Improvements in Device Review - FDA

NOVEMBER 2012

Improvements in Device Review Results of CDRH’s Plan of Action for Premarket Review of Devices

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

U.S. FOOD AND DRUG ADMINISTRATION

Improvements in Device Review Results of CDRH’s Plan of Action for Premarket Review of Devices

EXECUTIVE SUMMARY

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.................................................................................................................. I. THE PLAN OF ACTION 5 A. Reevaluation of Premarket Review Program

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B. Actions to Address Unpredictability and Improve Efficiency in Premarket Review

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1. Streamlining premarket review

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a. More efficient review of lower risk products

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b. Increasing reliance on national and international device studies and standards

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c. Reducing the time between approval and coverage

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2. Assuring predictable and consistent decision-making a. Enhancing reviewer training

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b. Providing better, timelier guidance to CDRH staff and industry on the requirements for approval and clearances c. Reducing the time between approval and coverage

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3. Improving the quality of submissions and clinical trial data

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4. Promoting greater transparency, interaction, and collaboration between the FDA and industry during premarket reviews

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5. Improving CDRH’s understanding of new device technologies

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.................................................................................................................. II. ADDITIONAL ACTIONS TO SUPPORT INNOVATION AND IMPROVE THE EFFICIENCY OF PREMARKET REVIEWS 10 A. Innovative Pathway

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B. Entrepreneurs-In-Residence

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C. Incentives for Conducting Clinical Trials in the U.S.

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.................................................................................................................. III. RESULTS OF THE PLAN OF ACTION 12 .................................................................................................................. IV. CONCLUSION 23

Executive Summary

I

n January 2011, the FDA announced a

reversed and is now pointing in the right

Plan of Action to modernize and improve

direction. Because all the negative trends

the FDA’s premarket review of medical

peaked in 2010 and steps to reverse these

devices. In the two years since FDA began

trends began in earnest in 2011, we generally

implementing the plan, the speed and

compared FDA’s performance under the Plan

predictability of device review have improved

against 2010 as the benchmark:

for the first time in almost a decade,

• The average time it takes to clear a 510(k)

including significant reductions in the time it

began declining in 2011, for the first time

takes FDA to review applications and the size

since 2005;

of application backlogs. The United States is the global leader in

• The backlog of 510(k)s pending for more than 90 FDA-days, which increased steadily

medical device innovation. Each year, millions

since 2005, dropped by almost two-thirds,

of American patients benefit from innovative

from its high in 2010;

medical devices that reduce suffering, treat

• The average time it takes to reach a decision

previously untreatable conditions, extend

on a PMA has been reduced by about one-

lives, and improve public health. The Food and

third since 2010; and

Drug Administration (FDA) is committed to a

• Without lowering the bar for clearance

premarket review system that gives American

or approval, the percentage of submitted

patients timely access to safe and effective

510(k)s that are cleared and PMAs that are

medical devices and facilitates innovation in

approved has increased since 2010, indicating

the device industry.

improvements in the quality of applications

To fulfill this commitment, the FDA’s 2011

and the consistency of review standards.

Plan of Action for premarket review includes 36 specific actions, some of which actually

These results have been achieved even

began in 2010, that were designed to increase

though the Plan of Action has not yet been

the predictability, consistency, transparency,

fully implemented. The FDA has met almost

efficiency, and timeliness of device premarket

all of its early implementation timelines. As

reviews. Over the previous decade, important

implementation continues and the impact of

indicators of the efficiency of the FDA’s

the Plan grows over the next several years,

device review program, including the average

the FDA expects our performance on review

length of review and the size of the backlog of

times and reductions in backlogs to continue

overdue applications, had steadily worsened.

to improve. The new process improvements

Since the FDA began implementing the Plan

and resources made available by this year’s

of Action, almost every major indicator has

reauthorization of the Medical Device User

U.S. Food and Drug Administration / Improvement s in Device Review

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Since the FDA began implementing the Plan of Action, almost every major indicator has reversed and is now pointing in the right direction.

Fee Act (MDUFA III) will accelerate the FDA’s

improvements in the efficiency of FDA

ability to make premarket review of devices

review, the industry will be able to bring

predictable, consistent, transparent, efficient,

safe and effective devices to market more

and timely.

quickly and at lower cost, providing better

The major goals of the Plan of Action are

healthcare for Americans. Greater efficiency

to: (1) create a culture change toward greater

and predictability will facilitate innovation,

transparency, interaction, collaboration, and

especially for small and start-up companies

the appropriate balancing of benefits and

which need venture capital to fund their

risks; (2) assure predictable and consistent

development of new technologies. An

recommendations, decision making, and

environment in which innovation can

application of the least burdensome principle;

thrive will in turn help maintain America’s

and (3) implement efficient processes and use

leadership in medical device development

of resources. To achieve these goals, specific

into the future.

initiatives in the Plan of Action focus on:

In addition to the Plan of Action, the FDA

• Streamlining the premarket review process;

has instituted several other programs to

• Making sure that premarket review is

create a supportive environment for device

predictable and decisions are consistent; • Improving the quality of industry

innovation in the U.S: • The Innovation Pathway is designed to bring

submissions and clinical trial data;

safe and effective breakthrough devices to

• Promoting greater interaction, and

market more quickly and at lower cost, in

collaboration between the FDA and industry

part through intense early collaboration

before and during premarket reviews; and

between the FDA and device innovators;

• Improving the FDA’s understanding of new

• The Entrepreneurs-In-Residence program

device technologies.

brings the perspectives of outside entrepreneurs, academics and venture

The turnaround in the length of premarket

capitalists into the FDA to develop strategies

reviews and the decrease in backlogs will

for promoting device innovation and

produce important benefits for patients

streamlining device development and

and the medical device industry. With the

review; and


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The turnaround in the length of premarket reviews and the decrease in backlogs will produce important benefits for patients and the medical device industry.

