FDA MEDICAL 

DEVICE REVIEWS

Evaluation is Needed 

to Assure Requests 

for Additional 

Information Follow a 

Least Burdensome 

Approach 

Report to Congressional Requestors

December 2017

GAO-18-140

United States Government Accountability Office
United States Government Accountability Office

Highlights of GAO-18-140, a report to 

congressional requestors

December 2017

FDA MEDICAL DEVICE REVIEWS

Evaluation is Needed to Assure Requests for 

Additional Information Follow a Least Burdensome 

Approach

What GAO Found

Since 1997, the Food and Drug Administration (FDA) has been required to 

consider the least burdensome means of evaluating certain types of medical 

devices for marketing, including when requesting that sponsors—generally 

manufacturers—seeking to market their medical devices provide information in 

addition to what was provided in their submissions. GAO found that, from 2001 

through 2016, FDA issued letters asking sponsors to provide such information for 

a majority of the more than 62,000 medical device submissions that it reviewed. 

Sponsors may formally disagree with the request on the grounds that it is not the 

least burdensome method needed for FDA to review the submission. For 

example, sponsors appealed FDA decisions internally to agency management 

63 times from 2013 through 2016, and of these, FDA identified 33 such appeals 

in which the sponsor raised an issue related to least burdensome requirements.

FDA agreed or partially agreed with the sponsors in 11 of these appeals. Medical 

device industry representatives noted that these appeals may not fully represent 

the number of such disagreements, because applicants are generally concerned 

that an appeal would damage their relationship with FDA and potentially 

negatively affect future device applications.

FDA provided staff training that was specifically dedicated to addressing the 

least burdensome requirements from 1997 through 1999. Since 1999, FDA has 

not offered a course dedicated to the least burdensome requirements, but has 

incorporated related concepts into other training programs, such as in a training

mandatory for most new reviewers. In response to the 21st Century Cures Act, 

enacted in 2016, FDA is providing new least burdensome training to all relevant 

employees, and said that 80 percent had received the training as of October 2, 

2017. Although FDA did not specifically evaluate the effectiveness of past

training on least burdensome requirements, it is implementing an evaluation of 

all device-related training, including the new least burdensome training. It also 

plans to complete a required audit of training on least burdensome requirements 

by June 2018.

FDA has not specifically evaluated implementation of the least burdensome 

requirements. However, in response to broader evaluations, such as an 

independent assessment of its medical device review process, the agency is in 

the early stages of developing processes that may improve its requests for 

additional information. For example, FDA plans to conduct an audit of letters 

requesting additional information. FDA is developing the audit’s methodology 

and expects it will assess whether the agency’s process was followed. However, 

due to their early stage, the extent to which these efforts will allow FDA to assess 

implementation of the least burdensome requirements is unclear. In 2002, FDA

stated that it planned to periodically assess the implementation of the least 

burdensome principles, and federal internal control standards identify the 

importance of performance metrics for such assessments. However, the agency 

has yet to develop performance metrics to do so. Until such measures are 

developed and used, FDA will not be able to evaluate whether it effectively and 

View GAO-18-140. For more information, consistently applies a least burdensome approach in its medical device reviews.

contact Marcia Crosse at (202) 512-7114 or

crossem@gao.gov. 

Why GAO Did This Study

Determining that a new medical device 

is safe and effective is a substantial 

investment of time and resources for 

the sponsor and FDA, the agency that 

regulates medical devices. FDA relies 

on the device sponsor to provide 

supporting data at the time of its 

original submission, and the agency 

can request additional information 

during the review. The Federal Food, 

Drug, and Cosmetic Act, as amended, 

requires that when FDA requests 

additional information from sponsors, 

the agency consider the least 

burdensome means of evaluating a 

medical device.

GAO was asked to provide information 

on FDA’s implementation of the least 

burdensome requirements in its 

medical device review process. This 

report (1) describes FDA’s requests for 

additional information and sponsor 

disagreements, (2) describes its least 

burdensome training efforts, and (3) 

describes FDA actions to improve its 

requests for additional information and 

examines the extent to which it has 

evaluated its implementation of the 

least burdensome requirements. GAO 

reviewed FDA documents and 

guidance and interviewed agency 

officials. GAO also interviewed officials 

from four relevant medical device 

manufacturing associations. 

What GAO Recommends

GAO is making one recommendation

that FDA develop and use 

performance metrics to evaluate the 

implementation of the least 

burdensome requirements. The 

Department of Health and Human 

Services agreed with GAO’s 

recommendation.
Page i GAO-18-140 Least Burdensome Medical Device Approvals

Letter 1

Background 5

FDA Frequently Requested Additional Information to Support 

Medical Device Reviews, and Sponsor Disagreements Often 

Related to Least Burdensome Requirements 14

FDA Offered Some Training on the Least Burdensome 

Requirements, and Evaluates its Training for Effectiveness 19

FDA is Taking Steps that May Improve Its Requests for Additional 

Information Overall, but Has Not Fully Evaluated Its 

Implementation of the Least Burdensome Requirements 23

Conclusions 28

Recommendation for Executive Action 29

Agency Comments 29

Appendix I Comments from the Department of Health and Human Services 31

Appendix II GAO Contact and Staff Acknowledgments 36

Table

Table 1: Medical Device Submissions Received and FDA 

Requests for Additional Information, 2001 through 2016 16

Figures

Figure 1: Original Medical Device Premarket Applications 

Approved by FDA, 2001 to 2016 6

Figure 2: 510(k) Medical Device Notifications Cleared by FDA, 

2001 to 2016 8

Contents
Page ii GAO-18-140 Least Burdensome Medical Device Approvals

Abbreviations

AI additional information 

CDRH Center for Devices and Radiological Health

FDA Food and Drug Administration

FDAMA Food and Drug Administration Modernization Act of 1997

HHS Department of Health and Human Services

MDUFA III Medical Device User Fee Amendments of 2012

MDUFA IV Medical Device User Fee Amendments of 2017

PMA premarket approval

This is a work of the U.S. government and is not subject to copyright protection in the 

United States. The published product may be reproduced and distributed in its entirety 

without further permission from GAO. However, because this work may contain 

copyrighted images or other material, permission from the copyright holder may be 

necessary if you wish to reproduce this material separately.
Page 1 GAO-18-140 Least Burdensome Medical Device Approvals

441 G St. N.W.

Washington, DC 20548

December 15, 2017

The Honorable Lamar Alexander

Chairman

Committee on Health, Education, Labor, and Pensions

United States Senate

The Honorable Richard Burr

United States Senate

The Food and Drug Administration (FDA), within the Department of 

Health and Human Services (HHS), is responsible for ensuring that 

medical devices sold in the United States provide reasonable assurance 

of safety and effectiveness and do not pose a threat to public health.1

Making this determination represents a substantial investment of time and 

resources for both FDA and the device sponsor, generally the 

manufacturer. For example, in 2014, FDA reviewed about 4,100 

submissions from sponsors seeking to market their medical devices, and 

each review ranged from an average of 125 days for lower-risk devices to 

an average of 330 days for higher-risk devices.2 In making its 

assessment, FDA relies on the sponsor to provide supporting data at the 

time of its initial premarket submission and may thereafter request 

additional data in the course of the review to obtain sufficient evidence 

supporting the safety and effectiveness of the medical device. However, 

any request for additional information has the potential to impose undue 

burden on the sponsor and delay the review of the device, and sponsors 

may opt to formally disagree with the necessity of the requested 

information.

Given the resource investment involved in getting a medical device to 

market, as well as the public health need, efforts have been made to 

streamline the decision-making process without compromising scientific 

 1

Medical devices range from simple tools, such as bandages and surgical clamps to 

complicated devices, such as pacemakers. Generally, medical devices include items used 

for the diagnosis, cure, mitigation, treatment, or prevention of a disease. See 21 U.S.C. § 

321(h). Throughout this report, the term device refers to a medical device that is not being 

regulated as a drug or a biological product.

2

Review times are for fiscal year 2014, the most recent data available. FDA, FY 2016 

Performance Report to Congress for the Medical Device User Fee Amendments (Silver 

Spring, Md.: September 2016).

Letter
Page 2 GAO-18-140 Least Burdensome Medical Device Approvals

integrity or FDA’s ability to protect the public health. For example, 

Congress has already taken several steps to reduce unnecessary 

burdens associated with the medical device review process. For certain 

types of premarket submissions, federal law requires FDA to utilize the 

“least burdensome” means possible in certain elements of the review 

processes of medical devices.3 FDA has laid out broad principles in 

guidance interpreting how those statutory provisions apply throughout its 

reviews.4 In 2016, Congress required FDA to provide training for 

appropriate staff on the meaning and implementation of the statutory least 

burdensome requirements and conduct periodic assessments of 

implementation to ensure that the least burdensome requirements are 

fully and consistently applied.

