On June 14, 2023, FDA issued a guidance titled Content of Premarket Submissions for Device 
Software Functions.1 This final guidance supersedes the Guidance for the Content of Premarket 
Submissions for Software Contained in Medical Devices, issued on May 11, 2005. The final 
guidance issued on June 14, 2023, provides information regarding the recommended 
documentation sponsors should include in premarket submissions for FDAs evaluation of the 
safety and effectiveness of device software functions. In particular, the final guidance includes 
information to help determine a devices Documentation Level (formerly known as Level of 
Concern). The purpose of the Documentation Level is to help identify the minimum amount of 
information that would support a premarket submission that includes device software functions.
Within the framework of the superseded guidance, self-monitoring blood glucose test systems 
for over-the-counter use were considered a device with a Moderate Level of Concern. Based on 
the devices risk in the context of the devices intended use, as discussed in the final guidance 
Content of Premarket Submissions for Device Software Functions, self-monitoring blood 
glucose test systems for over-the-counter use should generally address the recommendations for 
a Basic Documentation Level. The actual Documentation Level for your device may vary based 
on the specifics of your device. For more information about Documentation Level and 
recommended documentation for a premarket submission, sponsors are encouraged to review the 
guidance Content of Premarket Submissions for Device Software Functions. 
 
1 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/content-premarket-
submissions-device-software-functions. Self-Monitoring Blood Glucose Test 
Systems for Over-the-Counter Use 
Guidance for Industry and Food and 
Drug Administration Staff 
Document issued on: September 29, 2020. 
The draft of this document was issued on November 30, 2018. 
This guidance supersedes Self-Monitoring Blood Glucose Test Systems for 
Over-the-Counter Use: Guidance for Industry and Food and Drug 
Administration Staff, issued October 11, 2016. 
For questions regarding this document, contact Leslie Landree at leslie.landree@fda.hhs.gov, 
or at 301-796-6147. 
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-2013-D-1446.  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 
CDRH-Guidance@fda.hhs.gov to receive a copy of the guidance. Please include the 
document number 1756 and complete title of the guidance in the request.  Contains Nonbinding Recommendations 
Table of Contents 
I.  INTRODUCTION ........................................................................................................................................ 1 
II.  BACKGROUND ....................................................................................................................................... 2 
III.  SCOPE ....................................................................................................................................................... 3 
IV.  REDUCING THE RISK OF BLOODBORNE PATHOGEN TRANSMISSION ............................... 4 
A.  VALIDATED CLEANING AND DISINFECTION PROCEDURES ........................................................................ 5 
B.  DEMONSTRATION THAT THE DEVICE IS ROBUST TO CLEANING AND DISINFECTION PROCEDURES ............. 6 
V.  DEVICE DESCRIPTION ........................................................................................................................ 7 
VI.  PERFORMANCE EVALUATION FOR SMBGS ................................................................................ 8 
A.  PRECISION EVALUATION STUDY ............................................................................................................. 9 
B.  LINEARITY EVALUATION STUDY ........................................................................................................... 10 
C.  METHOD COMPARISON/USER EVALUATION .......................................................................................... 10 
1.  General Study Design: ......................................................................................................................... 10 
2.  Data Analyses: ..................................................................................................................................... 14 
D.  INTERFERENCE EVALUATION ................................................................................................................ 15 
1.  Endogenous/Exogenous Substances ................................................................................................... 15 
2.  Hematocrit ........................................................................................................................................... 18 
E.  FLEX STUDIES ....................................................................................................................................... 20 
1.  Test Strip Stability Testing ................................................................................................................... 22 
2.  System Operating Conditions Testing ................................................................................................. 23 
3.  Altitude Effects .................................................................................................................................... 24 
4.  Error Codes for Samples Outside the Measuring Range ................................................................... 24 
5.  Short Sample Detection ....................................................................................................................... 25 
6.  Sample Perturbation Study .................................................................................................................. 25 
7.  Intermittent Sampling .......................................................................................................................... 25 
8.  Testing with Used Test Strips .............................................................................................................. 26 
F. METER CALIBRATION AND QUALITY CONTROL MATERIALS ........................................................................ 26 
VII.  TEST STRIP LOT RELEASE CRITERIA ......................................................................................... 26 
VIII.  THIRD PARTY TEST STRIPS ........................................................................................................ 27 
IX.  SOFTWARE ........................................................................................................................................... 27 
X.  LABELING ............................................................................................................................................. 28 
APPENDIX 2.  SPECIAL 510(K)S AND SMBGS ........................................................................................... 38  Contains Nonbinding Recommendations 
Self-Monitoring Blood Glucose Test 
Systems for Over-the-Counter Use  
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
This guidance document describes studies and information that FDA recommends be used 
when submitting premarket notifications (510(k)s) for self-monitoring blood glucose test 
systems (SMBGs) which are for over-the-counter (OTC) home use by lay-users.1 This 
guidance document is intended to guide manufacturers in conducting appropriate 
performance studies and preparing 510(k) submissions for these device types and replaces 
the final guidance entitled Self-Monitoring Blood Glucose Test Systems for Over-the-
Counter Use issued on October 11, 2016. 
This guidance is not meant to address blood glucose monitoring test systems which are 
intended for prescription point-of-care use in professional healthcare settings (e.g., hospitals, 
physician offices, long term care facilities).  FDA addresses those device types in another 
guidance entitled, Blood Glucose Monitoring Test Systems for Prescription Point-of-Care 
Use (BGMS guidance).2 FDA is also issuing another BGMS guidance to reflect similar 
clarifications to the ones described in this guidance. 
1 While the majority of SMBG devices are intended for home use, this also applies to SMBG devices intended 
for home use that are obtained with a prescription from a healthcare professional. 
2 Available at  https://www.fda.gov/regulatory-information/search-fda-guidance-documents/blood-glucose-
monitoring-test-systems-prescription-point-care-use. 
1  Contains Nonbinding Recommendations 
For the current edition of the FDA-recognized standard(s) referenced in this document, see 
the FDA Recognized Consensus Standards Database Web site.3 For more information 
regarding use of consensus standards in regulatory submissions, please refer to the FDA 
guidance titled Appropriate Use of Voluntary Consensus Standards in Premarket 
Submissions for Medical Devices.4  
FDA's guidance documents, including this guidance, do not establish legally enforceable 
responsibilities.  Instead, guidances 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 guidances means that 
something is suggested or recommended, but not required. 
II. Background
Portable blood glucose meters that measure blood glucose values are used by millions of 
people with diabetes every day as an aid in diabetes self-management.  These devices are 
used by patients in a variety of settings, including in their homes, at work, and in schools.  
Historically, the FDA has not recommended different types of information in premarket 
submissions (510(k)s) for blood glucose monitoring systems (BGMSs) intended to be used 
by healthcare professionals as compared to SMBGs intended for home use by lay-users.  
However, it has become increasingly clear that these different use settings comprise distinct 
intended use populations with unique characteristics and different device design 
specifications, which manufacturers should take into account when designing their devices.  
Patients in professional healthcare settings can be acutely ill and medically fragile and are 
more likely than lay-users to present with physiological and pathological factors that could 
interfere with glucose measurements.  Further, the term lay-user encompasses a group of 
individuals with wide ranges in age, dexterity, vision, training received on performing 
testing, and other factors that can be critical to the patients ability to accurately use the 
device and interpret test results.  Finally, SMBGs and the associated test strips used by lay-
users are also more likely to experience varied storage and handling conditions compared to 
devices used in professional settings.  As such, SMBGs should be designed to be more robust 
and reliable to accommodate actual use conditions. We recommend manufacturers consider 
design features that will aid in user accessibility (for example, features that would increase 
accessibility to users with visual impairments). 
In order to distinguish between prescription use blood glucose meters, which are intended for 
use in point-of-care professional healthcare settings, and those intended for home use for 
self-monitoring by lay-users, the Agency is issuing two separate guidances for (i) BGMSs 
intended for use in point-of-care professional healthcare settings, and (ii) SMBGs intended 
for home use for self-monitoring by lay-users.  The FDA believes that by making this 
3 Available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm. 
4 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/appropriate-use-
voluntary-consensus-standards-premarket-submissions-medical-devices. 
2 Contains Nonbinding Recommendations 
distinction, SMBGs can be better designed to meet the needs of their intended use 
populations, thereby providing greater safety and efficacy.  
In recent years, concerns have been raised related to infection control issues involving blood 
glucose meters and lancing devices.  According to the Centers for Medicare and Medicaid 
Services (CMS) and the Centers for Disease Control and Prevention (CDC), blood glucose 
meters and lancing devices can transmit bloodborne pathogens if these devices are 
contaminated with blood specimens and are shared between users without effective cleaning, 
disinfecting, and appropriate infection control measures.5  Though SMBGs are intended for 
home use by lay-users, they should also be designed to withstand effective cleaning and 
disinfection procedures over the life of these devices.  These disinfection procedures should 
be properly validated (see Section IV below) for this type of device and appropriate 
instructions provided for the user.  Validation methods should take into account the way in 
which the device is used, i.e., by lay-users at home (or in other non-professional settings). 
III.  Scope 
This guidance document is limited to SMBGs, which are regulated under 21 CFR 862.1345, 
Glucose Test System.  The product code NBW applies to SMBGs. 
This document is not meant to address the following types of devices: 
  Blood glucose monitoring test systems intended for use in prescription point-of-care 
in professional healthcare settings (e.g., hospitals, physician offices, long term care 
facilities, etc.). 
  Devices used to screen and diagnose diabetes (such as clinical chemistry analyzers). 
  Continuous glucose sensors, implanted or external (e.g., continuous glucose 
monitoring systems (CGMs) or sensors within catheters). 
  Non-invasive glucose measurement devices (i.e., devices that do not require removal 
of a blood sample from a fingertip or other anatomical site). 
  Devices for measurement of blood glucose in neonates. 
The device types addressed in this guidance document typically use capillary whole blood 
from fingertip or alternative anatomical sites.  These device types are not intended for use in 
healthcare or assisted-use settings such as hospitals, physician offices, or long-term care 
facilities because they have not been evaluated for use in these professional healthcare 
settings, including for routine assisted testing or as part of glycemic control procedures. Use 
of these devices on multiple patients may lead to transmission of Human Immunodeficiency 
Virus (HIV), Hepatitis C Virus (HCV), Hepatitis B Virus (HBV), or other bloodborne 
pathogens. 
While FDA recommends that the information described in this guidance be included in 
premarket submissions for SMBGs, submissions containing alternative information may be 
                                                          
