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Final Guidance Documents: Self 

Monitoring Blood Glucose Systems 

for Over-the-Counter Use & Blood 

Glucose Monitoring Systems for 

Prescription Point-of-Care Use

Leslie Landree, Ph.D.

Division of Chemistry and Toxicology Devices 

Office of In Vitro Diagnostics and Radiological Health

Center for Devices and Radiological Health

November 21, 2016 CDRH Webinar
3 

Acronyms 

• SMBG – Self Monitoring Blood Glucose

• BGMS – Blood Glucose Monitoring System

• OTC – Over-the-Counter

• POC – Point-of-Care
4 

User Populations

• Use at home by lay users (people affected by 

diabetes with no experience managing the device)

• Use in health care settings by health care 

 professionals

− Hospitals 

− Nursing homes

− Physician’s offices

− Emergency Departments

− Emergency Response Units 
5 

Intended User Population

• Glucose meters manufacturers historically sought 

clearance for OTC use 

 

• Designed and validated for OTC use

 

• Increasingly clear that these different use settings 

comprise distinct intended use populations with 

unique characteristics 
6 

Glucose Meters

Glucose Meter final guidances published

Draft Guidance

January 7, 2014 

Final Guidance

October 7, 2016
7 

Finalized Guidance Documents

• Blood Glucose Monitoring Systems for 

Prescription Point-of-Care Use 

• For assisted testing, in health care settings (e.g., hospitals, 

doctor’s offices, long-term care facilities)

• Meters for multiple patient use

• Self-Monitoring Blood 

Glucose for Over-theCounter Use 

• For self-testing by home users

• Meters for single patient use
8 

Guidance Documents

• These guidance documents are:

– A description of FDA’s current thinking on the information 

manufacturers should submit to FDA for future glucose meter 

submissions

• These guidance documents are NOT:

– Guidelines or rules for how hospitals, HCPs, or patients should use 

glucose meters

– Rules for how laboratories should validate glucose meters
9 

Finalized Guidance Documents

• Most testing is unchanged from 

current submissions. However, the 

FDA modified the following:

• Accuracy

• Interferences

• Cleaning and Disinfection

• Flex Studies 

• Test strip manufacturing lot release criteria
10

Finalized Guidance Documents

• A few changes/clarifications from the draft

• Clinical Laboratory Improvement Amendments (CLIA) 

clarifications

• Performance goals

• Interference testing protocol
11

Blood Glucose Monitoring Test Systems 

for Prescription Point-of-Care Use 

(BGMS POC)

• Address only those systems intended for prescription POC use 

 in professional health care settings

• Don’t address those blood glucose monitoring systems intended 

for OTC use by people affected by diabetes at home
12

BGMS POC

Intended use setting

• Intended for POC use in professional health care settings 

 

• Studied in the intended use populations and labeled 

appropriately 

 

• 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

• Identify sub-populations in which the BGMS may function 

differently than in the broader intended use population 

 
13

Clinical Laboratory Improvement 

Amendments (CLIA) Waiver of 

professional use meters

• BGMSs cleared as prescription-use will not be 

 automatically waived 

• FDA recognizes the importance of CLIA-waived BGMs 

 in point-of-care settings

 
14

• User studies designed to simultaneously support both 

clearance and CLIA waiver

– The recommended number of samples

– Use of untrained intended users in a CLIA waived setting 

CLIA Waiver of professional use meters
15

BGMS POC Performance - Accuracy

• 350 patient samples spanning measuring range for each claimed 

sample type/matrix (e.g. arterial, venous, capillary whole blood) 

• Testing should be performed by the intended user (e.g., nurses, 

technicians) 

• Studies should be done in patients that accurately reflect the 

intended use population (e.g., neonatal, ambulatory, ICU patients, 

etc.) 