5

You asked us to provide information on FDA’s implementation of the least 

burdensome requirements, as well as any training FDA has done to 

ensure staff are aware of the statutory requirements. This report

1. describes FDA requests for additional information to support medical 

device reviews and how least burdensome requirements were related 

to sponsor disagreements about these requests,

2. describes FDA efforts to ensure that its employees are trained on the 

least burdensome requirements, and

3. describes the steps FDA has taken to improve its requests for 

additional information and examines the extent to which it has 

evaluated its implementation of the least burdensome requirements.

To describe FDA requests for additional information to support medical 

device reviews and how least burdensome requirements were related to 

sponsor disagreements about these requests, we analyzed agency 

documents, such as FDA’s guidance for industry and staff on the least 

burdensome provisions and FDA’s annual performance reports. For fiscal 

year 2001 through fiscal year 2016, the years for which FDA had reliable 

data, we analyzed counts of medical device submissions received and 

reviewed by FDA, as well as FDA’s requests for additional information 

 3

See 21 U.S.C. §§ 360c(a)(3)(D)(ii), 360c(i)(1)(D)(i)), 360e(c)(5).

4

See Food and Drug Administration, The Least Burdensome Provisions of the FDA 

Modernization Act of 1997: Concept and Principles; Final Guidance for FDA and Industry 

(Rockville, Md.: Oct. 4, 2002).

5

See 21st Century Cures Act, Pub. L. No. 114-255, § 3058(a), 130 Stat. 1033, 1128 (2016) 

(codified at 21 U.S.C. § 360c(j)).
Page 3 GAO-18-140 Least Burdensome Medical Device Approvals

from medical device sponsors. We also reviewed internal appeals and 

disputes of FDA decisions submitted by sponsors that FDA identified as 

being related to the least burdensome requirements. Information on 

internal appeals was limited to the period from May 2013 through fiscal 

year 2016.6 To assess the reliability of data FDA provided, we interviewed 

knowledgeable agency officials, conducted quality checks to identify any 

obvious errors, and compared the detailed data FDA provided to us with 

summary data that FDA had publicly reported on its website. We 

determined these data were sufficiently reliable for the purposes of our 

reporting objective. We also reviewed a non-generalizable sample of 

requests for additional information FDA issued to sponsors during the 

medical device review process.7 We interviewed FDA officials from the 

Center for Devices and Radiological Health (CDRH) responsible for 

reviewing medical devices. We also interviewed representatives of the 

medical device industry to obtain the industry’s perspectives on how the 

least burdensome provisions have been involved in FDA’s requests for 

additional information.8

To describe FDA efforts to ensure that its employees are trained on the 

least burdensome requirements, we asked FDA to identify any training 

activities for medical device review staff that related to the least 

burdensome requirements since they were first established with the 

enactment of the Food and Drug Administration Modernization Act of 

 6

FDA officials told us that, prior to May 2013, the agency did not have a formal 

mechanism to track internal appeals of significant decisions and, accordingly, did not have 

a comprehensive list of such appeals.

7

We reviewed a sample of 73 requests—known as deficiency letters or additional 

information (AI) letters—that FDA issued from 1997 through 2016. To obtain examples 

across years and FDA review types, we asked FDA to provide at least 2 letters from each 

year 1997 through 2016, with at least 1 related to a premarket approval (PMA) and 1 

related to a premarket notification, known as a 510(k), from each year. Medical devices 

are generally subject to one of two types of FDA premarket review processes. The PMA 

process, the most stringent type of premarket review, requires the sponsor to submit 

evidence providing reasonable assurance that the new device is safe and effective. The 

510(k) process requires the sponsor to demonstrate to FDA that the new device is 

substantially equivalent to a device already legally on the market, and therefore, does not 

require a PMA.

8

We interviewed representatives from four organizations that represented the medical 

device industry during its discussions with FDA: The Advanced Medical Technology 

Association, the Medical Device Manufacturers Association, the American Clinical 

Laboratory Association, and the Medical Imaging and Technology Alliance.
Page 4 GAO-18-140 Least Burdensome Medical Device Approvals

1997 (FDAMA).9 For certain of those activities, we examined the specific 

course materials so we could further illustrate how these materials 

referred to the least burdensome requirements. We also reviewed 

documentation describing FDA evaluations of this training, as well as 

planned evaluations. We interviewed FDA officials about how training on 

the least burdensome requirements had changed and about the planned 

changes to least burdensome training and training evaluations.

To describe the steps FDA has taken to improve its requests for 

additional information and examine the extent to which it has evaluated its 

implementation of the least burdensome requirements, we reviewed 

relevant statutes and guidance that set out relevant requirements for both 

reviewers and sponsors outlining FDA’s implementation of the least 

burdensome requirements and its plans for evaluation of that 

implementation. We also reviewed documentation describing, and spoke 

with relevant FDA officials about, performance metrics that the agency 

uses to monitor its implementation of the least burdensome requirements 

and evaluations the agency had conducted or planned to conduct. We 

compared the extent to which FDA has evaluated its implementation of 

the least burdensome requirements with federal standards for internal 

control.10

We conducted this performance audit from November 2016 to December 

2017 in accordance with generally accepted government auditing 

standards. Those standards require that we plan and perform the audit to 

obtain sufficient, appropriate evidence to provide a reasonable basis for 

our findings and conclusions based on our audit objectives. We believe 

that the evidence obtained provides a reasonable basis for our findings 

and conclusions based on our audit objectives.

 9

Pub. L. No. 105-115, 111 Stat. 2296 (1997) (codified as amended at 21 U.S.C. §§ 301 et 

seq.).

10GAO, Standards for Internal Control in the Federal Government (GAO-14-704G). 

Internal control is a process effected by an entity’s oversight body, management, and 

other personnel that provides reasonable assurance that the objectives of an entity will be 

achieved.
Page 5 GAO-18-140 Least Burdensome Medical Device Approvals

FDA classifies each medical device type intended for human use into one 

of three classes based on the level of risk it poses to the patient or the 

user and the controls necessary to reasonably ensure its safety and 

effectiveness.11 Examples of types of devices in each class include the 

following:

• Class I: tongue depressors, elastic bandages, reading glasses, and 

forceps;

• Class II: electrocardiographs, powered bone drills, and mercury 

thermometers; and

• Class III: pacemakers and replacement heart valves.

Before medical devices may be legally marketed in the United States, 

they are generally subject to one of two types of FDA premarket review 

processes.12

• Premarket approval (PMA) process: Class III device types are 

typically required to obtain FDA approval through the PMA process.13

Under this process, the medical device sponsor must submit an 

application that includes—among other things—full reports of 

 11Class I devices are those for which compliance with general controls, such as good 

manufacturing practices specified in FDA’s quality system regulation, are sufficient to 

provide reasonable assurance of their safety and effectiveness. Class II devices are 

subject to general and special controls, such as postmarket surveillance. Class III devices 

are those (1) for which insufficient information exists to determine whether general and 

special controls are sufficient to provide reasonable assurance of the safety and 

effectiveness of the device and (2) that support or sustain human life or are of substantial 

importance in preventing impairment of human health, or that present a potential 

unreasonable risk of illness or injury. See 21 U.S.C. § 360c(a)(1) and 21 C.F.R. § 860.3(c) 

(2017).

12A small percentage of devices enter the market by other means, such as through the 

humanitarian device exemption process, which allows market entry, without adherence to 

certain requirements, for devices benefiting patients with rare diseases or conditions. See 

21 U.S.C. § 360j(m) and 21 C.F.R. pt. 814, subpt H (2017).

13The requirements and procedures for submitting an application for premarket approval 

can be found at section 360e of title 21 of the U.S. Code. Premarket approval is not 

required for class I or class II devices or certain exempted devices such as those intended 

for investigational use that meet applicable requirements in 21 C.F.R. pt. 812. See 21 

U.S.C. § 360e(a).

Background

FDA Medical Device 

Review Process
Page 6 GAO-18-140 Least Burdensome Medical Device Approvals

investigations, typically including clinical data, providing reasonable 

assurance that the new device is safe and effective. The PMA 

process is the most stringent type of premarket review. A successful 

application results in FDA’s approval to market the device. From 2001 

through 2016, medical device sponsors submitted 651 PMA 

applications, and FDA approved for marketing 506 of those 

submissions. (See fig. 1.)

Figure 1: Original Medical Device Premarket Applications Approved by FDA, 2001 to 2016

Note: Applications were counted according to the fiscal year in which the application was received by 

FDA, even if an approval or another decision occurred in a subsequent fiscal year.

a

Applications with a decision other than approved may include applications that reached a “not 

approvable” decision or were otherwise withdrawn.

