FDA Overview of the Process for Clearance and Approval of Mass Spectrometry-based In - PowerPoint Presentation

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FDA Overview of the Process for Clearance and Approval of Mass Spectrometry-based In vitro Diagnostic Devices

MSACLApril 4, 2019Majda Haznadar, Kris Roth, Doug Jefferymajda.haznadar@fda.hhs.govkristian.roth@fda.hhs.govdoug.jeffery@fda.hhs.gov

www.fda.gov

Slide2

www.fda.gov

DISCLAIMER

This presentation is intended for informational purposes only and does not constitute legal or regulatory advice. Please see the Federal Food, Drug, and Cosmetic Act and 21 CFR Subchapter H for a full list of requirements by FDA

Slide3

Our Path Today

Majda:Device Risk ClassificationPre-submissions (Pre-Subs)510(k)De NovoKris:MALDI-TOF MS and ExemptionPanel Discussion: Majda, Kris, Doug

www.fda.gov

Slide4

In Vitro Diagnostic (IVDs) Are Medical Devices [21 CFR 809.3]:

Reagents, instruments, and systems used in diagnosis of disease or other conditions…In order to cure, mitigate, treat, or prevent disease…Intended for use in the collection, preparation, and examination of specimens taken from the human body.

www.fda.gov

Slide5

How Are IVDs Classified?

Regulatory path determined using a risk-based approach

Classification (I, II, orIII) depends on risk

Class I – most 510(k) exempt

Class III - PMA

Low likelihood of harm

High or unknown likelihood of harm,or how to prevent harm is unknown

.

Class II - 510(k)

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Risk

Depends

on

Intended

Use

of

device

Level

of

FDA

review

and

type

of

studies

required

depend

on

intended

use and

anticipated

risk

Level

of

risk

may

not be

related

to

the

technology

Controls

give

assurance

that

risk

is

low

Slide7

Classification/Controls

7

Class I – Low Risk - General Controls

Registration and ListingLabeling

Good Manufacturing Practices510(k) Clearance

Class II –Moderate risk - Special Controls

General controls insufficientPerformance standards

Special labeling requirementsPostmarket surveillance

Class

III – High

risk

–

General Controls

and

Premarket

Approval

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Submissions Are Reviewed by a Large Team of Experts

Clearance or Approval

Submission Sponsor (IVD Manufacturer)

Administrative Processing

Receipt of Electronic Documents

Tracking of Deadlines

Electronic Sign-in and Sign-out

Review Team

Lead Reviewer

Consultants: Technical, Analytical, Medical, Statistical

Division Management

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Pre-Subs

www.fda.gov

Slide10

Q-Subs cover many different submitter requests

www.fda.gov

Breakthrough Device Designation Requests**

*Determines if Investigational Device Exemption (IDE) is needed

**For certain medical devices and device-led combination products that provide for more effective treatment or diagnosis of life-threatening or irreversibly debilitating diseases or conditions

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Pre-Subs are one type of Q-Sub

Pre-submissions (Pre-Subs)Questions related to a future submissionCan be written feedback and a face to face meetingwritten feedback and a teleconference (easier to schedule)purely written feedback

www.fda.gov

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Pre-Subs have Broad Applicability

Future submission can be a PMA, 510(k), De Novo, CLIA Waiver, or IDE

www.fda.gov

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Pre-Subs have Broad Applicability

Future submission can be a PMA, 510(k), De Novo, CLIA Waiver, or IDECan address many types of questions, the more specific the better (more on this later)

www.fda.gov

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Pre-Subs have Broad Applicability

Future submission can be a PMA, 510(k), De Novo, CLIA Waiver, or IDECan address many types of questions, the more specific the better (more on this later)Can be useful at different stages of product development

www.fda.gov

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Uncertainty is Best Addressed Early

Course corrections are less expensive when made earlyMore opportunity to work towards win-win approaches

www.fda.gov

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Describe Your Device in Detail

