Investigational Device Exemption 
(IDE) Guidance for Retinal 
Prostheses 
Guidance for Industry and Food 
and Drug Administration Staff  
  
Document issued on: March 6, 2013  
 
The draft of this document was issued on April 17, 2009. 
 
 
 
For questions regarding this document contact Ethan Cohen, Ph.D. at 301-796-2485, 
ethan.cohen@fda.hhs.gov  (OSEL) or Bernard Lepri, OD, MS, M.Ed. at 301-796-6501, 
bernard.lepri@fda.hhs.gov (ODE).  
 
 
U.S. Department of Health and Human Services 
   Food and Drug Administration 
Center for Devices and Radiological Health 
 
Office of Science and Engineering Laboratories  
Office of Device Evaluation 
                                Contains Nonbinding Recommendations 
  
 
Preface 
  
 
Public Comment 
  
 
You may submit written comments and suggestions at any time for Agency consideration to the 
Division of Dockets Management, Food and Drug Administration, 5630 Fishers Lane, 
rm. 1061, (HFA-305), Rockville, MD, 20852.  Submit electronic comments to 
http://www.regulations.gov.  Identify all comments with the docket number listed in the notice 
of availability that publishes in the Federal Register.  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 e-mail request to 
dsmica@fda.hhs.gov to receive an electronic copy of the guidance or send a fax request to 
301-847-8149 to receive a hard copy.  Please use the document number 1809 to identify the 
guidance you are requesting. 
  
  Contains Nonbinding Recommendations 
  
 
Table of Contents 
  
 
1. Introduction ......................................................................................................................... 2 
2. Scope..................................................................................................................................... 3 
3. Device Description .............................................................................................................. 3 
a. Video Camera/Transducer and Attachments ..................................................................... 4 
b. Device Accessories ............................................................................................................ 5 
4. Risk Analysis ....................................................................................................................... 5 
5. Content and Format of Test Data ...................................................................................... 6 
a. Table of Contents ............................................................................................................... 6 
b. Tests Performed, Data Summaries, and Conclusions ........................................................ 6 
6. Pre-clinical Tests ................................................................................................................. 6 
a. Materials and Biocompatibility .......................................................................................... 6 
b. Animal Tests ...................................................................................................................... 7 
c. Electrode Stimulation Tests ............................................................................................... 8 
d. Durability Tests ................................................................................................................. 9 
e. Electronics ....................................................................................................................... 11 
f. Software ........................................................................................................................... 12 
g. Visible and Electromagnetic Radiation, and Magnetic Resonance Imaging (MRI) 
compatibility ........................................................................................................................ 13 
h. Sterilization and Packaging ............................................................................................. 14 
7. Clinical Tests ..................................................................................................................... 15 
a. Clinical Protocol .............................................................................................................. 15 
b. Unanticipated Adverse Device Effects ............................................................................ 16 
c. Safety Outcomes .............................................................................................................. 17 
d. Effectiveness Outcomes................................................................................................... 17 
e. Statistical Analysis Plan ................................................................................................... 20 
8. Informed Consent Document ........................................................................................... 20 
9. Patient Information and Labeling ................................................................................... 21 
Appendix A: List of Referenced Standards ........................................................................ 24 
 
 
 
 
 
 
  Contains Nonbinding Recommendations 
  
 
Investigational Device Exemption (IDE) 
Guidance for Retinal Prostheses 
Guidance for Industry and  
Food and Drug Administration Staff 
 
 
This guidance represents the Food and Drug Administration's (FDA's) current thinking 
on this topic.  It does not create or confer any rights for or on any person and does not 
operate to bind FDA or the public.  You can use an alternative approach if the approach 
satisfies the requirements of the applicable statutes and regulations.  If you want to discuss 
an alternative approach, contact the FDA staff responsible for implementing this 
guidance.  If you cannot identify the appropriate FDA staff, call the appropriate number 
listed on the title page of this guidance.  
  
1. Introduction 
This guidance is intended for FDA reviewers and members of industry who intend to submit 
an investigational device exemption (IDE) to the FDA to conduct feasibility and/or pivotal 
human clinical trials of their retinal prostheses in the United States to support a premarket 
approval (PMA) or a humanitarian device application (HDE). 
 
This document provides guidance about developing pre-clinical and clinical tests of retinal 
prosthetic devices. This guidance describes pre-clinical tests that you should conduct to 
characterize device safety before initiating any clinical testing.  
 
This device-specific guidance document should be considered in addition to other FDA 
publications on marketing or IDE applications and is not a replacement for those documents. 
The CDRH Device Advice website 
(http://www.fda.gov/http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Ho
wtoMarketYourDevice/default.htm) has additional information about PMA (21 CFR 814), 
HDE (21 CFR Part 814 Subpart H), and IDE (21 CFR Part 812) submissions. 
We recommend that you use this document as you develop data to support an IDE 
application. The pre-clinical and clinical tests mentioned in the guidance represent FDAs 
current thinking based on the information available at this time. Given the limited history 
with devices in this field, additional information may become available at a later date that 
suggests alternative test methods or functional assessments that may be more appropriate to 
assess the safety and effectiveness of retinal prostheses. For this reason, we strongly suggest 
the sponsors of such devices submit a Pre-Submission to facilitate discussion of clinical trial 
  2  Contains Nonbinding Recommendations 
  
 
designs, pre-clinical test protocols, and proposed indications for use for any specific retinal 
prosthesis. 
 
This guidance cites a number of voluntary consensus standards which are recognized by 
FDA. You may access a list of the FDA-recognized standards from the CDRH web site at 
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm. See Appendix A 
for a list of the voluntary standards referenced in this guidance.  You may also consult FDAs 
guidance Recognition and Use of Consensus Standards 
(http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/u
cm077274.htm).  
 
For the purposes of this guidance, you refers to the sponsor of the IDE investigation and 
we refers to FDA. 
 