• The FDA is creating incentives for device

promotes applications with higher-quality

developers to conduct their clinical studies

data while avoiding unnecessary or repeated

first in the U.S.

requests for additional information. These outcomes in turn improve the speed and

Timely patient access to important

predictability of premarket review and result

new technologies and prompt return on

in approval decisions based on valid scientific

investment depend on an efficient FDA

evidence about safety and effectiveness.

approval process. Increasingly, they also

All of the measures described in this report

depend on whether and when insurance

are designed to improve predictability and

carriers decide to reimburse for the use of

efficiency without compromising device

the new technology. The FDA is therefore

safety or effectiveness.

taking steps to improve collaboration with the

None of these changes could have been

Centers for Medicare and Medicaid Services

accomplished without the dedication of

(CMS) before, during and after premarket

the staff of the FDA’s Center for Devices

review with the goal of reducing the time

and Radiological Health (CDRH). Their

between approval and reimbursement of

knowledge, experience, and commitment

innovative devices.

to the public health are essential to the

Even as the FDA takes action to facilitate

FDA’s mission of bringing safe and effective

innovation and streamline premarket review,

medical devices to market. It is their hard

we have an equally important responsibility

work that has made the improvements in

to protect Americans from unsafe and

efficiency and timeliness described in this

ineffective devices. These goals do not have

report possible.

to be in conflict. For example, making sure that FDA staff and industry clearly understand the data required for approval


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I. The Plan of Action A. R eevaluation of Premarket Review Program

industry and the FDA and create delays in

In late 2009, CDRH began a re-evaluation of

It can also make it difficult for small and start-

its premarket review processes for medical

up companies to obtain investors.

devices. The re-evaluation was prompted by

bringing safe and effective products to market.

CDRH found that some of the responsibility

concerns about the premarket review process

for the problems in device review was

raised by industry, consumer groups, health

attributable to the FDA, some to industry, and

plans, health care providers, and the FDA

some to inadequate resources for the size of

employees that included inconsistencies in the

the workload. The main problems included:

premarket review program, negative trends

• Not enough guidance and training for staff

in premarket review times and backlogs, and

and industry on the standards and data

the growing complexity of medical devices

requirements for approval and clearance;

and medical device development. In August 2010, following extensive public input, CDRH released two reports that identified problems

• Too few front-line supervisors and not enough oversight by managers; • Very high reviewer and manager turnover at

in its premarket review processes and

CDRH (almost double that of the FDA’s drug

proposed actions to address their root causes.

and biologics centers);

The first report assessed the 510(k) premarket

• Unnecessary and inconsistent data

review process and the second addressed

requirements imposed on device

CDRH’s use of science in regulatory decisions

manufacturers;

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about devices.

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The biggest problem CDRH found in the premarket review process was

• Poor-quality clinical studies and device applications from some in industry; • CDRH’s rapidly growing workload, caused

unpredictability, including uncertainty

by the increasing complexity of devices, the

about the requirements for approval and the

increasing number and size of submissions,

likely length of the review process, as well

and industry meeting requests; and

as inconsistencies and mid-stream changes in what information was required to obtain

• L ack of adequate and stable funding for the device review program.

approval. When a premarket review process is unpredictable, it can increase costs for

The biggest problem CDRH found in the premarket review process was unpredictability … The Plan of Action is CDRH’s response. U.S. Food and Drug Administration / Improvement s in Device Review

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B. Actions to Address Unpredictability and Improve Efficiency in Premarket Review

such as inadequate staffing and high

The Plan of Action, issued in January 2011,

fee reserve, the increase in user fees under

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reviewer to manager ratios, are not addressed by the Plan. They are instead being addressed through greater expenditures from the user

is CDRH’s response to these findings. The

MDUFA III, and reorganizing CDRH’s

Plan and its update sets forth 36 actions many

premarket review offices.

of which are focused on the major causes of unpredictability. Key initiatives in the Plan are

1. Streamlining premarket review

designed to:

CDRH is taking action to improve the

• Streamline premarket review processes;

efficiency and timeliness of premarket

• A ssure predictable and consistent decision-

review by removing unnecessary regulatory

making;

burdens for well-understood, lower risk

• Improve the quality of submissions and clinical trial data;

devices, allowing the Agency to focus more resources on high-risk products. CDRH is also

• Promote greater transparency, interaction,

increasing use of national and international

and collaboration between CDRH and

standards, and harnessing the ideas of outside

industry before and during premarket

experts recruited to help streamline aspects of

reviews; and

the review process.

