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Within the framework of the superseded guidance, blood glucose monitoring systems for 
prescription point of care 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, blood glucose monitoring 
systems for prescription point of care 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. Blood Glucose Monitoring Test 
Systems for Prescription 
Point-of-Care 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 Blood Glucose Monitoring Test Systems for 
Prescription Point-of-Care 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-1445.  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 1755 and complete title of the guidance in the request.  Contains Nonbinding Recommendations 
Table of Contents 
I.  INTRODUCTION ..................................................................................................................................... 4 
II.  BACKGROUND ........................................................................................................................................ 5 
CLIA WAIVER OF PROFESSIONAL USE METERS .................................................................................................... 7 
III.  SCOPE ........................................................................................................................................................ 8 
IV.  REDUCING THE RISK OF BLOODBORNE PATHOGEN TRANSMISSION ................................ 8 
A.  VALIDATED CLEANING AND DISINFECTION PROCEDURES ...................................................................... 10 
B.  DEMONSTRATION THAT THE DEVICE IS ROBUST TO CLEANING AND DISINFECTION PROCEDURES ........... 11 
V.  DEVICE DESCRIPTION ....................................................................................................................... 12 
VI.  PERFORMANCE EVALUATION FOR PRESCRIPTION-USE BGMSS ........................................ 13 
A.  PRECISION EVALUATION STUDY ........................................................................................................... 13 
B.  LINEARITY EVALUATION STUDY ........................................................................................................... 15 
C.  METHOD COMPARISON/USER EVALUATION .......................................................................................... 15 
1.  General Study Design .......................................................................................................................... 15 
2.  Data Analysis ....................................................................................................................................... 20 
D.  INTERFERENCE EVALUATION ................................................................................................................ 21 
1.  Endogenous/Exogenous Substances ................................................................................................... 21 
2.  Hematocrit ........................................................................................................................................... 24 
3.  Oxygen ................................................................................................................................................. 26 
E.  FLEX STUDIES ........................................................................................................................................... 27 
1.  Test Strip Stability Testing ................................................................................................................... 28 
2.  System Operating Conditions Testing ................................................................................................. 30 
3.  Altitude Effects .................................................................................................................................... 30 
4.  Error Codes for Samples Outside the Measuring Range ................................................................... 31 
You should perform adequate analyses to demonstrate that your meter provides the appropriate error 
codes when measured glucose concentrations are outside of the BGMSs claimed measuring range, and 
include these results in your 510(k) submission. ........................................................................................ 31 
5.  Short Sample Detection ....................................................................................................................... 31 
6.  Sample Perturbation Study .................................................................................................................. 31 
7.  Intermittent Sampling .......................................................................................................................... 31 
8.  Testing with Used Test Strips .............................................................................................................. 32 
F.  METER CALIBRATION AND QUALITY CONTROL MATERIAL ...................................................................... 32 
VII.  TEST STRIP LOT RELEASE CRITERIA ........................................................................................... 32 
VIII.  THIRD PARTY TEST STRIPS ............................................................................................................. 33 
IX.  SOFTWARE ............................................................................................................................................ 33 
X.  LABELING .............................................................................................................................................. 33 
APPENDIX 1. SOURCES OF ERROR TO CONSIDER FOR BGMSS ....................................................... 39 
APPENDIX 2. SPECIAL 510(K)S AND BGMSS ............................................................................................ 42  Contains Nonbinding Recommendations 
Blood Glucose Monitoring Test 
Systems for Prescription 
Point-of-Care 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 blood glucose monitoring systems 
(BGMSs) which are for prescription point-of-care use. 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 Blood Glucose 
Monitoring Test Systems for Prescription Point-of-Care Use issued on October 11, 2016. 
This guidance is not meant to address self-monitoring blood glucose test systems (SMBGs) 
for over-the-counter (OTC) home use by lay-users. FDA addresses those device types in 
another guidance entitled Self-Monitoring Blood Glucose Test Systems for Over-the-
Counter Use (SMBG guidance).1 FDA is also issuing a revised SMBG guidance to reflect 
similar clarifications to the ones discussed in this guidance. 
For the current edition of FDA-recognized standards referenced in this document, see the 
FDA Recognized Consensus Standards Database Web site.2 For more information regarding 
use of consensus standards in regulatory submissions, please refer to the FDA guidance titled 
                                                          
1 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/self-monitoring-
blood-glucose-test-systems-over-counter-use. 
2 Available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm. 
4 Contains Nonbinding Recommendations 
Appropriate Use of Voluntary Consensus Standards in Premarket Submissions for Medical 
Devices.3  
FDAs guidance documents, including this guidance, do not establish legally enforceable 
responsibilities. Instead, guidances describe the Agencys current thinking on a topic and 
should be viewed only as recommendations, unless specific regulatory or statutory 
requirements are cited. The use of the word should in Agency guidances means that 
something is suggested or recommended, but not required. 
II.  Background 
Portable blood glucose meters that measure blood glucose values are used by millions of 
people every day as an aid in diabetes self-management. These types of devices are also used 
by healthcare professionals in a variety of clinical settings including acute and chronic care 
facilities, general hospital wards and intensive care units, physicians offices, assisted living 
facilities, and nursing homes. 
Historically, the FDA has not recommended different types of information in premarket 
submissions (510(k)s) for BGMSs intended to be used by healthcare professionals as 
compared to over-the-counter 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 that can impact device design specifications, and that 
manufacturers should take these unique characteristics into account when designing their 
devices. In order to distinguish between FDA recommendations for prescription use blood 
glucose meters, which are intended for use in point-of-care professional healthcare settings, 
and those intended for OTC 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. FDA believes that 
by making this distinction, each of the devices 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 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.4 Because BGMSs used in professional healthcare 
settings are more likely to be used on multiple patients, this type of use necessitates certain 
design features and the capacity for cleaning and disinfection to prevent the spread of 
bloodborne pathogens.5 We recommend manufacturers consider design features that will aid 
                                                          
