Balancing Premarket and Postmarket 
Data Collection for Devices Subject to 
Premarket Approval 
 
Guidance for Industry and Food and 
Drug Administration Staff 
 
 
Document issued on April 13, 2015. 
The draft of this document was issued on April 23, 2014. 
 
 
 
 
 
 
 
 
For questions about this document concerning devices regulated by CDRH, contact the Office of 
the Center Director at 301-796-5900. For questions about this document concerning devices 
regulated by CBER, contact CBERs Office of Communication, Outreach and Development 
(OCOD) at 1-800-835-4709 or 240-402-7800. 
 
 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
 
    
Center for Devices and Radiological Health 
Center for Biologics Evaluation and Research  Contains Nonbinding Recommendations 
 
Preface 
Public Comment 
You may submit electronic comments and suggestions at any time for Agency consideration to 
http://www.regulations.gov. Submit written comments to the Division of Dockets 
Management, Food and Drug Administration, 5630 Fishers Lane, Rm 1061, (HFA-305), 
Rockville, MD 20852. Identify all comments with the docket number FDA-2014-D-0090. 
Comments may not be acted upon by the Agency until the document is next revised or updated. 
Additional Copies 
CDRH 
Additional copies are available on the Internet at 
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/default.
htm. You can also request an electronic copy by sending an e-mail to CDRH-
Guidance@fda.hhs.gov. Use the document number 1833 to identify this as the guidance you are 
requesting. 
CBER 
Additional copies are available on the Internet at 
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformatio
n/Guidances/default.htm or by written request to: 
  Center for Biologics Evaluation and Research 
Office of Communication, Outreach and Development (OCOD) 
10903 New Hampshire Ave. 
Bldg. 71, Rm. 3128 
Silver Spring, MD 20993-0002 
You can also request a copy by calling 1-800-835-4709 or 240-402-7800, or by sending an email 
to ocod@fda.hhs.gov.  
 
  2  Contains Nonbinding Recommendations 
 
Table of Contents 
I.  Introduction ......................................................................................................................................................... 4 
II.  Background ......................................................................................................................................................... 5 
A.  Least Burdensome ........................................................................................................................................... 6 
B.  Benefit-Risk .................................................................................................................................................... 7 
III.  Postmarket Data .................................................................................................................................................. 8 
IV.  When Post-Approval Studies May Be Appropriate at the Time of PMA Approval ........................................... 9 
V.  Conditions of Approval..................................................................................................................................... 15 
A.  Post-Approval Studies ................................................................................................................................... 16 
B.  Reporting Requirements for Post-Approval Studies ..................................................................................... 16 
C.  Labeling ......................................................................................................................................................... 16 
D.  Registries ....................................................................................................................................................... 17 
VI.  Postmarket Actions ........................................................................................................................................... 17 
  3  Contains Nonbinding Recommendations 
 
Balancing Premarket and Postmarket 
Data Collection for Devices Subject to 
Premarket Approval 
Guidance for Industry and  
Food and Drug Administration Staff  
 
This guidance represents the Food and Drug Administration's (FDA's) current thinking on 
this topic. It does not create or confer any rights for or on any person and does not operate to 
bind FDA or the public. You can use an alternative approach if the approach satisfies the 
requirements of the applicable statutes and regulations. If you want to discuss an alternative 
approach, contact the FDA staff responsible for implementing this guidance. If you cannot 
identify the appropriate FDA staff, call the appropriate number listed on the title page of this 
guidance.  
I. Introduction  
This guidance clarifies the Food and Drug Administrations (FDA or the Agency) current policy 
on balancing premarket and postmarket data collection during FDA review of premarket 
approval applications (PMAs). More specifically, this guidance outlines how FDA considers the 
role of postmarket information in determining the extent of data that should be collected in the 
premarket setting to support premarket approval while still meeting the statutory standard of 
reasonable assurance of safety and effectiveness.1 
The right balance of premarket and postmarket data collection facilitates timely patient access to 
important new technology without undermining patient safety. FDA believes this guidance 
document will improve patient access to safe and effective medical devices that are important to 
the public health by improving the predictability, consistency, transparency, and efficiency of the 
premarket review process.  This guidance document is intended to support FDAs efforts to 
enhance timely availability of devices subject to premarket approval. 
This guidance describes FDAs existing statutory requirements under the Federal Food, Drug, 
and Cosmetic Act (FD&C Act), its implementing regulations, and current policies that support 
this policy.  In addition, FDA clarifies how FDA considers postmarket data as part of the benefit-
                                                           
