare Institute.
60National Research Council Institute of the National Academies (2006). Guidelines for the humane transportation 
of laboratory animals. Washington, DC: National Academies Press. Retrieved from 
http://www.nap.edu/openbook.php?record_id=11557&page=R1.
61See 21 CFR 58.43.
62See 9 CFR 3.8.
63Menor-Campos, D., Molleda-Carbonell, J., & Lopez-Rodriguez, R. (2011). Effects of exercise and human contact 
on animal welfare in a dog shelter. Veterinary Record, 169(16), 388.
14 Contains Nonbinding Recommendations
Animal Quarantine and Conditioning 
Animals should have an adequate amount of time for quarantine and stabilization64 before study 
enrollment  to allow for exclusion of animals with  any disease or condition that might interfere 
with the purpose or conduct of the study.65 Background levels of disease can adversely affect 
study data and should be minimized. For example, animals may have sub-clinical infections that 
can cause disease caused by the stress of surgery or dense housing. FDA also recommends 
initiating a program of socialization to minimize stress during the study; familiarity with 
handlers can reduce background stress, thus potentially minimizing additional confounding 
factors that could affect study results.
Food, Water, and Basic Husbandry 
The testing facility must have standard operating procedures for the housing (including pest 
management), feeding, handling, and care of animals.66 If contaminants that may affect study 
results are reasonably expected to be present in the feed and/or water, the limits should be stated 
in the protocol and an appropriate testing program described.
Sometimes large animals enrolled in chronic studies are transferred to a more typical agricultural 
setting where animals can graze on open pasture as a portion of their diet. In these cases, the 
testing facility should ensure that the animals nutritional needs are met, and the pasture is well-
maintained. Depending on the type and duration of the study, animals housed in agricultural 
settings may benefit from routine health checks, including fecal parasite checks and body 
condition scoring, to help avoid possible interference with study outcomes stemming from 
animal health issues.
IX. Records and Reports 
A final study report must be prepared for animal studies, and any corrections or additions to the 
final study report must be in the form of a report amendment by the study director.67 FDA 
recommends that the study director prepare the records and reports for the animal studies such 
that FDA can most efficiently evaluate the animal safety study.  
 
The Agency recommends copies of raw data68 be included as indexed secondary attachments to 
the final report (Appendix A - Example Organization of Animal Study Final Report ). These 
should include the following when appropriate:
 any data used for statistical analysis;
 copies of case report forms;
 copies of individual animal medical records;
 full clinical pathology reports with the laboratorys reference ranges for each analyte; and
64Russell WMS, Burch, RL. The Principles of Humane Experimental Technique. London: Methuen & Co.; 1959. 
Special edition published by Universities Federation for Animal Welfare, 1992, available at 
http://altweb.jhsph.edu/pubs/books/humane_exp/het-toc. 
65 See  21 CFR 58.43, 58.90(c). 
66 See 21 CFR 58.90.   
67 21 CFR 58.185(a)(c). 
68 Consistent with 21 CFR 58.3(k), raw data means any laboratory worksheets, records, memoranda, notes, or exact 
copies thereof, that are the result of original observations and activities of a nonclinical laboratory study and are 
necessary for the reconstruction and evaluation of the report of that study. 
15 Contains Nonbinding Recommendations
 copies of all images (e.g., gross, microphotographs, angiograms, radiographs, CT, 
magnetic resonance imaging (MRI)).
FDA recommends that a detailed justification of the animal model be provided with the study 
report. This justification should include a rationale for selection of the animal model and a brief 
review of the scientific evidence supporting this model. In cases where an animal model has not 
been established or where the animal model has limited use, selection of an animal model should 
include consideration of anatomical and physiological differences and a detailed description of 
the animal model limitations.
The final report must include the locations where all specimens, raw data, and the final report are 
to be stored.69 FDA also recommends dating all study observations. This helps to capture events 
accurately, which aids in the assessment of the inter-observational differences between study 
subjects.
Further, all raw data, documentation, protocols, final reports, and specimens (with certain 
exceptions) generated as a result of the animal study must be retained.70 FDA may request copies 
of additional raw data71 during the premarket review process depending on study results reported 
in the final report.
X. Preparation of Animal Study Reports for Medical 
Device Premarket Submissions 
When preparing premarket submissions, FDA recommends that the sponsor include a high-level 
summary of the animal testing that was conducted to demonstrate device safety, which includes 
performance and handling. When a series of studies has been conducted, the sponsor should 
explain the effect of the animal studies on device development and the final device design. The 
sponsor should also describe all device design changes that were implemented during animal 
testing. Lastly, the sponsor should describe and justify any modifications to the device design 
that were made to accommodate the animal model. Bookmarked and linked PDF files are 
recommended for FDA premarket submissions whenever possible.