3 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/appropriate-use-
voluntary-consensus-standards-premarket-submissions-medical-devices 
4 See information at http://www.cdc.gov/injectionsafety/blood-glucose-monitoring.html. 
5 Thompson, N.D. and Perez, J.F. (2009) Eliminating the blood: Ongoing outbreaks of hepatitis B virus 
infection and the need for innovative glucose monitoring technologies. Journal of Diabetes Science and 
Technology. 3(2), 283-288. 
5 Contains Nonbinding Recommendations 
in user accessibility (for example, features that would increase accessibility to users with 
visual impairments). 
In addition, concerns have been raised regarding the inability of currently cleared BGMSs to 
perform effectively in professional healthcare settings because these devices have not been 
adequately evaluated in some of the populations in which they are being used. Patients in 
professional healthcare settings are often fundamentally different than lay-users using these 
devices at home. Patients in professional healthcare settings can be acutely ill and medically 
fragile and are more likely to present physiological and pathological factors that could 
interfere with glucose measurements relative to lay-users. Errors in BGMS device accuracy 
can lead to incorrect insulin dosing, which, when combined with other factors, can lead to 
increased episodes of hypoglycemia. For hospitalized patients who may be seriously ill, 
glucose meter inaccuracies could further increase risk to health. 
Previously, most blood glucose meters, even those intended to be used by healthcare 
professionals, were submitted to FDA with claims for OTC home use by lay-users. Sponsors 
evaluated these devices for self-use by healthy people with diabetes or by healthcare 
professionals on healthy people with diabetes. However, they were actually being used by 
healthcare professionals as point-of-care (POC) devices to monitor blood glucose levels in 
diabetic and non-diabetic patients in various states of health. Scientific and clinical issues 
specific to the professional healthcare setting, which could affect glucose meter performance, 
were never evaluated for these devices. Use of BGMSs in professional healthcare settings on 
patients in various states of health and receiving intensive medical intervention and therapy, 
when they were evaluated and cleared based on studies performed in healthy subjects, can 
put patients at risk. Therefore, when devices are intended for use in professional healthcare 
settings, the intended use population should be accurately defined, distinct performance 
parameters should be met, and sponsors should demonstrate substantial equivalence of the 
device for that particular use. 
The intent of this guidance is to describe the studies that should be conducted to demonstrate 
BGMS performance for devices which are intended to be used in diverse professional 
healthcare settings on subjects in various states of health. Intended use populations for a 
BGMS may include patients in all professional healthcare settings, patients in specific 
healthcare settings (e.g., in emergency response vehicles), patients in long-term care 
facilities, or patients at a physicians office. The Agency expects that not all sponsors will 
seek clearance for their device to be used across all professional healthcare settings. BGMSs 
intended for POC use in specific professional healthcare settings should be studied in those 
specific populations in accordance with the recommendations in this guidance, and labeled 
appropriately. For BGMSs intended for use in many or all professional healthcare settings, it 
may be necessary to identify sub-populations in which the BGMS may function differently 
than in the broader intended use population. The identification and study of patient 
subpopulations is described in greater detail in Section VI.C below. In all cases, performance 
studies should account for factors such as disease state, patient condition, physiological state, 
and medications that might affect device performance in the intended use population for that 
BGMS. 
6 Contains Nonbinding Recommendations 
CLIA waiver of professional use meters 
FDAs clearance of a 510(k) submission for SMBGs intended for OTC home use allows 
automatic CLIA waived categorization (see 42 U.S.C. 263a(d)(3)). As described above, most 
blood glucose meters on the market today, even those used in healthcare professional 
settings, were previously submitted to FDA with claims for OTC use by lay-users and were 
therefore given CLIA waived categorization pursuant to regulation (see 42 CFR 493.15).  
The use of blood glucose meters cleared for OTC use in professional healthcare settings 
poses a number of additional risks to patients, as described above. By contrast, clearance of 
BGMSs as prescription devices intended for point-of-care use in professional healthcare 
settings, as described in this guidance, means that FDA expects that clearance of BGMSs for 
prescription point-of-care use will be categorized upon clearance as moderate complexity.  
However, FDA recognizes the importance of having CLIA-waived BGMSs in point-of-care 
professional healthcare settings and intends, through the studies described in this guidance, to 
facilitate CLIA waiver for these devices by recommending that the information described 
below be submitted in a dual 510(k)/CLIA waiver submission or an associated application 
for CLIA Waiver, and enabling BGMSs to be CLIA waived concurrently with their 510(k) 
clearance.6  
FDA has proposed several studies in this guidance that can be performed in a way that will 
allow sponsors to request FDA review of both their 510(k) submission and CLIA waiver for 
their BGMSs concurrently. For example, the recommended number of samples (for each 
sample type: arterial, venous, capillary blood) requested in the Method Comparison/User 
Evaluation (Section VI-C below) is specifically recommended to allow results from this 
study to be used to support a CLIA waiver application. The sponsor should plan to conduct 
these studies using untrained intended users in a CLIA waived setting. Based on feedback 
from the clinical community, we understand that because of the settings in which these 
devices are used, and the types of users who use them in clinical practice, it is beneficial to 
patients and the healthcare community that BGMSs be CLIA waived; therefore, sponsors 
should design their studies with CLIA waiver in mind. We recommend that sponsors refer to 
FDAs guidance entitled Recommendations for Clinical Laboratory Improvement 
Amendments of 1988 (CLIA) Waiver Applications for Manufacturers of In Vitro Diagnostic 
Devices7 to further understand how the studies described and recommended in this guidance 
can be performed to support CLIA waived status. We also encourage sponsors to contact the 
Agency with questions prior to starting their studies to ensure that the studies they plan to 
perform are designed to support CLIA waived use of their device.8
                                                          
6 For information on FDAs CLIA administrative procedures, see FDAs guidance entitled Administrative 
Procedures for CLIA Categorization  Guidance for Industry and Food and Drug Administration Staff. 
(https://www.fda.gov/regulatory-information/search-fda-guidance-documents/administrative-procedures-clia-
categorization). 
7Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/recommendations-
clinical-laboratory-improvement-amendments-1988-clia-waiver-applications. 
8 For further information regarding CLIA waivers by application, please see https://www.fda.gov/medical-
devices/ivd-regulatory-assistance/clia-waiver-application 
7 Contains Nonbinding Recommendations 
III.  Scope 
This guidance document is limited to BGMSs which are regulated under 21 CFR 862.1345. 
The following product codes are within the scope of this guidance document: 
CGA (glucose oxidase method) 
CFR (hexokinase method) 
LFR (glucose dehydrogenase method) 
This document is not meant to address the following types of devices: 
  SMBGs intended for home use by lay-users (product code NBW). Additional 
considerations (labeling or other) may be warranted for OTC devices. 
  Devices used to screen for and/or to 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 finger or other anatomical site). 
  Blood glucose test technologies labeled for specialized use (e.g., for automated 
monitoring to aid in glycemic control protocols). 
While FDA recommends that the information described in this guidance be included in 
premarket submissions for BGMSs, submissions containing alternative information may be 
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 (OIR) if you have questions 
regarding alternative intended uses or similar technologies. 
IV.  Reducing the Risk of Bloodborne Pathogen 
Transmission 
Since BGMSs 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. This is especially important for blood glucose meters used in professional settings 
which may be used in the care of multiple patients. According to the CMS and the CDC, 
blood glucose meters can transmit bloodborne pathogens, such as viral hepatitis, if these 
devices are contaminated with blood and are shared between users without effective cleaning
8 Contains Nonbinding Recommendations 
and disinfection.9 To minimize the risk of bloodborne pathogen transmission you should 
address the following in your device design and labeling: 
  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 and provide the validated 
cleaning and disinfection procedures for your BGMS device in your 510(k) 
submission as well as in the labeling. Cleaning and disinfection are different 
processes and warrants separate validation procedures and specifications. 
  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 viruses in choosing disinfectants to validate for use with your 
device.10
  Your BGMS device should be intended for use with only auto-disabling, single use 
lancing devices. Single use lancing devices are designed to be used only once, after 
which the blade is retracted, capped, or otherwise made unusable. The auto-disabling, 
single use lancing device you recommend for use with your BGMS device should be 
specified in your labeling. You should emphasize in the labeling that lancing devices 
are for single patient use and should NEVER be used for more than one person. Your 
labeling should instruct users to discard lancing devices in designated sharps 
containers. 
  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 
similar devices intended for single-patient use only (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. For additional information 
on labeling your reusable medical device, see FDAs guidance entitled Reprocessing 
Medical Devices in Health Care Settings: Validation Methods and Labeling.11
Validation of cleaning and disinfection procedures involves determining both that the 
cleaning and disinfection products are effective against the primary viruses of concern 
(Human Immunodeficiency Virus (HIV), Hepatitis B, Hepatitis C) and that the cleaning and 
disinfection procedures do not deteriorate the device or alter device performance. FDAs 
recommendations for such validation procedures are outlined in the following Subsections. 
                                                          