How does it work? How is the device used in clinical practice?

www.fda.gov

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Critical Element of a Pre-Sub: Intended Use (IU)

www.fda.gov

The most important part of any pre-sub

Analytical and clinical validation studies should support the IU of the proposed device

Clinical study should be conducted in the IU population

May be amended/modified over time

Slide18

IU Elements

www.fda.gov

Assay name

Technology

Instrument name

Sample matrices (serum, plasma)

Quantitative or qualitative

Clinical use – disease /condition

The clinical purpose (diagnosis, prognosis, monitoring)

The target population for whom the test is intended

Setting (clinical laboratory, point-of-care, etc.)

Slide19

IU Example (DEN170019)

www.fda.gov

The Vitamin D 200M Assay for the Topaz System is intended for in vitro diagnostic use in the quantitative determination of total 25-hydroxyvitamin D (25-OH-D) through the measurement of 25-hydroxyvitamin D3 (25-OH-D3) and 25-hydroxyvitamin D2 (25-OH-D2) in human serum using LC-MS/MS technology by a trained laboratory professional in a clinical laboratory. The Assay is intended for use with the Topaz System. The Vitamin D 200M Assay for the Topaz System is intended to be used in conjunction with other clinical or laboratory data to assist the clinician in making individual patient management decisions in an adult population in the assessment of vitamin D sufficiency.

Matrix

Condition

Intended Population

Analyte(s)

Instrument

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Analytical Performance Characteristics

www.fda.gov

Precision

Linearity/assay reportable range

Limit of Detection

Cross reactivity/ Interfering substances

Method comparison (to the predicate or reference method)

Matrix comparison

Traceability, Stability

Controls and calibrators

Reference range

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Clinical Performance Characteristics

www.fda.gov

Examples of parameters in clinical studies: Sensitivity/Specificity, Negative Predictive Value (NPV)/Positive Predictive Value (PPV) based on comparison to a gold standard (i.e., American College of Rheumatology (ACR) classification criteria, biopsy, etc.)

Inclusion/Exclusion criteria should be well defined

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Clinical Study Specimens

www.fda.gov

Specimens: where possible, the set of subjects and specimens to be tested include:

Specimens across the entire range of disease state to reflect the target population for the device (e.g. stage, grade)

Differential diagnosis specimens (normal samples are not appropriate for determining specificity)

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Pre-Sub Meeting Milestones

www.fda.gov

Timeline

Action

Day 15

Acceptance after receipt in Document Control Center (DCC)

If accepted, email states whether meeting agreed to or provides 2 alternative dates

Day 30

Meeting date agreed to or escalation to management

5 days Before Meeting

(or Day 70 if earlier)

Written Feedback

Meeting

Meet unless you cancelled

Q-Sub Closed

Meeting plus 15 Days

Your deadline for submitting meeting minutes

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Do ask Specific Questions

Our goal is to meet your current needIf your question is specific, we can address itIf your question is vague or too broad, we’ll do our best, but may miss your real need

www.fda.gov

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Which Questions are a Good Fit for a Pre-Sub or Submission Issue Mtng?

Does FDA agree with the proposal for use of contrived samples in analytical studies described in Section X? Is this sufficient for a 510(k)?We have provided a response to FDA's question about clinical study sample size, along with a justification based on a power analysis. Is this plan acceptable? If not please provide further guidance.Does FDA agree with all of our analytical performance studies?…

www.fda.gov

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Which Questions are a Good Fit for a Pre-Sub or Submission Issue Mtng?