• Premarket notification, or 510(k), process: Most medical devices 

requiring premarket review are subject to FDA’s premarket notification 

or 510(k) process.14 This includes class I and II device types that are 

 14See 21 U.S.C. § 360(k). 
Page 7 GAO-18-140 Least Burdensome Medical Device Approvals

not specifically exempted from the 510(k) notification requirement.15

Under this process, the medical device sponsor must notify FDA at 

least 90 days before it intends to market a new device and 

demonstrate to FDA that the new device is substantially equivalent to 

a predicate device, and therefore does not require a PMA.16 For most 

510(k) notifications, clinical data are not required and substantial 

equivalence will normally be determined based on comparative 

descriptions of intended device uses and technological 

characteristics, and may include performance data. A successful 

510(k) submission results in FDA’s clearance to market the device. 

From 2001 through 2016, medical device sponsors submitted 61,439 

premarket notifications and FDA cleared 51,028 devices for market. 

(See fig. 2.)

 15See 21 U.S.C. §§ 360(l), (m). See also section .9 of 21 C.F.R. pts. 862 to 892, e.g., 21 

C.F.R. §§ 862.9, 864.9 (2017) (defining the limitations of the exemptions). 

16Under federal regulations, a predicate device can be a device that (1) was legally 

marketed prior to May 28, 1976; or (2) was marketed on or after May 28, 1976, and was 

found to be substantially equivalent to a legally marketed device through the 510(k) 

premarket notification process; or (3) was reclassified by FDA from class III to class II or I. 

21 C.F.R. § 807.92(a)(3) (2017). Substantial equivalence or substantially equivalent 

means that the proposed device has the same intended use as the predicate device and 

the same technological characteristics as the predicate device or has different 

technological characteristics and information submitted to FDA demonstrates that the 

proposed device is as safe and effective as the predicate device and does not raise 

different questions of safety or effectiveness. 21 U.S.C. § 360c(i)(1)(A).
Page 8 GAO-18-140 Least Burdensome Medical Device Approvals

Figure 2: 510(k) Medical Device Notifications Cleared by FDA, 2001 to 2016

Note: Notifications were counted according to the fiscal year in which the notification was received by 

FDA, even if a clearance or other decision occurred in a subsequent fiscal year.

a

Notifications categorized as other than cleared were determined not substantially equivalent or were 

withdrawn, deleted, or not cleared due to another reason.

During premarket review under both the PMA and 510(k) processes, FDA 

and the medical device sponsor may engage in an interactive process. To 

start, there may be a pre-submission meeting between FDA and the 

sponsor, during which the parties discuss the upcoming review and try to 

resolve potential obstacles for approval or clearance. Then, FDA receives 

the premarket submission, makes a determination to accept or not accept 

the submission, and assigns a reviewer. In making its assessment 

whether to approve, or clear, a submission, FDA relies on the sponsor to 

provide supporting data as part of the submission. However, the agency 

can request additional information in the course of the review in order to 

make a determination of reasonable assurance of safety and 

effectiveness, or of substantial equivalence. This additional information 

can be obtained through informal interactions, such as a phone call or 

email. Alternatively, for more significant issues, FDA may make a more 
Page 9 GAO-18-140 Least Burdensome Medical Device Approvals

formal request for additional information, known as a deficiency letter in 

the case of a PMA application and additional information (AI) letter for a 

510(k) notification. FDA will issue such requests if the submission lacks 

significant information necessary for FDA to complete its review, and the 

agency will request the sponsor amend the submission to provide the 

necessary information regarding the device.

If a sponsor disagrees with an FDA regulatory decision concerning a 

medical device submission, including a CDRH employee’s decision to 

request additional information or a significant decision regarding approval 

or clearance of a medical device, it can take multiple actions.17

Specifically, a sponsor can, among other things, (1) contact the CDRH 

Ombudsman for assistance, (2) file an internal appeal of an FDA 

decision, or (3) request that the disagreement be resolved through 

CDRH’s Medical Device Dispute Resolution Panel, as described below.18

• Ombudsman: According to FDA’s guidance, prior to the agency 

reaching a regulatory decision, the most effective means of resolving 

a dispute between CDRH and an external stakeholder is through 

discussion and agreement. The CDRH Ombudsman is available to 

assist in clarifying issues, mediate meetings and teleconferences, and 

conduct discussions with the parties in an effort to resolve 

disagreements short of a formal review or internal appeal.

• Internal Appeal: Once FDA makes a regulatory decision, a sponsor 

can request a supervisory review of that decision, which we refer to as 

an internal appeal.19 For this process, the supervisor of an FDA 

employee will, at the request of a medical device sponsor, review a 

decision or action of the employee and issue a decision. The decision 

 17CDRH has defined the term “significant decision” to include decisions about premarket 

approval and substantial equivalence at the final stage of review (e.g., a not substantially 

equivalent or substantially equivalent in the case of a 510(k) submission, or an approval, 

not approvable, or denial in the case of a PMA submission). See FDA, Center for Devices 

and Radiological Health Appeals Processes: Questions and Answers About 517A -

Guidance for Industry and Food and Drug Administration Staff (Rockville, Md.: Sept. 29, 

2017).

18FDA offers several processes for medical device sponsors and other individuals outside 

of the agency to have decisions or actions taken by CDRH to be reviewed or 

reconsidered, including internal appeals, the Medical Devices Dispute Resolution Panel, 

petitions, and hearings. See generally, FDA, Center for Devices and Radiological Health 

Appeals Processes - Guidance for Industry and Food and Drug Administration Staff

(Rockville, Md.: May 17, 2013).

19This internal appeals process is outlined in 21 C.F.R. § 10.75 (2016).
Page 10 GAO-18-140 Least Burdensome Medical Device Approvals

rendered by the supervisor, acting as the review authority, customarily 

takes one of the following forms: overturning the decision of the 

employee; upholding the employee decision; or, in some 

circumstances, referring the matter back to the employee for 

reconsideration under defined conditions.

• Medical Device Dispute Resolution Panel: If the dispute remains 

unresolved, the sponsor may request that FDA convene the Medical 

Device Dispute Resolution Panel. The panel is intended to provide a 

means for independent review of a scientific controversy or dispute 

between a sponsor and FDA, and make a recommendation to the 

Center director. According to FDA’s guidance, the panel is primarily 

intended to address scientific controversies rather than other issues 

such as regulatory, legal, or statutory authority disputes.

As part of its commitments associated with the Medical Device User Fee 

Amendments of 2012 (MDUFA III), FDA agreed to participate in an 

independent, comprehensive assessment of the medical device 

submission review process.20 Acting on recommendations from the 

contractor that conducted the assessment, FDA established working 

groups for each submission type, including PMAs and 510(k)s, which 

studied existing review processes and made recommendations.21 In 

August 2017, the Medical Device User Fee Amendments of 2017 

(MDUFA IV) reauthorized FDA’s medical device user fee program, and 

FDA committed to another independent assessment.22 FDA has 

 20See Pub. L. No. 112-144, tit. II, 126 Stat. 993, 1002 (2012). See also FDA, MDUFA III 

Commitment Letter, 12. A significant portion of FDA’s annual appropriation for premarket 

medical device review and other activities consists of amounts derived from user fees paid 

by device manufactures. FDA was first authorized to collect medical device user fees in 

2002 under the Medical Device User Fee and Modernization Act (P.L. 107-250) and 

Congress has reauthorized the user fee program every 5 years to provide additional 

resources for certain FDA oversight activities. These fees are collected and available for 

obligation only to the extent and in the amount provided in advance in appropriations acts. 

In association with each user fee authorization, FDA has committed to performance 

goals—specific time frames within which FDA is to take action on submissions—and other 

actions related to the review of medical device submissions. These commitments are 

negotiated between FDA and industry stakeholders and submitted to congressional 

committees prior to each reauthorization.

21Booz Allen Hamilton, Independent Assessment of FDA Device Review Process 

Management: Deliverable 6: Final Implementation Evaluation Report for the Food and 

Drug Administration, a report prepared at the request of the Food and Drug 

Administration, February 1, 2016.

22FDA Reauthorization Act of 2017, Pub. L. No. 115-52, tit. II (Aug. 18, 2017). See also 

FDA, MDUFA Performance Goals and Procedures, Fiscal Years 2018 Through 2022, 21.
Page 11 GAO-18-140 Least Burdensome Medical Device Approvals

committed to hiring a contractor to conduct this assessment by the end of 

December 2017 with a second phase to begin in 2020.