9 Infection Prevention during Blood Glucose Monitoring and Insulin Administration 
http://www.cdc.gov/injectionsafety/blood-glucose-monitoring.html. 
10 Selected EPA-registered Disinfectants available at https://www.epa.gov/pesticide-registration  
11 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/reprocessing-
medical-devices-health-care-settings-validation-methods-and-labeling. 
9 Contains Nonbinding Recommendations 
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 such as the housing, touch 
pad, or buttons. You should make note of any physical indicators of deterioration during 
your validation study and provide this information for our review in your 510(k) 
submission. The disinfectant product you choose should be effective against HIV, 
Hepatitis B, and Hepatitis C viruses. Of these viruses, Hepatitis B virus 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. 
To demonstrate that your disinfection procedure is effective against Hepatitis B virus, 
you should perform disinfection efficacy studies to demonstrate 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, therefore minimizing 
the chance of affecting the glucose meter function. However, you should choose a 
disinfectant that is effective against Hepatitis B virus and is compatible with your device. 
If you intend to claim that your disinfection protocol is effective against other pathogens, 
you should consider submitting a pre-submission 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.12
We recommend you refer to the following standards when developing a disinfection 
protocol for your device: 
  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. 
                                                          
12 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/requests-feedback-and-
meetings-medical-device-submissions-q-submission-program 
10 Contains Nonbinding Recommendations 
B. Demonstration that the device is robust to cleaning and disinfection 
procedures 
You should demonstrate through bench studies that your BGMS device is robust to 
cleaning and disinfection procedures after multiple cleaning and disinfection cycles. You 
should describe in your 510(k) submission the study design and results demonstrating 
that the analytical performance of the BGMS is not impacted by the cleaning and 
disinfection procedures. 
You should address the following in your study design: 
  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). 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 your 
cleaning and disinfection instructions in the labeling. 
  We recommend using the same disinfectant product for both cleaning and 
disinfection. The effects of using multiple cleaning products on the efficacy of 
disinfectant products are not well understood. 
  You should demonstrate that the test strip port and all other openings which are 
susceptible to blood contamination and could either directly or indirectly be 
contacted during use are able to withstand your 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 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 
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 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 analyses and incorporate your 
validated cleaning and disinfecting procedures into your risk assessment. 
11 Contains Nonbinding Recommendations 
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 the following information in the device description portion of your 
510(k) submission: 
  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.13
  Description of the composition and levels of control material recommended for use 
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 among 
patients. 
Description of features controlled by the software, which should describe the following: 
o  Displays and user messages:  This includes how the BGMS determines and 
displays the glucose concentration, messages or displays that appear while a user 
is taking a measurement, and features such as how a user can retrieve past results 
from storage in the device. 
  
o  User prompts:  You should describe prompts that the BGMS 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 a 
user prompt include messages to the user to add specimen to the test strip, insert 
the test strip into the meter, calibrate the meter, or store a result, etc. 
  
o  Error messages and alerts: This includes any error messages or alerts that the 
BGMS 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 test strip is inserted incorrectly or removed prematurely; 
too small a sample is applied to the test strip; damaged, incorrect or deteriorated 
test strips are used; or when there is a low battery or excessively high ambient 
temperature. This should also include the methods by which the BGMS detects 
                                                          