FDA's guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidance documents describe the Agency's 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 guidance means that 
something is suggested or recommended, but not required.   
2. Scope  
This document is limited to retinal prostheses, (i.e., visual prosthetic devices implanted on or 
beneath the retina, and those on or beneath the outer surface of the globe), that use electrical 
stimulation to provide some level of visual perception for persons suffering from 
degenerative retinal conditions. 
This document does not apply to prostheses that stimulate the optic nerve or other higher 
brain areas such as the visual cortex or the lateral geniculate nucleus. In addition, prostheses 
that incorporate drugs or biological products may be combination products. The FDA Center 
with regulatory responsibility for a combination product is determined by the primary mode 
of action of the product and in some circumstances may not be CDRH. For additional 
information on combination product jurisdiction or to submit a Request for Designation, 
please refer to the FDA Office of Combination Products (see 
http://www.fda.gov/oc/combination).  
FDA believes that the devices addressed by this guidance document are significant risk 
devices as defined in 21 CFR 812.3(m). Sponsors intending to use these devices in a clinical 
investigation in the United States must therefore submit an IDE application to FDA and 
obtain FDA and IRB approval of the application before beginning the investigation (21 CFR 
812.20(a)). In addition to the requirement to obtain an FDA-approved IDE (21 CFR Part 
812), sponsors of such studies must comply with the regulations governing institutional 
review boards (IRBs) (21 CFR Part 56) and informed consent (21 CFR Part 50). 
3. Device Description  
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Your IDE application must include the complete investigational plan or, where appropriate, a 
summary of the investigational plan (21 CFR 812.20(b)(2)). In your investigational plan you 
should include a description of the prosthetic device and its functional components (21 CFR 
812.25(d)). Your description should include:  
  pictorial representations,  
  engineering drawings,  
  block diagrams of circuits, and  
  block diagrams of software interfaces.  
The block diagrams of the circuits should trace signal flow, processing, and logic of 
operation at the system level and the circuit level as appropriate. 
Your description of each functional component should include:  
  a complete set of electrical schematics,  
  a complete set of mechanical drawings,  
  detailed drawings and descriptions of all components including material composition 
and coatings,  
  electrical specifications and, where appropriate, references to laboratory testing that 
established these specifications,  
  mechanical specifications and, where appropriate, references to laboratory testing that 
established these specifications,  
  an explanation of how the implant design accommodates human eye and head size 
variation,  
  detailed engineering drawings of the electrode(s) in the stimulation array including 
the electrodes number, dimensions, spacing, material composition, insulation, 
flexibility, and the surface area/thickness of any coatings, and  
  detailed descriptions of any cabling including: interconnects from the electrodes to the 
application specific integrated circuit (ASIC), cable conductors, and cable insulation 
layers or associated coatings.  
a. Video Camera/Transducer and Attachments 
If your device utilizes a component to capture a picture of an image, we recommend you 
describe the following:  
  the type of photosensor or video input and processor used with the retinal implant,  
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  the resolution and configuration of its sensors, sensor location, low-light sensitivity, 
field of view, and ability to encode contrast in the visual scene,  
  any eye tracking capabilities, and  
  the means of attaching any external connectors, transmitters, telemetry coils, visual 
processors, and spectacles.  
We also recommend you describe the effects of coil distance and eye movements on 
telemetry data transmission during use.  
b. Device Accessories 
We recommend that you describe all device accessories used for programming, clinical 
fitting, testing, or home use of your device. You should include pictorial representations, 
engineering drawings, block diagram circuits, and block diagrams of software interfaces for 
accessories such as user controls, eye trackers, programming interfaces, software, cameras, 
spectacles, video processors, cables, connectors, and projection equipment. In addition, we 
recommend you describe the type of battery used in the device.  
c. Manufacturing Process 
You should provide a description of the manufacturing and inspection steps related to 
achieving critical specifications for the device, including the final device acceptance criteria.  
4. Risk Analysis  
You must include in your investigational plan a description and analysis of all increased risks 
to which subjects will be exposed by the investigation, as well as the manner in which these 
risks will be minimized (21 CFR 812.25(c)). You should describe in the IDE application the 
method you used to conduct this risk analysis and, in so doing, include sufficient detail to 
support the chosen method.  
To fulfill this risk analysis requirement, we recommend that you perform a Failure Mode and 
Risk Analysis summary on the electronic components and circuitry. Your Failure Mode and 
Risk Analysis summary should identify and assess the risks due to any potential electronic 
hazards/failures, the potential severity of these risks, and how to eliminate or reduce them. 
We recommend you supply a traceability matrix showing how you validated your risk 
mitigation features in the electronics of your visual prosthetic device. 
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5. Content and Format of Test Data 
a. Table of Contents  
We recommend you include a table of contents at the beginning of the submission that lists 
the specific tests that were performed.  
b. Tests Performed, Data Summaries, and Conclusions 
For each test performed, you should state the study objective, method (protocol) used, results, 
and conclusions. As applicable to your device, the report should contain:  
  minimum measured value (min),  
  maximum measured value (max),  
  mean, and  
  standard deviation (std. dev.) of the test data.  
We also recommend that you provide a narrative summary of your conclusions for each test 
conducted and explain whether the results support the safety and performance of your device.  
6. Pre-clinical Tests 
If you provide information on nonclinical laboratory studies in your IDE application, you 
must state whether such studies complied with 21 CFR Part 58, Good Laboratory Practice for 
Nonclinical Laboratory Studies (21 CFR 812.27(b)(3)). If such studies were not conducted in 
compliance with these regulations, you must state the reason(s) for noncompliance (21 CFR 
812.27(b)(3)).  
We recommend including the following testing information in your application. If you choose 
not to include any of the following information, you should explain why you believe such 
information is not relevant to your device.  
a. Materials and Biocompatibility  
You should completely describe the material compositions used in your retinal prosthetic 
device. For all implant material or material contacting the subject, you should provide 
detailed specifications for the formulation or chemical composition, particularly for materials 
with no history of intraocular or implant use. We recommend that you use generic names to 
describe the formulations of all device materials.  
You should provide material biocompatibility profiles for all subject-contacting device 
components, as described in the FDA guidance Use of International Standard ISO-10993, 
Biological Evaluation of Medical Devices Part 1: Evaluation and Testing 
  6  Contains Nonbinding Recommendations 
  