• Additional 50 high (<80 mg/dL glucose) and 50 low (>300 mg/dL 

glucose) samples (may be contrived) 

• Test strips used in studies should undergo typical shipping and 

handling conditions prior to use in the study
16

BGMS POC Performance - Accuracy

• Neonatal (<28 days old)

• 100 to 150 fresh neonatal capillary blood samples 

compared to reference
17

BGMS POC Accuracy

• FDA does not recognize ISO 15197:2013

• FDA guidances address some issues not addressed by 

 ISO 15197:2013

– Non-OTC use

– Design features

– Performance by intended user

– Improved performance in hypoglycemic range 

• FDA guidances describe studies designed to be compatible 

with ISO 15197:2013, but not identical 

 (guidance studies can be done to satisfy ISO, but not always vice-versa)
18

BGMS POC – Accuracy Goals

Changed slightly from draft

 

Draft Guidance Final Guidance

99% within +/-10% >70mg/dL

and

within +/- 7 mg/dL <70mg/dL

95% within +/-12% > 75 mg/dL

and

+/- 12 mg/dL <75 mg/dL

100% within +/- 20%

98% within +/- 15% >75 mg/dL

and

+/- 15 mg/dL <75 mg/dL
19

BGMS POC – Accuracy Goals

• Description of the study setting including the size, type and 

location

• Justifications for how the study conditions simulate intended 

use conditions

• Description of the shipping and handling conditions of the 

test strips prior to use in the study

• Outliers should be specifically addressed by manufacturers in 

the pre-market submission 
20

BGMS POC Performance

Potential Interferences

• Should evaluate the effect of potentially interfering 

endogenous and exogenous substances and conditions (e.g. 

lipemia, common medications, varying hematocrit levels, 

ascorbic acid, dopamine, L-dopa, methyl-dopa, triglycerides, 

uric acid, xylose) 

 

• Conduct a risk analysis to assess commonly used drugs in the 

intended use population 
21

BGMS POC Performance

Potential Interferences

 

• Recommend a comparison between a test sample that 

contains the potential interferent measured on the candidate 

device vs. a control sample containing solvent/vehicle also 

measured on the candidate device

• The relative bias (mg/dL) and percent bias with 95 percent 

confidence intervals should be provided instead of using 

“non-interference” criteria

 
22

BGMS POC Performance

Potential Interferences

• Hematocrit

– Span claimed hematocrit range, compare to 

 comparator method, 3 test strip lots

– Each meter replicate compared to the average of the 

comparator value. 

– Bias for samples with glucose ≥75 mg/dL should be less than 

5 percent on average, no individual value greater than 10 

percent

– For samples with glucose <75 mg/dL the absolute bias 

(mg/dL) should be provided with 95 percent confidence 

intervals with a clinical justification

– Minimum claimed range of 10-65 percent
23

BGMS POC Performance

Potential Interferences

• Oxygen

– If intended to be used in patients with a broad range of blood 

oxygen levels study should be conducted to demonstrate the 

range of blood oxygen levels device can be used with

– Supplement with blood oxygen levels of patients in Method 

Comparison/User Evaluation Study 

– If blood oxygen levels do not affect performance of device 

comprehensive justification should be provided supported by 

analysis of blood oxygen levels on device performance from 

Method Comparison/User Evaluation Study
24

Infection Control

• The majority of the infection control recommendations remained the 

same as what manufacturers are currently doing

• Meters should be designed such that all external materials can be 

cleaned and disinfected – seams, test strip port, other ports

• Validation studies differ mainly in the number of cleaning and 

disinfection cycles - should be representative of the amount of 

cleaning and disinfection that the meter will be exposed to in its use 

life (typically 3-5 year use life) 

• Include validated cleaning and disinfection instructions in the labeling
25

BGMS POC Flex Studies

• Demonstrate that the BGMS device design is robust 

(e.g., insensitive to environmental and usage 

variation) and that all known sources of error are 

effectively controlled 

• Design test systems to incorporate fail-safe 

mechanisms whenever technically practicable (e.g. 

lock-out functions) 
26

Flex Study Examples

• Used test strips

• Mechanical Vibration Testing 

• Shock testing

• Electromagnetic 

compatibility (EMC) Testing

• Electrostatic 

Discharge/Electromagnetic 

Interference Testing 

• Test strip stability testing 

Mechanical Vibration Testing 

• Temperature and humidity

 effects

• Altitude effects

• Short sample detection 

• Sample perturbation study 

• Intermittent sampling
27

Test Strip Lot Release Criteria 

• Test strip lot release criteria will be reviewed as part of the 

submission

• Test strip lot release criteria should be sufficient to ensure consistent 

quality of the test strips 

– should be designed to ensure that all released lots conform to the 

labeled BGMS device performance in the hands of the intended 

user. 

– These criteria should be more stringent than the criteria used to 

evaluate total error in the performance studies. 