13 Note that BGMSs intended for use in the U.S. should report results in mg/dL and in plasma equivalents. 
12 Contains Nonbinding Recommendations 
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 the 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 respond to an error message or alert. 
VI.  Performance Evaluation for PrescriptionUse 
BGMSs
Subsections A-F below indicate the types of device performance information that you should 
include in a 510(k) submission for a BGMS. Although many manufacturers design their 
BGMS 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 do not adequately protect patients using BGMSs 
in professional settings, and does not recommend using the criteria in ISO 15197 for BGMSs. 
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 recommended study designs and device performance criteria are 
discussed below in Subsections A-F. 
A. Precision Evaluation Study 
You should evaluate both within-run precision and intermediate precision for your 
BGMS and include these evaluations in your 510(k) submission. The following sections 
outline FDAs current thinking on appropriate study design and analyses to evaluate 
within-run and intermediate precision for BGMSs. 
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 device across the 
claimed measuring range, you should evaluate samples containing glucose concentrations 
within each of the five intervals provided in Table 1 below. 
13 Contains Nonbinding Recommendations 
Table 1. Glucose Concentrations for Precision Evaluations 
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 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. You should provide the results 
based on all data, and if you wish to exclude any data points (outliers), a separate, 
additional data analysis with those points excluded and a full description of the method of 
outlier identification and the results of your investigations into those outliers, should be 
included 
Intermediate Precision Evaluation: 
Intermediate precision measurement studies are bench studies designed to evaluate 
imprecision under simulated normal use conditions; for example, measurement by 
multiple operators 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 individual 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. 
14 Contains Nonbinding Recommendations 
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 you wish to exclude 
any data points, a separate, additional data analysis with those points excluded and a full 
description of the method of outlier identification and the results of your investigations 
into those outliers, should be included. 
B.  Linearity Evaluation Study 
You should evaluate the linearity of your BGMS 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 the guideline 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 glucose 
concentration range. You should clearly identify the number of altered samples (spiked, 
diluted, or glycolyzed) within your 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 
When testing samples from the intended patient population, you should design your study 
to accurately reflect system performance in the hands of the intended user. You should 
perform a set of comprehensive clinical evaluations to assess system accuracy to support 
the professional use of these devices in the intended use population. 
FDA recognizes that most study evaluations performed for 510(k) submissions occur in 
idealized conditions, thereby potentially overestimating the total accuracy of the BGMS, 
even when performed in the hands of the intended user. Nonetheless, it is important that 
you design your study to most accurately evaluate how the device will perform in the 
intended use population. Therefore, the study should be conducted in conditions that 
reflect the expected use of the device, as well as = environmental conditions that are 
consistent with the validated environmental conditions of the device (e.g., temperature, 
humidity, altitude, etc.). You should fully describe the conditions of your study in your 
510(k) submission. 
You should evaluate device accuracy for each claimed sample type (e.g., arterial, venous, 
capillary, heelstick whole blood, etc.) when the device is used by a POC operator.  
15 Contains Nonbinding Recommendations 
Evaluation of each sample type should include a minimum of 350 patients (e.g., samples 
from at least 350 patients for an arterial study, samples from at least 350 patients for a 
capillary study, samples from at least 350 patients for a venous study, etc.). FDA 
recommends sponsors perform their studies to support concurrent CLIA waiver at the 
time of clearance by performing the studies as described in this guidance with 
consideration to the aspects of study design described in FDAs guidance entitled 
Recommendations for Clinical Laboratory Improvement Amendments of 1988 (CLIA) 
Waiver Applications for Manufacturers of In Vitro Diagnostic Devices. 14 Different 
sample types (e.g., arterial and venous) can be acquired from the same patient and be 
used in the different studies. Each sample should be fresh and measured on both the 
candidate device (i.e., new device) and the comparator method. Samples do not have to 
be collected specifically for your studies; however, to obtain CLIA waiver, the tests 
should be done per the labeling instructions by untrained users typical of CLIA-waived 
users.  Note that patient information should be available for each sample to aid in the 
identification of potential interfering factors.  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. It is 
not necessary that POC operators perform the comparator method measurements in the 
study. 
For each claimed sample type, the samples tested should adequately span the claimed 
glucose measuring range of the BGMS device. Though it may be difficult to obtain 
samples at the extreme ends of the measuring range, the study for each sample matrix 
should contain at least 10 unaltered samples < 80 mg/dL and at least 10 unaltered 
samples between 300 mg/dL and the upper limit of the claimed measuring range of the 
device. It may be necessary to enroll more than 350 patients for each sample type in order 
to obtain the necessary unaltered samples. Testing should be performed by the intended 
POC operators (e.g., nurses, nurse assistants, etc.) to accurately reflect device 
performance in POC settings; at least 9 operators should participate in each study (e.g., 
capillary, venous, and arterial studies). Different operators may be used for each study. 
You should submit data from all subjects; no data or subjects should be excluded from 
your analysis. 
The subjects you enroll in the method comparison/user study should accurately reflect the 
intended use population of your device. In your 510(k) submission, you should describe 
the inclusion and exclusion criteria for enrolling study subjects, as well as the 
demographics of the subjects that participated in the study. If your intended use 
population is broad but includes patient sub-populations that might be particularly 
                                                          
14 For example, users should be untrained, and the studies should be performed in intended use settings in the 
midst of normal working conditions.  Please note that we intend to accept 350 patient samples for each sample 
type for the purposes of CLIA waiver studies for these devices.  Guidance is available at 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/recommendations-clinical-
laboratory-improvement-amendments-1988-clia-waiver-applications. 
16 Contains Nonbinding Recommendations 
vulnerable to potential interferences and/or health risks resulting from meter inaccuracy, 
you should identify and include patients from these specific vulnerable sub-populations 
in your study. You should define these sub-populations and provide a rationale for your 
definitions. For example, vulnerable sub-populations could be defined as patients in 
specific hospital wards, units, or departments, medical, neonatal, pediatric or surgical 
intensive care units (ICUs). Vulnerable subpopulations could, for example, also be 
defined as categories of patients with general types of medical conditionscardiac, 
surgical, pulmonary, or oncology patients. These sub-populations are provided as an 
example of common patient groups found in a hospital setting, however, if you would 
like to discuss other sub-populations or other aspects of your study with the Agency, we 
recommend that you submit a request for a Pre-Submission meeting 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.15
Your study should include at least 50 patients from each vulnerable patient sub-
population you have defined in order to collect sufficient performance data to support the 
use of your device in these populations. Please note that in some instances, in order to 
fully characterize your device in your intended use population, FDA suggests that you 
use more than 50 patients per subpopulation to ensure all conditions and medications 
have been evaluated. Furthermore, if you intend for your study to also support a broad 
intended use population, then you should ensure that your study population includes 
sufficient numbers of patients outside of the vulnerable subpopulations you identified to 
support the use of your device in the broader intended use population. This broader 
population might include in-patients dispersed throughout various hospital departments. 
Depending on the number of specific vulnerable sub-populations you identify, the 
collection of samples from more than 350 subjects for each sample type (venous, arterial, 
capillary) may be indicated to support the use of your device in your intended use 
population. Your results should clearly indicate the specific patient population associated 
with each sample and you should present the combined results for your entire intended 
use population and, separately, for each vulnerable patient subpopulation (if present). 
If you wish to claim suitability of your device with anti-coagulants, then within the 350 
(minimum) samples you collect for each sample type you should include at least 50 to 75 
patient samples per claimed anti-coagulant. 
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 the study. You should describe these shipping and handling conditions in your 510(k) 
submission. 
Method comparison and user performance studies for a BGMS should include multiple 
users and multiple blood glucose meters. Only auto-disabling, single use lancing devices 
                                                          