5 See information at http://www.cdc.gov/injectionsafety/blood-glucose-monitoring.html. 
3 Contains Nonbinding Recommendations 
sufficient if able to demonstrate substantial equivalence to a legally marketed predicate 
device.  
We recommend that you contact the Division of Chemistry and Toxicology Devices in the 
Office of In Vitro Diagnostics and Radiological Health if you have questions regarding 
alternate intended uses of your SMBG. 
IV.  Reducing the Risk of Bloodborne Pathogen 
Transmission 
Since SMBGs use blood specimens for glucose measurement, their design and instructions 
for use are very important factors in reducing the risk of bloodborne pathogen transmission 
during use.  According to the CMS and the CDC, blood glucose meters, as well as lancing 
devices, can transmit bloodborne pathogens, such as viral hepatitis, if these devices are 
contaminated with blood specimens and are shared between users without effective cleaning 
disinfecting, and appropriate infection control measures.  To minimize the risk of bloodborne 
pathogen transmission with single patient use SMBGs, you should address the following in 
your devices design and labeling: 
  All SMBGs should be intended for single patient use.  The intended use should 
clearly state that the SMBG is intended for home use by lay-users and should only be 
used on a single user.  
  Meters should be designed such that all external materials can be cleaned (removal of 
organic soil) and disinfected (microbicidal process).   
  All external surfaces of the meter, including seams and the test strip port, should be 
designed for both ease of use and ease of cleaning and disinfection. 
  You should develop an effective disinfection method that can be easily employed by 
lay-users at home.  You should provide the validated cleaning and disinfecting 
procedures for your SMBG in your 510(k) submission, as well as in the labeling.  
Cleaning and disinfection are different processes and warrant separate validation 
procedures and specifications.  See Sections IV.A and B below for details on the 
recommended cleaning and disinfecting validation studies. 
  You should validate the efficacy of any disinfectant you recommend for use with 
your device, as described below.  We recommend you consult the Environmental 
Protection Agencys (EPA) list of disinfectants that are registered for use against 
infectious bacteria and viruses6when choosing disinfectants to validate for use with 
your device. 
  You should clearly warn users that lancing devices are for single-patient use only and 
should NEVER be shared. 
  Labeling concerning safe device use can reduce the risk of user error; therefore, 
instructions for cleaning and disinfection should be clear and detailed.  The various 
test system components should be named in such a way that they are recognized as 
belonging to the same system or family of products, and to distinguish them from 
                                                          
6 Selected EPA-registered Disinfectants available at https://www.epa.gov/pesticide-registration. 
4 Contains Nonbinding Recommendations 
similar devices intended for multiple-patient use (e.g., ABC blood glucose test 
system, ABC blood glucose meter, ABC blood glucose test strips, etc.).  See Section 
X, (Labeling), below, for detailed labeling recommendations. 
Validation of cleaning and disinfection procedures involves both validation that the cleaning 
and disinfection products are effective against the primary viruses of concern (i.e., HIV, 
Hepatitis B, Hepatitis C) and validation that the cleaning and disinfection procedures do not 
deteriorate the device or alter device performance.  FDAs recommendations for such 
validation are outlined in the following sub-sections. 
A. Validated cleaning and disinfection procedures 
You should select cleaning and disinfection products that do not result in physical 
deterioration of the device overall, or any device component, including the housing, 
touch pad, or buttons.  You should make note of any physical indicators of deterioration 
during your validation study and provide this information in your 510(k) submission.  
The disinfectant product you choose should be effective against HIV, Hepatitis C, and 
Hepatitis B viruses.  Of these viruses, Hepatitis B is the most difficult to kill and prior 
outbreak episodes associated with blood glucose meters have been due to transmission 
of Hepatitis B viruses.  Therefore, disinfection efficacy studies should be performed to 
demonstrate effectiveness of the chosen disinfectant against Hepatitis B virus.  Please 
note that 70% ethanol solutions are not effective against viral bloodborne pathogens, 
and the use of 10% bleach solutions may lead to physical degradation of your device. 
You should demonstrate that your disinfection procedure is effective against Hepatitis B 
virus by performing disinfection efficacy studies to show that your procedure is effective 
with the external meter materials (e.g., case, display, buttons, etc.).  Studies have 
demonstrated that viruses can remain infective for different time periods, depending on 
the surface.  Viral survival may increase or decrease with the number of microbes present 
on a surface.  Increasing amounts of microbes can protect viruses from disinfection and 
damaging effects may also result from microbial proteases and fungal enzymes.  Factors 
that influence survival on surfaces include fomite properties, initial viral titer, virus 
strain, temperature, humidity, and suspending media.  The simplest disinfection method 
would be the use of towelettes pre-saturated with a selected disinfectant.  Disinfection 
with a towelette will reduce the risk of liquid getting into the meter, thereby minimizing 
the chance of your disinfection procedure affecting meter function.  However, you should 
choose a disinfectant that is effective against Hepatitis B virus and is compatible with 
your specific device.  If you intend to claim that your disinfection procedure is effective 
against other pathogens, you should consider submitting a pre-submission request to 
discuss this with the Agency prior to conducting your testing.  For information about the 
pre-submission process, see FDAs guidance entitled Requests for Feedback on Medical 
Device Submissions: The Pre-Submission Program and Meetings with Food and Drug 
Administration Staff.7  In addition, you should choose a disinfection method that uses 
products that would be readily available to the home user. 
                                                          
7 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/requests-feedback-
and-meetings-medical-device-submissions-q-submission-program. 
5 Contains Nonbinding Recommendations 
We recommend you refer to the following standards: 
  ASTM standard ASTM E1053-11, Standard Test Method for Efficacy of 
Virucidal Agents Intended for Inanimate Environmental Surfaces.  
  ASTM standard ASTM E2362 -09, Standard Practice for Evaluation of Pre-
saturated or Impregnated Towelettes for Hard Surface Disinfection.   
B. Demonstration that the device is robust to cleaning and disinfection 
procedures 
You should demonstrate through bench studies that your SMBG is robust to cleaning and 
disinfection procedures after multiple cleaning and disinfection cycles.  You should 
include in your 510(k) submission the study design and results demonstrating that the 
analytical performance of the SMBG is not impacted by the cleaning and disinfection 
procedures.   
You should address the following in designing your study: 
  Worst case scenarios with regards to cleaning and disinfection frequency and end 
user environment should be used to determine the number of cleaning and 
disinfection cycles that should be tested.  For example, the number of times you 
clean and disinfect the meter should be representative of the cleaning and 
disinfection that the meter will be exposed to during its use life (typically 3-5 
years) and may be greater than the number of cleaning and disinfection cycles 
recommended in the user instructions.  A cleaning step should precede the 
disinfection step for each cleaning and disinfection cycle. 
  The disinfection contact time used in the robustness study should be identical to 
the contact time used in the disinfection efficacy testing and described in the 
cleaning and disinfection instructions in the labeling. 
  We recommend using the same disinfectant product for both cleaning and 
disinfection.  The effects of multiple products on the efficacy of the disinfectant 
products are not well understood. 
  You should demonstrate that the test strip port and all other openings that are 
susceptible to blood contamination and could either directly or indirectly be 
contacted by the user are able to withstand your recommended cleaning and 
disinfection procedures.  You should ensure that you test parts of the meter that 
are particularly susceptible to blood contamination, such as the test strip port and 
any material seams.  It is important to be able to clean and disinfect all parts of 
your meter to reduce the risk of bloodborne pathogen transmission. 
  When evaluating your device after the cleaning and disinfection phase, you 
should ensure that the procedure does not cloud or deface the display of the meter 
and does not corrode or erode the plastic housing or buttons.  All these physical 
indicators of deterioration should be noted throughout your study and included in 
6 Contains Nonbinding Recommendations 
your 510(k) submission.  You should evaluate the accuracy of the meter using 
blood samples compared to results obtained by a comparator method (please refer 
to Section VI below for the definition of comparator method) to ensure that 
accuracy is not affected by repeated cleaning and disinfection.  The study should 
also evaluate the functionality of your meter features (as appropriate), for 
example, touch screen function, USB port function, speaking functions, etc., to 
ensure they are not affected by repeated cleaning and disinfection. 
  You should include infection control in your risk analysis and incorporate your 
validated cleaning and disinfecting procedures into your risk assessment. 
A description of the protocols and acceptance criteria for all studies should be included in 
your 510(k) submission. 
V.  Device Description 
You should provide a general description of the SMBG in your 510(k) submission.  
Typically, much of this information should also be included in the devices User Manual; 
however, some of the information is not appropriate for the intended lay-user (e.g., highly 
technical explanations) and should be included in the 510(k) submission only.  You should 
provide the following in your 510(k) submission: 
General device description: 
  Description of physical components of the system (including diagrams, where 
appropriate). 
  Manufacturers performance specifications. 
  Description and explanation of the test principle, including chemical reactions. 
  Description of the format of results, including units of measurement and whether 
results are reported in whole blood or plasma equivalents.8
  Description of the composition and levels of control material that can be used with 
your system. 
  User maintenance needs (e.g., batteries). 
  Features of the device, such as data transmission capabilities or features designed to 
enhance robustness, ease of use, or user accessibility (e.g. features designed to 
increase accessibility for users with visual impairments). 
  Features designed to minimize the risk of bloodborne pathogen transmission. 
Description of features controlled by the software, which should describe the following: 
  Displays and user messages:  This includes how the SMBG determines and displays 
the glucose concentration, messages, or displays that appear while a user is taking a 
                                                          
8 Note that SMBGs intended for use in the U.S. should report results in mg/dL and in plasma equivalents. 
7 Contains Nonbinding Recommendations 
measurement, and features such as how a user can retrieve past results from storage in 
the device. 
  
  User prompts: You should describe prompts that the SMBG provides to the user, 
expected user responses, and timing issues (e.g., how quickly does the user need to 
respond, what happens if they respond after the allowed time).  Examples of user 
prompts include messages to the user to insert the test strip into the meter, add blood 
sample to the test strip, calibrate the meter, or store a result, etc. 
  