In 1997, FDAMA added a requirement that the agency use the least 

burdensome approach during certain parts of PMA and 510(k) reviews.23

These requirements were intended to reduce unnecessary burdens 

associated with the premarket approval and clearance processes; 

however, they did not lower the statutory criteria for demonstrating a 

reasonable assurance of safety and effectiveness or substantial 

equivalence. While the language in FDAMA differs slightly for the PMA 

and 510(k) processes, in both instances FDA was directed to consider the 

“least burdensome” means of requesting information needed for its 

review. Specifically, FDAMA requires that when the agency specifies data 

that must be submitted as part of a PMA application, the agency must 

consider the least burdensome appropriate means of evaluating device 

effectiveness that would have a reasonable likelihood of resulting in 

approval.24 The agency must similarly consider the least burdensome 

appropriate means of demonstrating substantial equivalence when 

requesting information under the 510(k) notification process.25 In both 

cases, FDA is statutorily required to request only information that is 

necessary to support the determination that there is reasonable 

assurance of effectiveness or substantial equivalence, respectively.26

Subsequent laws have clarified the least burdensome requirements. In 

2012, the Food and Drug Administration Safety and Innovation Act 

 23See Pub. L. No. 105-115, §§ 205(a)-(b), 111 Stat. 2296, 2336-7 (1997) (codified as 

amended at 21 U.S.C. §§ 360c(a)(3)(D)(ii), 360c(i)(1)(D)(i)).

2421 U.S.C. § 360c(a)(3)(D)(ii) (“Any clinical data, including one or more well-controlled 

investigations, specified in writing by the Secretary for demonstrating a reasonable 

assurance of device effectiveness shall be specified as result of a determination by the 

Secretary that such data are necessary to establish device effectiveness. The Secretary 

shall consider, in consultation with the applicant, the least burdensome appropriate means 

of evaluating device effectiveness that would have a reasonable likelihood of resulting in 

approval.”).

2521 U.S.C. § 360c(i)(1)(D)(i) (“Whenever the Secretary requests information to 

demonstrate that devices with differing technological characteristics are substantially 

equivalent, the Secretary shall only request information that is necessary to making 

substantial equivalence determinations. In making such request, the Secretary shall 

consider the least burdensome means of demonstrating substantial equivalence and 

request information accordingly.”).

2621 U.S.C. §§ 360c(a)(3)(D)(iii), 360c(i)(1)(D)(ii).

FDA Least Burdensome 

Requirements
Page 12 GAO-18-140 Least Burdensome Medical Device Approvals

clarified that the term “necessary” means the minimum required 

information that would support either a determination that a PMA 

application provides reasonable assurance of the effectiveness of the 

device or a determination, for a 510(k) notification, of substantial 

equivalence between a new device and a predicate device.27 In 2016, the 

21st Century Cures Act added a provision applying the least burdensome 

concept to FDA’s requests for additional information in the PMA 

process.28 The law also applied the least burdensome concept to 

significant decisions, such as denials of PMA applications, requiring such 

decisions to include a brief statement regarding how least burdensome 

requirements were considered and applied.29 Additionally, the law 

mandated each FDA employee involved in premarket submission 

reviews, including supervisors, to receive training on the least 

burdensome provisions, and required the agency to conduct an audit of 

the training, among other things, no later than June 2018.30

Although FDA officials have noted that the least burdensome principles 

are broad and could apply to all activities within the PMA and 510(k) 

premarket review process, they noted that the requests for additional 

information represent a key juncture for the application of least 

burdensome requirements. According to agency officials and industry 

representatives, the requests for additional information—deficiency letters 

in the case of PMAs and AI letters for its 510(k) reviews—are when FDA 

and the sponsor could disagree on whether the requested information is 

necessary for the agency to reach a final decision on the medical device 

under review.

Following the enactment of FDAMA in 1997, FDA went through a process 

in collaboration with the medical device industry to define the least 

burdensome concept and develop an approach to implement the 

 27See Pub. L. No. 112-144, § 602, 126 Stat. 993, 1051 (2012) (codified as amended at 21 

U.S.C. §§ 360c(a)(3)(D)(iii), 360c(i)(1)(D)(ii)).

28See Pub. L. No. 114-255, § 3058(b), 130 Stat. 1033, 1129 (2016) (codified at 21 U.S.C. 

§ 360e(c)(5)).

29See Pub. L. No. 114-255, § 3058(c), 130 Stat. 1033, 1129 (2016) (codified at 21 U.S.C. 

§ 360g-1(a)(3)).

30See Pub. L. No. 114-255, § 3058(a), 130 Stat. 1033, 1128-9 (2016) (codified at 21 

U.S.C. § 360c(j)).

FDA Implementation of the 

Least Burdensome 

Requirements
Page 13 GAO-18-140 Least Burdensome Medical Device Approvals

provisions. Based on this, FDA released multiple guidance documents 

related to least burdensome requirements from 2000 through 2002.

• In November 2000 guidance, FDA outlined a four-part approach—

referred to as “four-part-harmony” by FDA staff—for communicating 

deficiencies to medical device sponsors in accordance with the least 

burdensome requirements.31 The guidance helps reviewers describe 

deficiencies identified in submissions in ways that are direct, concise, 

and complete, thus ensuring a more effective use of reviewers’ and 

sponsors’ time, effort, and resources. It also provides a suggested 

format for sponsors to respond to FDA. FDA updated this guidance in 

September 2017.32

• In 2002 guidance, FDA described its principles for implementing the 

least burdensome requirements and its activities to assess 

implementation.33 The guidance outlines FDA’s interpretation of the 

least burdensome concept as described in FDAMA, and explains its 

application to activities associated with PMA and 510(k) reviews. The 

guidance also states that FDA was in the process of developing tools 

to be used by both agency staff and its stakeholders to periodically 

assess the implementation of the least burdensome principles. It 

noted some measurement tools had already been developed and that 

additional tools were also needed to assess the impact of the least 

burdensome approach on expediting the development of new medical 

technologies.

In addition, FDA has included language about those requirements in other 

guidance documents. For example, in 2014, FDA issued guidance on the 

510(k) program that describes how the least burdensome principles may 

 31FDA, Guidance for Industry and FDA Staff: Suggested Format for Developing and 

Responding to Deficiencies in Accordance with the Least Burdensome Provisions of 

FDAMA (Rockville, Md.: Nov. 2, 2000). The guidance recommends communicating 

deficiencies in four parts: (1) Clearly identify the specific issue or question; (2) 

Acknowledge the information submitted and explain why the information provided did not 

adequately address the issue; (3) Establish the relevance of the request to the PMA 

determination of “reasonable assurance of safety and effectiveness” or a 510(k) 

determination of “substantial equivalence;” (4) Request the necessary additional 

information needed to adequately address the issue and, when possible, suggest 

alternate ways of satisfying the issue.

32FDA, Developing and Responding to Deficiencies in Accordance with the Least 

Burdensome Provisions Guidance for Industry and Food and Drug Administration Staff

(Rockville, Md.: Sept. 29, 2017).

33FDA, Least Burdensome Provisions: Concept and Principles, 2002.
Page 14 GAO-18-140 Least Burdensome Medical Device Approvals

affect the type of information necessary to demonstrate substantial 

equivalence at different decision points in the review of a 510(k).34

FDA requested sponsors provide additional information for a majority of 

the PMAs and 510(k)s it reviewed. For the period 2001 through 2016, 

FDA issued a large number of deficiency and AI letters relative to the 

number of submissions, although there was variation annually.35 For 

PMAs, the number of deficiency letters as a percentage of new PMA 

applications submitted ranged from about 54 percent to 113 percent 

annually, or 82 percent on average, from 2001 through 2016. For the 

years 2006 through 2010, this percentage, as well as the total number of 

letters was higher, and FDA issued more deficiency letters than there 

were PMA applications submitted. Similarly, AI letters as a percentage of 

total 510(k) notifications received ranged from about 58 percent to more 

 34FDA, The 510(k) Program: Evaluating Substantial Equivalence in Premarket 

Notifications: Guidance for Industry and Food and Drug Administration Staff (Rockville, 

Md.: July 28, 2014).

35FDA deficiency and AI letters often identified more than one deficiency in each letter and 

the information FDA requested varied. For example, in one letter to a PMA sponsor, FDA 

expressed concern with the safety and effectiveness data, and requested that a study 

include a larger sample size with a longer window for following up with participants after 

the study. In a letter to a 510(k) sponsor, FDA requested additional drawings of the 

device, as the drawings provided with the initial submission did not illustrate all device 

components.

FDA Frequently 

Requested Additional 

Information to 

Support Medical 

Device Reviews, and 

Sponsor 

Disagreements Often 

Related to Least 

Burdensome 

Requirements

FDA Issued Deficiency 

and Additional Information 

Letters for a Significant 

Proportion of PMAs and 

510(k)s
Page 15 GAO-18-140 Least Burdensome Medical Device Approvals

than 174 percent annually, or about 106 percent on average, from 2001 

through 2016. While the number of 510(k) notifications remained similar 

across the time period we examined, from 2009 through 2012, the 

number of AI letters issued each year was, on average, nearly double the 

number in other years. During this period, FDA issued more AI letters 

than there were 510(k) notifications submitted. Since 2014, these 

percentages have been lower for both PMAs and 510(k)s.