• Improve CDRH’s understanding of new device technologies.

a. More efficient review of lower risk products

A second important focus of the Plan is to

• To manage CDRH resources more efficiently

adjust CDRH’s internal culture to be more

and speed review times, CDRH has

open, interactive, and flexible, which is

developed a program to triage 510(k)s as

necessary to get safe and effective devices

they come into CDRH. Rather than assign

to market quickly. Therefore, many of the

510(k)s to reviewers in the order received,

Plan’s initiatives are designed to increase

CDRH will identify submissions eligible

interaction and transparency between

for rapid review, based on factors such as

CDRH and device manufacturers, increase

level of risk and quality of submission, and

CDRH engagement with outside experts, set

conduct reviews of those 510(k)s within 30

expectations for CDRH staff and industry,

days. The program has been successfully

and strengthen CDRH’s ability to adapt

piloted and will be expanded in 2013.

quickly to device innovations.

• Some devices that are considered high-risk

The Plan of Action established rapid

when they are first classified are eligible

deadlines for implementation. These

for reclassification to less restrictive

deadlines have almost all been met.

classifications (down-classification) when

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Some key initiatives of the Plan of Action

experience and data show they actually pose

and their implementation dates are described

lower risks. Down-classification in those

below. Causes of unpredictability and

cases reduces regulatory burdens and speeds

inefficiency that are driven by resources,

premarket review without compromising


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patient safety. In December 2011, CDRH

meet regulatory requirements through

issued guidance describing the FDA’s

less burdensome means, CDRH is drafting

intention not to enforce 510(k) requirements

a guidance on the appropriate use of

for more than 30 Class I and Class II 510(k)

voluntary consensus standards relating to

devices, pending formal down-classification

the safety and effectiveness of devices.

and exemption from 510(k) requirements through rulemaking.5 • To streamline the de novo classification process for devices that are not substantially

c. R educing the time between approval and coverage • Because patient access to novel devices

equivalent to a marketed device, CDRH

often turns on when insurance

issued draft guidance in October 2011. De

reimbursement becomes available, CDRH

novo classification can reduce regulatory

has been working to improve collaboration

burdens for devices that are not substantially

with the Centers for Medicare and

equivalent, but are not high-risk, and special

Medicaid Services (CMS) with the goal of

controls can be developed that make them

reducing the time between FDA approval

appropriate for classification in Class II,

and reimbursement, as well as the cost of

rather than Class III (PMA approval). (The

obtaining a coverage decision. For example,

Food and Drug Administration Safety

CDRH and CMS established a parallel

and Innovation Act amended the de novo

review process to reduce the time between

classification provision but the basic

FDA approval and CMS coverage. Under this

initiative remains intact.)

process, a device company, at its discretion,

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can request that CMS begin its national

b. Increasing reliance on national and international device studies and standards

coverage determination process while the

• To minimize costs to industry and speed

device that is implanted without open-

company’s device is under CDRH review. In the case of a novel heart valve replacement

access to safe and effective devices for U.S.

heart surgery, the FDA worked with CMS

patients, CDRH is drafting a guidance that

during premarket review. The result was a

describes the circumstances under which

“Coverage with Evidence Development”

the Center would rely on clinical studies

decision that relied on an FDA post-

conducted in other countries.

approval study requirement to support

• To work toward implementing international

CMS coverage, rather than requiring the

harmonization of regulatory requirements

company to conduct a separate study to

and information sharing, CDRH has created

support coverage. In addition, one of the

the International Medical Device Regulators

projects of the Entrepreneurs-In-Residence

Forum with other medical device regulators

program is to develop efforts to streamline

around the world, with the ultimate goal of

the approval to coverage pathway. (See

converging device regulatory processes while

section II.B.) We plan to announce the new

improving device safety. The forum has held

actions developed by the Entrepreneurs-in-

two meetings in 2012.

Residence and begin pilot testing, where

• To explain how device developers may

applicable, in Spring 2013.


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2. Assuring predictable and consistent decision-making

documents through development and

CDRH has taken several new actions to make

documents issued in 2011 increased by 22%

sure that its premarket review processes

over 2010; guidance production had already

are predictable and that its decisions are

increased in 2010 over 2009.

consistent. These include:

clearance. The number of guidance

• To clarify key aspects of the standard for clearance of a 510(k), CDRH issued draft

a. Enhancing reviewer training

guidance in December 20118 that will

• Before the Plan of Action, new CDRH

increase consistency in 510(k) decisions and

reviewers learned how to review applications

reduce internal disputes and delays.

mainly by experience. To improve the quality

• To clarify the criteria CDRH uses to

and consistency of reviews, CDRH launched

make benefit-risk determinations during

a mandatory Reviewer Certification Program

premarket reviews, CDRH issued final

in September 2011, combining required

guidance in March 2012 that will increase

courses and auditing of work product. CDRH

consistency and predictability in these

has also implemented new, mandatory

critical assessments.9 As of May 1, 2012,

training for all managers on the skills

the new framework has been applied to all

necessary to be a successful manager.