 
1 See section 515(d) of the Federal Food, Drug, and Cosmetic Act (FD&C Act).   
  4  Contains Nonbinding Recommendations 
 
risk framework described in FDAs guidance, Factors to Consider When Making Benefit-Risk 
Determinations in Medical Device Premarket Approval and De Novo Classifications, issued on 
March 28, 2012 (Benefit-Risk Guidance).2  This guidance and FDAs guidance Expedited 
Access for Premarket Approval Medical Devices Intended for Unmet Medical Need,3 issued on 
April 13, 2015 (EAP Guidance) describe how FDA considers balancing premarket and 
postmarket data collection during review of a PMA. 
FDAs guidance documents, including this one, do not establish legally enforceable 
responsibilities.  Instead, guidance documents describe the Agencys current thinking on a topic 
and should be viewed only as recommendations, unless specific regulatory or statutory 
requirements are cited.  The use of the word should in Agency guidance documents means that 
something is suggested or recommended, but not required.  
II.  Background 
FDAs mission is to protect and promote the public health.4  Part of FDAs mission is to assure 
that patients and providers have timely and continued access to safe and effective and high 
quality medical devices, and to facilitate medical device innovation.5 (Emphasis added).   
FDA recognizes that there are risks associated with every medical device on the market. At the 
time of device approval, certain safety and effectiveness questions may not be fully resolved due 
to significant obstacles, such as the time and cost involved to address possible rare adverse 
events or long-term safety issues, and because controlled clinical studies do not fully represent 
the benefit-risk profile of a device when used in real-world clinical practice. 
Getting the right balance between premarket and postmarket data collection  specifically, where 
appropriate, a greater reliance on postmarket collection, including real-world data collection, can 
reduce the extent of premarket data collection and directly impact when patients will have access 
to high-quality, safe and effective medical devices.  But, greater reliance on postmarket data 
collection could undermine patient safety if the necessary and timely data collection does not 
occur. 
Section 513(a)(3)(C) of the FD&C Act specifically requires FDA to consider the use of 
postmarket controls in lieu of collecting and reviewing all effectiveness data prior to PMA 
approval.  Specifically, section 513(a)(3)(C) states: 
                                                           
 
2 Available at: 
http://www.fda.gov/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm267829.htm. 
3 For more information on the Expedited Access Pathway program, see FDAs guidance, Expedited Access for 
Premarket Approval and De Novo Medical Devices Intended for Unmet Medical Need for Life Threatening or 
Irreversibly Debilitating Diseases or Conditions 
(http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM393978.
pdf). 
4 See http://www.fda.gov/AboutFDA/WhatWeDo/default.htm. 
5 See CDRH Mission, Vision and Shared Values, at 
http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDRH/ucm300639.htm. See 
also CBERs similar mission at 
http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CBER/ucm122878.htm. 
  5  Contains Nonbinding Recommendations 
 