Does FDA agree with the proposal for use of contrived samples in analytical studies described in Section X? Is this sufficient for a 510(k)?We have provided a response to FDA's question about clinical study sample size, along with a justification based on a power analysis. Is this plan acceptable? If not please provide further guidance.Does FDA agree with all of our analytical performance studies?…

www.fda.gov

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Address our Answers

When you submit your next submission…If you didn’t follow our advice, say why

www.fda.gov

Slide28

Write a Clear Cover Letter

What type of Q-Sub do you want?If Pre-SubDo you want written feedback only or do you want a meeting? If a meeting, propose three specific meeting datesOngoing Q-Sub? Same device and intended useWith whom should we correspond?

www.fda.gov

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Successful Meetings take Planning and Focus

Focus the meeting on what you want to get out of itDo not spend 10-15 minutes on a company history or its managementAllow 2/3 of the time for discussionLimit background review to 1/3Dedicate someone to take minutesShould not ask questions based on new information provided during the meeting – we may not be able to answer them

www.fda.gov

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Q-Submission Nomenclature – Amendments and Supplements

Amendments contain additional information about an existing request for feedback, for example:Slides Agenda updates Meeting minutes Meeting minutes disagreements Change of Submitter/CorrespondentSupplements contain new requests for feedback on the same device/indicationCan be any kind of Q-Sub

www.fda.gov

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In Summary, submit a Pre-Sub when…

A new intended useContains new technology or analytesClinical Implications UnclearPresents complex data/statistical questionsPresents a significantly new approach to analytical or clinical study designs or analysesUses a predicate or reference method that is unclear or uncertain

www.fda.gov

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510(k)Pre-Market Submissions

www.fda.gov

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What is a 510(k)?

Demonstration of Substantial Equivalence (SE) to legally marketed device in U.S. also known as a predicateFor Class II and Class I (reserved) devices.

www.fda.gov

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A 510(k) Is Required When…

Introducing device to the market for the first timeChanging a device’s indications for use/intended use and/or labeling Making modification(s) to device that could affect safety or effectiveness

www.fda.gov

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A 510(k) Is NOT Required For…

A Private Label Distributer who does not modify device or labelingonly adds company name or language like “distributed by__”Re-packager or Re-labeler who does not alter the labelingNot selling device in USManufacturer of partsDevices Exempt by Statute or Regulation – there are currently 1003 class II devices exempt from 510(k) regulations. Calibrators and controls, recently exempt.

www.fda.gov

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510(k)’s Intent

There are two outcomes to a 510(k) application:Substantially equivalent (SE) to a predicateNot Substantially equivalent, automatically into class IIIPMA – approval of Class III devicesDe Novo

www.fda.gov

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510(k) Remains the Principle Pathway to Obtain Market Authorization for Most Devices

The 510(k) program was established more than 40 years ago CDRH receives ~3000 510(k)s per year~90% are found SE and go to marketPremarket Notification (510(k)) procedures are found in 21 CFR Part 807, Subpart EWhen a submission is requiredExemptions from notificationFormat and content of the submissionContent and format of a 510(k) summary or statementConfidentiality of information

www.fda.gov

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A Device Must Be Compared To…

A legally marketed device (a predicate) that does not require a PMA, i.e.A pre-amendment device (a device used as an IVD prior to 1976)A device found by FDA to be Substantially Equivalent (SE)A reclassified deviceA device classified by a De Novo petition “Paper predicates” can be used

www.fda.gov

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A Paper Predicate

A paper predicate is a device that only satisfies the LEGAL REGULATORY requirement that you are classified based on the classification of a device you are substantially equivalent to. You DO NOT have to compare performance of your device with the paper predicate.It is your responsibility to establish the ACCURACY of your device, this is usually done through a method comparison with the predicate. You measure “TRUTH” through a reference method or through clinical diagnosis/truth.For example, drugs of abuse immunoassays use GC-MS as their comparator. Troponin assays used clinical diagnosis for acute myocardial infarction.

www.fda.gov

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What Does FDA Review in a Submission?