If your animal study was not conducted in compliance with 21 CFR Part 58, FDA recommends 
you include a statement in your submission explaining the reasons why the study was not in 
compliance with the GLP Regulations, as well as a detailed description of all deviations from the 
regulation. FDA recommends the statement include information that will help FDA reconstruct 
the study, explain any confounding variables, and demonstrate that authentic and complete test 
data have been collected and reported.
If multiple animal studies are being submitted, FDA recommends that sponsors present animal 
studies in chronological order so that the Agency can follow the device design history and in vivo 
safety profile from the first to the last study. Each final study report should include a table of 
contents that lists each supplementary report (e.g., in-life veterinarian report, pathology report),
69See 21 CFR 58.185(a)(13).
7021 CFR 58.190(a).
71As defined under 21 CFR 58.3(k).
16 Contains Nonbinding Recommendations
and if applicable, copies of raw data. An example organizational template for relevant content of 
an animal study report for regulatory submissions is provided in Appendix A.
The list below is intended as an example of the organization of a final report for recommended 
and required content.72
Executive Summary 
This summary should also include the following information for each animal study:
 the rationale for the animal model;
 any differences between the animal model and humans that may have affected the study; 
and
 the specific animal study methodology used.
FDA recommends providing a table for each study that allows FDA to track individual 
parameters for animals through the study stages. This table should include the following 
information:
 unique animal ID(s) (e.g., USDA, institutional/testing facility, study cohort);
 allocation to study subgroups;
 endpoints for each study group, if applicable;
 the number of animals in each group;
 study duration;
 the device design iteration used;
 type(s) of procedure(s) performed;
 fate or disposition of each animal; and
 summary of study outcomes.
If animals are purchased with individual USDA IDs but then subsequently identified with an 
institutional ID and then further described by a group ID, this information should be clearly 
described and presented in the report so that a chain of custody of any individual test or control 
animal is possible.
Final Study Report 
Each animal study must have a final report that is signed and dated by the study director.73 The 
final study report for each animal study must include the information specified in the GLP 
Regulation, including but not limited to a description of all circumstances that may have affected 
the quality or integrity of the data.74 Any change to the signed and dated study protocol must be 
reported as an amendment and attached to the final study report.75
72This outline does not include all of the requirements of 21 CFR 58.185. For more information on required content 
necessary to be in compliance with Part 58 reporting requirements, please see 21 CFR 58.120 and 21 CFR 58.185.
73See 21 CFR 58.185(b).
74See 21 CFR 58.185(a)(9).
75See 21 CFR 58.120(b).
17 Contains Nonbinding Recommendations
The report must include a quality assurance statement that specifies the dates and phases of study 
during which inspections were made and reported to management and the study director.76 This 
can help provide documentation that the study was conducted per the protocol such that the 
methods, procedures, recording, and reporting of raw data are truthful and accurate, and that the 
facilities, equipment, personnel, methods, practices, records, and controls are in conformance 
with the GLP Regulations.77
The final study report must also include the signed and dated reports of each individual scientist 
or other professional involved in the study.78 The following section provides recommendations 
on commonly included reports from other professionals involved in the study.
(1) In-Life Veterinarian Report 
One of the advantages of animal studies is the opportunity to assess the clinical response to a 
device and/or procedure. Study animals are maintained in a controlled environment, which 
facilitates in-life observations. In contrast, the environment in clinical studies may be more 
difficult to control, which can lead to loss of follow-up data. Therefore, FDA recommends that 
the final study report include an in-life report from the study veterinarian that summarizes all key 
events for each animal enrolled in the study. The report should include copies of the individual 
animal medical records maintained in standard POVMR format, including any provision of 
veterinary care.
(2) Pathology Report  
The pathology report represents the pathologists best judgment regarding relevant tissue 
changes and their interpretation in the context of the study. The pathology report should include 
a table that correlates the gross pathological findings with the histopathologic findings in each 
animal/tissue. It should include a narrative that describes and interprets all observed adverse 
tissue findings. The pathologist should justify any statements regarding whether any adverse 
outcomes are or are not device-related with appropriate information from gross pathology data, 
histopathology data, and in-life assessments, including the relevance of any extenuating 
circumstances (e.g., concurrent disease).
FDA recommends that the pathologist describe any non-standard methods used to collect tissues 
as well as the methods of fixation, cutting, and staining.79 The pathologist should describe the 
sectioning methods, noting the tissue type and device orientation as appropriate. Diagrams may 
be helpful in illustrating device location and how the device should be sectioned for histology.