PMAs and devices going through de novo classification.

b. P roviding better, timelier guidance to CDRH staff and industry on the requirements for approval and clearance.

c. R educing unnecessary and inconsistent data requests • To address unnecessary and inconsistent

Up-do-date guidance to industry and staff on

data requests to industry, CDRH issued

the requirements for approval and clearance

two SOPs. The first SOP, implemented in

is essential to a predictable, efficient review

November 2011,10 makes sure that a request

process. CDRH has taken several actions to

for additional information from CDRH to

improve the speed of guidance development

a device sponsor will not be sent unless

and has begun to issue many new guidance

approved by the appropriate level manager.

documents intended to clarify approval and

The second SOP, implemented in December

clearance standards, including both general

2011,11 strengthens consistency when review

and device-specific guidances.

staff change during the review by requiring

• To streamline CDRH’s guidance

supervisory concurrence for information

development process, CDRH issued a

sought by a new reviewer that is different

standard operating procedure (SOP) in

from what was requested for premarket

August 2011, making it possible to issue

submissions in previous communications.

more guidance for manufacturers and

• To actively monitor the quality and

CDRH staff on approval and clearance

performance of CDRH’s scientific programs

requirements, and to keep guidances

and ensure consistency and predictability

up-to-date. CDRH has also instituted a

in CDRH scientific decision-making, CDRH

tracking system to better manage guidance

established the internal Center Science

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Council in March 2011.12 The Center

are modifications to the device or important

Science Council is an advisory and decision-

new data that necessitate such a change or

making body made up of senior CDRH staff.

other conditions are not met.16

3. Improving the quality of submissions and clinical trial data

5. Improving CDRH’s understanding of new device technologies

• CDRH issued draft guidance in August 2011

• To provide rapid access to scientific,

on how to design good-quality clinical trials

engineering, and medical expertise and

that are likely to support FDA approval.

help reviewers understand new device

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• Most CDRH requests for additional data are

technologies, CDRH successfully piloted a

to address deficiencies the sponsor should

program to develop the Network of Experts

have known how to avoid. Reviewing

from outside the FDA who can be called on

poor quality submissions requires use

by CDRH to help answer scientific questions

of FDA resources that could be more

quickly. Use of the expertise of the network

efficiently spent on complete submissions.

of physicians, scientists, and engineers

In July 2012, CDRH issued draft guidance

will improve the quality and timeliness

explaining the criteria for refusing to file a

of premarket reviews of these devices.17

deficient PMA,14 and, in August 2012, issued

CDRH is currently expanding the program.

draft guidance explaining the criteria for

Already almost 20 health care professional

refusing to accept a deficient 510(k).

and scientific organizations have signed

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agreements to participate.

4. Promoting greater transparency, interaction, and collaboration between the FDA and industry during premarket reviews

• To help reviewers understand the challenges of technology development, manufacture, and use and become informed about specific current and emerging technologies, CDRH

Early, informative meetings and

has begun implementing the Experiential

interactions between CDRH staff and device

Learning Program. The program provides

manufacturers about what data should be in

CDRH reviewers with real-world training

an application increase the predictability of

experiences through visits to manufacturers,

the review process. They also reduce requests

research facilities, and health care facilities.

for additional information, the number of

• The new Center Science Council’s

review cycles, and premarket review times.

responsibilities include incorporation of

• To make pre-submission meetings more

new science and technology into regulatory

useful, CDRH issued a draft guidance in

decision-making across CDRH.18

July 2012 explaining what information applicants and reviewers should provide to each other. It also provided timeframes for scheduling and holding these meetings. The guidance clarified that CDRH would provide written feedback that CDRH anticipates would not change unless there


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II. A dditional Actions to Support Innovation and Improve the Efficiency of Premarket Reviews

A. Innovation Pathway

intensify collaboration between CDRH and

First announced in February 2011, the

innovators early in the device development

Innovation Pathway is part of CDRH’s

process, even before an application is

Innovation Initiative, a program intended

submitted to the FDA. The goal of these new

to help maintain the position of the United

tools and deeper collaboration is to improve

States as the world’s leader in medical

the ability of the Innovation Pathway to make

device innovation. CDRH recognized that

the regulatory process timelier and less costly

breakthrough technologies often present

for cutting-edge medical technology. Outside

scientific and regulatory challenges. The

experts from the Entrepreneurs-In-Residence

Innovation Initiative therefore included the

program helped develop Innovation Pathway

creation of the Innovation Pathway—a new

2.0. (See II. B. below.)

approach for timely review of important

To test drive the new tools in Innovation

new technologies. The Innovation Pathway

Pathway 2.0, CDRH has identified three

is intended to address the barriers that can

investigational devices to treat end-stage renal

impede an innovative device’s path to market,

disease (ESRD), selected from 32 applicants

and reduce the time and cost of device

who responded to a CDRH challenge. CDRH

development, assessment and premarket

will begin to accept additional devices into

review. The first product to use the Pathway

the Innovation Pathway program in the

during its pilot phase was a highly innovative

coming months. The Innovation Pathway

robotic arm prosthesis controlled by a

is also being used as a living laboratory to

microchip implanted in the brain.

rapidly test new approaches to premarket

In April 2012, CDRH launched “Innovation

review. Those approaches that work will be

Pathway 2.0.” Innovation Pathway 2.0 offers

implemented across CDRH’s other device

new decision tools for the review of early

review pathways.

feasibility studies as well as methods to

The goal of the Innovation Pathway is to make the regulatory process timelier and less costly for cutting-edge medical technology.