Intended Use/Indications for UseAnalytical performance testingClinical performance testingDevice labeling (package insert/instructions for use)

www.fda.gov

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CDRH Recognizes Guidelines for IVDs

www.fda.gov

Clinical and Laboratory Standards Institute (CLSI)

Use of CDRH-recognized guidelines can make performance testing and submission review faster and more efficient

Precision

Analytical Sensitivity

AND MANY MORE!

http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm

Liquid Chromatography-Mass Spectrometry Methods

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General Recommendations for Analytical Performance Testing

www.fda.gov

Use Recognized CLSI Guidelines

Use Real Patient Samples from the Intended Use Population and Intended Matrix

Test Samples that Cover the Analytical Measuring Range and at Medical Decision Points

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Use Finalized Device for All Performance Testing

www.fda.gov

Sample Processing

LC-MS Analysis

Data Processing

Final Output

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Tips to a Successful Submission (Do’s)

www.fda.gov

Stay informed with new

guidances

Read the FDA

Decision Summaries

of predicates to help determine what may be requested

Be organized and include page numbers, headings, and table of contents

Proofread everything. Ensure consistency throughout submission. Tell the story of equivalence

Read the labeling for claims not consistent with the proposed IFU

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Tips to a Successful Submission (Don’ts)

www.fda.gov

Avoid data dump

Follow the 510(k) Format Guidance

Provided info should have a purpose

Expect a 510(k) review to be interactive. BE AVAILABLE to answer questions. A quick conversation between the reviewer and the sponsor can add clarity to a submission. This can speed up review.

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De Novo Classification Request

www.fda.gov

Slide47

What is a De Novo Classification Request?

Classification process for novel devices whose type has not been previously classifiedBased on riskPredicate cannot be identifiedDevice has a new intended use or technical characteristics that raise new questions of safety and effectiveness

www.fda.gov

Slide48

De Novo Classification Establishes…

New necessary controlsNew regulationNew Product Code

www.fda.gov

Slide49

Sponsor

submits510(k)

FDA returns

a determination of NSE

FDA

grants

de novoSponsor submitsde novoFDA declinesde novo

De

Novo

Pathway

Established by

FDA

Modernization

Act of 1997

(FDAMA)

Slide50

Direct De

Novo Pathway Established by FDA Safety and Innovation Act – FDASIA of 2012

Sponsor

submits de novo application

FDA

grantsde novoFDA declinesde novo

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Is A Device Eligible for De Novo

www.fda.gov

Classification

–

should be

Class

I

or

II

Search

FDA

databases

for

regulations

Search

the

510(k) and PMA

databases

and

compare

the

intended

use of

your

device

to

those of cleared devices on Decision

Summaries

513(g)

–

official request

for

classification of

a

currently

unclassified

device

Submit

a

pre-submission

for

FDA

feedback

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Your Device is NOT a De Novo Candidate If…

www.fda.gov

You

have

received

an

NSE

decision based on

performance

Your

device

is of a type

that

is classified as

Class

III

–

high

risk

A

predicate

device

exists

General

controls

would

be

inadequate

to

mitigate

the

identified risks and special

controls

cannot

be developed

De Novo

process cannot

be used

to

reclassify

a

device that

is

already

in

Class

III

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Components of the De NovoSubmission

Cover Letter identifying the submission as a De NovoDevice nameAdministrative informationRegulatory history(prior 510(k), pre-submissions, IDE)Intended UseDevice description – technologic characteristics

www.fda.gov

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Classification summaryReview of existing regulationsRationale for why device doesn’t fit existing regulationsClassification recommendationInclude justificationIdentify special controls if Class II

www.fda.gov

Components

of the

De

Novo

S

ubmission

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Evidence of Safety and EffectivenessAnalytical testingClinical testingEnsure that data supports intended useLabeling– 21 CFR Part 809.10

www.fda.gov

Components

of the

De

Novo

S

ubmission

Slide56

Analysis of Benefit/riskCharacterize risks to healthCorrelate each health risk to a mitigationDiscuss how general controls/special controls mitigate risksRefer to Benefit-Risk Guidance documentBenefit-Risk Guidance Document - Factors to Consider When Making Benefit-Risk Determinations in Medical Device Premarket Approval and De Novo Classifications. https://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm517504.pdf

www.fda.gov

Components

of the

De

Novo

S

ubmission

Slide57

Information I Hope You Take Away…

Pre-Subs are available to help you mitigate riskPlease talk to us if you are unsure, and be willing to listen to what we sayRisk reduction is most effective when done earlyHave focused questions

www.fda.gov

Slide58

Information I Hope You Take Away…

Pre-Subs are available to help you mitigate risk510k is a Class II device needs to demonstrate substantial equivalence to a legally marketed device in the U.S.

