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February 12, 2019
Coordinated Development of Antimicrobial 

Drugs and Antimicrobial Susceptibility Test 

Devices

Ribhi Shawar, Ph.D., ABMM, FAM

Branch Chief, General Bacteriology and Antimicrobial Susceptibility Branch

Division of Microbiology Devices

Office of In Vitro Diagnostics and Radiological Health (OIR)

Center for Devices and Radiological Health (CDRH)

U.S. Food and Drug Administration (FDA)

ribhi.shawar@fda.hhs.gov

February 12, 2019
3

• Background

– Types of Devices

– Important Regulations, Timelines, and Guidance

• FDA Review of Traditional Drug and Device Submissions

• Concerns: Time Lag Between Drug Approval and Antimicrobial 

Susceptibility Test Availability

• Coordinated Development Activities

• FDA Initiatives to Streamline the Process

• Highlights

Outline
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Objectives

• To familiarize stakeholders with the history of the Coordinated 

Development of Antimicrobial Drugs and Antimicrobial Susceptibility 

Test Devices and the regulatory review process for timely availability 

of devices

• To provide an update on the FDA Guidance for coordinated 

development and the various supportive activities 
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• Antimicrobial Susceptibility Test Device

– An antimicrobial susceptibility test is a device that incorporates 

concentrations of antimicrobial agents into a system for the purpose of 

determining in vitro susceptibility of bacterial pathogens isolated from clinical 

specimens. Test results obtained after incubation are used to determine the 

antimicrobial agent of choice to treat bacterial diseases.

– The FDA regulates these devices under different regulations and uses 

multiple product codes depending on the type of devices. 

Definitions — Antimicrobial Susceptibility Test Device
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• Disk Diffusion-Based Devices (Zone Diameter)

• Dilution-Based Devices (Minimum Inhibitory Concentration)

– Agar Gradient Diffusion

– Visually (Manually)-Read Panels

– Instrument-Read Panels (Automated), Algorithm-Driven Devices

• From colonies or Positive Blood Cultures

Types of Antimicrobial Susceptibility Test Devices

• Variations in Testing Methods Can Include:

– Specific Media 

– Inoculation Methods

– Complex Software/Instrumentation
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• Class II, require a 510(k) premarket notification (that is, non-exempt)

• Subject to 90 day review cycle

• Regulations (21 CFR): 

– Colonies (depending on device type):866.1640, 866.1645, 866.1620

– Positive Blood Culture: 866.1650 

• The Center for Drug Evaluation and Research (CDER) and the Center 

for Devices and Radiological Health (CDRH) guidances that outline: – Types of Studies 

– Data Requirements 

– Evaluation Criteria

• FDA-recognized guidelines and standards (for example, Clinical and 

Laboratory Standards Institute)

Relevant Antimicrobial Susceptibility Test Device 

Review Timelines, Regulations, and Guidances
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21 CFR 

866.1650

21 CFR 

866.3365

21 CFR 

866.3373

Culture Media Test Discs

NAATs from colony, 

+ blood culture, and 

direct specimen

Automated Test Systems

Novel Technology

(Cellular Analysis System)

Multiplex NAAT from

+ blood culture

NAAT and 

MTB-complex

21 CFR 

866.1640

Regulations

Future 

Regulations

New Organism/Resistance

Mechanisms

21 CFR 

866.1620

21 CFR 

866.1700

21 CFR 

866.1645

Multiplex NAAT 

from LRT

21 CFR 

866.3985

Diversity of Regulations for Antimicrobial Susceptibility 

Test Device and Antimicrobial Resistance Markers

 Nucleic Acid Amplification Test (NAAT)

 Mycobacterium tuberculosis (MTB)

 Lower Respiratory Tract (LRT) 
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FDA Review of Traditional Drug and 

Device Submissions

Investigational New Drug 

Application (IND) Submitted
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Microbiology Information: Drug 
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Microbiology Information: Antimicrobial Susceptibility Test 

Device

Antimicrobial Susceptibility Test Device Timeline 

(Disk)*

R&D

• Drug manufacturer works with disk 

manufacturer to produce 

Investigational Use Only/ Research 

Use Only disks (their brand**) 

during phase II-III drug studies

510(K)