15 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/requests-feedback-
and-meetings-medical-device-submissions-q-submission-program. 
17 Contains Nonbinding Recommendations 
should be used in these studies. You should incorporate your labeling instructions for 
cleaning and disinfection in your user study protocol to ensure that the meters are 
appropriately cleaned and disinfected during the course of this study, and include any 
additional measures necessary 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). The study protocol should also include 
details on how often and when gloves worn by the trained health professionals should be 
changed between subjects. Meters should be cleaned and disinfected after each subject, 
using validated procedures for all studies performed. Refer to Section IV, above 
(Reducing the Risk of Bloodborne Pathogen Transmission) for additional information 
regarding the validation of cleaning and disinfecting of BGMSs. 
BGMS test results are used by healthcare professionals to make critical decisions about 
treatment; therefore, it is important that the results are accurate so that medical decision 
errors are better avoided. In order to demonstrate that a BGMS is sufficiently accurate for 
use by health care professionals, you should demonstrate that 95% of all values are 
within +/- 12% of the comparator method for glucose concentrations > 75 mg/dL and 
within +/- 12 mg/dL at glucose concentrations < 75 mg/dL. In addition, 98% of values 
should be within +/- 15% of the comparator method for glucose concentrations >75
mg/dL and within +/- 15 mg/dL at glucose concentrations < 75mg/dL. The BGMS 
should be as accurate as possible to avoid critical patient management errors.Though we 
expect that BGMSs will be able to meet these criteria, there may be instances where 
meters may be determined to be substantially equivalent 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. In instances where your 
BGMS is unable to meet these criteria, youshould provide aclinical justification for all
test results, including those that exceed the above-mentioned criteria,and describe why 
the potential for that error would not affect patient safety when extrapolated to the 
intended use setting (e.g., when extrapolated to the volume of testing performed in the 
intended use setting). FDA will review your justification to determine whether the data 
suggest that patients may be put at risk or whether your justification and any proposed 
mitigationsare adequate. 
Hematocrit and sodium values should be measured and recorded for each study subject to 
help identify potential interference with the device and to inform investigations into 
outlier results. Similarly, blood oxygen levels should be measured and recorded for each 
patient for any arterial blood study. You should present these individual values in the 
510(k) submission along with the BGMS and comparator method results. It is not 
necessary that hematocrit, sodium, and blood oxygen measurements be made by POC 
operators. 
We expect that the measuring range of the meter will meet the clinical needs of the 
intended use population. BGMSs intended for prescription-use in the hospital setting 
should be able to measure blood glucose accurately down to 10 mg/dL and up to 500 
mg/dL, or a clinical justification should be provided for alternate measuring ranges. 
BGMSs intended for use outside a hospital setting and which will not reasonably be used
18 Contains Nonbinding Recommendations 
to test neonatal samples should be able to measure blood glucose accurately down to 20 
mg/dL. The BGMS device should identify and provide an error code in situations where 
the measured glucose level falls outside of the devices stated measuring range. For 
example, if BGMS XYZ has a measuring range that can detect glucose concentrations 
down to 10 mg/dL, then blood samples with glucose concentrations below 10 mg/dL 
should provide an appropriate error code (e.g., LOW - Less than 10). 
You should 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 BGMSs are used in the U.S. and you should 
include an explanation of why you believe each site is representative. 
  Criteria used to select study subjects. 
  Description of the patient demographics, including age, disease states, and all 
medications for each patient. 
  Sample types collected (arterial, venous, capillary). 
  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. 
Accuracy at Extreme Glucose Values: 
Because the study described above using real patient samples may not provide a robust 
evaluation of BGMS performance in the extreme upper and lower ends of the measuring 
range, you should perform additional studies using blood samples altered to achieve 
glucose concentrations of less than 80 mg/dL and greater than 300 mg/dL. This additional 
extreme glucose value study should be performed separately from the method 
comparison/user evaluation described above and may be performed in a laboratory 
setting, though untrained intended users typical of users in a CLIA waived setting should 
perform the testing to support CLIA waiver of the device. 
Your study of accuracy at extreme glucose values should include a minimum of 50 
prepared samples with glucose concentrations < 80 mg/dL and a minimum of 50 prepared 
samples with glucose concentrations > 300 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 appropriate glucose 
concentrations. Samples should be measured on both the BGMS device and the 
comparator method. You should analyze this data separately from the user evaluation 
data but using the same methods described below for the user evaluation. FDA will apply 
the same review criteria to both studies. 
Neonatal Studies: 
If your intended use population includes neonates, you should perform studies to support 
performance in neonatal samples (defined as samples from subjects less than 28 days 
19 Contains Nonbinding Recommendations 
old). Neonatal blood is known to differ from adult blood and these differences may have 
a direct impact on the safety of blood glucose monitoring in that population. For example, 
neonatal blood often has higher hematocrit levels (51 to 65%) and lower blood glucose 
concentrations (20 to 80 mg/dL) compared to adult blood. 
You should evaluate device performance with neonatal samples in direct comparison to 
the comparator method by testing 100 -150 fresh neonatal blood specimens, including 
samples from neonates less than 24 hours old. Samples should be collected and measured 
by at least three POC users in a POC setting. Glucose concentrations should be measured 
with the BGMS and the comparator method, and the hematocrit levels for each patient 
should also be measured and reported in the study. You should present your results as 
described below in the Data Analysis Subsection. Data from all subjects in the study 
should be submitted in your 510(k), and no subjects should be excluded from the data 
analysis. 
Since it may be difficult to obtain samples at the extreme low end of the measuring range 
using real neonatal patient samples, you should perform additional studies using blood 
samples (either adult blood or maternal cord blood) altered to achieve glucose 
concentrations between 10 and 50 mg/dL.  Blood specimens used in these additional 
studies should be adjusted to at least two levels of hematocrit at or near 40% and 65%, in 
order to simulate the high hematocrit levels of neonatal blood. This will allow you to 
provide a robust evaluation of device performance in the extreme lower end of the 
measuring range for simulated neonatal blood. These additional studies should be 
performed separately from the neonatal studies described above and may be performed in 
a laboratory setting (e.g., at the manufacturers facility), however, untrained users typical 
of CLIA-waived users should perform the testing to support CLIA waiver of the device. 
2.  Data Analysis 
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 minimum accuracy criteria) should also be included in your 
510(k) submission. 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, oxygen levels, and sodium 
levels during your study. You should include the following in your description of the 
results:  
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 using 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 suitable analysis procedure (e.g., Linear Regression, Deming regression), and the 
20 Contains Nonbinding Recommendations 
estimate of the deviation (standard error).  Difference plot of Y-X vs X analysis 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 results in the following tabular format for each sample matrix. In 
Table 2 and Table 3 below, X= the number of samples within the specified difference 
from the comparator method, and Y= total number of samples. 
Summary of data within specified mg/dL of the comparator method. 
Table 2. For glucose concentrations <75 mg/dL: 
Within  Within  Within  Within  Exceeds 
+/- 5 mg/dL +/- 10mg/dL +/- 12mg/dL +/- 15 mg/dL +/- 15 mg/dL
X/Y (%)  X/Y (%)  X/Y (%)  X/Y (%)  X/Y (%) 
Table 3. For glucose concentrations >75mg/dL:
Within Within Within Within Within Exceeds
+/- 5% +/- 10% +/- 12% +/- 15% +/- 20% +/- 20%
X/Y (%)  X/Y (%) X/Y (%) X/Y (%) X/Y (%) X/Y (%)
       