FDA officials acknowledged the historical increase in the number of 

deficiency and AI letters and noted the more recent decrease. The 

officials attributed this decrease to a number of changes the agency 

agreed to in MDUFA III. For example, FDA implemented a policy to 

review submissions for administrative completeness prior to accepting the 

submission. They said this allowed the agency to limit deficiency and AI 

letters to issues related to the quality of the data provided and the studies 

conducted in support of the submission rather than to administrative 

issues. Also as a result of MDUFA III, the agency implemented an 

interactive review process to increase informal interaction between FDA 

and applicants and to minimize the number of review questions 

communicated through deficiency and AI letters. (See table 1.)
Page 16 GAO-18-140 Least Burdensome Medical Device Approvals

Table 1: Medical Device Submissions Received and FDA Requests for Additional Information, 2001 through 2016

Fiscal 

year

Original premarket applications (PMA) 510(k) notifications

Applications 

received

FDA information 

requests 

(deficiency 

letters)

FDA information 

requests as a 

percentage of 

applications

Notifications 

received

FDA information 

requests 

(additional 

information 

letters)a

FDA information 

requests as a 

percentage of 

notifications

2001 67 36 54 4,229 2,599 61

2002 41 29 71 4,301 2,477 58

2003 43 29 67 4,195 2,859 68

2004 53 46 87 3,585 2,647 74

2005 47 32 68 3,627 3,128 86

2006 39 43 110 3,832 3,891 102

2007 35 37 106 3,634 4,354 120

2008 30 34 113 3,819 5,164 135

2009 32 34 106 4,080 6,257 153

2010 43 45 105 3,852 6,692 174

2011 43 41 95 3,805 6,300 166

2012 24 21 88 3,983 6,193 155

2013 29 25 86 3,866 3,411 88

2014 28 17 61 3,610 2,962 82

2015 42 29 69 3,570 2,996 84

2016 55 37 67 3,389 2,993 88

Total 651 535 82 61,377 64,922 106

Source: GAO analysis of Food and Drug Administration (FDA) data. | GAO-18-140

Note: In this table, requests for additional information are included in the fiscal year that the related 

applications or notifications were received, even if the requests were issued in a subsequent fiscal 

year. Data for fiscal years 2009, 2012, 2013, 2015 and 2016 include some submissions that are still 

under review and therefore FDA had not issued final deficiency or additional information letters for 

each submission.

a

FDA did not have counts of additional information letters readily available. Therefore, for each year, it 

provided the percentage of 510(k) notifications that are known to have received one, two, three, or 

four additional information letters. We used the percentages to calculate an estimated number of 

additional information letters.

We identified changes in how the deficiency letters and AI letters 

referenced the least burdensome requirements. Based on our sample of 

73 letters from 1997 through 2016, FDA included an explicit 

acknowledgment of the least burdensome requirements in the letters 

issued from 2001 through 2009. However, based on our review, this 
Page 17 GAO-18-140 Least Burdensome Medical Device Approvals

practice ended in 2010, and later letters did not include this standard 

language.36 Representatives from the medical device industry told us that 

including the least burdensome language in the deficiency letters was a 

good practice because it raised awareness of the least burdensome 

principles. In September 2017, FDA released updated deficiencies 

guidance that, according to FDA officials, instructs staff how to better 

articulate the reason that the information is needed in accordance with 

the least burdensome requirements.37 This guidance does not set forth 

boilerplate language regarding the least burdensome requirements for 

use in deficiency letters, but does include examples of well-constructed 

deficiencies, definitions for major and minor deficiencies, and a statement 

that FDA will attempt to resolve minor deficiencies interactively.

The least burdensome requirements were often a significant contributing 

factor in disagreements raised by medical device sponsors, according to 

FDA officials and available FDA data. According to FDA, the most 

effective means of resolving disagreements is through discussion and 

mediation, and to that end, the Ombudsman’s office is routinely involved 

in discussions between firms and medical device reviewers during the 

review process. For example, in 2016, the CDRH Ombudsman was 

involved with PMA and 510(k) medical device reviews 360 times out of 

3,444 submissions. Although the agency was unable to identify which of 

these interactions were related to least burdensome requirements, 

agency officials told us that a substantial number likely resulted from a 

difference of opinion between the applicant and FDA on the appropriate 

level of scientific evidence, a portion of which likely have a least 

burdensome component.

The least burdensome provisions were also frequently related to issues 

that applicants raised during internal agency appeals of FDA decisions of 

PMA and 510(k) reviews. Although FDA did not have readily available 

data on appeals that occurred prior to 2013, the agency was able to 

 36FDA also stopped including boilerplate language on the least burdensome requirements 

in its guidance documents in November 2009. According to agency officials, the language 

had been included inconsistently in past guidance documents, and officials concluded it 

was more important to articulate least burdensome principles than to merely include stock 

language about the least burdensome requirements.

37FDA, Developing and Responding to Deficiencies in Accordance with the Least 

Burdensome Provisions Guidance for Industry and Food and Drug Administration Staff, 

Sept. 29, 2017.

Though Data are Limited, 

Least Burdensome 

Requirements were a 

Significant Contributing 

Factor in Disagreements 

Raised by Medical Device 

Sponsors
Page 18 GAO-18-140 Least Burdensome Medical Device Approvals

provide information about the 63 appeals of significant decisions that 

occurred from 2013 through 2016.38 Of these 63 appeals, FDA identified 

33 appeals—2 related to PMAs and 31 related to 510(k)s—in which the 

issue identified by the sponsor was related to least burdensome 

principles. According to medical device industry representatives, 

sponsors may not always pursue an appeal, so the number of official 

appeals may not represent the extent of least burdensome-related issues 

that sponsors experience. They said the sponsor may determine it is best 

to avoid conflict that could complicate future device submissions and 

comply with the request for additional information, even if it disagrees.

Of these 33 appeals, FDA agreed, or partially agreed with the sponsor for 

11 appeals, which resulted in FDA overturning the decision or reopening 

the file and continuing the review. For the remaining 22 appeals, the 

agency upheld the initial reviewer decision. The following presents 

examples of appeals where the issue identified by the sponsor was 

related to the least burdensome requirements.

• In one appeal related to a 510(k) review, the sponsor objected to the 

reviewer’s finding that the device was not substantially equivalent to a 

device already on the market. The sponsor stated that it had provided 

sufficient data for a substantial equivalence determination, and the 

FDA reviewer’s request for additional risk mitigation measures and 

supplemental testing was unwarranted and inappropriate. The review 

authority determined that, while the information provided in the 510(k) 

premarket submission was not sufficient to establish substantial 

equivalence, some of FDA’s requests were unwarranted. As a result 

of the appeal, FDA reopened the file and provided the sponsor an 

opportunity to respond to a new set of requests for additional 

information.

• In an appeal related to a PMA review, the sponsor contended that 

FDA’s not approvable decision reflected an inconsistent and 

erroneous interpretation of the clinical data supporting the safety and 

effectiveness of the subject device, and that the data it had provided 

was sufficient for FDA to reach an approved decision. The sponsor 

 38Prior to May 2013, FDA did not have a formal mechanism to track internal appeals of 

significant decisions and, accordingly, does not have a comprehensive list of such appeals 

of 510(k) and PMA decisions. However, the agency was able to identify 141 additional 

appeals—not limited to significant decisions and not a comprehensive list—involving 

510(k) and PMA submissions that occurred from about 2005 through 2012 by reviewing 

other records. 
Page 19 GAO-18-140 Least Burdensome Medical Device Approvals

further contended that the review staff failed to utilize the principles 

outlined in FDA guidance. The review authority upheld FDA’s initial 

decision and determined there was not sufficient valid scientific 

evidence to demonstrate a reasonable assurance that the subject 

device was safe and effective under the proposed conditions of use.

The Medical Device Dispute Resolution Panel, which provides another 

avenue to resolve disagreements between sponsors and the agency, has 

also addressed issues related to the least burdensome requirements. 

Since the panel was created following FDAMA in 1997, medical device 

sponsors have requested that FDA resolve three disagreements through 

this avenue, each related to PMAs. Although not tracked by FDA, at our 

request, officials reviewed the records and found that one of the three 

disputes was related to the least burdensome requirements. Specifically, 

for a September 2001 dispute, FDA officials said the sponsor requested 

the panel after FDA initially found that the data from the clinical study 

submitted by the sponsor did not sufficiently support effectiveness. After 

reviewing evidence from the applicant and from FDA, the dispute 

resolution panel determined that the sponsor had provided sufficient 

evidence to prove effectiveness, and the device was ultimately approved.

