510(k) workshop FINAL - Hogan Lovells · 510(k) Workshop Strengthening the ... • FOIA process can...

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510(k) Workshop510(k) Workshop

Strengthening the Center for Strengthening the Center for Devices and Radiological HealthDevices and Radiological Health’’s s

510(k) Review Process510(k) Review Process

February 18, 2010

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Issues Related to Predicate Issues Related to Predicate DevicesDevices

Christy ForemanDeputy Director for Science and Regulatory Policy

Office of Device EvaluationCenter for Devices and Radiological Health

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Issues Related to Predicate Devices

Background:• The basis for the 510(k) process is a

determination regarding substantial equivalence to a predicate device.

• Available knowledge about the preamendment device established safety and effectiveness for the device type at the time of initial classification.

• SE determination means that the device is at least as safe and effective.

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Challenges: Manufacturers May Lack Sufficient Information to Select an Appropriate Predicate

• FDA provides information on our website – can this be improved?

• FOIA process can be slow and only provides redacted information

• 510(k) summaries often lack critical details• 510(k) statements rely on manufacturer responses which can

be difficult for FDA to police• Firm’s promotional material may not reflect what was actually

cleared and information submitted to FDA may be inaccurate• Product code process lacks transparency

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Challenges: “Old” Predicate Devices• How can the program effectively and

efficiently evolve if devices from 1976 set the bar for comparison?

• How can the agency deal with predicate devices with sub-par performance compared to the other devices in the class? Most tools available to FDA to rectify these predicates are labor- and time-intensive.

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Challenges: Incremental Design Changes and Device Creep

• Modifications to 510(k) devices are often not submitted unless it is a one that could significantly affect safety or effectiveness or it is a modification in intended use

• Equivalence studies allow for “not much worse than” – over time this can allow device performance to deteriorate

• Incremental changes over time may collectively be significant• Current 510(k) may or may not “catch up” design• Comparative performance may be based on marketed device

rather than cleared device

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Challenges: Split and Multiple Predicates• When is it appropriate to use more than

one predicate?• Using intended use from one device and

the technology from another creates problems in assessing substantial equivalence (SE)

• Difficult to assess SE when predicate is from a different device panel/regulation

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Challenges: Indications versus Intended Use• Lack of clarity on the distinction between

indications and intended use• Lack of clarity leads to program inconsistencies• Lack of regulatory definitions for terms• What information serves as the basis for

establishing indications and intended use?• Prior to the required IFU form, determining

indications can be difficult in older submissions• General to specific interpretation issues (and

vice versa)




February 18, 2010


Issues Related to New Issues Related to New Technologies and Scientific Technologies and Scientific

EvidenceEvidence

Arleen PinkosScientific Reviewer

Office of In Vitro Diagnostic Device Evaluation and SafetyCenter for Devices and Radiological Health

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Background513(i) of the FDCA

(1)(A) …"substantial equivalence" means…

• same intended use….• same technological characteristics as the

predicate device …

OR

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Background513(i) of the FDCA

(1)(A) …"substantial equivalence" means…

• has different technological characteristics and the information includes appropriate clinical or scientific data

• does not raise different questions of safety and effectiveness

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Challenges

Two primary challenges:• Determining what type and the extent of evidence that is

needed to make a decision • Decision making

Road map:• Example to demonstrate several of the challenges• Other issues:

• New technologies• Off-label use• Manufacturing • De Novo

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ExampleSurgical Robotic System

• Endoscope - visual exploration• Incorporate simple instruments to

manually perform simple surgical procedures

• Higher resolution images added• More sophisticated instruments (e.g.,

lasers) to perform more complicated procedures (e.g., organ removal)

• Robotics added

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Evidence Required

• Indications for Use - is a general or specific claim appropriate?

• New technologies - when do they raise a different type of safety and effectiveness question?

• How do incremental changes effect the services provided to the patient?

• Evidence needed?• Bench studies• Animal studies• Human clinical trials- most often needed when:

• We can’t predict the outcome• Changes might alter clinical effectiveness• Might lead to a new clinical practice

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Evidence Required

• When is it necessary to demonstrate the clinical utility?

• How should FDA interpret clinical studies?• How can FDA provide assurance that the

device will perform as intended in real-world use?

• How should FDA deal with poorly designed studies after the fact?

• Substantially Equivalent - To what?

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Other Issues

• Technological differences• Off-label use• Manufacturing• Evaluation of Automatic Class III

Designation (de Novo Process)

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Technological Differences

Examples of situations when clinical studies may be needed:• Nanotechnology - may impact safety and

effectiveness, or the impact of the change may be unknown

• Algorithms - statistical modeling where calculations are used to provide clinical diagnosis, screening, etc.

What criteria should be used?• When is a device different enough that it should no

longer be a 510k?• When are the questions that are raised different

enough?

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Off-label Use• 513(i)(1)(E) of the FDCA addresses curbing of off-label

use• SE determinations about intended use are based on proposed

labeling• Unless FDA believes there is a likelihood that it will be used for

another purpose, and• That use could cause harm

• FDA may require a statement in the labeling which provides information about that off-label use (SE with limitations)

• Sponsors often pursue and get clearance for a “narrow” claim when it is obvious they’re interested in something else

• Ineffectiveness of using labeling to address risks of off-label use:• May encourage off-label use• Users often do not see the labeling

• More appropriate to ask for the right studies?