• Disk manufacturer submits no new 

data to CDRH (references drug 

label information)

• CDRH consults with CDER

• Device FDA review is ≤ 90 days 

unless additional information/data 

is needed

*Assuming no issues were identified to prevent development/approval of disk correlates

**For brands not evaluated through this pathway, separate studies are needed to support a 510(k)
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Microbiology Information: Antimicrobial Susceptibility Test 

Device

Antimicrobial Susceptibility Test Device Timeline 

(Minimum Inhibitory Concentration)

R&D

• Sponsor can contact FDA with questions 

(pre-submission process)

• Device manufacturer conducts research 

and development

• Studies conducted on final design

510(K)

• 510(k) submitted in conformance with 

Antimicrobial Susceptibility Test 

Special Controls Guidance

• CDRH evaluates data, including 

minimum inhibitory concentration, 

breakpoint and indicated organisms 

from drug label

• FDA review is ≤ 90 days unless 

additional information/data is needed

*Assuming no issues were identified to prevent development/approval of disk correlates

**For brands not evaluated through this pathway, separate studies are needed to support a 510(k)
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BEFORE Coordinated Development

New Drug Approval to Antimicrobial Susceptibility Test Device Clearance: Elapsed 

Time (Months)
14

Improved 

Patient 

Care

Coordinated 

Development

Drug

Device

CDER

CDRH

Coordinated 

Development
15

Coordinated Development Workshop and Draft Guidance

September 29, 2016, Silver Spring, MD

o Overview of antimicrobial susceptibility test devices landscape from 

different perspectives (agenda topics covered)

Clinician—New drugs and susceptibility test results/updated 

breakpoints

Laboratory—Routine drug susceptibility testing, 

drug/organism combinations, and quality control /training

Drug Sponsors—Agreements between sponsors, 

breakpoints, research use only testing, and complexity of 

development process

Diagnostic Device Manufacturers—Susceptibility Test 

Manufacturer’s Association, development cycle, FDA review, 

and breakpoint revisions

o How American Society for Microbiology and Clinical and Laboratory 

Standards Institute can help with the process

o Two panel sessions were held to clarify questions from audience
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• 54 Comments Received from Stakeholders

oIndustry (36), Professional Societies (11), Trade Associations (7)

• 4 Comment Types

oPolicy (10), Editorial (9), Procedural (19), Technical (16)

Comments to the Docket

Substantive changes to the content of the draft guidance 

were made based on comments to the docket
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• Intended to assist drug sponsors and device manufacturers who are planning to 

develop new antimicrobial drugs and antimicrobial susceptibility test devices 

• Specifically, the guidance intends to accomplish the following: 

– Describe interactions between drug sponsors and device manufacturers for coordinated 

development of a new antimicrobial drug and an antimicrobial susceptibility test device; 

– Explain the considerations for submitting separate applications to CDER (drug) and CDRH 

(device) when seeking clearance of an antimicrobial susceptibility test device to coincide with, 

or soon following, antimicrobial drug approval; and 

– Clarify that the review of the new antimicrobial drug product and antimicrobial susceptibility test 

device(s) will remain independent.

Scope
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• Provide recommendations to the medical device and drug 

industries on how to work together to facilitate timely clearance of 

antimicrobial susceptibility test devices by the FDA

• Minimize time between the approval of new antimicrobial drugs and 

clearance of antimicrobial susceptibility tests used to determine the 

potential effectiveness of those drugs

Goals of the Guidance
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Final Guidance Published January 17, 2019
20

From Draft to Final: Summary of Changes

• Process for coordinated development: 

– Clarified process and timeline for coordinated development of antimicrobial 

drugs and antimicrobial susceptibility test devices. 

– Added a flowchart depicting the recommended interactions between drug 

and device manufacturers, CDER, and CDRH to facilitate coordinated 

development. 