  Error messages and alerts:  This includes any error messages or alerts that the SMBG 
displays. You should describe how the system responds to errors in user action, user 
inaction, or system status.  Suggested examples of error messages or alerts include: 
when a strip is inserted incorrectly or removed prematurely; too small a sample is 
applied to the test strip; damaged, incorrect or deteriorated strips are used; or when 
there is a low battery or excessively high ambient temperature.  This should also 
include the methods by which the SMBG detects and alerts the user when glucose 
levels are outside of the linear range of the system.  You should describe at what 
point each message is triggered and describe any self-diagnostic routines that the 
system performs. 
It is important that you identify the expected responses by the user to error messages or 
alerts.  This includes whether and how the user should input information or press certain 
buttons to correctly set up the meter or to respond to an error message or alert.  
VI.  Performance Evaluation for SMBGs 
Subsections A-F below indicate the types of device performance information that you should 
include in a 510(k) submission for a SMBG.  Although many manufacturers design their 
SMBG validation studies based on the International Organization for Standardization (ISO) 
document 15197: In vitro diagnostic test systemsRequirements for blood glucose 
monitoring systems for self-testing in managing diabetes mellitus, FDA believes that the 
criteria set forth in the ISO 15197 standard are not sufficient to adequately protect lay-users 
using SMBGs because, for example, the standard does not adequately address the 
performance of over-the-counter blood glucose test systems in the hypoglycemic range (low 
blood glucose readings range) or across test strip lots.  Therefore, FDA recommends 
performing studies to support 510(k) clearance of a SMBG according to the 
recommendations below. 
In this guidance, the term comparator method refers to a laboratory-based glucose 
measurement method that has been well-validated for precision and accuracy and that is 
traceable to a higher order, e.g., an internationally recognized reference material and/or 
method.  The traceability chain should include as few stages as possible to reduce bias.  
FDAs current thinking on the issues that should be addressed and the recommended study 
designs and device performance evaluations are discussed below in Subsections A-F. 
8 Contains Nonbinding Recommendations 
A. Precision Evaluation Study 
You should evaluate both within-run precision and intermediate precision for your 
SMBG and include these evaluations in your 510(k) submission.  The following outlines 
FDAs current thinking on appropriate study design and analyses to evaluate within-run 
precision and intermediate precision for SMBGs. 
Within-Run Precision Evaluation: 
In this guidance, within-run precision studies are bench studies designed to evaluate 
imprecision under conditions of repeated measurement of the same sample with different 
meters and multiple test strip lots.  In order to assess imprecision of the SMBG across the 
claimed measuring range, you should evaluate samples containing glucose concentrations 
within each of the five intervals provided in Table 1 below: 
Table 1. Glucose Concentrations for Precision Evaluation 
Interval  Glucose Concentration 
Range (mg/dL) 
1  30-50 
2  51-110 
3  111-150 
4  151-250 
5  251-400 
You should determine within-run precision using venous whole blood samples. Altered 
venous whole blood samples such as those that are spiked, diluted, or allowed to 
glycolyze in order to obtain the appropriate glucose concentrations are acceptable in 
order to facilitate coverage of the entire claimed glucose measuring range.  However, you 
should clearly identify all altered samples (spiked, diluted, or glycolyzed) in all submitted 
data.  A minimum of 500 test strips from at least 10 vials and 3 manufacturing lots should 
be used in this study.  For each sample concentration, a minimum of 10 meters should be 
used, with at least 10 measurements taken by each meter (i.e., at least 100 measurements 
per concentration).  Test strips should be taken from the same vial and/or package for 
each meter. 
We recommend you present the results as the mean value of all measurements per meter 
for each glucose concentration range with the corresponding standard deviation (SD) and 
percent coefficient of variation (CV). In addition, for each glucose concentration range in 
Table 1, you should also provide the mean value, standard deviation (with 95% 
confidence intervals), and percent CV for data combined over all meters. You should 
describe the statistical procedures used in the analysis.  
Provided results should be based on all data; if any outlier samples were excluded from 
any of your statistical analyses, you should fully describe the method of outlier 
identification, identify the excluded samples, and provide the results of your root cause 
investigations into the outlier samples. 
Intermediate Precision Evaluation: 
9 Contains Nonbinding Recommendations 
Intermediate precision measurement studies are bench studies designed to evaluate 
imprecision under simulated normal use conditions; for example, measurement over 
multiple days using multiple reagent system lots.  These studies may be performed with 
prepared control solutions rather than whole blood samples. 
The total number of meters and operators in these studies is at the discretion of the 
sponsor; however, a minimum of 10 meters should be used for each glucose 
concentration.  Intermediate precision should be evaluated over a minimum of 10 days, 
taking at least 1 measurement per meter per day of a sample from each glucose 
concentration interval listed in Table 1.  This should produce a minimum of 10 
measurements per meter for each glucose concentration and 100 total measurements per 
glucose concentration.  You should use a minimum of 500 test strips from a minimum of 
10 vials or packages that cover a minimum of 3 manufacturing lots.  These test strips 
should be taken from the same vial and/or package for each meter.  
For each glucose concentration in Table 1, you should present data for each test strip lot, 
as well as for pooled lots, including the mean value of the measurements for each meter 
with the corresponding standard deviation (SD) and percent coefficient of variation (CV).  
You should also present the mean value, standard deviation (with 95% confidence 
intervals), and percent CV for data combined over all meters.  You should describe the 
statistical procedures you use and provide results based on all data.  If any outlier samples 
were excluded from any of your statistical analyses, you should fully describe the method 
of outlier identification, identify the excluded samples, and provide the results of your 
root cause investigations into the outliers. 
B. Linearity Evaluation Study 
You should evaluate the linearity of your device across the entire claimed measuring 
range.  We recommend that studies include an evaluation of at least 11 evenly spaced 
concentrations tested and analyzed according to Evaluation of the Linearity of 
Quantitative Measurement Procedures: A Statistical Approach, CLSI document EP6-A.  
Linearity studies should be performed using venous whole blood samples.  Altered 
venous whole blood samples, such as those that are spiked, diluted, or glycolyzed, are 
acceptable in order to facilitate coverage of the entire claimed measuring range.  You 
should clearly identify the number of altered samples (spiked, diluted, or glycolyzed) 
within the 510(k) submission.  
You should submit a detailed description of the study design, target concentrations, a list 
of all data collected in this study, summary of the results and conclusions drawn from the 
study, and a description of the statistical analysis used. 
C. Method Comparison/User Evaluation 
1.  General Study Design: 
We recommend that you design a single evaluation to assess both system accuracy in the 
hands of the intended users as well as other aspects to support lay-use, such as an 
assessment of labeling and usability.  This type of design will more accurately reflect the 
10 Contains Nonbinding Recommendations 
device performance in the hands of the intended user, thereby providing a better estimate 
for total accuracy of your SMBG.  
FDA recognizes that most study evaluations performed for 510(k) submissions occur in 
idealized conditions, thereby potentially overestimating the total accuracy of the SMBG, 
even when performed in the hands of the intended user.  It is important to design your 
study to most accurately evaluate how the device will perform in the hands of the 
intended use population.  Therefore, the study should be conducted under conditions that 
reflect the expected use of the device by the intended use population (e.g., temperature, 
humidity, altitude, etc.), but does not warrant the inclusion of the entire range of 
environmental conditions (environmental conditions are validated separately in Flex 
Studies discussed in Section VI.E below).  You should fully describe the conditions of 
your study in your 510(k) submission. 
You should include at least 350 different subjects in your user evaluation.  In order to 
robustly assess the accuracy of your device, it is important that the glucose value on the 
comparator method be as reliable as possible.  Therefore, more than one comparator 
measurement may be taken and averaged for each sample in order to allow a better 
estimate of the true glucose value of that sample.  However, no measurements should be 
excluded from the 510(k) submission and a justification should be provided for any data 
that is excluded from the analysis.  If you are planning to include claims that your device 
can be used at alternative anatomical sites (e.g., forearm, palm, etc.), you should test 
samples using your device from 350 subjects for each alternative anatomical site for 
which you are seeking clearance and evaluate the results relative to samples measured 
with the comparator method. 
For each claimed anatomical site, the samples should adequately span the claimed 
measuring range of the SMBG.  Though it may be difficult to obtain samples at the 
extreme ends of the measuring range, the study should contain at least 10 unaltered 
samples with blood glucose concentrations < 80 mg/dL, and at least 10 unaltered samples 
between 250 mg/dL glucose and the upper limit of the claimed measuring range of the 
device.  It may be necessary to enroll more than 350 patients for each anatomical site 
(fingertip, forearm, palm, etc.) in order to obtain the necessary unaltered samples.  Data 
from all subjects in the study should be submitted in your 510(k) (even if more than 350 
samples are collected), and no subjects should be excluded from the data analysis. 
The subjects you enroll in the method comparison/user study should accurately reflect the 
intended use population of the SMBG.  The study group should be comprised of both 
naive and non-naive SMBG users.  At least 10% of the study participants should be naive 
to SMBGs and may include non-diabetic subjects.  You should describe the inclusion and 
exclusion criteria for enrolling the study participants, as well as the demographic 
characteristics of the subjects that participated in the study. 
Prior to testing, study subjects should be given the draft device labeling (instructions for 
use, user manual, etc.) that is representative of the labeling that will be provided to the 
user with the marketed device.  If major revisions are made to the labeling after the user 
11 Contains Nonbinding Recommendations 
evaluation has concluded, an additional user study may be indicated if there is no other 
method available to validate that the changes made do not affect user performance.  For 
purposes of the study, the instructions for use should be written in English only; 
translations into other languages should not be provided to study participants.  Prior to 
the study, you should perform a readability assessment (in terms of grade level) of the 
user manual, test strip insert, and control solution insert.  For a product intended for 
home use by lay-users, the reading level should be at an 8th grade level or less.  We 
recommend using the Flesch-Kincaid, SMOG, or equivalent computer program to 
assess the readability grade level of the labeling.  You should describe the assessment 
and results in your 510(k) submission. 
The study subjects should obtain their own fingertip capillary (or alternate anatomical 
site(s)) sample and perform a blood glucose test using only the draft device labeling as 
instructions.  No other training or prompting should be provided to the user, and they 
should not receive assistance from a study technician or healthcare provider to obtain the 
test result.  Study subjects should be sequestered in such a way that they cannot observe 
or be influenced by the testing technique of other study participants or technicians.  Once 
the study participant has obtained their own result using the SMBG, the technician should 
then obtain an additional capillary sample for testing using the comparator method.  Since 
the intended user population of SMBGs is the lay-user, it is not expected for the 
technician to also obtain capillary results on the SMBG for comparison to the comparator 
value. 
Your study should include a minimum of 10 test strip vials or packages that cover a 
minimum of 3 test strip lots.  All test strips used in the study should have undergone 
typical shipping and handling conditions from the site of manufacture to a U.S. user prior 
to being used in the study.  You should describe these shipping and handling conditions 
in your 510(k) submission. 
Hematocrit values should be determined and recorded for each of the study participants.  
You should present individual hematocrit values in the 510(k) submission along with the 
meter results. 
Blood glucose test results are used by people with diabetes to make critical decisions 
about their treatment; therefore, it is important that the results are accurate so that 
nutritional and drug dosing errors are better avoided.  Your studies should demonstrate 
that your SMBG is sufficient for this purpose by showing that 95% of all SMBG results 
in this study are within +/- 15% of the comparator results across the entire claimed 
measuring range of the device and that 99% of all SMBG results are within +/- 20% of 
the comparator results across the entire claimed measuring range of the device.  You 
should include all results in the 510(k) submission.  Though we expect that with the 
technologies available, SMBG devices will be able to meet these criteria, there may be 
instances where meters may be determined to be substantially equivalent even when 
performance does not meet these criteria because, for example, other features of the 
meter or its setting of use provide benefits that compensate for different performance.  
For all SMBG test results that are >20% relative to the comparator method, you should 
12 Contains Nonbinding Recommendations 
provide a clinical justification for why the errors occurred and describe why the potential 
for that error does not affect user safety when extrapolated to the intended use setting 
(e.g., when billions of tests are performed).  We will review any submitted justification to 
determine whether the data suggest that patients may be put at risk, or whether the 
justification and any proposed mitigation are adequate. 
FDA understands that some SMBGs may not be able to measure reliably within 15% of 
the comparator method at very low glucose concentrations.  If this is the case, you should 
raise the lower end of the claimed measuring range to the concentration where your 
device is sufficiently accurate, according to the above described criteria.  To meet the 
clinical needs of the user population, SMBGs should minimally be able to measure blood 
glucose accurately between 50 mg/dL and 400 mg/dL, or a clinical justification should be 
provided for alternate measuring ranges.  A SMBG should identify and provide an error 
code in situations where the measured glucose value falls outside of the devices stated 
measuring range.  For example, meter XYZ has a measuring range that can detect glucose 
concentrations down to 50 mg/dL; therefore, blood samples with glucose concentrations 
below 50 mg/dL should provide an appropriate error code (e.g., LOW - Less than 50 
mg/dL). 
Method comparison and user performance studies for a SMBG should include multiple 
blood glucose meters being used amongst the 350 lay-user study participants.  Individual 
lancing devices should be used for each subject and meters should be cleaned and 
disinfected using validated instructions during the course of this study.  You should 
provide procedures to mitigate the risk of potentially transmitting disease between 
healthcare providers and subjects during the study (for example, use of disposable gloves 
or other physical barriers), including details on how often and when gloves worn by the 
trained health professionals should be changed between subjects.  Refer to Section IV 
above (Reducing the Risk of Bloodborne Pathogen Transmission in Diabetes Care) for 
additional information regarding the validation of cleaning and disinfecting of SMBGs.  
You should describe these aspects of the study in your 510(k) submission. 
You should also describe the following in your 510(k) submission: 
  Study setting, including the size, type, and location of each site and a justification 
of how the selected study conditions simulate intended use conditions.  Study 
sites should be representative of where SMBGs are used in the U.S. and you 
should include an explanation of why you believe each site is representative of 
where SMBGs are used. 
  Criteria used to select study subjects, including inclusion and exclusion criteria.  
Include patient demographics (age range, education level, native language, 
laboratory or healthcare work experience, disease state) and whether they are a 
naive SMBG user or not. 
  Details of procedures performed by lay-users and study technicians. 
  Instructions provided to users in the study.  (Note:  All instructions should be 
provided to users in English only.) 
13 Contains Nonbinding Recommendations 
  Type of sample collected (anatomical collection site(s)). 
  Number of test strip lots, number of test strip vials, and number of meters used in 
the study. 
  Description of the shipping and handling conditions of the test strips prior to use 
in the study. 
  A user questionnaire should be provided for the study participants to fill out after 
completing the study.  A copy of the blank questionnaire and the analysis of the 
results should also be provided. 
Accuracy at Extreme Glucose Values 
Because the user study described above using real patient samples may not provide a 
robust evaluation of SMBG performance in the extreme upper and lower ends of the 
claimed measuring range, you should perform additional studies using blood samples 
altered to achieve glucose concentrations of less than 80 mg/dL and greater than 250 
mg/dL.  These samples should mimic unaltered patient samples as closely as possible.  
This additional extreme glucose value study should be performed separately from the 
user study (see Section VI.C) described above and may be performed in a laboratory 
setting. 
Capillary whole blood samples should be used for these studies - a professional may 
need to collect the capillary blood to ensure the sample size is sufficient.  You should 
include a minimum of 50 prepared samples containing glucose concentrations below 
80 mg/dL and 50 samples greater than 250 mg/dL.  These samples should evenly 
cover the lower and upper limits of the claimed measuring range.  Samples may be 
altered by spiking or allowing the samples to glycolyze in order to obtain the 
appropriate glucose concentrations.  Samples should be measured on both the SMBG 
and the comparator method.  You should analyze these data separately from the user 
evaluation data but using the same methods described below for the user evaluation 
studies.  FDA will apply the same review criteria to both studies. 
2.  Data Analyses: 
Data exclusion and outliers: 
You should present all data in the 510(k) submission, including cases in which the meter 
displays an error code, a High or Low message, or no result.  All outliers (e.g., data 
points that do not conform to the minimum accuracy criteria) should also be included.  
You should investigate all outlier results and describe the results of these investigations, 
providing explanations for the occurrence of outliers when possible.  To help inform your 
investigations into outlier results, you should collect information regarding patient 
medications, hematocrit measurements, and disease states during your study.    
Analysis of results: 
You should present the difference between individual study subject results and results of 
the comparator method (or mean of the comparator measurement, if multiple replicates 
are measured on the comparator method) by plotting the data on an X-Y graph.  The plot 
should include the regression line and line of identity.  Your summary of results should 
include the slope and y-intercept, along with 95% confidence intervals, calculated using a
14 Contains Nonbinding Recommendations 
suitable analysis procedure (e.g., Linear Regression, Deming Regression), and the 
estimate of the deviation (standard error).  Difference plot of Y-X vs X may also be 
presented.  You should describe all statistical methods used and clearly identify and 
describe any outliers in the analysis. 
Tabular data presentation: 
You should present the results of your analysis in the following tabular format for each 
sample matrix.  In Table 2 below, X= the number of samples within the specified 
difference from the comparator method, and Y= total number of samples. 
Table 2. Summary of data within specified mg/dL of the comparator method for 
glucose concentrations across the entire range: 
Within +/- 5%  Within +/- 10%  Within +/- 15%  Within +/- 20% 
X/Y (%)  X/Y (%)  X/Y (%)  X/Y (%) 
D. Interference Evaluation 
You should evaluate the effect of potentially interfering endogenous and exogenous 
substances and conditions, such as icterus, lipemia, and varying hematocrit levels, as well 
as the effect of common medications on your SMBGs performance.  Conditions that are 
known to interfere with glucose monitoring test systems, such as ketoacidosis, should be 
included in the labeling as limitations.  If you would like the labeling to not include these 
limitations or if you would like to remove these conditions from the labeling, you should 
provide interference testing demonstrating that these conditions do not interfere with your 
device. 
1.  Endogenous/Exogenous Substances 
Study design: 
You should perform interference testing using samples containing glucose concentrations 
across the range of the device.  Specifically, testing should be performed in samples with 
target glucose values of approximately 50 - 70 mg/dL, 110-130 mg/dL, and 225-270 
mg/dL to evaluate clinically relevant decision points. 
You should evaluate each potentially interfering substance at clinically relevant 
concentrations, and should test all substances at the highest concentration that could 
potentially be observed in a whole blood sample; if significant interference is observed, 
you should perform dilutions of the interferent to determine the concentration at which 
interference begins to occur.  For example, if interference is observed with 20 mg/dL 
acetaminophen, additional testing should be performed with samples containing lower 
concentrations of acetaminophen, such as 15 mg/dL, 10 mg/dL and 5 mg/dL, to 
determine the lowest concentration of acetaminophen where interference is first 
observed.  If the results from the additional testing determine that interference is not 
observed in the sample containing 5 mg/dL acetaminophen and interference is observed 
in the sample containing 10 mg/dL acetaminophen, then 5 mg/dL is the highest 
concentration of acetaminophen where no interference is observed. 
15 Contains Nonbinding Recommendations 
The substances listed below in Table 3 represent known or potential interferents for 
current blood glucose measurement technologies and comprise the minimal list of 
substances that should be tested for interference. 
Table 3. List of Known or Potential Interferents for SMBGs: 
Interferent  Recommended Test 
Concentration 
Acetaminophen  20 mg/dL 
Ascorbic acid  6 mg/dL 
Conjugated Bilirubin  50 mg/dL 
Unconjugated Bilirubin  40 mg/dL 
Cholesterol  500 mg/dL 
Creatinine  15 mg/dL 
Dopamine  0.09 mg/dL 
EDTA*  0.1 mg/dL 
Galactose  60 mg/dL 
Gentisic acid  1.8 mg/dL 
Reduced Glutathione  4.6 mg/dL 
Hemoglobin  1000 mg/dL 
Heparin*  300 IU/dL 
Ibuprofen  50 mg/dL 
L-Dopa  0.75 mg/dL 
Maltose  480 mg/dL 
Mannitol  1800 mg/dL 
Methyldopa  2 mg/dL 
Salicylic acid  60 mg/dL 
Sodium  180 mmol/L 
Tolbutamide  72 mg/dL 
Tolazamide  9 mg/dL 
Triglycerides  1500 mg/dL 
Uric acid  23.5 mg/dL 
Xylose  600 mg/dL 
Sugar Alcohols**  0.09 mg/dL 
*The inclusion of EDTA and Heparin in this table refers to their use as therapeutic substances and not as 
anticoagulants for sample preparation. 
**All common sugar alcohols, including but not necessarily limited to, sorbitol, xylitol, lactitol, isomalt, 
maltitol should be independently tested. 
In addition to the list of potential interferents provided in Table 3, you should conduct an 
interference risk analysis and carry out bench studies to evaluate interference from 
additional drugs commonly used in your intended use population.  These bench studies of 
additional drugs should be conducted in the same manner described in this Section. 
You should provide a reliable estimate of the interference predicted for each potential 
interferent.  To do this, we recommend the following method of measuring and 
calculating interference.  First, blood samples should be generated at each target glucose 
16 Contains Nonbinding Recommendations 
concentration described above.  Each glucose sample should be tested in replicates with 
the comparator method (we suggest at least 4 replicates in order to reduce standard error) 
to establish the glucose concentration in the sample.  The glucose samples should then be 
split into a test sample to which a specific amount of potential interferent is added and a 
control sample containing solvent/vehicle in lieu of the potential interfering substance.  
Both control samples and test samples should be measured in replicates on the SMBG.  
At least three test strip lots should be used for this evaluation.  Each of the control and 
test samples should be tested on your SMBG in replicates of 30 across the three lots (10 
replicates per lot of test strips for a total of 30 replicates per sample).  The mean of 
replicates should be calculated for each control and test sample.  The relative bias 
(mg/dL) and percent bias should be calculated using the results of the control sample 
relative to test sample for each concentration of potential interferent.  These results 
should be submitted with 95% confidence intervals as part of your 510(k) submission. 
For SMBGs, the degree of acceptable interference may vary by substance tested and the 
intended patient population of your device.  Therefore, you should report in your 510(k) 
submission the interference testing data as well as the expected imprecision of the system 
at that glucose concentration.  If interferences are observed, you should propose 
appropriate labeling to address any observed interferences; the labeling language 
appropriate for the observed interference will be discussed during the review of the 
510(k) submission. 
As new drugs are developed that could potentially interfere with your device, or new 
interfering substances are identified for other SMBGs, you should evaluate these new 
drugs or substances for potential interference with your device.  For example, if a new 
drug intended to treat cardiac complications in diabetic patients is approved, you should 
conduct a careful evaluation to determine whether the new drug interferes with your 
device.  You should report to FDA if significant new interferences are observed with 
your device or with any cleared glucose monitoring devices that are on the market.  New 
drugs/potential interferents should also be evaluated when new or significantly modified 
technology is introduced. 
Data Analysis: 
You should provide raw data sets as well as a summary table for all interference results. 
Please note that the summary tables should be presented separately for each test strip lot 
and for all lots pooled for each glucose level tested.  Table 4 below provides a sample 
format of a summary table. 
Table 4. Recommended Summary Table Format: 
Test Strip Lot #(s) 
Mean  Confidence 