 
(http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/u
cm080735.htm). We recommend that you document the biocompatibility of the device and its 
associated insertion tools by conducting appropriate tests with the finished device or a 
facsimile that has undergone similar manufacturing processing, including sterilization. 
Literature and/or test references for the same material which has undergone the same 
manufacturing process are generally acceptable. You should also include histology 
evaluations, where applicable. 
Bacterial Endotoxin Testing  
We recommend that you provide bacterial endotoxin test results on implanted device 
components using a validated test method that includes inhibition and enhancement 
testing, such as USP 34:2011, <85> Bacterial Endotoxins Test, or AAMI 
ST72:2002/(R)2010, Bacterial endotoxins - Test methodologies, routine monitoring, 
and alternatives to batch testing. 
Leachables Testing 
We recommend that you determine the stability of the retinal prostheses material 
components in a saline environment through detection and quantification of possible 
degradation products from hydrolysis and changes in physical appearance. The test 
device should consist of the implant including all external material components (e.g., 
polymers, metals, ceramics, coatings, etc.) used in the construction of the finished 
device. Your extraction study should be designed to evaluate the stability of these 
materials in a saline environment at 35 C for a period of at least five years or at an 
elevated temperature for a similar equivalent exposure. The saline media should be 
qualitatively and quantitatively analyzed at the end of the extraction for possible 
extractable components of the test material(s). The results should be evaluated to 
assess the risk for potentially harmful effects from the extractable components and 
they should be recorded in the device risk assessment. 
 