D. Interference Evaluation
Youshould 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 devices performance. Conditions that are 
known to interfere with glucose monitoring test systems, such as ketoacidosis, should be 
included in the labeling as limitations unless you have provideddata demonstrating that 
these conditions do not interfere with your device.
1. Endogenous/ExogenousSubstances
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 between 50- 70mg/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. When performing your studies, you should test all substances at the 
highest concentration that could potentially be observed in a whole blood sample; if 
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 
21 Contains Nonbinding Recommendations 
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. 
The substances listed below in Table 4 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 4. List of Known or Potential Interferents for BGMSs: 
Interferent  Recommended Test 
Concentration 
Acetaminophen  20 mg/dL 
Ascorbic acid  6 mg/dL 
Conjugated Bilirubin  50 mg/dL 
Unconjugated  40 mg/dL 
Bilirubin 
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. Separate studies should be performed to validate the use of these 
substances as anticoagulants used for sample preparation (as described in Section C, above). 
**All common sugar alcohols, including but not necessarily limited to, sorbitol, xylitol, lactitol, isomalt, 
maltitol should be independently tested. 
22 Contains Nonbinding Recommendations 
In addition to the list of potential interferents provided in Table 4, 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 
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 BGMS. At 
least three test strip lots should be used for this evaluation. Each of the control and test 
samples should be tested on your BGMS 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 BGMSs, 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 BGMSs, 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 5 below provides a sample 
format of a summary table. 
23 Contains Nonbinding Recommendations 
Table 5. 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 
60 mg/dL  20 mg/dL 
Acetaminophen  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, 
a list of 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 method comparison 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 BGMS to assess whether your device can safely be used across the 
claimed hematocrit range in the intended use population. The observed hematocrit levels 
may be very broad in the intended use population for this type of device; the intended 
patient population may reasonably be expected to have hematocrit levels between 10 and 
65%. Therefore, we recommend a minimum hematocrit range of 10-65% as the claimed 
range for BGMSs. 
You should evaluate hematocrit interference by measuring 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 10-65%, you should test samples at 
10, 15, 20, 25, 30, 35, 42, 50, 55, 60 and 65% 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
sample.  You should test a minimum of 3 test strip lots to evaluate interference from 
24 Contains Nonbinding Recommendations 
hematocrit. Each sample should be tested on your new BGMS 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 
BGMS (Mean ). Using the Mean  and the estimate of the true glucose 
BGMS BGMS
concentration in the sample, Mean , you should estimate a bias and percent bias as 
Comp
(Mean -Mean ) and (Mean -Mean )/Mean  correspondingly, for 
BGMS Comp BGMS 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 BGMS with 120 mg/dL glucose:  
Average of  Average of  %Bias 
Number of 
Hematocrit  Comparator  BGMS  (Mean -
BGMS
measurements 
(%)  measurements  measurements  Mean )/ 
Comp
for BGMS 
(Mean )  (Mean )  Mean  
Comp BGMS 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% 
(2) Estimation of Bias due to Hematocrit 
25 Contains Nonbinding Recommendations 
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, and BGMSs are designed to perform optimally with such samples; 
therefore, bias due to hematocrit is considered 0% (or 0 mg/dL) for the sample with 
hematocrit value equal to the average (42%).  The estimate bias due to hematocrit for 
each sample should be calculated by subtracting the bias at the average hematocrit 
(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 BGMS with 120 mg/dL glucose: 
Average of  Average of  %Bias 
Number of 
Hematocrit  Comparator  BGMS  (Mean - %Bias due to 
BGMS
measurements 
(%)  measurements  measurements  Mean )/  hematocrit 
Comp
for BGMS 
(Mean )  (Mean )  Mean  
Comp BGMS 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. 
3.  Oxygen 
Study design: 
A typical professional use setting can include patients with a broad range of blood 
oxygen levels. If you intend for your BGMS to be used in patients with a broad range of 
blood oxygen levels, you should conduct a study using a validated method appropriate to 
the sample type to demonstrate the range of blood oxygen levels with which your device 
can be used. You should supplement the results of this study by collecting data on the 
blood oxygen levels of patients in your Method Comparison/User Evaluation Study 
(Subsection C, above), as appropriate, and conducting an analysis for any oxygen effects 
on BGMS performance. If you believe that blood oxygen levels do not affect the 
performance of your device you should provide a comprehensive justification for this, 
26 Contains Nonbinding Recommendations 
which should be supported by any analysis of interference of blood oxygen levels on 
device performance, as evaluated in your Method Comparison/User Evaluation Study 
(Subsection C, above). 
E. Flex Studies     
Generally, the risk of an erroneous result may be greater for POC tests than laboratory-
based tests. This is because there are fewer controls in place in POC settings to mitigate 
risks and the users may be untrained and may not know how to identify or address an 
incorrect result. You should demonstrate that your BGMS 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 the 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 BGMS 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 BGMS 
to prevent operator error, such as guides or channels that prevent improper strip 
placement. We recommend that BGMS design incorporate fail-safe mechanisms 
whenever 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 BGMS malfunction or problem. They 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 BGMS, 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. 
In order to identify all relevant flex studies for your BGMS 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. 
27 Contains Nonbinding Recommendations 
Below, we have identified flex studies that we believe are important for you to perform 
and recommend including in the 510(k) submission of your BGMS. 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 BGMS does not perform adequately in flex studies, we recommend that you 
either provide a justification, determined by means of thorough risk analysis, as to why 
adequate performance in that flex study is not necessary, or alternatively, you should 
indicate an additional implemented validated control mechanism. FDA will review such 
justifications to determine whether the proposed mitigation strategies are adequate to 
protect patients. 
In the case of the following flex studies, verification should include performance testing; 
however, it is sufficient if you provide information indicating that flex studies have been 
conducted in accordance with an FDA-recognized industry standard. We recommend you 
include information regarding the type of testing performed, the reference standard 
followed, the acceptance criteria, and whether the BGMS met 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 
We have also identified additional flex studies (described below) that manufacturers 
should perform in order to demonstrate adequate system performance in intended use 
settings. 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 for each study: 
  Study goal 
  Study protocol 
  Methods used to apply samples to test strips 
  Sample type and any anticoagulants used 
  Study results 
  Conclusions made from the study  
The recommended flex studies as well as recommended study designs are outlined 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 
28 Contains Nonbinding Recommendations 
You should perform studies that assess test strip performance throughout the test strip 
stability claims, including both 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 throughout the 
recommended storage 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. 
Separate testing of test strip and meter shipping and storage conditions is not necessary 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 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 CV and accuracy calculated in these studies 
are within the labeled performance of the BGMS. 
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 BGMS. Samples may be altered by spiking with glucose or allowing the samples 
to glycolyze in order to evaluate the extreme end of the systems 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:  
29 Contains Nonbinding Recommendations 
This study should be performed using whole blood samples that span the claimed 
measuring range of the BGMS. 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 (e.g., 30-50, 100-150, 200-300, 350-500 mg/dL) should be measured with 
the BGMS 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 BGMS when used under 
various operating temperature and humidity conditions. These studies should be designed 
to represent actual use conditions experienced by BGMS 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 BGMS by including ranges outside of the claimed operating range. Testing 
should incorporate the four extreme temperature and humidity combinations (high 
temperature/low humidity; high temperature/high humidity; low temperature/low 
humidity; low temperature/high humidity), or other testing combinations, if a suitable 
rationale can be provided. Measurements made on whole blood samples with your 
candidate device should be compared to values obtained using the candidate device at a 
nominal condition (such as 23oC, 40% relative humidity). 
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 
BGMS 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 BGMSs in the United States includes high altitude conditions and, 
therefore, manufacturers should conduct studies to assess the effects of altitude on their 
BMGS, or should provide a justification for why altitude does not have an effect on the 
performance of their BGMS. 
An altitude effects study should compare results from whole blood samples with your 
candidate device 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 BGMS at a minimum of 
10,000 feet above sea level. 
30 Contains Nonbinding Recommendations 
4.  Error Codes for Samples Outside the Measuring Range 
You should perform adequate analyses to demonstrate that your meter provides the 
appropriate error codes when measured glucose concentrations are outside of the 
BGMSs 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 sample volume) can 
lead to inaccurate results. To avoid the risk of inaccurate results, BGMSs should be able 
to detect that a short blood sample that 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 your BGMS. 
In your short sample detection studies, you should include blood samples with known 
glucose concentrations in the following three ranges: 50-65, 100-120, and 200-250 
mg/dL. You should test blood samples with your candidate device 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 BGMS or the test 
result falls outside of the devices stated performance range. 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 
measurement and alters the volume of the initial sample application. You should 
adequately demonstrate how your BGMS 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 
BGMS 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, 100-
120, 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 the 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 
31 Contains Nonbinding Recommendations 
measurement is complete. You should adequately demonstrate how your BGMS handles 
intermittent sampling by conducting an intermittent sampling study. 
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 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, including whether a result is reported by the device, 
whether the 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 BGMS performs when a used test 
strip is inserted. We recommend that BGMSs be designed to automatically recognize the 
insertion of used test strips. Insertion of used test strips into a blood glucose meter should 
not provide glucose measurement results to the user. If an automatic used test strip 
recognition function has been incorporated into your BGMS, you should perform a 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 Material 
Your 510(k) submission should describe how your BGMS 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 (e.g., 
how the meter is calibrated or coded for each test strip lot). At least two levels of quality 
control material should be available for use with your system. 
VII.  Test Strip Lot Release Criteria 
Your test strip lot release criteria should be sufficient to ensure consistent quality of the 
BGMS 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 
BGMS 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 BGMS device 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.  
32 Contains Nonbinding Recommendations 
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 BGMS. 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 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 manufacturer. 
IX.  Software 
For software descriptions of BGMSs, their components, and accessories, we recommend 
that you follow FDAs guidance entitled Guidance for the Content of Premarket 
Submissions for Software Contained in Medical Devices,16 Generally, we consider 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 therapeutic 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 
Cybersecurity in Medical Devices;17
  FDA guidance Postmarket Management of Cybersecurity in Medical Devices;18
  FDA Fact Sheet: The FDAs Role in Medical Device Cybersecurity  Dispelling 
Myths and Understanding Facts.19
X.  Labeling 
                                                          