The pathology report should include high-resolution, properly illuminated, color, gross, and 
photomicrograph images of all abnormal findings and corresponding normal tissues from all test 
and control animals. The gross images and photomicrographs should be labeled with a minimum 
of the animal ID, study group ID, size marker, and date. All photomicrographs should also 
indicate tissue section, magnification, scale, stain, and any other important identifiers. The 
accompanying legend should fully describe the pathological changes in the tissues.
76See 21 CFR 58.35(b)(7), 58.185(a)(14).
77See 21 CFR 58.35(b)(1)(7).
7821 CFR 58.185(a)(12).
79Dettmeyer, R. (2013). Forensic histopathology: Fundamentals and perspectives. Heidelberg, Germany: Springer.
18 Contains Nonbinding Recommendations
(3) Other Reports/Forms 
Depending on the nature of the study, the final study report should also include any other reports 
that are signed and dated by contributing scientists. Examples include but are not limited to 
clinical pathology, radiology, or other forms of imaging, and behavioral studies. Clinical 
pathology reports should identify the laboratory performing the tests, the laboratorys reference 
range values, and the clinical pathology data for each animal. A table, presenting clinical 
pathology results by animal and time point and including laboratory reference ranges, can help 
FDA interpret larger data sets. If applicable, FDA recommends sponsors provide copies of 
completed case report forms, and surgical/anesthesia monitoring forms in the final study report, 
to aid in the interpretation of study results.
The study director should  ensure that the report details the source of the animals.
Additionally, the final study report should include documentation of protocol approval by an 
Institutional Animal Care and Use Committee (IACUC)80 before initiation of the study or, if 
conducted outside the United States, an equivalent approved protocol.
80See 9 CFR 2.31.
19 Contains Nonbinding Recommendations
Appendix A  Example Organization of Animal Study Final 
Report 
The list below is intended as an example of the organization and content of a final report This 
example does not include all the requirements of 21 CFR 58.185. For more information on 
required content necessary to be in compliance with 21 CFR Part 58 reporting requirements, see 
21 CFR 58.120 and 21 CFR 58.185.
I. A coversheet for each animal study that includes:
A. Title of the report
B. Report identification numbers (as applicable):
1. IACUC/ethics committee protocol number
2. Study director protocol number(s)
3. Testing facility protocol number(s), if applicable
C. Contact information (i.e., mailing address, street address, city, state, country, and 
ZIP code for each contact) for the following entities:
1. Sponsor
2. Sponsor representative, if different than sponsor
D. Testing facility name and address
E. Study initiation and completion dates
F. Final report signatures with date of signature:
1. Study director
2. QAU
3. Key personnel
II. Table of contents (preferably hyperlinked)
III. List of abbreviations and definitions
IV. Copy of the approved protocols, including:
A. Final GLP study protocol
B. IACUC-approved protocol with documentation of approval (if different from the 
GLP study protocol) 
V. Final test report that includes:
A. Overview/executive summary of animal study:
B. Body of test report
1. Study objectives and endpoints with acceptance criteria
2. Study time point(s)
3. Animal model and number of animals enrolled
4. Characterization of test and control articles:
a. Design iteration of device used, i.e., how design iteration compares 
to the final device version intended for clinical use in humans
b. Referenced serial or model numbers
20 Contains Nonbinding Recommendations
5. Description of methods used, including surgical/procedural approach and 
technique, imaging, animal monitoring, wellness interventions (as 
applicable), necropsy, and histology as appropriate
6. Study deviations and amendments
7. Statistical analysis plan
8. Study results, organized by objective
a. Deployment/procedural results, including system/equipment 
compatibility
b. Impact of animal on device (e.g., structural integrity)
c. Biologic (physiological) response to the device
d. Imaging
e. Adverse events
9. Conclusions: 
a. Comparison with controls
b. Success in meeting acceptance criteria
c. Discussion of study limitations
C. Quality assurance compliance statement 
VI. Indexed attachments, if applicable:
A. Copies of raw data and individual test reports used to draw study conclusions
B. Signed and dated contributing scientist(s) reports (i.e., interventionist, surgeon, 
radiologist, clinical veterinarian, clinical pathologist, pathologist, 
neuro/behaviorist).
C. Animal medical records, including baseline and interim health examinations
D. Surgery and anesthesia monitoring forms
E. Imaging reports
F. Clinical pathology results, with reference ranges
G. Completed case report forms
H. Animal vendor reports/invoices
21