FDA officials indicated that training specific to the least burdensome 

requirements was held in the years following the enactment of FDAMA in 

1997. FDA was unable to provide records of that training, including its 

content. However, officials told us that the training was specific to the 

least burdensome requirements and offered from 1997 through 1999. 

FDA officials said the agency offered other presentations in subsequent 

years that they said covered similar least burdensome topics. For 

example, the agency provided slides from a presentation created in 2000 

that provided an overview of FDA’s implementation of the requirements.

FDA Offered Some 

Training on the Least 

Burdensome 

Requirements, and 

Evaluates its Training 

for Effectiveness

FDA Offered Some Early 

Least Burdensome 

Training at Limited Times, 

and Has Incorporated 

Related Information in 

Broader Training
Page 20 GAO-18-140 Least Burdensome Medical Device Approvals

Although FDA officials told us this least burdensome specific training was 

not offered after 1999, they identified various other trainings that they said 

incorporated the least burdensome concept. For example, a 2005 

presentation on clinical trial design has multiple slides on least 

burdensome requirements, and specifically states that a course objective 

is to “understand how least burdensome principles apply.” Least 

burdensome requirements are also mentioned in other training materials 

where they may not be the focus—for example one slide of a presentation 

on biomarkers included a mention of least burdensome requirements.

Officials also identified the training program for new reviewers that FDA 

implemented in 2011 as a source of training on least burdensome 

principles. Specifically, the Reviewer Certification Program is a training 

curriculum that FDA has required most new device reviewers to complete 

since 2011. The training curriculum covers a wide variety of courses on 

topics related to a reviewer’s responsibilities.39 While none of these 

courses is specific to the least burdensome requirements, there are 

courses covering related topics. For example, there is one course on 

technical writing that includes FDA’s guidance on developing deficiencies 

with least burdensome principles. Five other courses on different topics 

mention either the least burdensome requirements or related principles, 

such as a course on FDA’s legislative history that included a slide 

identifying the least burdensome statutory provisions as an element of 

FDAMA, though the slide did not explain the least burdensome 

requirements or provide additional context. Of the 490 staff assigned to 

review PMAs and 510(k)s, FDA indicated that as of the end of calendar 

year 2016, 335 had completed the Reviewer Certification Program, 150 

started working on premarket submissions prior to the beginning of 2011, 

and the remaining 5 individuals did not complete the training for varying 

reasons.40

In response to the 21st Century Cures Act, enacted in December 2016, 

FDA is providing mandatory online training specific to the least 

 39In the materials that FDA provided for the Reviewer Certification Program, there were 18 

separate presentations.

40According to FDA, 8 of the 150 reviewers who started working on premarket 

submissions prior to the beginning of 2011 later completed the training. According to FDA, 

reasons that reviewers starting after 2011 did not complete the training include that they 

were short-term employees such as fellows or visiting scientists, passed initial testing and 

were not required to take the complete reviewer certification coursework, or were not 

required to take the reviewer certification program, as a decision based on general 

management discretion. 
Page 21 GAO-18-140 Least Burdensome Medical Device Approvals

burdensome requirements. FDA indicated that the training focuses on key 

behaviors that reflect the least burdensome approaches as documented 

in updated guidance that FDA issued in September 2017. FDA officials 

told us that, as of October 31, 2017, 91 percent of CDRH staff had 

received the new least burdensome specific training. In addition to the 

online training, FDA plans other activities, such as follow-up office-level 

briefings to address questions or concerns and an introductory podcast 

from the CDRH director. In addition to providing this training to current 

employees, FDA plans to incorporate least burdensome requirement 

training into new employee orientation and the Reviewer Certification 

Program, and plans to include ongoing support and promotion of least 

burdensome principles through a center working group on the least 

burdensome requirements. In addition to course-based training, FDA 

officials told us that least burdensome concepts are conveyed to 

reviewers through mentoring. Officials explained that much of the training 

on the least burdensome requirements occurs through mentoring and 

conversations with supervisors, and that those encounters are not 

documented.

While FDA has not had processes in place to evaluate its medical device 

training, it is implementing such processes for all training, including 

courses related to the least burdensome requirements. In its June 2014 

report, the contractor performing the independent evaluation noted that 

CDRH did not have mechanisms in place to measure the quality and 

effectiveness of its training programs.41 The report noted that FDA should 

identify metrics and incorporate methods to better assess review process 

training satisfaction, learning, and staff behavior changes. FDA officials 

explained that while they had customer reaction evaluations for trainings 

for at least 24 years, they started evaluating training participant learning 

with the Reviewer Certification Program starting in 2010.

FDA is in the process of implementing a training evaluation model, which 

includes various levels of evaluation, from assessing participant response 

 41Booz Allen Hamilton, Independent Assessment of FDA Device Review Process 

Management, Deliverable 10: Final Report on Findings and Recommendations, a report 

prepared at the request of the Food and Drug Administration, June 11, 2014. 

FDA Is Implementing 

Evaluations of All Training 

Courses for Medical 

Device Review Staff, 

including Courses that 

Address the Least 

Burdensome 

Requirements
Page 22 GAO-18-140 Least Burdensome Medical Device Approvals

to the training to evaluating its impact on the agency.42 As of 2017, FDA 

reported it was evaluating training programs to determine participant 

learning and preparing to evaluate whether that learning changed 

participant behavior. Officials told us they anticipate beginning to conduct 

evaluations that assess agency impact in fiscal year 2018, and they plan 

to have the model completely implemented for all trainings by fiscal year 

2020. FDA currently evaluates its Reviewer Certification Program to 

determine participant learning, and though the least burdensome 

requirements are not specifically addressed in the Reviewer Certification 

Program evaluation materials FDA provided to us, they did include 

questions on topics related to least burdensome requirements.

In addition to its current training evaluation plan, FDA is also required by

the 21st Century Cures Act to conduct an audit of the training and its 

effectiveness in implementing the least burdensome requirements.43

Specifically, the training audit is to be conducted by the ombudsman 

responsible for premarket reviews, identified by FDA as the CDRH 

Ombudsman.44 According to a draft plan, FDA plans to conduct training 

evaluations, a process review of 510(k) and PMA documentation to 

assess reviewer compliance with FDA procedures, and seek feedback 

from industry on its experience with the premarket review process and 

how the least burdensome requirements are applied. Officials indicated 

that criteria are still under development and that they hoped to have them 

further developed in the first quarter of 2018, with the authorizing 

legislation requiring completion of the audit by June 2018, 18 months 

after enactment of the law.

 42The model used by FDA is the Kirkpatrick Model, a standard for evaluating the 

effectiveness of training. It consists of 4 levels: Level 1—Reaction—evaluates how 

participants respond to the training; Level 2—Learning—measures if they actually learned 

the material; Level 3—Behavior—considers if they are using what they learned on the job; 

and Level 4—Results—evaluates if the training positively impacted the organization.

43See Pub. L. No. 114-255, § 3058(a), 130 Stat. 1033, 1128-9 (2016) (codified at 21 

U.S.C. § 360c(j)(2)).

44FDA officials noted that although the CDRH Ombudsman would not typically conduct 

such an audit, it is statutorily specified to do so. Therefore, officials said that the 

Ombudsman is coordinating with other center staff to develop the audit plan.
Page 23 GAO-18-140 Least Burdensome Medical Device Approvals

Some stakeholders and others have raised concerns about the 

consistency and clarity of FDA’s requests for additional information during 

medical device reviews. For the past 17 years, FDA has required 

reviewers to only request information that is necessary to make a PMA 

determination of “reasonable assurance of safety and effectiveness” or a 

510(k) determination of “substantial equivalence” in their review of a 

submission.45 Representatives of one of the organizations representing 

the medical device industry noted the high percentages of medical device 

submissions that involve a letter, and some of their member companies 

have said that FDA reviewers may request additional information as a 

result of intellectual curiosity rather than a “need to know.” In addition, the 

independent assessment’s 2014 report, funded by FDA as part of 

MDUFA III, found inconsistent decision-making among FDA review staff 

throughout various stages of the review process, including additional 

 45FDA’s past and current guidance recommends that reviewers attempt to resolve minor 

issues interactively, such as by phone, rather than issuing a formal letter. FDA also 

recommends that information requested in deficiency letters and AI letters should address 

the more complicated and complex issues (i.e., major deficiencies) unless minor issues 

are related to the resolution of substantive issues or remain unresolved at the time the 

major deficiencies are raised. Under current guidance, additional considerations may also

be included but do not require a response. See FDA, Developing and Responding to 

Deficiencies in Accordance with the Least Burdensome Provisions, 2, Nov. 2, 2000 and 

FDA, Developing and Responding to Deficiencies in Accordance with the Least 

Burdensome Provisions Guidance for Industry and Food and Drug Administration Staff, 2-

3, Sept. 29, 2017. 