Pyrogen Testing 
 
The implant and its insertion devices should be tested for material-mediated 
pyrogenicity using the Rabbit Pyrogen Test (USP <151>) unless justification can be 
given.  For device materials, firms should assess the risk of the presence of non-
endotoxin pyrogens. See FDAs Guidance for Industry:Pyrogen and Endotoxins 
Testing: Questions and Answers (available at 
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/uc
m314718.htm).  
b. Animal Tests 
We recommend that you conduct animal testing on an active finished device (one that can be 
turned off) to establish adequate safety before commencing a substantive human trial. We 
also recommend that you design a staged testing approach that includes evaluation of several 
animals which are implanted long term. 
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Since implantation may induce failure modes not predicted by device bench testing, we 
recommend that animal studies evaluate the ocular tissue biocompatibility of the implanted 
prosthetic device and its associated components and stimulation arrays. The unimplanted eye 
may be used for comparison. The animal study test reports should include the following 
items:  
  study protocol and objective,  
  study design including the species, strain and number of animals used,  
  stimulation levels and rates used (if present),  
  visually evoked response testing (if present) such as electroretinograms or visually or 
electrically evoked potentials, and  
  histology of the eye and retina with particular attention to regions of device 
implantation or attachment.  
We also recommend you provide an analysis of the animal testing data and a description of 
any modifications made to the device as a result of this testing.  
Acute Tests  
You should test the prosthesis electrodes to stimulate the retina near their maximal limits in 
an animal model for a period of 24 hours. The animal may be sedated. After testing, you 
should perform a gross pathological and a detailed histological examination of the eye and its 
layers. 
Long-Term Tests  
You should implant the final form of the fully functional retinal prosthetic device in the eye 
of a model animal for at least 6 months. The device does not have to be activated and 
stimulating for the entire duration of implantation to verify device functionality. It may be 
appropriate to test the device (have it active and stimulating) only within the first 2 weeks 
after implantation and again just before explantation to characterize the functionality of the 
device. 
After explantation, you should examine the eye and its layers histologically for any pathology 
associated with the implant. We also recommend you evaluate the explanted device at a 
magnification sufficient to detect any failure mechanisms such as corrosion or insulation 
degradation.  
c. Electrode Stimulation Tests 
You should report the stimulation testing range and limits for the electrodes in the array. For 
each electrode tested, we recommend you describe the following items:  
  the range of stimulation values you plan to test in subjects,  
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  whether the pulses are current- or voltage-regulated,  
  whether the stimulation is bipolar or monopolar,  
  the pulse charge densities to be tested in mC/cm2 per phase,  
  the charge/phase delivered,  
  the pulse sequence and polarities, for example, monophasic or biphasic,  
  the frequencies of pulse/train stimulation you plan to test,  
  the waveforms and duration/phase of the pulses/pulse trains you plan to test,  
  the resistance of the electrodes,  
  the maximal voltage delivered per pulse,  
  whether the pulses are capacitively coupled, charge-balanced or asymmetric, the 
charge recovery method and, 
  the leakage resistance of the electrodes to the stimulator case, if applicable.  
We recommend you also describe briefly how the maxima of the above stimulation 
parameters will overlap in subject tests on single electrodes. For example, you should 
describe the maximal pulse charge density, pulse frequency, and stimulus duration of the test. 
d. Durability Tests 
We recommend you plan for and begin to conduct the durability testing described below. 
Prior to initiating human studies you should be able to provide an estimate of the following 
parameters: 
Design Lifetime and Performance Durability Tests  
We recommend that you describe the design lifetimes for both the implanted and external 
device components. We recommend that you design the implanted components of your 
device to withstand a minimum of 5 years simulated use or provide a rationale for a shorter 
duration.  We also recommend that you address the durability of the stimulation electrodes by 
conducting a series of accelerated lifetime tests to evaluate the durability of the 
electrodes/electrode arrays to electrical stimulation toward the prosthetic design lifetime. In 
addition, we recommend that you perform these tests at the maximal stimulation rate in a 
saline bath at 37oC or higher. 
You should also assess the durability of the implant by performing a series of accelerated 
lifetime tests. These tests should evaluate the durability of the complete implant, mounts, 
bands, and telemetry coils (if present) to maximal rate stimulation, power reception, and 
telemetry. In addition, we recommend you assess the durability of the external device 
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components by performing a series of lifetime tests on the external visual processor 
electronics, optical sensors, and telemetry coils (if present). 
Calculation of Estimated Lifetimes  
We recommend that you relate the assessment of device lifetime to the results of the tests 
conducted, which may include stress, hermeticity, corrosion, fatigue test analysis, and any 
other tests necessary to evaluate potential device failure modes. You should include 
documentation about how the estimated device lifetime was derived from the tests conducted. 
We recommend you describe all failure modes and effects found in your device tests, and the 
criticality of any failures found. 
Hermeticity Tests  
A key factor in determining the lifetime durability of the prosthetic device is maintaining 
device hermeticity. We recommend you supply data on the design to be used in the clinical 
study using accelerated lifetime tests. You should test the device until failure. We also 
recommend you evaluate the hermeticity of your complete device using product lifetime 
immersion tests in a saline solution at 37oC or higher.  Tests that evaluate the items listed 
below may be done concurrently. 
Evaluation of Coating Durability  
For devices and associated cable assemblies coated with water-resistant films, we 
recommend you provide a study demonstrating that your coating remains effective after 
immersion testing.  With coatings that are critical to device function, the test should be of a 
sufficient temperature and duration to detect coating failures.  We also recommend you report 
any cracks, delamination, or scratches, and their observed dimensions. You should 
substantiate the level of magnification that you use in your inspection method, based on the 
size of the defect that would cause device failure. 
Potential for Corrosion  
We recommend that you evaluate the potential for corrosion in designs that allow 
micromotion between components, such as cable interconnects or suture holes that may 
disrupt an associated insulation coating or passive film. 
Welding and Bonding Patency Tests  
We recommend that you validate the adequacy and reliability of any welding or bonding 
processes used in device fabrication, and their inspection methods. We also recommend you 
describe the inspection process of how device hermeticity of the case (if present) and cabling 
is validated and determined. Last, we recommend that you describe any validation tests 
performed such as helium leak tests or impedance spectroscopy. 
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Flexion Testing  
We recommend you conduct tests of your retinal prosthesis that simulate the actual forces 
experienced under flexion when it is mounted in its intended location on or in the eye. We 
recommend you conduct the tests in saline, at 37oC or higher. 
  To assess surgical insertion stresses, we recommend that you demonstrate how your 
device and its cables will withstand surgical implantation, suturing, and any folding.  
  We also recommend that you explain the clinical relevance of the loading conditions 
used for the accelerated flexion testing. 
  You should also assess flex stresses exerted during normal eye movement. We 
recommend you perform long-term durability testing that models the physiological 
loads and boundary conditions that your retinal prosthesis and its cables are likely to 
experience in its intended ocular location, under normal visual function and daily 
saccadic eye movement.  
e. Electronics 
We recommend you supply accurate specifications and fabrication data supporting the 
design, thermal dissipation, electronic circuitry, ASIC, interconnects, cabling, and 
transmission coils of the implant.  
Eye Orientation and Radio Frequency Link Safety  
If the unit uses an external power source and signal, you should supply documentation 
showing that power is received by the implant through the full range of eye rotational angles. 
We also recommend you include safety data documenting how the device responds to loss of 
power or signal in response to excessive rotation of the eye.  
Eye Movements  
If your device contains a camera or optical sensor not mounted directly to the eye itself, you 
should document how your device will respond to the subject's eye movements.  
Safeguards  
You should describe the safety features built into the device such as electromagnetic 
interference (EMI) rejection filters, direct current leakage detection, recovery from power 
loss, electrode stimulation limits, error logs, hardware watchdogs and resets to validate 
proper device function. 
Batteries  
We recommend you describe the type of battery used in the device, its composition, location, 
and indicate the projected battery life. You should indicate whether the battery is disposable 
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or rechargeable, and how the battery is replaced. In addition, you should describe any 
protection circuitry against inserting the battery with incorrect polarity or shorting.  
Mobile Unit Controls  
We recommend you describe how the portable subject controller of your retinal prosthesis 
addresses usability, if applicable (i.e., human factors): 
  audible machine state indicators or warnings,  
  tactilely discernable instrument controls,  
  impact resistance,  
  presence of an accessible safety or power cutoff switch,  
  water and perspiration resistance, and  
  ease of battery insertion for replacement.  
We recommend you review the FDA guidance on human factor design in instrument control, 
Medical Device Use-Safety: Incorporating Human Factors Engineering into Risk 
Management-- Identifying, Understanding, and Addressing Use-Related Hazards 
(http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/u
cm094460.htm).  
f. Software 
We recommend you describe in detail the physician fitting software, device programming, 
patient software controls, and protections against excessive stimulation levels. We also 
recommend you describe how the software is configured for home use and user adjustment. 
We recommend you address the following issues, as applicable to your device:  
  any fail-safes,  
  resets and presets,  
  software validation tests,  
  power down/recovery,  
  low power situation,  
  device feedback of proper function,  
  software limits on device outputs, and  
  any protection against user or clinician programming error.  
  12  Contains Nonbinding Recommendations 
In addition, we recommend you validate all patient and clinician software as described in 
Guidance for the Content of Premarket Submissions for Software Contained in Medical 
Devices 
(https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/
GuidanceDocuments/ucm089593.pdf).  The kind of information we recommend you submit 
is determined by the level of concern, which is related to the risks associated with software 
failure. The level of concern for a device may be minor, moderate, or major. The Software 
guidance describes how you should assess the level of concern for an individual device. You 
should also refer to the guidance, General Principles of Software Validation 
(http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/u 
cm085281.htm). 
g. Visible and Electromagnetic Radiation, and Magnetic Resonance
Imaging (MRI) compatibility 
We recommend you demonstrate reasonable assurance that use of the device results in neither 
serious bodily injury nor device malfunction or failure due to electromagnetic emission or 
interference. We suggest you also describe the radiopacity of the unit and its associated 
implanted components. 
Visible or IR Emission 
If the device or any of its components emit visible or infrared (IR) radiation into the eye, we 
recommend you evaluate the radiation levels and compare them to levels noted in ISO 15004-
1,2:2007 Ophthalmic instruments - Fundamental requirements and test methods or ISO 
10939:2007 Ophthalmic instruments - Slit-lamp microscopes or equivalent. 
If diffuse illumination of the eye is employed by the device (e.g., IR illumination for pupil 
tracking), we recommend you document that the irradiance does not exceed ANSI 
RP27.1:2005 or- RP27.3:2007 standards: Recommended Practice for Photobiological Safety 
for Lamps and Lamp Systems-or equivalent. 
Electromagnetic Compatibility 
We recommend you evaluate your retinal prosthesis for compatibility with electromagnetic 
interference from various field strength MRI scanners, metal detectors, high voltage sources 
and devices emitting strong magnetic fields. Other devices that should be evaluated if 
applicable include common wireless communication devices, diathermy units, and cardiac 
defibrillators. 
For electromagnetic compatibility testing of the external device components, we recommend 
you follow IEC 60601-1-2 Medical Electrical Equipment - Part 2: General Requirements for 
Safety; Electromagnetic Compatibility  Requirements and Tests (General) or an equivalent 
method. Also refer to Electromagnetic Compatibility (EMC) on FDAs website. 
(http://www.fda.gov/Radiation-
EmittingProducts/RadiationSafety/ElectromagneticCompatibilityEMC/default.htm) 
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MRI Compatibility  
We recommend that you inform the subject and the dispensing physician of any MRI or EMC 
exposure hazards and incompatibilities associated with the retinal prosthesis such as metal 
detectors, radiofrequency identification (RFID), wireless devices, or subways, among others.  
h. Sterilization and Packaging 
We recommend that you describe the sterilization process for each part of the retinal 
prosthesis, such as the implant component and surgical insertion tools. Portions of the device 
that are implanted or that contact breached skin or tissue should be sterilized to a sterility 
assurance level (SAL) of 10-6. Whenever possible, the device should be sterilized in its final 
package. 
We recommend that you describe the validation of each sterilization process, with reference 
to any sterilization standards you have followed. You should describe the packaging for each 
device or component and include package integrity testing to support the ability of the 
packaging to maintain sterility in the as-manufactured state and over the stated shelf life. The 
device should also be demonstrated to withstand aging in its sterile package. 
 