16 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/guidance-content-
premarket-submissions-software-contained-medical-devices. 
17 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/content-premarket-
submissions-management-cybersecurity-medical-devices-0. 
18 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/postmarket-
management-cybersecurity-medical-devices.  
19 Available at https://www.fda.gov/media/123052/download.  
33 Contains Nonbinding Recommendations 
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. 
Distinct labeling (e.g. user manual, quick start guide (optional), package inserts for both test 
strips and controls, and box and container labels for the meter, test strips, and control 
materials) appropriate for the intended user of the BGMS should be provided for each device 
component. 
The following items are intended to further assist you in complying with the requirements of 
21 CFR 809.10 for all labeling. You should refer to that regulation for the complete list of 
labeling requirements for in vitro diagnostic devices. 
1.  All device labels and 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 should be named in such a way that they are recognizable as belonging to the 
same system, or family of products, and to distinguish them from those components 
intended for single-patient use only (for example, 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 (21 CFR 
809.10(a)(2) and 21 CFR809.10(b)(2)). 
3.  You must include the symbol statement Rx only or  only or the statement Caution: 
Federal law restricts this device to sale by or on the order of a ___, the blank to be filled 
with the word physician, dentist, veterinarian, or with the descriptive designation 
of any other practitioner licensed by the law of the State in which the practitioner 
practices to use or order the use of the device, in your label and labeling (21 CFR 
809.10(a)(4) and 21 CFR 809.10(b)(5)(ii)). 
4.  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 biological source of the enzyme and a description of the 
reaction. Labeling should clarify whether results are determined in terms of whole blood 
or plasma equivalents. BGMSs intended for use in the U.S. should report results in terms 
of plasma equivalents. 
5.  The labeling must provide instructions for specimen collection and preparation, including 
special precautions regarding specimen collection. as per 21 CFR 809.10(b)(7). 
Instructions should include a statement to users on the importance of thoroughly washing 
and drying the skin before taking a sample because contaminants on the skin may affect 
results. 
6.  You must include a statement of limitations of the procedure in your labeling (21 CFR 
809.10(b)(10)). Labeling must state known extrinsic factors or interfering substances 
affecting results, as per 21 CFR 809.10(b)(10). This should include, but is not limited to, 
the following: 
34 Contains Nonbinding Recommendations 
a.  Testing conditions that may cause clinically significant errors (due to bias or 
imprecision) with your device (e.g., specific drugs, oxygen therapy, testing with 
venous, arterial, or neonatal blood, high altitude, or EMC interference). Sponsors 
should indicate the most extreme conditions (e.g., the highest altitude, highest and 
lowest temperatures, etc.) at which the device should be used based on the results of 
performance testing. 
b.  Clinical situations, patient populations, or conditions in which the BGMS 
performance may not be acceptable. For example, FDA recommends statements 
such as the following: inaccurate results may occur in severely hypotensive 
individuals or in dehydrated patients or patients in shock; inaccurate results may 
occur for individuals experiencing a hyperglycemic-hyperosmolar state, with or 
without ketosis. 
c.  Limitations against alternative site testing and use for tight glycemic control (unless 
appropriate studies are performed and included in the 510(k) submission). Labeling 
should also state that results from alternative sampling sites (if used) should not be 
used to calibrate continuous glucose monitoring systems (CGMS) or entered into 
insulin dose calculators for dosage recommendations. 
7.  Labeling must provide appropriate storage instructions adequate to protect stability of the 
product (21 CFR 809.10 (b)(5)(iv)). This type of information should be provided for all 
components of the system, including control solutions, test strips, etc. 
8.  Labeling must describe details of calibration and quality control procedures (21 CFR 
809.10(b)(8)(v) and 21 CFR 809.10(b)(8)(vi)). This is to help ensure optimal 
performance of the system. 
9.  Labeling must include expected values (21 CFR 809.10(b)(11)). FDA recommends that 
the expected values in the package insert should be those for non-diabetics. FDA does not 
recommend including additional ranges adjusted for diabetics because such ranges are 
individually determined by a clinician. The expected values should be cited from in-
house studies or up-to-date reference sources. 
10. 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 suggested representations 
below for an example. Performance should be presented separately for each anatomical 
site, matrix (arterial, capillary, etc.), and any additional specific claims (e.g. neonatal). 
We recommend the following types of presentations to show the results of your accuracy 
studies in user manuals and package inserts. 
Suggested Representation of Accuracy for Prescription-use Only Devices  Example: 
The [XYZ] meter and [XYZ] reagent strips for the [XYZ] monitoring system were tested on 
capillary blood samples from 350 patients, and the results were compared to the comparator 
method (e.g., YSI). The tables show differences in glucose values between the XYZ device 
and the comparator method. Table 8 below represents samples for glucose results lower than 
35 Contains Nonbinding Recommendations 
70 mg/dL (by the XYZ device). Table 9 below table represents samples for glucose results 
greater than or equal to 70 mg/dL. 
Table 8. Glucose results lower than 75 mg/dL 
Difference range between ABC laboratory  Within  Within  Within  Within
comparator method and the XYZ device  +/- 5  +/- 10  +/- 12  +/- 15 
mg/dL mg/dL mg/dL mg/dL
The percent (and number) of samples for  90%  95%  96%  98% 
which the difference between the XYZ  (126/140) (133/140) (135/140) (137/140)
device and ABC laboratory comparator
method were within the difference range 
shown in the top row. 
Table 9. Glucose results greater than or equal to 75 mg/dL
Difference range between ABC  Within  Within  Within Within Within
laboratory comparator method and  +/- 5% +/- 10% +/- 12% +/- 15% +/- 20%
the XYZ device.
The percent (and number) of  80%  95% 96% 98% 100%
samples for which the difference  (168/210) (199/210) (202/210) (206/210) (210/210)
between the XYZ device and ABC 
laboratory method were within the 
difference range shown in the top 
row. 
The tables above show that 347(137+210) of the 350 samples met the defined acceptance 
criteria.
Note:  When glucose meter results are compared to the laboratory results, differences below 
70 mg/dL are expressed in mg/dL, while those greater than or equal to 70 mg/dL are 
expressed inpercent.
11.You 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. 
12.Label and labeling must include statements of warning or precautions as appropriate to 
the hazard presented by the product on the outer container and the insert (21 CFR 
809.10(a)(4) and 21 CFR 809.10(b)(5)(ii)). 
You should clearly andprominently state the important warnings for your devices, for 
example,in a section titled Important Safety Instructions. You should stress the risk of 
disease transmission when using BGMSsand reference any relevant public health 
notifications, standard practice guidelines, or other resources available to users. At a 
minimum, the following warnings should be included:
              