FDA is Taking Steps 

that May Improve Its 

Requests for 

Additional Information 

Overall, but Has Not 

Fully Evaluated Its 

Implementation of the 

Least Burdensome 

Requirements

FDA Is Implementing 

Processes to Improve the 

Consistency and Clarity of 

Its Requests for Additional 

Information during Medical 

Device Reviews
Page 24 GAO-18-140 Least Burdensome Medical Device Approvals

information requests.46 While the 2014 report did not address least 

burdensome requirements explicitly, it examined related processes. For 

example, according to the report, there was inconsistent decision-making 

among FDA review staff throughout various stages of the review process, 

including a lack of clarity regarding FDA reviewer thresholds for triggering 

deficiency letters. The report recommended that FDA develop criteria and 

establish mechanisms to improve consistency in decision-making 

throughout the review process.47

To address problems identified during the independent assessment, FDA 

is implementing several initiatives to improve center processes. FDA 

officials told us that, in anticipation of MDUFA IV, they recognized a need 

for a dedicated quality management infrastructure. In 2014, FDA 

established a Quality Management Unit to improve center processes, 

which they said would include those related to the least burdensome 

requirements. The unit completed a framework that outlined its vision and 

mission and established organizational objectives, such as developing a 

document control system, providing training, and conducting quality 

assessments, audits, and management reviews.

In addition, FDA officials told us that starting in October 2017, FDA 

planned to fulfill its MDUFA IV commitments to improve the clarity and 

consistency of its deficiency letters and AI letters after releasing updated

guidance.

• In September 2017, FDA published guidance reflecting the 

commitments under MDUFA IV that all deficiency letters and AI letters 

include a statement indicating the specific basis for any cited 

deficiencies.48 According to FDA officials, this new approach will help 

ensure that the letters more consistently ground requests for 

information in the specific reason that FDA is requesting the 

information from the sponsor. For example, FDA may cite a law, final 

rule, or specific scientific issue as the basis for its request, rather than 

 46Booz Allen Hamilton, Independent Assessment of FDA Device Review Process 

Management, Deliverable 10: Final Report on Findings and Recommendations, 2014.

47FDA created an action plan in response to this recommendation. The independent 

assessment’s 2016 report included information on the implementation of this action plan,

but the initial results of the implementation activities were not measured due to an 

insufficient observation period.

48FDA, Developing and Responding to Deficiencies in Accordance with the Least 

Burdensome Provisions, 2017.
Page 25 GAO-18-140 Least Burdensome Medical Device Approvals

providing a more general statement of the request’s relevance. 

According to industry representatives, in the past, FDA reviewers 

have, at times, asked for additional information without including 

justification, and may have requested additional information as a 

result of intellectual curiosity rather than a “need to know.” The 

representatives stated that this new policy may better ensure the 

reviewers apply the least burdensome approach to their review.

• The updated guidance also explains that all deficiency letters and AI 

letters will undergo supervisory review prior to issuance to ensure that 

the information requested is relevant to a marketing authorization 

decision, all four elements of the deficiency are included, deficiencies 

are prioritized from most to least significant, and each deficiency is 

appropriate to include in light of the totality of all deficiencies. Officials 

told us that while supervisory concurrence was previously needed, 

under the new guidance, supervisors are now expected to review for 

certain criteria. For example, in the past, supervisors may have 

considered whether four-part harmony was addressed in each 

deficiency letter, but under the updated guidance this is now an 

expected practice. Officials said this will increase the extent to which 

deficiency letters are consistently constructed.

• In the MDUFA IV commitment letter, FDA agreed to base all 

deficiency letters and AI letters on a complete review of the 

submission and include all deficiencies. Therefore, FDA officials told 

us that any deficiencies identified following that letter would generally

be limited to issues raised as a result of new information. For 

example, if FDA asked for information on bio-compatibility testing, 

FDA will first review that information, and based on that review may 

ask for new information. In that instance, the information responding 

to the initial deficiency is new information. FDA officials said that past 

letters should also have included all deficiencies, but this may have 

been done inconsistently.

To further standardize its process for reviewing medical device 

submissions and developing requests for additional information, FDA is 

developing and implementing smart templates. FDA officials told us that 

these templates guide device reviewers through a standardized process 

for each submission. For example, they help reviewers identify the types 

of information necessary and include prewritten deficiency letters that 

have been approved by internal experts. FDA has had a smart template 

in place for the 510(k) process since 2013, according to FDA reports. 

FDA indicated that the template is already required for certain offices and 

divisions within CDRH, and plans for full adoption in the future. FDA 

officials told us that the agency also developed templates for de novo 
Page 26 GAO-18-140 Least Burdensome Medical Device Approvals

premarket submissions, which are currently available for voluntary use 

and will likely be mandatory in fiscal year 2018.49 Officials told us they 

plan to hire a person to develop a template to guide PMA reviews, which 

will likely take most of 2018. They told us the use of the smart template 

for PMAS will likely become mandatory for use by all reviewers in 2019. 

In addition to improving the consistency of deficiency letters, FDA officials 

said the information generated from the templates could be used to track 

deficiencies and requests for additional information, as well as provide 

information on the number and type of deficiencies in the letters. FDA 

officials told us that the plans for database and back-end analytical 

capabilities using information from the smart templates were less certain 

and dependent on available resources, and they pointed out that the 

information technology infrastructure can present unforeseen challenges.

FDA has not established performance metrics that would allow it to 

evaluate its implementation of the least burdensome provisions. FDA 

officials told us that the agency does not track concerns related to the 

least burdensome requirements, such as by examining dispute data to 

identify those that may be related. According to FDA’s 2002 guidance, the 

agency was in the process of developing tools to be used by both agency 

staff and its stakeholders to periodically assess the implementation of the 

least burdensome requirements.50 The FDA guidance identified a need 

for additional tools to accurately assess the agency’s incorporation of the 

least burdensome principles into its various regulatory activities and to 

assess the impact of the least burdensome approach on expediting the 

development of new medical technologies. Agency officials told us FDA 

had not developed these tools, but was now in the process of making 

other tools available. For example, they cited the development of the 

smart templates that will guide reviewers as they evaluate medical device 

submissions and generate deficiency letters. Officials noted that, given 

the scientific nature of the inquiry, and because least burdensome is a 

 49An applicant may request a risk-based classification under the de novo process for a 

new device of low to moderate risk, or for which there is no predicate device upon which 

to base a determination of substantial equivalence. See 21 U.S.C. § 360c(f)(2). 

50The guidance references two checklists that had already been developed at the time of 

the guidance. These checklists run through a list of whether or not least burdensome 

principles have been applied in early collaboration meetings between FDA and the device 

sponsor. FDA officials confirmed that early collaboration meetings are rarely used in 

CDRH, as they have been effectively superseded by the pre-submission process. See 

FDA, Least Burdensome Provisions: Concept and Principles, iii, 2002.

FDA Has Not Developed 

Metrics to Evaluate 

Implementation of the 

Least Burdensome 

Requirements, and While 

a New Audit Process 

Could Aid Oversight, Its 

Scope Is Still Unclear
Page 27 GAO-18-140 Least Burdensome Medical Device Approvals

general principle, developing a metric specific to the least burdensome 

requirements is a challenge. While this can be a challenge, FDA officials 

have noted that they are attempting to identify surrogate measures that 

can provide an indication that the reviewer considered the least 

burdensome requirements when making a request. According to federal 

standards for internal control, performance metrics are important for 

management to have relevant, reliable, and timely information available 

for management decision–making and external reporting purposes.51

Without such a metric, FDA may be asking medical device sponsors to 

provide information unnecessarily or in less efficient ways that are not in 

compliance with the requirement to use the least burdensome approach 

to medical device reviews.

FDA is in the process of developing an audit program that could provide it 

with information on its implementation of the least burdensome 

requirements. FDA has committed to conducting annual quality audits, 

which will be led by CDRH’s Quality Management Unit. Accordingly, FDA 

plans to identify, with industry input, areas to audit at least once per year. 

Initially, the agency has agreed to complete an audit of deficiency letters 

and pre-submissions by the end of fiscal year 2020. As of August 2017, 

FDA was still planning the deficiency letters audit, and developing its 

methodology and identifying audit outcomes. FDA officials told us the 

agency plans to finalize a deficiency letters audit plan by the spring of 

2018 and begin data collection by early summer of 2018. Officials 

explained that the audit will focus on processes—for example, the audit 

will not examine the scientific content of deficiency letters but will instead 

focus on whether CDRH has followed existing policies and procedures 

surrounding deficiency letters. In addition, the Quality Management Unit 

was still in the process of hiring most of its staff. As of August 2017, FDA 

officials told us the unit had 6 staff reporting to an Associate Director, and 

CDRH plans to gradually hire 20 more staff by 2020, starting once 

MDUFA IV funds are available beginning in October 2017.