Interferent  Control  Test 
Glucose  Bias  %  Interval 
Interferent  Concentration  Sample  Sample 
Value  (mg/dL)  Bias  around 
(mg/dL)  Mean  Mean 
(Comparator)  % Bias 
Acetaminophen  60 mg/dL  20 mg/dL 
17 Contains Nonbinding Recommendations 
120 mg/dL  20 mg/dL 
250 mg/dL  20 mg/dL 
In your 510(k) submission, you should include a detailed description of the study design, 
all data collected in this study, the summary tables indicated above, and a description of 
the conclusions drawn from the study. 
2.   Hematocrit 
Study Design: 
Because a reasonably sized user evaluation study may not include the full range of 
hematocrit values expected in the intended use population, you should perform a separate 
study to determine how much analytical error is contributed by varying hematocrit levels.  
This should constitute a bench study designed to evaluate the effect of hematocrit on the 
performance of your SMBG to assess whether the potential for errors affects patient 
safety in the intended use population across your claimed hematocrit range.  The 
observed hematocrit levels may be very broad in the intended use population for this type 
of device; the majority of intended users may reasonably be expected to have hematocrit 
levels between 20% and 60%.  Therefore, we recommend 20-60% as the claimed 
hematocrit range for this type of device.  If your device is subject to significant 
interference from hematocrit within that range, you should include limitation statements 
in your labeling cautioning against use when certain physiological conditions are present 
or suspected (e.g., anemia, etc.).  Because lay-users generally have no way to adequately 
determine their hematocrit status, SMBGs should be able to adequately measure glucose 
across the range of 30-55% hematocrit (which includes the greatest proportion of users).  
If your SMBG cannot detect glucose across this range, it is possible that your device may 
present new technological characteristics from the predicate that raise different questions 
of safety and effectiveness and may not be determined to be substantially equivalent. 
You should evaluate hematocrit interference by measuring blood samples containing 
various glucose concentrations.  The samples should be prepared to contain designated 
levels of hematocrit that span the claimed hematocrit range for the device.  Blood 
samples may be altered by spiking or allowing them to glycolyze to obtain desired 
glucose concentrations.  Specific percentages of hematocrit may be achieved for each 
sample by manipulating the plasma to packed cell ratio following centrifugation.  
Hematocrit levels tested should span the claimed range in 5% intervals, as such, 5% 
intervals allow for a more accurate assessment of bias from hematocrit interference than 
using broader intervals.  Additionally, a sample having a nominal hematocrit of 42% 
should be tested.  For example, if your claimed hematocrit range is from 20-60%, you 
should test samples at 20, 25, 30, 35, 42, 50, 55, and 60% hematocrit.  The samples 
should also span the claimed measuring range for blood glucose.  Samples should include 
5 different blood glucose concentrations evenly spread and targeted to the following 
ranges: 30  50, 51  110, 111  150, 151  250, and 251  400 mg/dL. 
Each sample should be tested on the comparator method in multiple replicates (we 
recommend a minimum of 4 replicates).  A mean of the comparator measurements 
(Mean ) should give greater confidence in the true glucose concentration of the 
Comp
18 Contains Nonbinding Recommendations 
sample.  You should test a minimum of 3 test strip lots to evaluate interference from 
hematocrit.  Each sample should be tested on your new SMBG in replicates of 30 (10 
replicates per lot of test strips, for a total of 30 replicates per sample).  
Data Analysis: 
An analysis should be performed for each of the 5 blood glucose concentrations tested 
and each test strip lot.  The bias should first be determined with respect to the comparator 
method and then with respect to the nominal hematocrit samples, so that the hematocrit 
effect can be isolated. 
(1) Estimation of Bias to Comparator Method 
For each sample, you should calculate the average of 30 replicates of your new 
SMBG (Mean ).  Using the Mean  and the estimate of the true glucose 
SMBG SMBG
concentration in the sample, Mean , you should estimate a bias and percent bias as 
Comp
(Mean -Mean ) and (Mean -Mean )/Mean  correspondingly, for 
SMBG Comp SMBG Comp Comp,
each sample.  The results should be presented as in the table below and in graphical 
format appropriate for each specific glucose concentration range. 
For glucose concentrations less than 75 mg/dL, the analysis should be presented as a 
graph where the X-axis represents hematocrit values and the Y-axis represents the 
absolute bias values.  For glucose concentrations greater than or equal to 75 mg/dL, 
the analysis should be presented as a graph where the X-axis represents hematocrit 
values and the Y-axis represents percent bias values. 
Table 5.  Example table of bias calculated versus the comparator method for the 
hematocrit evaluation on a SMBG with 120 mg/dL glucose: 
Average of  Average of  %Bias 
Number of 
Hematocrit  Comparator  SMBG  (Mean -
SMBG
measurements 
(%)  measurements  measurements  Mean )/ 
Comp
for SMBG 
(Mean )  (Mean )  Mean  
Comp SMBG Comp
10  118.0  30  127.6  8.1% 
15  118.4  30  127.6  7.8% 
20  122.4  30  130.4  6.5% 
25  120.7  30  127.1  5.3% 
30  123.7  30  129.5  4.7% 
35  121.5  30  127.1  4.6% 
42  119.7  30  124.6  4.1% 
50  121.3  30  125.4  3.4% 
55  120.8  30  122.7  1.6% 
60  120.1  30  119.5  -0.5% 
65  118.1  30  116.0  -1.8% 
70  117.5  30  115.6  -1.6% 
19 Contains Nonbinding Recommendations 
(2) Estimation of Bias due to Hematocrit 
In order to isolate the effect of hematocrit on device performance, the bias relative to 
a sample having a nominal hematocrit (42%) should be determined.  This nominal 
hematocrit is representative of the average hematocrit value of the intended use 
population; therefore, bias due to hematocrit is considered 0% (or 0 mg/dL) for the 
sample with hematocrit value equal to the average hematocrit value (42%).  The 
estimate bias due to hematocrit for each sample should be calculated by subtracting 
the bias at the average (42%) from the bias of each sample. 
Table 6. Example table of bias due to hematocrit calculated for the nominal 
hematocrit value of 42% on a SMBG with 120 mg/dL glucose: 
Average of  Average of  %Bias 
Number of 
Hematocrit  Comparator  SMBG  (Mean - %Bias due to 
SMBG
measurements 
(%)  measurements  measurements  Mean )/ hematocrit 
Comp
for SMBG 
(Mean )  (Mean )  Mean  
Comp SMBG Comp
10  118.0  30  127.6  8.1%  4.0% 
15  118.4  30  127.6  7.8%  3.7% 
20  122.4  30  130.4  6.5%  2.4% 
25  120.7  30  127.1  5.3%  1.2% 
30  123.7  30  129.5  4.7%  0.6% 
35  121.5  30  127.1  4.6%  0.5% 
42  119.7  30  124.6  4.1%  0.0% 
50  121.3  30  125.4  3.4%  -0.7% 
55  120.8  30  122.7  1.6%  -2.5% 
60  120.1  30  119.5  -0.5%  -4.6% 
65  118.1  30  116.0  -1.8%  -5.9% 
70  117.5  30  115.6  -1.6%  -5.7% 
You should include in your 510(k) submission a detailed description of the study design, a 
list of all data collected in this study, the summary tables indicated above, and a summary of 
the conclusions drawn from the study.  
E. Flex Studies 
Compared to professional healthcare settings, there are typically fewer controls in place 
in home use settings to mitigate the risk of erroneous results.  In addition, users are often 
untrained and may not know how to identify or address an erroneous result.  It is 
therefore assumed that devices intended for home use by lay-users are designed so that 
the risk of an erroneous result is far less than with laboratory-based tests.  You should 
therefore demonstrate that your SMBG design is robust (i.e., insensitive to environmental 
and usage variation) and that all known sources of error have been assessed through a 
detailed risk assessment and are effectively controlled.  In general, flex studies should be 
used to demonstrate robust design while risk management should be used to demonstrate 
20 Contains Nonbinding Recommendations 
identification and effective control of error sources, although the two are not mutually 
exclusive. 
Most risk control measures should be fail-safe mechanisms or failure alert mechanisms.  
Examples of fail-safe mechanisms are lock-out functions to ensure that a SMBG does not 
provide a result when test conditions are inappropriate, such as when there is a 
component malfunction or operator error.  Other examples are measures within the 
SMBG to prevent operator error, such as guides or channels that prevent improper strip 
placement.  We recommend that the SMBG design incorporate fail-safe mechanisms 
whenever it is technically practicable.  If fail-safe mechanisms are not technically 
practicable for some risks, failure alert mechanisms should be used.  Failure alert 
mechanisms notify the operator of any SMBG malfunction or problem.  These may 
include measures such as internal procedural controls or electronic controls.  Devices 
with such mechanisms allow the operator to correct the error, or put the operator on 
notice that the results will be unreliable due to the error.  For example, in cases where the 
result exceeds the reportable range (i.e., extremely high or low glucose result) and the 
result is a critical value, the device should give a message such as "high" or "low." 
Flex studies, or studies that stress the operational boundaries of a SMBG, should be used 
to validate the insensitivity of the test system to performance variation under stress 
conditions.  Where appropriate, flex studies should also be used to verify and/or validate 
the effectiveness of control measures at operational limits.  Flex studies are particularly 
important for SMBGs as these devices are intended for use by lay-users and undergo a 
variety of environmental and user-associated conditions that could affect system 
performance. 
In order to identify all relevant flex studies for your SMBG device, we recommend that 
you conduct a systematic and comprehensive risk analysis that identifies all potential 
sources of error, including test system failures and operator errors, and identify which of 
these errors can lead to a risk of a hazardous situation.  You should then identify control 
measures, including fail-safe mechanisms and failure alert mechanisms that will reduce 
risks for these sources of error.  When the control measures have been implemented, you 
should (1) verify that each control measure has been properly implemented, and (2) 
verify and/or validate the effectiveness of each control measure.  When appropriate, flex 
studies should be used to verify and/or validate the effectiveness of these control 
measures.  
Below, we have identified several flex studies that you should perform and include in the 
510(k) submission of your SMBG.  At the same time, we encourage you to continue to 
perform risk analyses to determine whether your device includes any unique or new 
features that should be validated through additional flex studies.  
If your SMBG does not perform adequately in flex studies, we recommend you either 
provide a justification, determined by means of thorough risk analysis, as to why 
adequate performance in that flex study is not critical to the safe and effective use of the 
device, or indicate an additional implemented validated control mechanism.  FDA will 
21 Contains Nonbinding Recommendations 
review any justifications to determine whether the proposed risk mitigations are adequate 
to protect patients. 
In the case of the following flex studies, verification should include performance testing; 
however, it is acceptable for you to provide documentation indicating that flex studies 
have been conducted in accordance with an FDA-recognized industry standard in your 
510(k) submission.  We recommend you include the type of testing performed, the 
reference standard followed, the acceptance criteria, and whether the SMBG passed these 
acceptance criteria. 
The flex studies we recommend performing in this manner are: 
  Mechanical Vibration Testing 
  Shock Testing 
  Electromagnetic compatibility (EMC) Testing 
  Electrostatic Discharge/Electromagnetic Interference Testing 
Unless otherwise indicated, we recommend that you clearly identify all flex studies 
performed on your device in your 510(k) submission.  A detailed description of the 
following attributes should be included in your 510(k) submission: 
  Study goal 
  Study protocols 
  Methods used to apply samples to test strips 
  Sample type and any anticoagulants used 
  Study results 
  Conclusions made from the study  
We have also identified additional flex studies (described below) that we recommend be 
performed in order to demonstrate adequate system performance in intended use settings.  
A list of these recommended flex studies as well as recommended study designs are 
included below in Subsections 1-8.  These flex studies should be performed using fresh 
venous or capillary whole blood samples, not control solutions. 
1.  Test Strip Stability Testing 
You should perform studies that assess test strip performance throughout the test strip 
stability claims, including closed and open vial claims.  Two studies should be performed 
to support test strip stability: 1) closed vial stability (shelf life) should be performed to 
assess the recommended shelf life and conditions when the vial is stored closed 
throughout the claimed expiration dating, at different combinations of temperature and 
humidity spanning the recommended storage conditions; and 2) open vial stability should 
be performed to mimic conditions under which an individual would actually use the strips 
where the vial is opened and closed throughout its claimed open vial life and stored at 
different combinations of temperature and humidity spanning the recommended storage 
22 Contains Nonbinding Recommendations 
conditions. We suggest that you submit only the study protocols for these test strip 
stability assessments, the acceptance criteria, and the conclusions of any studies which 
have been completed. 
These studies (shelf life and open vial stability) should be designed to span both the 
claimed temperature range and humidity range at various time points throughout the 
duration of the respective claim.  The time points that are assessed (e.g., 1 month, 3 
months, 2 years) should be specified in the protocol.  Combinations of real-time and 
accelerated stability studies are acceptable.  However, if accelerated studies are provided, 
real-time studies should be ongoing and the protocols and acceptance criteria should be 
provided for both study types. 
You should perform adequate precision and accuracy evaluations at each identified time 
point.  The following are provided only as examples of such studies.  Through these 
evaluations, you should demonstrate that the precision and accuracy calculated in these 
studies are within the labeled performance of the SMBG. 
Precision Evaluation:  
Precision with Control Materials 
This study should be completed over 5 days and use glucose controls.  At least two 
meters should be included in this study and at least 10 measurements should be taken 
per glucose control level, per meter. 
Precision with Whole Blood Samples 
This study should use whole blood samples spanning the claimed measuring range of 
the SMBG.  Samples may be altered by spiking with glucose or allowing the samples 
to glycolyze in order to evaluate the extreme ends of the systems claimed measuring 
range.  At least two meters should be included in this study and at least 10 
measurements should be taken per glucose level, per meter. 
Accuracy Evaluation:  
This study should be performed using whole blood samples that span the claimed 
measuring range of the SMBG.  It is acceptable for samples to be spiked with a known 
concentration of glucose or allowed to glycolyze to achieve the desired concentration in 
order to evaluate the extreme ends of the systems measuring range.  Glucose 
concentrations spanning the claimed measuring range (e.g., 30-50, 100-150, 200-300, 
350-500 mg/dL) should be measured with the SMBG and compared to values obtained 
with the comparator method. 
2.  System Operating Conditions Testing 
You should perform a study to assess the performance of your SMBG when used under 
various operating temperature and humidity conditions.  These studies should be 
designed to represent actual use conditions experienced by SMBG users.  Tested 
temperature and humidity ranges should not only cover the operating ranges that 
adequately reflect the intended use environment, and that are specified in the device 
labeling, but should also stress the SMBG by including ranges outside of the claimed 
23 Contains Nonbinding Recommendations 
operating range.  Testing should incorporate the four extreme temperature and humidity 
combinations (high temperature/low humidity, low temperature/high humidity, high 
temperature/high humidity, low temperature/low humidity) or other testing combinations 
if a suitable rationale can be provided.  Measurements made on whole blood samples 
with your candidate device under various operating temperature and humidity conditions 
should be compared to values obtained using the candidate device at a nominal condition 
(such as 23oC, 40% relative humidity). 
Separate testing of test strip and meter shipping and storage conditions is not warranted if 
the temperature and humidity studies outlined here use only packaged blood glucose 
meters and blood glucose test strips that have undergone appropriate storage conditions 
and the longest possible shipping duration (both as specified by the manufacturer). 
You should also include in your 510(k) submission a summary of any identified outliers 
that were excluded from statistical analysis, the method of outlier identification, and the 
results of outlier investigations. 
We also encourage manufacturers to consider ways in which temperature and/or humidity 
detectors might be incorporated into test strip containers to alert users when strips have 
not been handled correctly or stored according to recommended and validated conditions. 
3.  Altitude Effects 
Relative to sea level, high altitude comprises a complex set of environmental differences 
and can induce multiple physiological changes, any or all of which might interfere with 
your SMBGs performance.  For example, high altitude often involves extremes of 
temperature and humidity and can result in changes to hematocrit and blood pressure.  
The intended use environment of SMBGs in the United States includes high altitude 
conditions and, therefore, manufacturers should conduct studies on the effects of altitude 
on their SMBG device, or provide a justification for why altitude does not have an effect 
on the performance of their SMBG. 
An altitude effects study should compare results from whole blood samples with your 
candidate device at the different high-altitude conditions relative to values obtained using 
the candidate device at a nominal condition (such as sea level).  These studies should also 
include a pressure change.  Studies based on oxygen tension instead of pressure change 
are not adequate, because oxygen tension is only one component that changes with 
altitude.  Altitude pressure changes can be accomplished by physically increasing altitude 
(e.g., in an airplane, on a mountain), or by simulating increasing altitudes and 
atmospheric conditions in a pressurized chamber.  Results should support the altitude 
labeling claim for your device.  You should provide your definition for terms, such as 
sea level.  The definition of sea level should not extend above 500 feet.  You should 
test your SMBG at a minimum of 10,000 feet above sea level. 
4.  Error Codes for Samples Outside the Measuring Range 
24 Contains Nonbinding Recommendations 
You should perform adequate analyses to demonstrate that your meter provides the 
appropriate error codes when measured glucose concentrations are outside of the 
SMBGs claimed measuring range, and include these results in your 510(k) submission. 
5.  Short Sample Detection 
Blood glucose measurement from short samples (samples of reduced blood volume) can 
lead to inaccurate results.  To avoid the risk of inaccurate results, SMBGs should be able 
to detect that a short blood sample has been applied to the test strip and should not 
provide a result to the user.  Short sample detection systems should not rely on visual 
verification by the user.  
The volume that classifies a test sample as a short sample is dependent upon the SMBG 
device.  In your short sample detection studies, you should include blood samples with 
known glucose concentrations in the following three ranges: 50-65 mg/dL, 100-120 
mg/dL, and 200-250 mg/dL. You should test blood samples with your candidate SMBG 
at each of the glucose concentrations listed above.  Results obtained from the candidate 
device should be compared to results using the candidate device at a nominal condition 
(such as the claimed minimum sample volume).  Blood samples with serially reduced 
volumes should be measured on the device until an error is either generated by the 
SMBG or the test result falls outside of the devices claimed performance characteristics.  
In your 510(k) submission, you should describe the results from the candidate device 
under both test and nominal conditions, as well as include the sample volumes tested for 
each glucose concentration range.    
6.  Sample Perturbation Study 
Sample perturbation occurs when a user has applied an appropriate volume of blood to 
the test strip for glucose measurement but an event, such as wicking of blood away from 
the test strip, flicking of the test strip, or flicking of the meter, occurs during the start of 
the measurement and alters the volume of the initial sample application.  You should 
adequately demonstrate how your SMBG handles sample perturbation through a sample 
perturbation study. 
In a sample perturbation study, a sample should be applied to the test strip and after the 
SMBG device has begun to read the sample, but before the measurement is complete, the 
test strip should be perturbed.  The sample perturbation study should incorporate blood 
samples with known glucose concentrations in the following three ranges: 50-65 mg/dL, 
100-120 mg/dL, and 200-250 mg/dL.  In your 510(k) submission, you should describe 
your protocol, including your specific method of perturbing the test sample, as well as 
candidate device results compared to results using the candidate device under a nominal 
condition (such as strips with no perturbation).  
7.  Intermittent Sampling 
Intermittent sampling occurs when a short sample is applied to a test strip, a glucose 
measurement begins, and the user adds more sample to the test strip before the glucose 
measurement is complete.  You should adequately demonstrate how your SMBG handles 
intermittent sampling by conducting an intermittent sampling study. 
25 Contains Nonbinding Recommendations 
The intermittent sampling study should incorporate blood samples with known glucose 
concentrations in the following three ranges: 50-65, 100-120, and 200-250 mg/dL.  You 
should perform intermittent sampling studies that are representative of actual events.  For 
instance, approximately one half of the sample should be applied to the test strip prior to 
the start of sample measurement, then the other half of the sample should be applied to 
the strip after a set period of time, such as once the sample starts reading.  For systems 
that allow a second sample of blood to be added to the test strip without producing an 
error message, different time delays throughout the claimed period of second application 
should be tested once the sample starts reading, but before the measurement is complete.  
You should describe how the device responds to this scenario in your 510(k) submission, 
including whether a result is reported, whether this result is accurate (relative to the 
nominal condition, such as with the minimum claimed sample volume), and when an 
error code is reported. 
8.  Testing with Used Test Strips 
You should perform a study to demonstrate how your SMBG device performs when a 
used test strip is inserted.  We recommend that SMBG devices be designed to 
automatically recognize the insertion of used test strips.  Insertion of used test strips into 
a SMBG should not provide glucose measurement results to the user.  If an automatic 
used test strip recognition function has been incorporated into your SMBG, you should 
perform a flex study to demonstrate the functionality of this recognition system.  In your 
510(k) submission, you should provide the study protocol, acceptance criteria and results 
of your used test strip study. 
F. Meter Calibration and Quality Control Materials 
The use of external control solutions allows users to periodically check that the SMBG 
and test strips are working together properly and that the device is performing correctly.  
The use of external control solutions by the user should be promoted.  At least two levels 
of control material should be specified in the labeling as available to the user. 
Control solutions provided should not be labeled in a descriptive manner such as low, 
normal, or high, since that may be misleading to the user; users may confuse a label 
that says normal as meaning that value is a clinically normal value even when the 
control concentration is not within the normal range that is recommended by that 
individual users physician.  Therefore, control solutions should be labeled non-
descriptively (e.g., numerically: 1, 2, 3). 
Your 510(k) submission should describe how the candidate device recognizes and 
distinguishes control materials from patient specimens, either automatically or manually 
by the user, as well as explain how the system compensates for differences between test 
strip lots (i.e. how the meter is calibrated or coded for each test strip lot). 
VII.  Test Strip Lot Release Criteria 
26 Contains Nonbinding Recommendations 
Your test strip lot release criteria should be set to ensure consistent performance of your 
SMBG test strips.  You should provide a description of the lot release criteria and a summary 
of the sampling scheme in your 510(k) submission.  In addition, you should explain how the 
system compensates for differences between strip lots or strip types. 
We recommend that you select a sampling scheme appropriate for the operation of your 
SMBG device to test each outgoing test strip lot or batch.  Your test strip lot release criteria 
should be designed to ensure that all released lots conform to the labeled SMBG performance 
in the hands of the intended user.  Therefore, these criteria typically should be tighter than 
the criteria used to evaluate total error in the performance studies, in order to achieve targeted 
performance in the intended user population.  
VIII.  Third Party Test Strips 
Third party test strips refer to test strips manufactured and distributed by a company other 
than the company that manufactures and distributes the glucose meter.  Third party test strip 
manufacturers should ensure that they are aware of any design changes to the meter because 
such changes could affect compatibility of the test strip with the meter.  Because test strips 
and meters work as integral systems, third party test strip manufacturers should sufficiently 
address in their 510(k) submissions how they will mitigate the risk of incorrect results due to 
meter design changes.  One way to effectively ensure that the third party test strip 
manufacturer is made aware of any design changes to the meter is by having in place an 
agreement between the third party test strip manufacturer and the meter manufacturer. 
IX.  Software 
For software descriptions of SMBGs, their components, and accessories, we recommend that 
you review FDAs guidance entitled Guidance for the Content of Premarket Submissions 
for Software Contained in Medical Devices.9 Generally, FDA considers blood glucose 
meters to be moderate level of concern devices because glucose results will be the basis for 
treatment, including determination of insulin dosage by the patient or health care provider.  
Incorrect glucose results or failure of the software to detect an error could result in improper 
diabetes management.  (Also, see Section V, above, regarding software descriptions in your 
510(k) submission.) 
In addition, for any such changes, manufacturers should develop and implement appropriate 
cybersecurity controls to ensure device cybersecurity and maintain device functionality and 
safety. The following online resources may be helpful in developing and maintaining these 
cybersecurity controls: 
  FDA guidance Content of Premarket Submissions for Management of 
                                                          