• Applicability of the guidance to molecular devices: 

– Revised to indicate that the processes of coordinated development outlined 

in the document are applicable to molecular devices for the detection of 

antimicrobial resistance markers that infer drug resistance and to traditional 

growth-based microbiological devices. 
21

Clarification of the:

• Need for improved coordination between drug and device development

• Process for coordinated development

• Types of antimicrobial susceptibility test devices to include molecular 

devices

• Recommended timing for submission of antimicrobial susceptibility test 

devices to CDRH in relation to submission of the new drug application to 

CDER

• Process for coordinated development in without a pre-submission 

• Content of a pre-submission, if utilized

Changes to Final Guidance Based on 

Comments to the Docket
22

Coordinated Development-Drug & Device Manufacturers

Antimicrobial Susceptibility 

Device Clearance

Submit 510(k)

Antimicrobial 

Susceptibility Test 

Device 

Manufacturer

Pre-submission or Pre-submission Supplement(s)

• Plans for coordinated development

• Description of relationship with drug sponsor

• Anticipated need for Investigational Device Exemption (IDE)

• Plans for data collection and analysis

• Share 510(k) plans

CDRH Review

Pre-submission is 

not necessary but 

recommended 

during drug 

development

A 510(k) may be 

submitted while 

the New Drug 

Application is 

under review

CDRH Review

Device clearance 

can either coincide

with or shortly after 

drug approval
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Functions of Coordinated Development

Does

• Streamline the time between drug approval and 

device clearance - antimicrobial susceptibility 

test availability coincides with drug approval

• Promote meaningful discussion between drug 

developers, device manufacturers and the FDA

• Provide drug developers access to antimicrobial 

susceptibility test device technology during 

clinical studies

• Provide device manufacturers access to 

organisms obtained during drug development

• Improve patient care

Does Not

• Change existing regulatory requirements or 

timelines for drug or device review and 

approval or clearance
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Pre-Submission Interaction Topics (1)

General:

• Outline of studies that will have been or will be performed

• Provisional breakpoints and indicated organisms

• Expected timeline

• Assessment of Broth Microdilution variability for the drug

• Description of any specific Broth Microdilution modifications 

to standardize drug testing

• Anticipated procurement of resistant or on-scale strains

• Information regarding Drug/Device agreements 

• Specific questions to allow better FDA feedback
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Specific for Antimicrobial Susceptibility Test Device Evaluation Studies

• Isolates can be provided by the drug manufacturer

• Organisms from drug evaluation studies can be used as challenge/stock 

isolates for device evaluation

• Broth Microdilution devices should test a wide range of dilutions to allow 

flexibility for breakpoint changes (and avoid truncated minimum inhibitory 

concentration values)

• Disk brands not included during drug trials will require separate studies to 

support a 510(k) for their brand

• Any additional information specific to the drug

– Specific resistance mechanisms

– Special reporting instructions (resistance mechanisms, media, etc)

Pre-Submission Interactions Topics (2)
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Activities to Date
27

AFTER Coordinated Development
28

Additional Advancements

• The Centers for Disease Control and Prevention (CDC) & 

FDA Antimicrobial Resistant Isolate Bank

Isolates from the AR Isolate Bank can be used to support in vitro diagnostic device premarket 

submissions. To date, it has contributed to 13 clearances/approvals for Antimicrobial Susceptibility 

Test and other infectious disease test submissions since its launch in 2015. 

• 21st Century Cures
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Benefits to Public Health

• Earlier availability of a diversity of antimicrobial susceptibility 

test diagnostics for improved patient care

• Contributes to antimicrobial stewardship

• Improved ability to monitor emergence of antimicrobial 

resistant strains

With 21st Century Cures

• Flexibility in drug testing and reporting

• Streamlined device updates and labeling
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• AST Special Controls Guidance

https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDoc

uments/ucm388961.pdf

• Coordinated Development Guidance

https://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDoc

uments/UCM521421.pdf

• Coordinated Development Guidance Docket 

https://www.federalregister.gov/documents/2019/02/01/2019-00569/coordinateddevelopment-of-antimicrobial-drugs-and-antimicrobial-susceptibility-test-devices

• CDC & FDA Antimicrobial Resistant Isolate Bank

https://www.cdc.gov/drugresistance/resistance-bank/index.html

• FDA and 21st Century Cures

https://www.fda.gov/RegulatoryInformation/LawsEnforcedbyFDA/SignificantAmendmentstothe

FDCAct/21stCenturyCuresAct/default.htm

Resources
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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 Heading: Specialty Technical Topics; Subheading: In 

Vitro Diagnostics

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