www.fda.gov

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Information I Hope You Take Away…

Pre-Subs are available to help you mitigate risk510k is a Class II device needs to demonstrate substantial equivalence to a legally marketed device in the US.De Novo is a risk-based pathway for clearance of a novel device without an existing predicate, which have technical characteristics that raise new questions of safety and effectiveness

www.fda.gov

Slide60

Resources

Guidance Documents

Guidance Documents (Medical Devices and Radiation-Emitting Products)

https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/default.Htm

Division of Industry and Consumer Education (DICE)

The Division of Industry and Consumer Education (DICE) answers questions (by phone and email) from the medical device industry and consumers of medical devices and radiation-emitting electronic products.

https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/ContactDivisionofIndustryandConsumerEducation/default.htm

Device Advice: Comprehensive Regulatory Assistance

Device Advice is intended to provide industry with information that is accurate, timely, comprehensive, and useful

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

The Q-Submission Guidance

Requests for Feedback on Medical Device Submissions: The Pre-Submission Program and Meetings with FDA Staff

http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM311176.pdf

eCopy Program

The page contains links to Guidance, video, FAQ, and tools, including a validation module

https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/ucm370879.htm

510(k) Database

https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm

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Thank You

Majda Haznadar

Majda.Haznadar@fda.hhs.gov

Slide62

Kristian Roth, Ph.D.

Chief, Bacterial Multiplex and Medical Counter Measures Branch

Division of Microbiology Devices

Office of In Vitro Diagnostics and Radiological Health

Center for Devices and Radiological Health

U.S. Food and Drug Administration

April 4, 2019

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MALDI-TOF MS AND COLONY IDENTIFICATION:

Step 1 2 3

Sample Preparation Measurement

Results

Growth of organism from any specimen source on AGAR media

With CHCA matrixAutomated measurementIn a specific mass range Peak detection

Pattern matching against the database

Slide64

Risk Based Regulatory Framework

www.fda.gov

Risks

Benefits

Goals

:

Get safe and effective devices to market as quickly as possible (premarket review).

Ensure that currently marketed devices remain safe and effective (Total Product Life Cycle (TPLC)).

Slide65

Mass spectrometer for clinical use

§ 862.2860 Mass spectrometer for clinical use. (a)

Identification.

A mass spectrometer for clinical use is a device intended to identify inorganic or organic compounds (e.g., lead, mercury, and drugs) in human specimens by ionizing the compound under investigation and separating the resulting ions by means of an electrical and magnetic field according to their mass.

(b)

Classification.

Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part

807 of this chapter

subject to §

862. 9

.

[52 FR 16122, May 1, 1987, as amended at

65 FR 2309

, Jan. 14, 2000]

Slide66

Class I

Mass spectrometers used in a clinical setting need to be designed and manufactured in compliance with the Quality System Regulations, 21 CFR Part 820 and labeled for IVD use Section 809.10.

NOTE: Risk classification comes from the assay, not the instrument

Slide67

Limitations of Exemption

Sec. 866.9 Limitations of exemptions from section 510(k) of the Federal Food, Drug, and Cosmetic Act

(c) The device is an in vitro device that is intended:

(6) For identifying or inferring the identity of a microorganism directly from clinical material;

Slide68

IVD tests incorporating a MS

Kit reagents (e.g., matrix)

Calibrator

Target slides

Sample Prep Station

Reference database

Software (e.g., acquisition, analysis, middleware)

Mass spectrometer

The test constitutes everything needed to achieve the claims in the Intended Use statement.