9 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-content-
premarket-submissions-software-contained-medical-devices. 
27 Contains Nonbinding Recommendations 
Cybersecurity in Medical Devices;10
  FDA guidance Postmarket Management of Cybersecurity in Medical Devices;11
  FDA Fact Sheet: The FDAs Role in Medical Device Cybersecurity  Dispelling 
Myths and Understanding Facts.12
X.  Labeling 
The labeling of a SMBG includes the user manual, the quick start guide (optional), the 
package inserts for both test strips and controls, and the box and container labels for the 
meter, test strips, and control materials.  The package inserts for test strips and controls, and 
the user manual, should be simple, concise, and easy to understand.  Graphics such as line 
drawings, illustrations, icons, photographs, tables, and graphs are very useful tools.  
Manufacturers should ensure that the same terms are used consistently throughout the 
labeling to identify the device and its parts, avoiding synonyms or alternate phrases.  We 
recommend that you refer to the following documents for information on important 
principles for developing clear and complete home use IVD labeling: 
  FDAs guidance entitled Guidance on Medical Device Patient Labeling; Final 
Guidance for Industry and FDA.13
  CLSI GP-14: Labeling of Home-Use In Vitro Testing Products; Approved Guideline. 
  FDAs Device Advice website entitled In Vitro Diagnostic Labeling Requirements.14
Technical information required by 21 CFR 809.10(b) should be described so that lay-users 
can understand the information or locate the information, if warranted.  Detailed technical 
information (e.g., chemical details of test principle or statistical analyses of data) may be 
presented in a separate section followed by clarifying statements appropriate for lay-users. 
The 510(k) submission must include labeling in sufficient detail to satisfy the requirements 
of 21 CFR 807.87(e).  Final labeling must also satisfy the requirements of 21 CFR 809.10. 
The following items are intended to further assist sponsors in complying with the 
requirements of 21 CFR 809.10 for test strip and meter labeling.  You should refer to that 
regulation for the complete list of labeling requirements for in vitro diagnostic devices.     
1.  All device labeling must contain the proprietary and common names of the device (21 
CFR 809.10(a)(1) and 21 CFR 809.10(b)(1)).  The various test system components 
                                                          