– Criteria to assure statistical confidence for full lot

• Manufacturers should provide a description of the lot release criteria 

and a summary of the sampling scheme in the pre-market submission 
28

Self-Monitoring Blood Glucose Test 

Systems for Over-the-Counter Use 

 (SMBG OTC)

• Meant to address only those blood glucose monitoring systems intended for 

use by people affected by diabetes at home 

• Encompasses individuals with wide ranges in age, dexterity, vision, training 

received on performing testing, and other factors that can be critical in the 

patient’s ability to accurately use the device and interpret test results 

• SMBG systems (meters and associated test strips) should be designed to be 

robust and reliable to accommodate actual use by people affected by 

diabetes (e.g. more varied storage and handling conditions compared to 

devices used in professional settings 

• Not meant to address blood glucose monitoring systems intended for use in 

prescription point-of-care settings 
29

SMBG OTC Performance - Accuracy

• User evaluation – assess system accuracy in the hands of 

intended users, labeling assessment and usability

• Under conditions reflective of the expected use 

• Minimum of 350 different subjects for each claimed sample type 

(e.g. fingerstick, palm, thigh) 

• At least 10 percent of the participants should be low awareness 

of SMBGs, may include non-diabetic subjects

• Test strips should have undergone typical shipping and handling 

conditions prior to the study.

• Additional 50 high (>250 mg/dL glucose) and 50 low (<80 mg/dL 

glucose) samples (may be contrived)
SMBG OTC - Accuracy Goal 

Not changed from draft

 

Draft Guidance Final Guidance

95% within +/-15% 95% within +/- 15%

99% within +/- 20% 99% within +/- 20%
31

SMBG OTC - Accuracy Goal

• Outliers, results >20 percent relative to the comparator method, 

should be specifically addressed by providing a clinical 

justification for why the errors occurred and why the errors 

when extrapolated to the intended use setting do not affect 

user safety

• Claimed measuring range should minimally span 50 – 400 mg/dL 

glucose
32

SMBG OTC Performance

Potential Interferences

• Same study design as for BGMS – common endogenous and 

exogenous substances 

– Comparison between a test sample on the candidate 

device vs. a control sample on the candidate device 

– The relative bias (mg/dL) and percent bias with 95 

percent confidence intervals should be provided instead 

of using “non-interference” criteria
33

SMBG OTC Performance 

Potential Interferences

• Hematocrit

 - Claimed hematocrit range of 20-60 percent 

 (ideal)

 - Minimum claimed range 30-55 percent 

 hematocrit 
34

SMBG OTC – Infection Control

• Similar to BGMS guidance and not much different from what manufacturers 

are currently doing

• Validation studies differ mainly in the number of cleaning and disinfection 

cycles - should be representative of the amount of cleaning and disinfection 

that the meter will be exposed to in its use life (typically 3-5 year use life) 

• Meters should be designed such that all external materials can be cleaned 

and disinfected – seams, test strip port, other ports

• Include validated cleaning and disinfection instructions in the labeling
35

SMBG OTC Performance

• Flex studies

• Test strip manufacturing lot release criteria
36

SMBG OTC Labeling

SMBG labeling changes added for clarity

Warning against use on multiple patients (due to risk of 

infection) 

This device is not intended for use in health care or

assisted-use settings such as hospitals, physician offices,

or long-term care facilities because it has not been

cleared by FDA for use in these settings, including for

routine assisted testing or as part of glycemic control

procedures. Use of this device on multiple patients may

lead to transmission of Human Immunodeficiency Virus

(HIV), Hepatitis C Virus (HCV), Hepatitis B Virus HBV), or

other bloodborne pathogens. 
37

SMBG OTC Labeling

• Accuracy information placed prominently in the labeling – on 

outer box label, test strip inserts and user manuals

– Currently no way for users distinguish meters

– Labeling aimed at allowing users and their health care 

 professionals to ability to choose the best meter for their 

 needs

– Recommend data be presented in tabular format as well as 

graphically on the outer box

– Examples are included in the guidance document
38

SMBG OTC Labeling

Outer box accuracy information to help patients choose the 

meter that is right for them:
39

Implementation

• Working with manufacturers on phasing in the 

 guidance documents
Questions?

Division of Industry and Consumer Education: 

DICE@fda.hhs.gov

Slide Presentation, Transcript and Webinar 

Recording will be available at:

http://www.fda.gov/training/cdrhlearn

Under the heading: Specialty Topics; Sub- heading: Device Specific Topics