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Manufacturing IssuesConstraints on 510(k) Program

GMPs may not be part of the SE decision (Section 513(f)(5) of the FDCA) unless… “substantial likelihood that such failure will potentially present a serious risk to human health”

• Impacts• Ability to have a pre-clearance inspection of the facility• Manufacturing information may not be in the 510(k)

• Detailed engineering information about device design • Lot release criteria - assures on-going quality

• Majority of recalls are due to manufacturing and design control problems

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Evaluation of Automatic Class III Designation Process (de Novo)

The de Novo Petition Process (down-classification process for devices without a predicate)

• Determination of • Low or moderate risk• Adequate evidence about its safety and effectiveness

• Determination of the appropriate degree of regulation• General controls• Special controls

• What type of criteria are appropriate?




February 18, 2010


Issues Related to the Following Issues Related to the Following Types of Submissions: Bundled, Types of Submissions: Bundled, 33rdrd Party, and Submissions which Party, and Submissions which

Contain StandardsContain Standards

Barbara ZimmermanDeputy Director for Premarket Program Management


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Issues Related to Bundling

Background:

• Two types:• Bundled Submissions

• E.g. similarly designed dental implants• Bundled Devices

• E.g. bedside monitors with multiple parameters (heart rate, arrhythmia detection, NIBP)

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Issues Related to Bundling

Challenges:

• Timeline• Bundling across:

• Review Divisions• Indications for Use• Regulations

• Difficult to identify bundled products after clearance

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Issues Related to the Use of Standards

Background:• Standards are used to streamline the review

process for FDA and Industry

Agency Resources:• FDA Recognized Consensus Standards

Database• Standards Data Report (Form 3654)

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Background:• Guidance: Use of Standards in Substantial

Equivalence Determinationshttp://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM073756.pdf

• Guidance: Recognition and Use of Consensus Standardshttp://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm077274.htm

• Guidance: Frequently Asked Questions on Recognition of Consensus Standardshttp://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm074973.htm

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Challenges:• Lack of verification of stated conformity to

standards• Many standards do not contain objective

pass/fail criteria or performance limits• Inconsistencies in the use of consensus

database (e.g. not using the appropriate standard or not using the most recent recognized version)

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Challenges:

• Use of Form 3654• not a declaration of conformity document• validates the “Extent of Recognition” was

followed and any deviations

• How to appropriately declare conformity to a standard

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Issues Related to 3rd Party Review

Background:• Accredited Parties established ~1996• An alternative route for 510(k) review• Intended to speed the 510(k) review

process and to help FDA manage its large 510(k) workload

• Approximately 300 applications (8%) are submitted each year

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Issues Related to 3rd Party Review

Challenges:• Poor quality submissions

• most 3rd-party-eligible devices do not have a device-specific guidance

• Accredited Parties do not have access to previous decision/reviews of the device type




February 18, 2010

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Issues Related Postmarket Issues Related Postmarket Surveillance and New Information Surveillance and New Information

about Marketed Devicesabout Marketed Devices

Heather S. RosecransDirector, 510(k) Staff


Issues Related to Postmarket Surveillance and New Information

Background: • FDA’s postmarket controls for 510(k)

devices are limited• Changes to a cleared device subject to

510(k) require a new 510(k) or the firm’s documentation to the file as to why a 510(k) is not needed

• It is difficult to fix/modify or remove a cleared 510(k)

Challenges: FDA’s authority to mandate postmarket surveillance studies after SE determination is limited

• If information collected under a postmarket study suggests significant safety and effectiveness issues, difficult to apply to device and previously cleared devices

• Unlike PMAs, there is no explicit authority for FDA to require a “condition of approval” study for clearance of a 510(k) device



Challenges: FDA has limited authority to rescind 510(k) clearance

• In the absence of a robust rescission authority, it is difficult for FDA to address problematic predicates

• Situations that have led to rescission include:• False information material to the SE has been

discovered• New information has shown the device may have

significant safety and effectiveness problems• Concerns about the “domino effect” of a rescission for the

predicates• FDA proposed a 510(k) rescission regulation in 2001

Challenges: FDA collects postmarket information on 510(k) device types, but how should it impact future 510(k) review?

• How should postmarket information be applied to devices under review?• Issues relating general postmarket

information to specific devices• “Level playing field” issue


Challenges: Final printed labeling is not required prior to an SE determination for a 510(k)

• 510(k) holders change the labeling from the draft submitted in the 510(k)

• Initial burden is on a 510(k) holder to determine if the change to labeling requires a new 510(k) or not

• For exempt devices, FDA does not routinely review even draft labeling


Challenges: FDA does not require the purchase, sale, or transfer of ownership of a 510(k) be reported to FDA

• Difficult for FDA to investigate adverse events, assign inspections and take appropriate enforcement actions

• Difficult for FDA to verify changes in ownership reported voluntarily

• Over 120,000 cleared 510(k)s

Issues Related to Postmarket and Ne Surveillance w Information

Summary

• Increasing transparency is essential.• Achieving consistency is critical.• Developing clear definitions, guidance,

and additional authorities may be required.• Utilizing rational application of guiding

principles is vital.

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