10 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/content-premarket-
submissions-management-cybersecurity-medical-devices-0. 
11 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/postmarket-
management-cybersecurity-medical-devices.  
12 Available at https://www.fda.gov/media/123052/download.  
13 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-medical-
device-patient-labeling. 
14 Available at https://www.fda.gov/medical-devices/device-labeling/vitro-diagnostic-device-labeling-
requirements. 
28 Contains Nonbinding Recommendations 
should be named in such a way that they are recognized as belonging to the same system 
or family of products (ABC blood glucose test system, ABC blood glucose meter, ABC 
blood glucose test strips, etc.) to aid in identification of system components. 
2.  You must include the intended use of the product in your label and labeling documents 
(21 CFR 809.10(a)(2) and 21 CFR809.10(b)(2)).  The intended use for SMBGs for home 
use by lay-users should be similar to the example below:  
The XYZ Blood Glucose Monitoring System is intended for use in the quantitative 
measurement of glucose in-capillary whole blood from the finger.  It is intended for use 
by people with diabetes mellitus at home as an aid in monitoring the effectiveness of a 
diabetes control program.  The XYZ Blood Glucose Monitoring System is intended to be 
used by a single person and should not be shared. 
3.  The label and labeling must include warnings appropriate to the hazard presented by the 
product (21 CFR 809.10(a)(4) and 21 CFR 809.10(b)(5)(ii)). 
You should include the following warning prominently on the outer box label and 
package insert. 
Use of this device on multiple patients may lead to transmission of Human 
Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV), Hepatitis B Virus (HBV), 
or other bloodborne pathogens. 
4.  The labeling must include the chemical, physical, physiological, or biological principles 
of the procedure, as per 21 CFR 809.10(b)(4).  The discussion of these principles should 
include identification and source of the enzyme and description of the reaction.  Labeling 
should specify whether results are determined in terms of whole blood or plasma 
equivalents.  SMBGs intended for use in the U.S. should report results in terms of plasma 
equivalents. 
5.  The label must include a means by which the user may be assured that reagents meet 
appropriate standards of identity, strength, quality, and purity at the time of use, as 
described in 809.10(a)(6) and 21 CFR 809.10(a)(10).  
6.  The labeling must provide instructions for specimen collection and preparation (21 CFR 
809.10(b)(7)).  Instructions should include a statement to users on the importance of 
thoroughly washing with soap and water and drying the skin before taking a sample, 
because contaminants on the skin may affect results.  See also instructions for cleaning 
and disinfection below.  
7.  The labeling must provide a step-by-step outline of recommended procedures (21 CFR 
809.10(b)(8)), and operating instructions for the instrument (21 CFR 809.10(b)(6)(v)).  
Numbering, rather than bullets, should be used for clarity when appropriate (e.g., 
procedural steps, etc.).  
29 Contains Nonbinding Recommendations 
8.  The labeling must include a statement of limitations of the procedure, including known 
extrinsic factors or interfering substances affecting results (21 CFR 809.10(b)(10)).  You 
should include testing conditions that may cause clinically significant errors (due to bias 
or imprecision) with your SMBG (e.g., specific drugs, oxygen therapy, high altitude). 
You should indicate the most extreme conditions (e.g., the highest altitude, highest and 
lowest temperatures, etc.) at which the device has been validated based on the results of 
performance testing. 
9.  The labeling should clearly indicate to users what display they can expect to see when 
their measured glucose is lower or higher than the claimed measuring range of the meter.  
For example, meter XYZ has a measuring range that goes down to 50 mg/dL.  All 
glucose values measured below 50 mg/dL will provide an appropriate message indicating 
the results are below the meter range.  Meter XYZs labeling would include a statement 
explaining this error code: When your glucose value is less than 50 mg/dL you will see 
the following error code: Less than 50. 
10. The labeling must describe details of calibration and of quality control procedures and 
materials (21 CFR 809.10(b)(8)(v) and 21 CFR 809.10(b)(8)(vi)).  This is to help ensure 
optimal performance of the SMBG.  This section should include recommendations for 
how and when to perform quality control checks and instructions for what to do if the 
control material values are not within the manufacturers allowable range.  As part of the 
quality control information in your labeling, we recommend sponsors advise users that 
they should periodically review their technique and compare a result obtained with their 
meter to a result obtained using a laboratory method or a well-maintained and monitored 
system used by their healthcare provider. 
11. The labeling must include expected values (21 CFR 809.10(b)(11)).  FDA recommends 
that the expected values should be those for non-diabetics.  FDA does not recommend 
including additional ranges adjusted for diabetics because such ranges are individualized 
and determined by the clinician.  The expected values should be cited from in-house 
studies or up-to-date reference sources. 
12. The labeling must include specific performance characteristics (21 CFR 809.10(b)(12)).  
Sponsors should briefly describe all studies and summarize results in the package inserts.  
FDA recommends that this include performance data summaries from in-house and user 
studies.  For presentation of accuracy, in particular, see the charts below for an example.  
Performance should be presented separately for each anatomical site and matrix. 
13. So that lay users have the ability to choose the SMBG that is right for them, it is 
important to clearly describe the accuracy of the device in a way that is easy for them to 
understand.  It is also important for this information to be located in a prominent place in 
product labeling so that lay-users can understand the performance of an individual 
SMBG, both prior to purchase and also when they are learning to use the device they 
have purchased.  Therefore, the outer meter box labeling, the package insert for the test 
strip, and the user manual should all have easy to understand depictions of the clinical 
study results. 
30 Contains Nonbinding Recommendations
In the package insert for the test strips and the user manual for the SMBG, accuracy 
information should be placed prominently within the labeling.  We recommend that this 
information be included in the section where the labeling describes how a user will obtain 
a result.  In the test strip package insert, this section should be large and centrally placed 
so that users understand the performance of the system using these test strips.  We 
recommend the following types of presentations to convey the results of your accuracy 
studies in the device user manual and test strip package inserts.  
Suggested Representation of Accuracy for Home Use by Lay-Users - Example
Your ABC Meter result may vary slightly from your actual blood glucose value.  This may 
be due to slight differences in technique and the natural variation in the test technology.    
The chart below shows the results of a study where 350 typical users used the ABC meter 
to test their blood glucose level.  For example, in this study, the ABC meter gave results 
within 15% of their true blood glucose level 340 out of 350 times. 
Difference range between the true  Within  Within  Within  Within 
blood glucose level and the ABC  5 % 10 % 15 % 20%
meter result.
The percent (and number) of meter  57%  94%  97%  100% 
results that match true blood glucose  (200/350) (330/350) (340/350) (350/350)
level within x%
Accuracy information should also be included on the SMBG outer meter box labeling, as 
well as in the test strip package inserts and user manual.  We recommend that this outer box 
label accuracy information refer readers to the package insert and graphically represent the 
user study data.  An example of this type of presentation is shown below.  Numbers represent 
the number of meter results that were within the level of accuracy shown, relative to the 
laboratory device.
Accurate 350outof350(100%ofresults)
350 out of 350 (100% of results)
Results
More 
Accurate
226622  oouutt  ooff  335500 ((7755%%  ooff  rreessuullttss))
Results
Most 
Accurate 175 out of 350(50% of results)
175 out of 350 (50% of results)
Results
31 Contains Nonbinding Recommendations 
Accuracy key   Percentages listed are meter 
result as compared to 
laboratory result 
Accurate Results  Meter result is +/-15% of 
laboratory result
More Accurate Results  Meter result is +/-10% of 
laboratory result
Most Accurate Results  Meter result is +/-5% of 
laboratory result
14. The labeling must describe the principles of operation for the instrument as well as 
service and maintenance information (21 CFR 809.10(b)(6)).  Labeling should include a 
list or summary of error messages, descriptions of what those error messages mean, and 
appropriate troubleshooting procedures for those error messages.  
15. You should provide in the labeling a working U.S. toll free telephone number for user 
assistance, and include hours of operation and U.S. time zone, if applicable.  If user 
assistance is not provided 24 hours/7 days a week/365 days a year, sponsors should 
provide instructions for what measures the user should take when user assistance is not 
available.  
16. The label and labeling must include statements of warning or precautions as appropriate 
to the hazard presented by the product (21 CFR 809.10(a)(4) and 21 CFR 
809.10(b)(5)(ii)).  We recommend that you include instructions to lay-users to contact 
their healthcare provider if they obtain results that are not consistent with the way they 
feel, and to not change their medication regimen without approval from a healthcare 
provider. 
You should clearly and prominently state the important warnings for this device towards 
the beginning of the labeling, in a section containing Important Safety Instructions.  
Important warnings and safety information should be included on all test system 
instructions (user manual, test strip labeling, etc.). 
The labeling should stress the risk of disease transmission when using SMBGs and 
reference any relevant public health notifications, standard practice guidelines, or other 
resources available to users.  At a minimum, the following warnings should be included: 
  The meter and lancing device are for single patient use.  Do not share them with 
anyone including other family members!  Do not use on multiple patients! 
  All parts of the kit are considered biohazardous and can potentially transmit 
infectious diseases, even after you have performed cleaning and disinfection. 
You should include these references: 
32 Contains Nonbinding Recommendations 
  FDA Public Health Notification: Use of Fingerstick Devices on More than One 
Person Poses Risk for Transmitting Bloodborne Pathogens: Initial 
Communication.15
  CDC website on Infection Prevention during Blood Glucose Monitoring and 
Insulin Administration.16
In the section(s) describing how to obtain a blood sample, you should reiterate the risk 
of bloodborne pathogen transmission.  Instructions should emphasize that a lancing 
device is intended only for a single user and should not be shared.  You should stress that 
users should clean their hands thoroughly with soap and water after handling the meter, 
lancing device, or test strips. 
The user manual should contain detailed instructions for how and when users should 
perform cleaning and disinfection procedures for the meter, based on the validation 
studies performed.  Specifically, the instructions should include the following: 
  An explanation of why the cleaning and disinfection should be performed, in 
language that is appropriate for the intended user.  You should explain the 
difference between cleaning and disinfection. 
  The recommended frequency at which a user should clean and disinfect the 
device.  For example, the meter should be cleaned and disinfected at a minimum 
of once per week.  An explanation should be provided for how this number relates 
to the number of validated cycles over the life of the device.  The use life of the 
device should be clearly stated. 
  A list of the materials needed for cleaning and disinfection should be provided.   
Instructions on how these products can be purchased or prepared should be clearly 
outlined. 
  A detailed procedure describing what parts of the device should be cleaned and 
disinfected, the amount of time the cleaner or disinfectant should remain on the 
meter (contact time), etc.  You should include graphics/photographs to assist the 
user. 
  A statement that users should clean hands thoroughly with soap and water after 
handling the meter, lancing device, or test strips.  
  A contact telephone number, for technical assistance or questions, should be 
prominently listed in the cleaning and disinfection section, along with a list of 
signs of external deterioration and deteriorating performance that the user should 
look for.    
17. If studies have not been presented supporting the use of alternative site testing (AST) for 
a SMBG, you should include a prominent warning in the package insert and user manual 
against use of the device for AST.  Sampling from anatomical sites other than the 
                                                          