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The EIR program was initially intended to last six months, but was so successful that CDRH is continuing it. B. Entrepreneurs-In-Residence

requirements, and reducing the length of time

CDRH has created an Entrepreneurs-in-

between FDA approval of devices and their

Residence (EIR) program as part of the

reimbursement by insurers.

Administration’s Strategy for American bring state-of-the-art thinking in business

C. Incentives for Conducting Clinical Trials in the U.S.

processes, device innovation, decision science,

CDRH is creating incentives for device

and information technology to device reviews.

developers to conduct clinical studies first

Under the EIR program, CDRH is harnessing

in the U.S., by streamlining the clinical trial

the ideas of outside experts to support device

(IDE) process, and by providing industry with

innovation and streamline premarket review.

guidance to clarify the criteria for approving

Innovation. The EIR program is designed to

In the first round of the EIR program, CDRH recruited 20 outside entrepreneurs and

clinical trials. • To help manufacturers submit clinical

device innovators from industry, universities,

trials that will support rapid approval,

the venture capital sector, and elsewhere to

CDRH issued draft guidance in August

join CDRH and HHS officials in developing

2011, describing appropriate clinical trial

strategies to support medical device

designs to fulfill premarket clinical data

innovation. Some of the outside experts were

requirements.19

on-site at CDRH either full- or part-time,

• To create incentives to conduct the earliest

working alongside CDRH staff; others made

feasibility studies, including first-in-human

visits to CDRH during their terms. This group

studies, here in the U.S., CDRH issued a

of outside experts helped CDRH develop

draft guidance in November 2011,20 which

and implement the Innovation Pathway

explains when feasibility studies can be

2.0, designed to bring breakthrough devices

conducted earlier in device development.

to market more quickly and at lower cost

The draft guidance also explains how

through intense early collaboration between

device developers may in some cases make

the FDA and device innovators.

successive changes in the design of the

The EIR program was initially intended to last six months, but was so successful in developing Innovation Pathway 2.0 that

device or the study without first seeking additional FDA approval. • A s noted above, experts in the

CDRH is continuing it. In the second round,

Entrepreneurs-In-Residence program

the EIR program is focused on streamlining

are currently working on methods of

clinical trials, striking the right balance

streamlining clinical trials.

between premarket and post-market


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III. Results of the Plan of Action

T

he medical device premarket review

yet know if that trend is changing.) These

programs first began to show signs

positive trends began in 2011, the first year of

of slowing down in 2000 to 2001,

the Plan. We have therefore compared CDRH’s

when the FDA began to see an increase in

performance in the past two years against 2010.

the percentage of PMAs that received a major

• The average time it takes to clear a 510(k)

deficiency letter. This was followed in 2002

began declining in 2011, for the first time

to 2003 with a steady annual increase in

since 2005;

the percentage of 510(k)s for which CDRH

• The backlog of 510(k)s pending for more

made a request for additional information as

than 90 FDA-days, which increased steadily

well as an increase in the average number of

since 2005, dropped by almost two-thirds,

review cycles. In 2004 to 2005, total review

from its high in 2010;

times for PMAs and 510(k)s (including FDA

• The percentage of 510(k)s in which CDRH

and manufacturer time) began to increase.

requested additional information from the

At the same time, there was a decrease in

manufacturer during the first review cycle

the percentage of 510(k)s that resulted in a

has begun to decrease, following a steady

determination of substantial equivalence and

rise from 2002 through 2010;

the percentage of PMAs that resulted in an

• The average time it takes to reach a decision

approval. In addition, the backlogs of overdue

on a PMA has been reduced by about one-

510(k)s and PMAs began to increase.

third since 2010; and

These negative trends continued steadily,

• Without lowering the bar for clearance

peaking for all indicators in 2010, until CDRH

or approval, the percentage of submitted

began to address them comprehensively

510(k)s that receive positive (substantially

through the Plan of Action. In the 2 years since

equivalent) decisions has climbed almost

the Plan began to be implemented, all the

10% from its low in 2010 following a steady

major indicators have reversed for the first time

decline since 2004, and the percentage of

since 2005, with the exception of PMA major

filed PMAs that are approved, which has

deficiency letters. (Given the small number

been declining since 2005, rose 20% from

of 2012 PMAs eligible for analysis, we do not

its low in 2010.

The average time it takes to reach a decision on a PMA has been reduced by about one-third since 2010.


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Chart 1. Average Time to Decision: 510(k)s* (Decisions on 510(k)s received in each FY as of September 30, 2012)

*Substantially Equivalent (SE) and Not Substantially Equivalent (NSE) decisions only, i.e., excludes “Other” decisions such as Withdrawn and Deleted; times may not add to total due to rounding. **Some decisions still pending; FY 2011 cohort is only 98% closed and average times will increase.