If the device is sterilized by ethylene oxide, ethylene oxide residual levels for the intraocular 
portion of the device should be consistent with the levels specified for intraocular lenses in 
ANSI/AAMI/ISO 10993-7 Biological Evaluation of Medical Devices - Part 7: Ethylene 
Oxide Sterilization Residuals. 
We recommend you use the following sterilization and packaging standards for devices 
sterilized by the applicable method:  
  ANSI/AAMI/ISO 17665-1:2006 Sterilization of health care products - Moist heat - 
Part 1: Requirements for the development, validation, and routine control of a 
sterilization process for medical devices.  
  ANSI/AAMI/ISO 11135-1:2007 Sterilization of health care products - Ethylene oxide 
- Part 1: Requirements for the development, validation, and routine control of a 
sterilization process for medical devices. 
  ANSI/AAMI/ISO 11137-1:2006/(R) 2010 Sterilization of health care products - 
Radiation - Part 1: Requirements for development, validation, and routine control of a 
sterilization process for medical devices.  
  ANSI/AAMI/ISO 11607-1-2:2006 Packaging for terminally sterilized medical devices 
 Parts 1 and 2. 
  ASTM F1980-07  Standard Guide for Accelerated Aging of Sterile Barrier Systems 
for Medical Devices.  
  AAMI/ANSI ST67:2003/(R) 2008 Sterilization of health care products - 
Requirements for products labeled "STERILE" 1st edition ST67:2003/(R). 
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7. Clinical Tests 
We recommend you provide a written overview in your IDE application of all anticipated 
phases of the clinical investigation, outlining the studies you plan to conduct at each phase 
and describing any plans to pool data from more than one phase. Specifically, you should 
provide a detailed description of the initial feasibility study (i.e., study to refine clinical 
metrics or device design) and provide an overview of your later phase studies, if these 
studies are already in the planning stages. We recommend that you plan to follow subjects 
for three years or longer.   
We recommend that surgery be performed only to implant the test device and not 
simultaneously correct other ocular conditions to avoid compromising demonstrations of 
clinical safety or effectiveness in your IDE studies. If device implantation will be performed 
simultaneously with other procedures because it is deemed necessary for patient safety and 
for the evaluation of the device, justification should be provided to account for potential 
confounding introduced by the second procedure in the analyses of the study endpoints. 
a. Clinical Protocol 
Since IDE clinical testing generally follows a phased approach, the sections on clinical 
testing and device labeling will have different levels of importance for feasibility study 
protocols compared to pivotal studies of the final device design intended to support a 
marketing application. 
 For each planned clinical study we recommend you provide:  
  the indications for use, which should include the target population, 
  the study type [e.g., pivotal, expansion (continuation of a feasibility or pivotal study), 
or feasibility trial],  
  the design of the study, including objectives, any masking, randomization, and 
controls or shams used for comparison,  
  the total time planned for subject follow-up,  
  the number of subjects you plan to enroll (sample size),  
  the number of investigational sites, both inside and outside the U.S.,  
  the subject inclusion and exclusion criteria including: 
  a defined age range for participants and the range of visual acuities and 
o
visual conditions considered acceptable for subject enrollment. A 
cognitive assessment is recommended in order to provide consideration for 
psychosocial factors such as subject coping/adjustment ability, family 
support, expectations of their participation, and ability to communicate 
and participate in all aspects of research.  
  15  Contains Nonbinding Recommendations 
  
 
  other health-related conditions, medications, etc., that would confound 
o
study outcomes, or may be contraindicated for the proposed procedure 
resulting in exclusion from the study. We recommend that you document 
the reasons for not enrolling subjects who were screened under the 
protocol.  
  primary safety and effectiveness endpoints described as specific objective clinical 
targets, and other endpoints such as optical evaluation of the placement of the 
electrode array near the retinal tissue. 
  a study plan detailing tests and testing methodologies, and the stimulation range, 
rates, and levels you plan to test in the subjects.  
  Describe how you will sample (the number of repetitions and analysis) the 
o
subjects visual performance to adequately characterize pre-operative 
vision. This should be done at least three times total on three different days 
preoperatively. Post-operatively, the protocol should also include repeated 
measures to minimize variability in the assessments used to evaluate study 
endpoints. 
  All testing with the device should be done through a non-dilated pupil. 
o
  a schedule/time table of all clinical tests to be performed for pre- and post-operative 
evaluation of the subjects. We recommend you evaluate subjects visual performance 
at intervals of at most three months for the first year and at intervals of at most six 
months thereafter.  
  the participating investigators, if known. 
 
b. Unanticipated Adverse Device Effects 
Investigators must report all unanticipated adverse device effects1 to the sponsor and to their 
reviewing IRBs, in accordance with 21 CFR 812.150(a)(1). Unanticipated adverse device 
effect means any serious adverse effect on health or safety or any life-threatening problem or 
death caused by, or associated with, a device, if that effect, problem, or  death was not 
previously identified in nature, severity, or degree of  incidence in the investigational plan or 
application (including a supplementary plan or application), or any other unanticipated 
serious  problem associated with a device that relates to the rights, safety, or  welfare of 
subjects (21 CFR 812.3(s)). When devising a list of anticipated adverse device effects for 
the protocol, the sponsor should consider that an event that would ordinarily be anticipated, 
but at a very low degree of incidence, should be considered unanticipated if it exceeded the 
expected degree of incidence. This is of particular concern in studies with a small number of 
                                                           
1 Although the term "adverse events" is commonly used instead of "adverse effects," the latter term is the 
defined and used throughout the IDE regulations. See 21 CFR 812.3(s), 21 CFR 812.5(a), 21 CFR 812.38(c), 21 
CFR 812.46(b), 21 CFR 812.140(a)(3), 21 CFR 812.140(b)(5), and 21 CFR 812.150(a)(1) & (b)(1).  
 