Slide69

Challenges

1976-2012 – Single analyte regulation – one 510(k) per analyte

Post-2012 – Multiplex guidance – Syndromic panel approach – 10-20 analytes per 510(k)

2013 MALDI-

ToF

Colony ID – 162 Analytes – Not syndromic – No reliable method to predict reactivity

Slide70

DEN130013

VITEK MS v2.0 System – VITEK MS, v2.0 Knowledge Base, target, prep station, matrices

Mass range - 3,000 - 17,000 Daltons

337 nm nitrogen laser

Fixed acquisition parameters

E. coli

ATCC 8739 is used to as a calibrator

~160 claimed organisms and complexes

Slide71

CORE ELEMENTS FOR PREMARKET SUBMISSION (510(k) or de novo

Intended use/indications for use

Analytical Performance

Reproducibility; Specificity; Sample Stability; Culture Age

Clinical Performance

Challenge Panel and Clinical Isolate testing

Device description (platform, reagents, software)

Labeling (package insert)

Database SOP

Slide72

Analytical Validation Studies

3 site reproducibility with representative organisms

Limit of Detection

Specificity with a closely related panel

Sample stability and culture age

Carryover

100 organism challenge panel

Clinical isolates -

Slide73

Clinical Validation

Testing fresh cultures from patient samples

Comparator method was 16s sequencing and Standard of Care biochemical testing as needed

2256 GP; 3656 GN; 1156 yeast = 7068 total

Levels of evidence vary

Bacteroides fragilis

– 70/71

Staphylococcus epidermidis

– 86/88

Kingella

denitrificans

– 3/3

Slide74

Clinical Validation Data

Slide75

Reporting Results

• A single identification is displayed when one significant organism or group is retained.

• Low Discrimination identifications are displayed when more than one significant organism or organism group are retained, but not for more than 4 organisms.

• When more than 4 organisms or organism groups are found, the organism is considered as non-identified. In this case, a list of possible organisms is displayed and the sum of confidence values is less than 100.

• When no match is found, the organism is considered as non-identified

Non-clinically validated organisms include:

• Organisms with insufficient clinical performance data.

• Organisms not found in human clinical samples as reported in the scientific literature.

Slide76

21 CFR 866.3361. A mass spectrometer system for clinical use for the identification of microorganisms is a qualitative in vitro diagnostic device intended for the identification of microorganisms cultured from human specimens. The device is comprised of an ionization source, a mass analyzer and a spectral database. The device is indicated for use in conjunction with other clinical and laboratory findings to aid in the diagnosis of bacterial and fungal infections.

Class II: Premarket Submission

Slide77

FDA Cleared Devices

SUBMISSION #

PRODUCT

COMPANY

APPROVAL DATE

REGULATION

PRODUCT CODE

DEN130013

VITEK MS

bioMerieux

Inc.

8/21/2013

866.3361

PEX

K130831

MALDI BIOTYPER CA (MBT-CA) SYSTEM

BRUKER DALTONICS INC

11/21/2013

866.3361

PEX

K142677

MALDI Biotyper CA System

BRUKER DALTONICS INC

3/27/2015

866.3361

PEX

K162950

VITEK MS

bioMerieux Inc.

7/22/2017

866.3361

PEX

K163536

MALDI Biotyper CA (MBT-CA) System MBT smart CA System

BRUKER DALTONIK GMBH

7/26/2017

866.3361

PEX

DEN170081

MALDI Biotyper CA (MBT-CA) System MBT smart CA System

BRUKER DALTONIK GMBH

4/20/2018

866.3378

QBN

K181412

VITEK MS

bioMerieux

Inc.

12/21/2018

866.3378

QBN

Slide78

Candida Auris

By 2017 MS had become a critical tool in the microbiology lab

Emerging infections are a significant public health concern and challenge the 510(k) paradigm

How can we quickly address emerging public health needs while ensuring the safety and effectiveness of IVD tests?