As shown in Chart 1, between 2005 and 2010, the average time it took to clear a 510(k)

poor initial submissions. The Plan of Action includes initiatives

steadily rose from 90 days (3 months) to

designed to avoid unnecessary requests

153 days (5 months). This includes the time

for additional data or changes in data

spent by CDRH in review and time spent

requirements and to improve the quality of

by manufacturers in responding to requests

submissions. As a result, the average time it

for additional information. The amount of

takes to clear a 510(k) looks to be stabilizing

time spent by manufacturers in responding

and possibly declining for the first time since

to CDRH requests grew steadily, with some

2005. Both FDA time and manufacturer time

increase in FDA time, resulting in the rise

appear to be stabilizing or decreasing.

in total review time. This increase in the

Because the submissions in prior fiscal

average time to a decision, which is a better

years have not all received a final decision,

measure of premarket review times and is a

it is not possible to calculate the exact

new performance goal under MDUFA III, had

amount of the change for the entire cohort.

several causes, including an increase in the

The dotted lines between 2010 and 2011

number of additional requests for data, mid-

reflect the fact that submissions without a

stream changes in data requirements, and

final decision are not included in the totals.


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When approximately 98% of the 510(k)s received in each fiscal year from 2007 to 2011 had a final decision, the average number of days to a decision decreased. Chart 2. Average Time to Decision: 510(k)s* Comparison when 98% of decisions have been made on the 510(k)s received in an FY

*SE and NSE decisions only; times may not add to total due to rounding.

The next chart provides a more meaningful

2012 510(k) reviews, and therefore does not

comparison to previous fiscal years, by

reveal the most recent trends.

comparing the time-to-decision when

When approximately 98% of the 510(k)s

approximately 98% of the 510(k)s in each

received in each fiscal year from 2007 to 2011

fiscal year cohort from 2007 to 2011 had a

had a final decision, the average number of

final decision. Using the figure of 98% allows

days to a decision decreased from a high of

a valid comparison to FY 2011. By necessity,

147 days in 2010 to 143 days in 2011.

however, it does not include figures for FY

As the number of 510(k)s and the


14

The Plan of Action includes a number of initiatives to make the 510(k) review process more efficient and to clarify the standards for review and clearance. Chart 3. 510(k)s Pending* at End of Year

*Under review or on hold **FY 2012 is as of June 30, 2012

complexity of devices steadily increased, so

for more than 90 FDA-days has now dropped

did the backlog of 510(k)s pending for more

by more than two-thirds (67%), from its high

than 90 days. The Plan of Action includes

of 146 in 2010 to a post-2005 low of 48. The

a number of initiatives to make the 510(k)

total number of 510(k)s pending (though not

review process more efficient and to clarify

overdue) has also dropped 12% from 1,916 in

the standards for review and clearance. As

2010 to 1,682 as of June 30, 2012.

Chart 3 shows, the backlog of 510(k)s pending

A 510(k) for a new device may be cleared


15

The trend has now reversed. In 2011, SE determinations rose to 78% and in 2012, SE determinations rose to 80%. Chart 4. Percentage of 510(k)s Determined to be Substantially Equivalent

if the device is found to be “substantially

initiatives to clarify and provide training on

equivalent” to an already marketed device.

clearance standards for 510(k)s and to improve

When a 510(k) receives a “not substantially

the quality of submissions. For six consecutive

equivalent” (NSE) determination, it may

years the percentage of SE determinations

sometimes be due to correctable deficiencies

steadily decreased, reaching a low of 73% in

in the submission or a misunderstanding of

2010. The trend has now reversed. In 2011, SE

the standards for clearance. In those cases, an

determinations rose to 78% and in 2012, SE

NSE determination represents an inefficient

determinations rose to 80%. This has occurred

use of manufacturer and FDA resources.

without any decrease in the standards for

CDRH’s Plan of Action includes several

clearance, suggesting that the increase may be


16

The percentage of 510(k)s in which CDRH requested additional information from the manufacturer during the 1st review cycle has begun to decrease. Chart 5. Percentage of 510(k)s With Additional Information (AI) Request on 1st FDA Review Cycle

*10 months

due to better quality 510(k) submissions and

stream changes in data requirements, and

more consistent decision making.

poor-quality applications. The Plan of Action

The percentage of 510(k)s in which CDRH

addresses each of those problems and the

requested additional information from the

number of requests for additional information

manufacturer during the 1st review cycle

has now begun to decrease.

has begun to decrease, following a steady

The average number of days between the

rise from 2002 through 2010. The rise in

filing of a PMA and an approval or non-

information requests was caused by the

approval decision (“MDUFA decision”)

increasing complexity of the devices, mid-

increased substantially between FY2003 and


17

As a result, the total time to decision has begun to decrease. Chart 6. Average Time to MDUFA Decision: PMAs* (Decisions on PMAs filed in each FY as of September 30, 2012)

*Includes all filed original PMAs; times may not add to total due to rounding **Some decisions still pending, average times will increase; percent of PMAs with MDUFA decision: FY05=98% (46/47); FY10=98% (42/43); FY11=81% (35/43)