36 Contains Nonbinding Recommendations 
  Users need to adhere to Standard Precautions when handling or using this device. 
All parts of the glucose monitoring system should be considered potentially 
infectious and are capable of transmitting blood-borne pathogens between patients 
and healthcare professionals. For more information, refer to 2007 Guideline for 
Isolation Precautions: Preventing Transmission of Infectious Agents in 
Healthcare Settings.20
  The meter should be cleaned and disinfected following the manufacturers 
instructions after use on each patient. This Blood Glucose Monitoring System 
may only be used for testing multiple patients when Standard Precautions and the 
manufacturers cleaning and disinfection procedures are followed. 
  Only auto-disabling, single use lancing devices may be used with this device. 
In the section describing how to obtain a blood sample (see also item 4, above, 
regarding sample collection), you should re-iterate the risk of bloodborne pathogen 
transmission and state that only an auto-disabling, single use lancing device should be 
used. We recommend that you incorporate Standard Precautions and practices in your 
instructions. Include any graphics demonstrating correct blood draw procedures and 
ensure that the pictures show users wearing gloves. 
In addition, we recommend that you refer users to the following practice guidelines: 
Biosafety in Microbiological and Biomedical Laboratories (BMBL).21
CLSI (Clinical Laboratory Standards Institute) Document M29-A3: Protection of 
Laboratory Workers From Occupationally Acquired Infections. 
You should stress that the operator should remove their gloves, clean their hands, and 
wear a new pair of clean gloves before testing each patient. 
13. You must include a step-by-step outline of procedures (21 CFR 809.10(b)(8)). Labeling 
must list any points that may be useful in improving precision and accuracy, as per 21 
CFR 809.10(b)(8). 
FDA recommends that the user manual should contain detailed instructions for how users 
are to perform cleaning and disinfection procedures for the meter between patients. 
This information should be based on the validation studies performed as described above 
in Section IV. You should also include the following: 
  An explanation of why the cleaning and disinfection should be performed. 
  The recommended frequency of cleaning and disinfection, i.e., between each 
patient. 
                                                          
20 Available at http://www.cdc.gov/hicpac/2007ip/2007isolationprecautions.html. 
21 Available at http://www.cdc.gov/biosafety/publications/bmbl5/. 
37 Contains Nonbinding Recommendations 
  The materials needed for cleaning and disinfection and how they can be 
purchased or prepared. 
  A detailed procedure describing what parts of the device should be cleaned and 
disinfected, what should not be cleaned and disinfected (avoided), the amount of 
time the disinfectant should remain on the meter (contact time), etc. You should 
include graphics/photographs to assist the user. Again, be sure that all graphics 
show the user wearing gloves. 
  A statement that, after cleaning and disinfection, users gloves should be 
removed, hands cleaned, and a new pair of clean gloves worn before proceeding 
to the next patient. 
  A contact telephone number for technical assistance or questions should be 
prominently listed in the cleaning and disinfection section. 
We recommend you also include the references below: 
FDA Public Health Notification: Use of Fingerstick Devices on More than One Person 
Poses Risk for Transmitting Bloodborne Pathogens: Initial Communication.22
Infection Prevention during Blood Glucose Monitoring and Insulin Administration.23
                                                          
22 Available at https://wayback.archive-
it.org/7993/20170111013014/http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm224025.htm. 
23 Available at http://www.cdc.gov/injectionsafety/blood-glucose-monitoring.html. 
38 Contains Nonbinding Recommendations 
Appendix 1. Sources of Error to Consider for BGMSs 
Table 10 below lists sources of error associated with the design, production, and use of 
BGMSs. 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 10  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 alternate 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) 
  Incorrect incorporation of results into overall treatment plan 
(prescription-use) 
  Use of strips not validated for use on the meter 
39 Contains Nonbinding Recommendations 
Reagent    Expired strips or reagents 
  Damaged or contaminated strips 
  Failure of strips, calibrators, or quality control materials to perform 
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 
 Incorrect manufacture
 
40 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) 
 
41 Contains Nonbinding Recommendations 
Appendix 2. Special 510(k)s and BGMSs 
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 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 perform 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 BGMS device 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.24 Sponsors should also consult the document on FDAs website How to Prepare 
a Special 510(k).25
As noted above, to be eligible for a special 510(k), the manufacturer should be modifying 
their own legally marketed device. This usually means that the candidate device and 
predicate device are part of the same device design file. Similarities between the candidate 
and predicate devices alone do not necessarily mean that the candidate device is a 
modification of the predicate device. 
We recommend that you contact the Office of In Vitro Diagnostics and Radiological Health 
(OIR) to discuss any specific questions you have regarding your BGMS devices eligibility 
to be submitted as a special 510(k). 
                                                          
24 Available at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/new-510k-
paradigm-alternate-approaches-demonstrating-substantial-equivalence-premarket-notifications. 
25 Available at https://www.fda.gov/medical-devices/premarket-notification-510k/how-prepare-special-510k. 
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