Slide79

DEN170081

A path to update device-specific organism reference libraries in the Least Burdensome Manner

www.fda.gov

Slide80

Purpose of De Novo

To facilitate a pathway for updates to established MALDI TOF libraries using a standard SOP for organisms with previously cleared processing methods. Candida auris was chosen because it is an emerging pathogen that is often multidrug-resistant, meaning that it is resistant to multiple antifungal drugs commonly used to treat Candida infections. C.auris isolates were obtained from various culture collections, including the U.S. Centers for Disease Control and Prevention’s and the FDA’s Antibiotic Resistance Isolate Bank. ‘in silico’ testing included a set of 6822 spectra

www.fda.gov

Slide81

Purpose of De Novo-continued

Facilitate a pathway for third parties to create supplemental databases using previously cleared functions that acquire, process and analyze spectra as a legally marketed clinical mass spectrometry MALDI TOF microbial identification.Related Special Control*:Documentation that the manufacturer’s risk mitigation strategy ensures that their device does not prevent any device(s) with which it is indicated for use, including incorporated device(s), from achieving their intended use (e.g., safety and effectiveness of the functions of the indicated device(s) remain unaffected). https://www.accessdata.fda.gov/cdrh_docs/pdf17/DEN170081.pdf

www.fda.gov

Slide82

Highlights of Special Controls

Any sample collection device used must be FDA-cleared, -approved, or -classified as 510(k) exempt with an indication for in vitro diagnostic use.Website to access reference library content or alternative agreed to by FDA

www.fda.gov

https://www.accessdata.fda.gov/cdrh_docs/pdf17/DEN170081.pdf

Slide83

Moving Forward-Intent to Exempt

With this De Novo we plan to write an order to exempt certain mass spectrometry microorganism identification system processes (e.g., pre-analytical steps) from an additional premarket review after a system process receives a first-time FDA marketing authorization (e.g., 510(k) clearance).

In accordance with standard regulatory processes, the agency will first publish a notice in the Federal Register noting our intent to propose the exemption. The FDA will then consider public comments submitted to the Federal Register on this proposal before it is finalized.

Slide84

Intent to Exempt

This exemption from 510(k) for clinical mass spectrometry microbial differentiation system will apply only to those devices that have initially demonstrated acceptable performance within existing or reasonably foreseeable characteristics of commercially distributed devices within that generic type.

A manufacturer of a clinical mass spectrometry microbial differentiation system is

still required to submit a 510(k) to FDA before introducing a device or delivering it for introduction into commercial distribution

when the device meets any of the conditions described in 21 CFR §

Slide85

Use the Pre-Submission Review Program (Pre-Sub)

Free regulatory advice by FDA:

Specific sponsor questions and device IU determine the nature of FDA feedback

Allows informal discussion of potentially complicated questions regarding:

Regulatory pathway

Study design

Not binding

for the FDA or Sponsor

Max 75 day review timeline

Interactive, flexible,

confidential

Slide86

Clear & precise “intended use” (IU)Complete device descriptionScientific evidence supporting the IUData demonstrating safety and effectiveness of the device The known and potential benefits out weigh the known and potential risksGood Mfg. Quality System in place 21 CFR 820 ISO13485Labeling 21 CFR 809.10 (b)

www.fda.gov

Principles of a Successful IVD

Pre-Market Submission

Slide87

510(k)’s Determined to be SE

Slide88

Useful Sources of Information

Search: FDA Device Advice

Overview of IVD Regulationhttps://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/ucm123682.htm De Novo Classification ProcessRequests for Feedback on Medical Device SubmissionsThe pre-submission programClinical Trials and IDE Guidance DocumentsBenefit-Risk Factors to Consider When Determining Substantial Equivalence

Device Advice: Comprehensive Regulatory Assistance - FDA

Slide89

Thank-you!

Kristian.Roth@fda.hhs.gov

Slide90