FY2009, from 320 days (10.5 months) to 464

has begun to decrease. It is not possible to

days (15.2 months). Causes for this increase

calculate the exact amount of the decrease

in review times included the increasing

for the entire cohort because the PMAs filed

complexity of the devices, poor-quality

in FY2010 and FY2011 have not all received

applications, necessary and unnecessary

a MDUFAl decision. The next chart provides

requests for additional information, and

a more meaningful comparison of previous

changes in data requirements. The Plan of

fiscal years, looking at the time-to-decision

Action addressed each of these issues. Some

when approximately 81% of the applications

of these efforts began for applications filed

in each cohort had a MDUFA decision. Using

in 2010. As a result, the total time to decision

figure of 81% allows a valid comparison to


18

When approximately 81% of the applications filed in each fiscal year from 2007 to 2011 had a MDUFA decision, the average number of days to a decision decreased 32%. Chart 7. Average Time to MDUFA Decision: PMAs* (Comparison when approx. 81% of decisions have been made on the PMAs filed in an FY**)

*Includes all filed original PMAs; times may not add to total due to rounding **Proportion of decisions made (MDUFA decision): FY07 = 28/35; FY08 = 23/30; FY09 = 26/32; FY10 = 35/43; FY11 = 35/43

FY 2011. By necessity, however, it does not

decreased from a high of 389 days (12.7

allow a comparison to FY 2012 and does not

months) in 2009 to 266 days (8.7 months) in

reveal the most recent trends.

2011, a reduction in review time of almost a

When approximately 81% of the applications filed in each fiscal year from

third (32%). The number of PMAs pending at the end

2007 to 2011 had a MDUFA decision,

of the year does not necessarily represent a

the average number of days to a decision

backlog, since a number of them may not be


19

The Plan of Action includes several initiatives to improve the efficiency of the PMA review process, including better allocation of review resources and reducing unnecessary data requests. Chart 8. PMAs Pending * at End of Year (Comparison when approx. 81% of decisions have been made on the PMAs filed in an FY**)

*All original PMAs under review or on hold

overdue. Regardless, the increase in pending

and make sure that review decisions are

PMAs from 2007 to 2010 points to the risk

consistent. As a result, the number of

of an increase in overdue PMAs and to

pending PMAs has begun to decrease for the

inefficiencies in the review process. The Plan

first time in six years.

of Action includes several initiatives to clarify

The number of PMAs for which a major

how benefits and risks should be weighed in

deficiency letter was sent to the manufacturer

a PMA, improve the quality of applications,

began to increase in 2000 and peaked in 2010.


20

The Plan of Action includes several initiatives to clarify how benefits and risks should be weighed in a PMA, improve the quality of applications, and make sure that review decisions are consistent.

Chart 9. Percentage of PMAs with Major Deficiency Letter on 1st FDA Review Cycle*

*Includes all filed original PMAs (1st cycle completed for all cohorts) **10 months

It began to decrease in 2011, but early data in

approved began declining in 2005, when

2012 appear to show a small increase. Given

the FDA approved 90% of filed PMAs, and

the small number of 2012 PMAs currently

reached a low of 59% in 2010. CDRH’s

eligible for analysis, we will not be able to

Plan of Action includes several initiatives

identify the trend until the set of PMAs filed

to clarify how benefits and risk should be

in 2012 is more complete.

weighed in a PMA, and improve the quality

The percentage of filed PMAs that are

 

of applications, and to make sure that review


21

Since 2010, the percentage of filed PMAs that are approved has risen to 70%. This has occurred without any decrease in the standards for approval. Chart 10. Percentage of PMA’s Approved*

**Based on original PMAs that were accepted for filing

decisions are consistent. Since 2010, the

suggesting that the increase may be due

percentage of filed PMAs that are approved

to better quality applications and more

has risen to 70%. This has occurred without

consistent decision making.

any decrease in the standards for approval,


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IV. Conclusion

T

he United States is the global leader

is now pointing in the right direction for the

in medical device innovation. Each

first time in many years.

year, millions of American patients

Although many challenges remain, the

benefit from innovative medical devices that

turnaround in the length of premarket

reduce suffering, treat previously untreatable

reviews and the decrease in backlogs will

conditions, extend lives, and improve public

produce important benefits for patients

health. The FDA is committed to a premarket

and the medical device industry. With the

review system that gives American patients

improvements in the predictability and

timely access to safe and effective medical

efficiency of FDA review as a result of the

devices and sustains innovation in the device

Plan of Action and MDUFA III, the industry

industry.

will be able to bring safe and effective devices

The FDA’s Plan of Action to modernize

to market more quickly and at lower cost,

and improve the FDA’s premarket review of

providing better healthcare for Americans.

medical devices has successfully increased

Greater efficiency and predictability will

the predictability, consistency, transparency,

create a foundation for innovation, especially

efficiency, and timeliness of premarket

for small and start-up companies that need

review. Over the previous decade, important

venture capital to fund their development

indicators of the efficiency of the FDA’s

of new technologies. An environment in

device review program, including the average

which innovation can thrive will in turn help

length of review and the size of the backlog of

maintain America’s leadership in medical

overdue applications, had steadily worsened.

device development into the future.