15 Available at https://wayback.archive-
it.org/7993/20170111013014/http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm224025.htm. 
16 Available at http://www.cdc.gov/injectionsafety/blood-glucose-monitoring.html. 
33 Contains Nonbinding Recommendations 
fingertip (i.e., forearm, upper arm, thigh, calf, or palm), may be indicated for some 
SMBGs.  
Some users may prefer obtaining blood from alternative sampling sites because of less 
pain or greater choice in puncture sites.  However, studies have shown that during times 
of rapidly changing glucose (i.e., after meals, medication, or exercise), the glucose level 
in blood from the alternative site may be significantly different from the glucose level in 
blood from the fingertip.  Additionally, glucose levels in ASTs may not rise as high or 
fall as low as levels in the fingertip.  This can result in a delay, or a failure to detect, 
hypoglycemia when glucose is measured in alternative sites during non-fasting times. 
When alternative sampling sites have been validated, and are indicated, you should 
clarify that results from these sites may lag behind fingertip samples during periods of 
glucose change, or reduced peripheral circulation (e.g., shock). 
You should include the following limitations relating to AST testing in your package 
inserts: 
  Alternative site sample results may be different from fingertip sample results when 
glucose levels are changing rapidly (e.g., after a meal, after taking insulin, or during 
or after exercise). 
  Do not rely on test results at an alternative sampling site, but use samples taken 
from the fingertip, if any of the following applies: 
you think your blood sugar is low. 
  