  16  Contains Nonbinding Recommendations 
  
 
subjects. Unanticipated adverse device effects could include, but are not limited to, the 
following: migration or extrusion of prosthesis, endophthalmitis, and electric shock.  
 
We recommend that sponsors describe in their protocol any use of a Clinical Events 
Committee, a Data and Safety Monitoring Board, or a core laboratory. Sponsors must 
immediately conduct an evaluation of any unanticipated adverse device effects in accordance 
with 21 CFR 812.46(b). You must report the results of such evaluations to FDA and all 
reviewing IRBs within 10 working days after first receiving notice of the adverse effect. 21 
CFR 812.150(b)(1).  
c. Safety Outcomes 
Other than for initial feasibility studies of limited enrollment, which usually involve fewer 
than 10 subjects, you should identify a primary safety endpoint in your protocol. You should 
also capture rates of surgical complications and potential longer-term adverse events. The 
choice of safety endpoint and list of potential adverse events will depend on the device design 
and the patient population for which the device will be indicated. A risk analysis should 
identify the most likely types of adverse events and also attempt to identify acceptable levels 
for the most probable and the most serious adverse events.  The acceptable level of risk will 
depend upon the possible benefit and the level of visual function and health condition of the 
enrolled eyes.  The statistical plan should justify the sample size based upon these safety 
considerations, in addition to providing justification based upon effectiveness. 
One approach would be to base your primary safety endpoint in the protocol on adverse event 
rates obtained from the medical literature for similar surgical procedures, such that all events 
do not exceed a predetermined target rate. For certain small patient populations, such as those 
that would qualify the device as a Humanitarian Use Device, in order to support safety and 
probable benefit in a Humanitarian Device Exemption application, target rates may not need 
to be identified in the protocol, but instead the risk/benefit analysis performed at the study 
conclusion should characterize the expected rates for similar surgical procedures to provide 
only a frame of reference to which the safety performance of your investigative device can be 
compared. 
d.  Effectiveness Outcomes 
Primary effectiveness endpoints of visual performance should provide quantitative 
documentation of implanted subjects performance in support of device effectiveness. 
Depending on the patient population and the nature of the underlying condition, the 
effectiveness endpoints can be selected from the list of assessments below.  Your IDE 
submission should include a rationale for the effectiveness endpoint(s) selected. 
We recommend that the following effectiveness assessments be performed as appropriate to 
your device.  
  17  Contains Nonbinding Recommendations 
  
 
Assessments of Visual Function   
Low Vision Letter Acuity  
We recommend the study protocol evaluate visual acuity using validated letter chart 
tests for low vision. Manual acuity levels such as count fingers do not provide an 
adequate quantitative measure of visual performance. We recommend your tests place 
limits on the subjects response time. 
Grating Acuity 
We recommend you test subjects for full-field grating acuity using a forced-choice 
paradigm and fixed time interval of presentation. We also recommend you evaluate 
subjects using stimuli projected in a darkened room. A staircase testing procedure 
may be employed to aid in determining the grating resolution threshold. You should 
include grating spatial frequencies that cover the entire acuity range specified by the 
study inclusion criteria. In addition, we recommend you evaluate the subjects ability 
to detect grating contrast.  
Spatial Mapping of Stimulated Visual Phosphene Fields  
We recommend you conduct a careful assessment of the subjects phosphene visual 
field map when stimulating individual (or pairs) of stimulus array electrodes. This 
should include two-point discrimination tests of the central electrodes in the stimulus 
array. For retinal prostheses with intraocular photosensors, we recommend projecting 
test spots directly onto the retinal implant. For a retinal prosthesis that relies on an 
external head or eyeglass mounted camera for visual input, we recommend generating 
a phosphene visual field map while simultaneously monitoring the subjects 
implant eye and head position to account for movements during stimulation of 
individual electrodes. The protocol should include methods or devices to compensate 
for eye and head movements in perimetric tests mapping the subjects phosphene 
fields. 
Form Vision Assessment 
To assess the ability of the prosthetic array to provide the implanted subject with 
timely form or pattern vision, we recommend short-duration, timed single letter or 
symbol recognition tests to avoid excessive use of compensatory head, eye, or camera 
movements.  
 Assessments of Functional Vision and Patient Reported Outcomes   
Assessments that evaluate the subjects functional vision may provide a better 
understanding of what users visual capabilities are in real-world situations.   
Laboratory and contrived environments control the actual independent variables that 
are the source of visual problems for the visually impaired population. These 
independent variables include, but are not limited to glare, shadows, depth, variability 
in ambient light, weather conditions, etc.  While laboratory assessments and contrived 
  18  Contains Nonbinding Recommendations 
  