Since the FDA began implementing the Plan, almost every major indicator has reversed and

1. CDRH Preliminary Internal Evaluations — Volume I: 510(k) Working Group Preliminary Report and Recommendations, August 2010. Available online at: http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDRH/CDRHReports/ ucm220272.htm. 2. C DRH Preliminary Internal Evaluations — Volume II: Task Force on the Utilization of Science in Regulatory Decision Making Preliminary Report and Recommendations, August 2010. Available online at: http://www.fda.gov/AboutFDA/CentersOffices/ OfficeofMedicalProductsandTobacco/CDRH/CDRHReports/ucm220272.htm. 3. CDRH Plan of Action for 510(k) and Science Recommendations. Jan. 2011. Available online at: http://www.fda.gov/downloads/ AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDRH/CDRHReports/UCM239450.pdf. 4. C DRH, Accomplishments: CDRH Plan of Action for 510(k) and Science. Available online at: http://www.fda.gov/AboutFDA/ CentersOffices/OfficeofMedicalProductsandTobacco/CDRH/CDRHReports/ucm276286.htm. 5. Enforcement Policy for Premarket Notification Requirements for Certain In Vitro Diagnostic and Radiology Devices, Dec. 20, 2011. Available online at: http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ UCM283948.pdf. 6. FDA, Draft Guidance for Industry and Food and Drug Administration Staff - De Novo Classification Process (Evaluation of Automatic Class III Designation), Oct. 3, 2011. Available online at: http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/ GuidanceDocuments/ucm273902.htm.


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7. CDRH, Guidance Development, August 1, 2011. Available online at: http://www.fda.gov/downloads/MedicalDevices/ DeviceRegulationandGuidance/GuidanceDocuments/UCM266073.pdf. 8. FDA, Draft Guidance for Industry and Food and Drug Administration Staff - The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications [510(k)], December 27, 2011. Available online at: http://www.fda.gov/MedicalDevices/ DeviceRegulationandGuidance/GuidanceDocuments/ucm282958.htm. 9. FDA, Factors to Consider When Making Benefit-Risk Determinations in Medical Device Premarket Approval and De Novo Classifications, Mar. 28, 2012. Available online at: http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/ GuidanceDocuments/UCM296379.pdf. 10. CDRH, SOP: Decision Authority for Additional or Changed Data Needs for Premarket Submissions, Nov. 9, 2011. Available online at: http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDRH/CDRHReports/ucm279288.htm. 11. CDRH, SOP: Management of Review Staff Changes During the Review of a Premarket Submission. Dec. 27, 2011. Available online at: http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDRH/CDRHReports/ucm285034.htm. 12. C DRH Center Science Council FAQs, Mar. 31, 2011. Available online at: http://www.fda.gov/AboutFDA/CentersOffices/ OfficeofMedicalProductsandTobacco/CDRH/CDRHReports/ucm249249.htm. 13. FDA, Draft Guidance for Industry, Clinical Investigators, and Food and Drug Administration Staff - Design Considerations for Pivotal Clinical Investigations for Medical Devices, Aug. 15, 2011. Available online at: http://www.fda.gov/MedicalDevices/ DeviceRegulationandGuidance/GuidanceDocuments/ucm265553.htm. 14. F DA, Draft Guidance for Industry and Food and Drug Administration Staff : Acceptance and Filing Review for Premarket Approval Applications (PMAs), Jul. 31, 2012. Available online at: http://www.fda.gov/downloads/MedicalDevices/ DeviceRegulationandGuidance/GuidanceDocuments/UCM313368.pdf. 15. FDA, Draft Guidance for Industry and Food and Drug Administration: Refuse to Accept Policy for 510(k)s, Aug. 13, 2012. Available online at: http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM315014.pdf. 16. FDA, Draft Guidance for Industry and FDA Staff: Medical Devices: The Pre-Submission Program and Meeting with FDA Staff, July 13, 2012. Available online at: http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm310375.htm. 17. FDA, Network of Experts- Expert Utilization Standard Operating Procedure (DRAFT), Oct. 4, 2011. Available online at: http://www. fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDRH/CDRHReports/ucm271521.htm. 18. CDRH Center Science Council Charter, Jun. 8, 2012. Available online at: http://www.fda.gov/AboutFDA/CentersOffices/ OfficeofMedicalProductsandTobacco/CDRH/CDRHReports/ucm249248.htm. 19. F DA, Draft Guidance for Industry, Clinical Investigators, and Food and Drug Administration Staff: Design Considerations for Pivotal Clinical Investigations for Medical Devices, Aug. 15, 2011. Available online at http://www.fda.gov/MedicalDevices/ DeviceRegulationandGuidance/GuidanceDocuments/ucm265553.htm. 20. FDA, Draft Guidance for Industry and Food and Drug Administration Staff - Investigational Device Exemptions (IDE) for Early Feasibility Medical Device Clinical Studies, Including Certain First in Human (FIH) Studies, Nov. 10, 2011. Available online at http:// www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm277670.htm.

U.S. Food and Drug Administration / Improvements in Device Review

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