In addition to these more specific efforts, FDA also plans to continue its 

overall evaluation of the medical device review process. The 2016 

independent assessment resulting from MDUFA III broadly evaluated 

FDA’s device review process, and although it mentioned least 

burdensome requirements only briefly, it addressed a number of related 

 51GAO-14-704G.
Page 28 GAO-18-140 Least Burdensome Medical Device Approvals

elements, including the quality of the review process and staff training.52

Under MDUFA IV, FDA committed to another independent assessment in 

two phases: (1) an evaluation of FDA’s implementation of the corrective 

action plan FDA developed in response to the MDUFA III assessment 

and (2) an evaluation of FDA’s premarket device review program to 

identify efficiencies that should be realized as a result of the process 

improvements and investments under MDUFA III and IV, among other 

things. As with the prior assessment, the new assessment will likely 

examine processes related to the least burdensome requirements, though 

the extent to which it will address the requirements is not yet known. 

Agency officials told us that FDA has committed to hiring a contractor by 

the end of December 2017.

FDA must balance the need to obtain sufficient data to determine the 

safety and effectiveness of medical devices under review, with the 

potential for undue burden and approval delays if unnecessary data is 

requested. Assuring that the agency uses the least burdensome method 

to complete its review helps to ensure it is able to make decisions about 

medical device approval in a timely way. While FDA implemented 

guidance and training related to the least burdensome requirements 

following the passage of FDAMA in 1997, it has taken few steps to 

develop performance metrics to evaluate the extent to which reviewers 

are using a least burdensome approach when reviewing medical device 

submissions. Recently, FDA implemented several changes that have the 

potential to improve its oversight of the least burdensome requirements 

and the clarity with which reviewers communicate the need for additional 

information. While planned audits of FDA’s medical device review 

process have the potential to provide the agency with evaluation tools 

through which to assess performance, these audits are still early in their 

development and the extent to which they will allow FDA to assess 

implementation of the least burdensome requirements is unclear. A 

complete and thorough assessment will be important for the agency to 

assure itself and external stakeholders that its reviews adhere to the least 

burdensome principles and requirements and thus are appropriately 

balanced.

 52Booz Allen Hamilton, Independent Assessment of FDA Device Review Process 

Management: Deliverable 6: Final Implementation Evaluation Report for the Food and 

Drug Administration, 2016.

Conclusions
Page 29 GAO-18-140 Least Burdensome Medical Device Approvals

We are making the following recommendation to FDA:

The Commissioner of FDA should develop performance metrics and use 

them to evaluate the implementation of the least burdensome 

requirements, such as during its planned audits of medical device 

deficiency letters. (Recommendation 1)

We provided a draft of this report to HHS. HHS concurred with our 

recommendation and provided written comments, which are reprinted in 

appendix I. In its written comments, HHS agreed that appropriate 

implementation of the least burdensome requirements is essential to 

FDA’s evaluation of its PMA and 510(k) medical device submissions, and 

agreed that it is important for FDA to evaluate how successfully it is 

implementing the requirements. HHS also reiterated FDA’s commitment 

to the least burdensome principles and provided an overview of its related 

efforts, several of which were noted in our draft report. HHS noted its 

concern that our draft report did not sufficiently capture all of FDA’s

efforts. While HHS cited FDA’s efforts related to improving the science 

underlying its regulatory decisions, which could reduce burden on medical 

device sponsors, our review focused on the steps involved in FDA’s 

review process. In this regard, HHS concurred with our recommendation 

that it develop performance metrics and use them to evaluate the 

implementation of the least burdensome requirements, such as during its 

planned audits of medical device deficiency letters. In response to this 

recommendation, HHS indicated that FDA intends to assess how it 

follows least burdensome requirements as part of these audits. We 

continue to encourage FDA to develop the evaluation tools necessary to 

ensure it conducts a complete and thorough assessment of its 

implementation of the least burdensome requirements. In addition to 

these general comments, HHS provided technical comments, which we 

incorporated as appropriate.

As agreed with your office, unless you publicly announce the contents of 

this report earlier, we plan no further distribution until 30 days from the 

report date. At that time, we will send copies of this report to the 

Secretary of Health and Human Services and other interested parties. In 

addition, the report will be available at no charge on the GAO website at 

http://www.gao.gov. 

If you or your staff have any questions about this report, please contact 

me at (202) 512-7114 or crossem@gao.gov. Contact points for our 

Recommendation for 

Executive Action

Agency Comments
Page 30 GAO-18-140 Least Burdensome Medical Device Approvals

Offices of Congressional Relations and Public Affairs may be found on 

the last page of this report. GAO staff who made major contributions to 

this report are listed in appendix II.

Marcia Crosse

Director, Health Care
Appendix I: Comments from the Department of 

Health and Human Services

Page 31 GAO-18-140 Least Burdensome Medical Device Approvals

Appendix I: Comments from the Department 

of Health and Human Services
Appendix I: Comments from the Department of 

Health and Human Services

Page 32 GAO-18-140 Least Burdensome Medical Device Approvals
Appendix I: Comments from the Department of 

Health and Human Services

Page 33 GAO-18-140 Least Burdensome Medical Device Approvals
Appendix I: Comments from the Department of 

Health and Human Services

Page 34 GAO-18-140 Least Burdensome Medical Device Approvals
Appendix I: Comments from the Department of 

Health and Human Services

Page 35 GAO-18-140 Least Burdensome Medical Device Approvals
Appendix II: GAO Contact and Staff 

Acknowledgments

Page 36 GAO-18-140 Least Burdensome Medical Device Approvals

Marcia Crosse (202) 512-7114 or crossem@gao.gov

In addition to the contact above, William Hadley (Assistant Director), 

Matthew Byer (Analyst-in-Charge), Luke Baron, and William Garrard 

made key contributions to this report. Also contributing were Sam 

Amrhein and Jennifer Rudisill.

Appendix II: GAO Contact and Staff 

Acknowledgments

GAO Contact

Staff 

Acknowledgments

(101234)
The Government Accountability Office, the audit, evaluation, and investigative 

arm of Congress, exists to support Congress in meeting its constitutional 

responsibilities and to help improve the performance and accountability of the 

federal government for the American people. GAO examines the use of public 

funds; evaluates federal programs and policies; and provides analyses, 

recommendations, and other assistance to help Congress make informed 

oversight, policy, and funding decisions. GAO’s commitment to good government 

is reflected in its core values of accountability, integrity, and reliability.

The fastest and easiest way to obtain copies of GAO documents at no cost is 

through GAO’s website (http://www.gao.gov). Each weekday afternoon, GAO 

posts on its website newly released reports, testimony, and correspondence. To 

have GAO e-mail you a list of newly posted products, go to http://www.gao.gov

and select “E-mail Updates.”

The price of each GAO publication reflects GAO’s actual cost of production and 

distribution and depends on the number of pages in the publication and whether 

the publication is printed in color or black and white. Pricing and ordering 

information is posted on GAO’s website, http://www.gao.gov/ordering.htm. 

Place orders by calling (202) 512-6000, toll free (866) 801-7077, or 

TDD (202) 512-2537.

Orders may be paid for using American Express, Discover Card, MasterCard, 

Visa, check, or money order. Call for additional information.

Connect with GAO on Facebook, Flickr, LinkedIn, Twitter, and YouTube.

Subscribe to our RSS Feeds or E-mail Updates. Listen to our Podcasts.

Visit GAO on the web at www.gao.gov and read The Watchblog.

Contact:

Website: http://www.gao.gov/fraudnet/fraudnet.htm

E-mail: fraudnet@gao.gov

Automated answering system: (800) 424-5454 or (202) 512-7470

Orice Williams Brown, Managing Director, WilliamsO@gao.gov, (202) 512-4400, 

U.S. Government Accountability Office, 441 G Street NW, Room 7125, 

Washington, DC 20548

Chuck Young, Managing Director, youngc1@gao.gov, (202) 512-4800

U.S. Government Accountability Office, 441 G Street NW, Room 7149 

Washington, DC 20548

James-Christian Blockwood, Managing Director, spel@gao.gov, (202) 512-4707

U.S. Government Accountability Office, 441 G Street NW, Room 7814, 

Washington, DC 20548

GAO’s Mission

Obtaining Copies of 

GAO Reports and 

Testimony

Order by Phone

Connect with GAO

To Report Fraud, 

Waste, and Abuse in 

Federal Programs

Congressional 

Relations

Public Affairs

Strategic Planning and 

External Liaison

Please Print on Recycled Paper.