 
environments may be acceptable for a non-pivotal study in which preliminary device 
effectiveness is to be evaluated, real world assessments should be used in pivotal 
studies.   We recommend that you use the test procedures described below, as 
appropriate to your device. 
Orientation and Mobility  
We recommend an orientation and mobility assessment of your subjects real-world 
performance as measured by an independent, trained orientation and mobility 
professional. An independent professional is not part of the company that 
manufactures and investigates the device. The orientation and mobility professional 
should evaluate the functional visual ability of each implanted subject by observing 
the subject travel independently in real-world situations. This information cannot be 
statistically analyzed because the individual needs of each subject vary tremendously. 
The visual environments in which they exist and need to improve function will also 
vary significantly. This information will be used to corroborate objective findings 
such as visual acuity, visual fields, etc.   
Activities of Daily Living  
Your protocol should include an assessment of daily living measured by an 
independent trained low-vision professional. The low-vision professional should 
evaluate the functional visual ability of each implanted subject by observing the 
subject perform daily self-care tasks such as dressing, grooming, cooking, and eating, 
etc., as applicable. 
Patient Reported Outcomes (PROs) 
A PRO questionnaire should be administered to all subjects to assess the overall 
benefit of the retinal prosthesis when used in the home and other settings outside the 
clinic. The questionnaire should include questions regarding symptoms applicable to 
an implantable retinal prosthesis and its overall impact on health-related quality of life 
in low vision subjects.  It is also recommended that depression be assessed as 
depression is often correlated to low-vision subjects.  Subjects should be 
appropriately referred for further assessment and management as per their outcome on 
any measure of depression. 
We recommend that a self-administered questionnaire be used to avoid bias. 
The questionnaire items should have previously been referenced in the peer-reviewed 
literature and their reliability and validity undergone some degree of evaluation.  
FDAs Guidance for Industry Patient-Reported Outcome Measures:  Use in 
Medical Product Development to Support Labeling Claims 
(http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/
Guidances/UCM193282.pdf) should be consulted for further guidance, particularly 
for evaluating the adequacy of a PRO instrument as a measure to support device 
claims, if the manufacturer wishes to make such claims. Investigators should be aware 
  19  Contains Nonbinding Recommendations 
  
 
that some devices will require the subjects to have vision rehabilitation training in 
order to assist them in the use of the device and the potential new vision it may afford 
them.  In these instances, the PRO questionnaires will be an assessment of the training 
program more so than the device itself. In order to be an assessment of the device 
effectiveness, the questionnaire should be administered without rehabilitation 
training.  
Some examples of existing questionnaires that measure the parameters listed above 
and can be used in combination are the short form of the National Eye Institutes 
Visual Function Questionnaire (VFQ-25) (impact on quality of life), Massofs 
Activity Inventory, Turanos Assessment of Mobility, The Melbourne Low Vision 
Index, VA VFQ-48, and the Patient Health Questionnaire (PHQ-9) (depression).  
Other possible scales for assessing depression include the GDS-15 (Geriatric 
Depression Scale) and Becks Depression Scale (short form). The questionnaires used 
should be appropriately matched to the age range of subjects enrolled in the clinical 
investigation and should match the population being studied. For example, the MMPI 
(Minnesota MultiPhasic Personality Inventory) would not be suitable as a tool 
because it was based on a psychiatric prison population.   
e. Statistical Analysis Plan  
The protocol for a pivotal clinical study should include a statistical analysis plan (SAP). The 
SAP should describe how the study results will be analyzed and provide specific hypothesis 
tests and/or confidence intervals for analyses of primary and secondary endpoints of device 
safety and effectiveness. Effectiveness analyses should compare the outcomes for the active 
experimental device to the control condition (e.g., inactive device) or sham procedure control 
group. The SAP should include a sample size justification based upon the number of subjects 
needed to evaluate all primary effectiveness and safety outcomes, and important secondary 
outcomes. When testing multiple hypotheses, the plan should address how the overall Type I 
error rate will be preserved. Based upon your best estimate of expected loss to follow-up, you 
should adjust the number to be enrolled so that you have sufficient patient numbers at key 
time points. Your trial should be sized to address the possibility of continued follow-up 5-10 
years after implantation for your clinical trial cohort (i.e., studies that FDA may require under 
21 CFR 814.82(a)(2) as a condition of the approval of your future marketing application).2 
For studies that include long-term follow-up, your IDE must include consent by all subjects 
for such follow-up (21 CFR 50.25(a)(1)).In addition, post-approval studies enrolling new 
subjects may be required.  
8. Informed Consent Document  
                                                           
2 See also the guidance entitled Procedures for Handling Post-Approval Studies Imposed by PMA Order, 
available at 
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm070974.htm. 
  20  Contains Nonbinding Recommendations 
  
 
Your IDE application must include a copy all information to be provided to subjects to obtain 
informed consent (21 CFR 812.20(b)(11)). In your application we recommend that you 
explain your method of administering the informed consent documents (ICD), and how this 
method will account for the functional visual limitations of subjects enrolling in the study. 
Your ICD must contain the elements specified in 21 CFR 50.25. 
Required elements include, but are not limited to:  
  a description of the procedures to be followed in the study (21 CFR 50.25(a)(1)),  
  the expected duration of the subject's participation in the study (21 CFR 50.25(a)(1)); 
this includes any long term follow-up,  
  a description of any reasonably foreseeable risks or discomforts to the patient (21 
CFR 50.25(a)(2)); this includes surgical and postoperative risks and complications 
and short- and long-term risks and discomforts resulting from implantation of the 
prosthetic device and any associated electronics,  
  a description of any benefit to the subject or to others which may reasonably be 
expected from the research (21 CFR 50.25(a)(3)), and  
  any additional costs to the subject that may result from participation in the research 
(21 CFR 50.25(b)(3).  
In addition, we recommend that an ICD for a retinal prosthesis describe: 
  the frequency of subject tests required for the study,  
  options for explantation should the subject be dissatisfied with the implanted device, 
and  
  the need for periodic ocular health evaluations by an eye care professional beyond 
completion of the study, for as long as the implant remains in the eye.  
9. Patient Information and Labeling 
Your investigational plan must include copies of all labeling for the device (21 CFR 
812.25(f)). Labeling of investigational medical devices must comply with 21 CFR 812.5. 
Among other requirements, the label must include the statement, "CAUTION--
Investigational device. Limited by Federal (or United States) law to investigational use," and 
the label or other labeling must describe all relevant contraindications, hazards, adverse 
effects, interfering substances or devices, warnings, and precautions. See CDRH Device 
Advice, IDE FAQs 
(http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDev
ice/InvestigationalDeviceExemptionIDE/ucm051480.htm) for additional information about 
IDE labeling. 
What follows is information specific to the labeling of investigational retinal prostheses. 
  21  Contains Nonbinding Recommendations 
  