you are not aware of symptoms when you become hypoglycemic. 
  
the results do not agree with the way you feel. 
  
after a meal. 
  
after exercise. 
  
during illness. 
  
during times of stress. 
  
Do not use results from alternative site samples to calibrate continuous glucose 
 
monitoring systems (CGMS), or for insulin dose calculations.
 
34 Contains Nonbinding Recommendations 
Appendix 1.  Sources of error to consider for SMBGs 
Table 7 below lists sources of error associated with the design, production, and use of 
SMBGs.  We do not intend for this to be a complete list.  You should consider all sources of 
error based on your knowledge of your specific device.  Documents such as CLSI EP-18A2 
(Risk Management Techniques to Identify and Control Laboratory Error Sources) and ISO 
14971 (Medical devices  Application of risk management to medical devices) also provide 
lists of preanalytical, analytical, and post-analytical errors to consider.  
Table 7  Examples of Sources of Error 
Category  Source of error or failure 
Operator  Failure to follow procedure correctly, for example: 
Sample contamination 
 
Incorrect specimen collection (e.g., poor lancing technique and 
 
incorrect volume) 
Application of an insufficient amount of blood to the strip or incorrect 
 
application of blood to strip 
Use of a sample from an alternative site at inappropriate times or 
 
from a site not validated by the manufacturer 
Application of the specimen to the strip more than once (for example, 
 
if the user believes not enough specimen was added the first time) 
Incorrect insertion of strip into meter 
 
Inaccurate timing 
 
Use of contaminated, outdated, or damaged strips or reagents, 
 
including calibrators or quality control materials 
Failure to understand or respond to meter output 
 
Errors in meter maintenance or cleaning 
 
Errors in calibration or failure to calibrate or otherwise adjust the 
 
meter or check performance with quality control materials, as 
directed by labeling 
Incorrect saving or use of stored data 
 
Improper storage or handling of the meter, calibrators, quality 
 
control materials, or test strips, or improper maintenance of the 
meter 
Inadvertent changes of parameters (such as units of measurement) 
 
Failure to contact physician when necessary 
 
Use of strips not validated for use on the meter 
 
Reagent    Expired strips or reagents 
Damaged or contaminated strips 
 
Failure of strips, calibrators, or quality control materials to perform 
 
35 Contains Nonbinding Recommendations 
adequately 
Incorrect manufacturing; product fails to conform with specifications 
 
Incorrect dimensions of reagent strip 
 
Interference with chemical reaction on strip (e.g., reducing 
 
substances) 
Inadequate design of container for strips or other reagents; failure to 
 
prevent deterioration; failure of desiccant used to keep strips dry 
Environmental    DEVICE EFFECTS 
Temperature 
 
Humidity 
 
Altitude; hyperbaric oxygen therapy conditions 
 
Electromagnetic radiation 
 
Visible light; sunlight 
 
  HUMAN FACTORS 
Lighting, glare off meter surfaces 
 
Distractions, visual and auditory 
 
Stressful conditions 
 
Limited manual dexterity 
 
Software    Confusing or obscure user prompts and feedback 
Incorrect mathematical algorithm 
 
Undetected or unrecognized signal errors 
 
Timing failure 
 
Incorrect storage of test results in memory, including matching result 
 
with correct patient or time of test 
Other software failures 
 
Hardware  Electronic failure 
 
Physical trauma or vibration 
 
Damage to the device from incorrect strip dimensional tolerances 
 
(third party manufacturer) 
Electrostatic discharge 
 
Electromagnetic/radiofrequency interference 
 
Battery reliability, lifetime, and replacement 
 
Component(s) failure 
 
Incorrectly manufactured 
 
36 Contains Nonbinding Recommendations 
System  Physical trauma or vibration 
 
Incorrect calibration/adjustment (between lots of strips) 
 
Calibration failure, interference, instability or use beyond the 
 
recommended period of stability 
Labeling not geared to intended user 
 
Meter or operation complexity not geared to intended user 
 
Inadequate training 
 
Clinical  Interference from endogenous substances 
 
Severe conditions (e.g., dehydration, hypoxia, hyperglycemic-
 
hyperosmolar state, hypotension or shock, ketoacidosis) 
Interference from other exogenous substances (e.g., maltose 
 
intravenous solutions) 
37 Contains Nonbinding Recommendations 
Appendix 2.  Special 510(k)s and SMBGs 
What is a special 510(k) and how does it apply to your blood glucose meter submission? 
A special 510(k) submission is an alternative to the traditional method of demonstrating 
substantial equivalence for certain modifications to a manufacturers own previously cleared 
device, The Agency believes that the rigorous design control procedure requirements 
outlined in the Quality System Regulation (QS reg) [See 21 CFR part 820] produce highly 
reliable results that can form, in addition to the other 510(k) content requirements, a basis for 
the substantial equivalence determination.   
As such, under the special 510(k) option, a manufacturer who is intending to modify his/her 
own legally marketed device should conduct and present the risk analysis and the necessary 
verification and validation activities, to demonstrate that the design outputs of the modified 
device meet the design input requirements.  Once the manufacturer has ensured the 
satisfactory completion of this process, a "Special 510(k): Device Modification" may be 
submitted. 
Eligibility for a Special 510(k) 
To determine whether a modified SMBG is eligible to be submitted as a special 510(k), you 
should consult the FDA guidance entitled The New 510(k) Paradigm - Alternate 
Approaches to Demonstrating Substantial Equivalence in Premarket Notifications - Final 
Guidance.17 Sponsors should also consult the document on FDAs website How to Prepare 
a Special 510(k).18
As noted above, a special 510(k) is appropriate where the candidate device is a modification 
of a sponsors own legally marketed device, which would serve as the predicate for the 
modified device.  This usually means that the candidate device and predicate device are part 
of the same device design file.  The existence of similarities between the predicate device A 
and candidate device B does not, by itself, necessarily mean that device B is a modification 
of device A. 
We recommend that you contact the Office of In Vitro Diagnostic Devices and Radiological 
Health (OIR) to discuss any specific questions you have regarding your SMBGs eligibility 
to be submitted as a special 510(k). 
                                                          
17 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/new-510k-
paradigm-alternate-approaches-demonstrating-substantial-equivalence-premarket-notifications. 
18 Available at https://www.fda.gov/medical-devices/premarket-notification-510k/how-prepare-special-510k. 
38