 
Indications for Use  
The labeling should be consistent with the indications for use statement that identifies the 
intended patient population. For these prosthetic devices, the target population should be a 
visually impaired disease population that may benefit from using the device.  
Contraindications  
The labeling must include information on all relevant contraindications (21 CFR 812.5(a)). 
Contraindications are conditions under which the device should not be used because the risk 
of use clearly outweighs any possible benefit. Contraindications may include coexisting 
retinal pathologies or prior damage to an element of the visual pathway, such as the optic 
nerve. 
Warnings and Precautions  
The labeling must describe all relevant hazards, adverse effects, interfering substances or 
devices, warnings, and precautions (21 CFR 812.5(a)). For example, your labeling must alert 
users to potentially injurious outcomes associated with use or misuse of the device and must 
describe actions users should take to avoid potentially injurious events. The precautions in 
your labeling should alert users to exercise special care for the proper use of the device.  
Depending on the device design or component composition, applicable warnings or 
precautions may include information about the compatibility of the device with various 
strength field MRI scanners, wireless devices, metal detectors, high voltage sources, and 
devices emitting strong magnetic fields. This information should include possible interactions 
with metal detectors, diathermy units, or cardiac defibrillators. Warnings or precautions about 
device use during specific activities such as walking, running, and swimming in specific 
environments may also be appropriate for some devices. These warnings should also be 
reflected on the patient implant card.  
General Directions for Use  
We recommend you include directions for preparation and use of the device and information 
about environmental conditions for storing the device, batteries, and any accessories. 
Surgical Procedure 
The labeling should describe steps to prepare or validate device functionality before 
implantation. We recommend you include a clear description of all device components, 
inserters, viewing devices, electronics, accessories, and surgical tools used for implantation.  
Labeling should also describe the implantation procedure itself. It should indicate that the 
procedure should be performed under sterile conditions in an operating room. It should 
specify, for example, the routes of entry, the incisions, the sutures and dressing, all drugs, and 
all devices (such as the types and/or sizes of vitrectomy cannulae) used in the surgical 
procedure. It should also describe any adverse events that can be anticipated to occur during 
the procedure, and how to prevent, manage, and/or mitigate them. 
  22  Contains Nonbinding Recommendations 
  
 
The labeling should further recommend use of a consistent medication regimen, including an 
anesthesia regimen, during the procedure and throughout the course of the study, as 
appropriate and feasible. Finally, it should describe the post-operative test procedures to 
verify implant integrity and proper placement.  
 
To the degree possible, we recommend that subjects medication remain unaltered both 
before and during the clinical trial, other than those drugs prescribed in the clinical protocol 
for the post-operative recovery period. Additional surgery or medication used to treat 
unanticipated ocular conditions/complications should be recorded. 
Accessory Devices 
In addition, we recommend your labeling describe any accessory devices that are packaged 
with your device when no separate labeling for such accessory devices is available. For 
example, labeling should include a description of a surgical insertion or positioning device 
packaged with your device. 
Subject Materials  
In the IDE application, as part of the investigational plan, you should include items such as 
the subject user guide and implant card that will be provided to subjects.  
 
  23  Contains Nonbinding Recommendations 
  
 
Appendix A 
List of Referenced Standards 
For additional information about the Standards referenced in this document, please contact 
CDRHs Standards Program 
(http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Standards/default.htm) 
or by calling 301-796-6574. 
 
ISO 15004-1 2006, Ophthalmic instruments - Fundamental requirements and test methods. - 
Part 1: General requirements applicable to all ophthalmic instruments.  
ISO 15004-2: 2007, Ophthalmic Instruments - Fundamental requirements and test methods 
Part 2: Light hazard protection. 
ISO 10939: 2007 Ophthalmic instruments - Slit-lamp microscopes. 
ANSI RP27.1:2005,  Recommended Practice for Photobiological Safety for Lamps and Lamp 
Systems. - General Requirements. 
ANSI RP27.3:2007 Recommended Practice for Photobiological Safety for Lamps and Lamp 
Systems.- Risk Group Classification and Labeling. 
IEC 60601-1-2:2001 Medical Electrical Equipment  Part 1-2: General requirements for 
safety  Collateral standard: Electromagnetic compatibility  Requirements and tests. 
ANSI/AAMI/ISO 10993-7 Biological Evaluation of Medical Devices - Part 7: Ethylene 
Oxide Sterilization Residuals Electromagnetic Compatibility  Requirements and Tests 
(General).  
ANSI/AAMI/ISO 17665-1:2006 -Sterilization of health care products - Moist heat - Part 1: 
Requirements for the development, validation, and routine control of a sterilization process 
for medical devices.  
ANSI/AAMI/ISO 11135-1:2007 Sterilization of health care products - Ethylene oxide - Part 
1: Requirements for the development, validation, and routine control of a sterilization process 
for medical devices.  
ANSI/AAMI/ISO 11137 -1:2006/(R) 2010  Sterilization of health care products - Radiation - 
Part 1: Requirements for development, validation, and routine control of a sterilization 
process for medical devices.  
ANSI/AAMI/ISO 11607-1:2006/(R) 2010 Packaging for terminally sterilized medical 
devices - Part 1: Requirements for materials, sterile barrier systems and packaging systems, 
3ed. 
  24  Contains Nonbinding Recommendations 
  
 
ANSI/AAMI/ISO 11607-2:2006/(R) 2010 Packaging for terminally sterilized medical 
devices - Part 2: Validation requirements for forming, sealing and assembly processes, 1ed.  
ASTM F1980-07, Standard Guide for Accelerated Aging of Sterile Barrier Systems for 
Medical Devices.  
ISO-10993, Biological Evaluation of Medical Devices Part 1: Evaluation and Testing.  
USP 34:2011, <85> Biological Tests and Assays, Bacterial Endotoxin Test (LAL). 
USP 34:2011, <151> Pyrogen Test (USP Rabbit Test).  
AAMI ST72:2002/(R)2010, Bacterial endotoxins - Test methodologies, routine monitoring, 
and alternatives to batch testing. 
ASTM F1980-07  Standard Guide for Accelerated Aging of Sterile Barrier Systems for 
Medical Devices.  
AAMI/ANSI ST67:2003/(R) 2008 Sterilization of health care products - Requirements for 
products labeled "STERILE" 1st edition ST67:2003/(R). 
 
 
  25