In making a determination of a reasonable assurance of the effectiveness of a device for 
which [a premarket approval application] has been submitted, the Secretary shall consider 
whether the extent of data that otherwise would be required for approval of the 
application with respect to effectiveness can be reduced through reliance on postmarket 
controls. 
As discussed below, FDA has long applied postmarket controls as a way to reduce premarket 
data collection, where appropriate, while assuring that the statutory standard for approval of 
reasonable assurance of safety and effectiveness is still met.  This guidance provides a resource 
for industry and FDA staff on how FDA determines when it is appropriate for a sponsor6 of a 
PMA to collect some data (clinical or non-clinical) in the postmarket setting instead of in the 
premarket setting. 
FDA believes that applying postmarket controls to reduce premarket data collection, when 
appropriate, improves patient access to safe and effective medical devices that are important to 
the public health.  As discussed in this guidance, there are certain circumstances where FDA may 
consider it acceptable to collect certain data in the postmarket setting instead of in the premarket 
setting.  FDA applies careful postmarket monitoring to support continued safety and 
effectiveness of the device. 
A.  Least Burdensome 
Section 513(a)(3)(D)(ii) of the FD&C Act, a least burdensome provision, mandates that when 
FDA requests clinical data related to demonstrating a reasonable assurance of effectiveness, 
FDA only request clinical data that are necessary to establish device effectiveness for PMAs.  
FDAs guidance entitled, The Least Burdensome Provisions of the FDA Modernization Act of 
1997: Concept and Principles (Least Burdensome Guidance), issued October 4, 2002,7 
interprets least burdensome as a successful means of addressing a premarket issue that involves 
the most appropriate investment of time, effort, and resources on the part of industry and FDA, 
and specifies that the least burdensome provisions do not affect the statutory premarket review 
standards for devices.8   
As discussed in the Least Burdensome Guidance, the role of postmarket information should be 
considered in determining the appropriate type and amount of data that should be collected in the 
premarket setting to support premarket approval.  Postmarket information should also be 
considered for assuring long-term device safety and effectiveness, wherever appropriate.  
Reliance on postmarket controls (e.g., compliance with the Quality System regulations, post-
approval studies, postmarket surveillance, and the Medical Device Reporting requirements) 
                                                           
 
6 The use of the term sponsor in this guidance is used, depending on the context, to refer to sponsors of 
investigational device exemption (IDE) applications, PMA applicants, as well as sponsors of PMA-approved 
devices. 
7 http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm085994.htm. 
8 Section 513(a)(3)(D)(iv) provides that [n]othing in this [least burdensome provision] shall alter the criteria for 
evaluating an application for premarket approval of a device.   
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should be considered as a mechanism to reduce the extent of the premarket data for PMAs, while 
still ensuring that the statutory standard for premarket approval is met. 
B.  Benefit-Risk 
Under section 513(a) of the FD&C Act, FDA determines whether PMAs provide a reasonable 
assurance of safety and effectiveness by weighing any probable benefit to health from the use 
of the device against any probable risk of injury or illness from such use, among other relevant 
factors.  A reasonable assurance of safety occurs when it can be determined, based upon valid 
scientific evidence, that the probable benefits ... outweigh any probable risks, and can be 
demonstrated by establishing the absence of unreasonable risk of illness or injury associated 
with the use of the device for its intended uses and conditions of use.9   
To aid in this process, PMA sponsors submit valid scientific evidence, including one or more 
clinical investigations where appropriate, which FDA reviews to determine whether the device 
will have the effect it purports or is represented to have under the conditions of use prescribed, 
recommended, or suggested in the labeling of the device.10  FDA staff review the data 
submitted as part of the PMA and determine  based on a number of factors  if the data support 
the intended use and indications for use, and if the data analysis demonstrates that the probable11 
benefits of the device outweigh its probable risks.   
FDAs Benefit-Risk Guidance12 discusses the principal factors that FDA considers when making 
benefit-risk determinations during the premarket review process for certain medical devices.  As 
part of this guidance, FDA provides clarity regarding how FDA considers postmarket data in the 
context of the benefit-risk assessment discussed in the Benefit-Risk Guidance.   
When reviewing a PMA, FDA has the authority to impose postmarket requirements, including 
the conduct of post-approval studies and postmarket surveillance, as a condition of approval for 
devices subject to premarket approval.13  As discussed in section VI of this guidance, there are 
several actions that the sponsor or the FDA may, as appropriate, take in the postmarket setting as 
a result of the required conditions of approval.  For example, FDA may take enforcement action 
if the sponsor has not met the required conditions of approval, including failure to initiate or 
complete a post-approval study specified in the approval order for the device.  
                                                           
 
9 21 CFR 860.7(d)(1). 
10 Section 513(a)(3) of the FD&C Act.  
11 In general, probable and probability in this guidance have the same connotation as in 21 CFR 860.7(b)(3), i.e. 
they refer to the likelihood of the patient experiencing a benefit or risk.  Hypothesis testing, formal concepts of 
probability and predictive probability, and likelihood, typically are critical elements in the assessment of probable 
benefit and risk.  FDA does not intend for the use of the term probable benefit in this guidance to refer to the 
regulatory context for Humanitarian Device Exemptions (HDE) under section 520(m) of the FD&C Act, and FDAs 
implementing HDE regulations.   
12 See footnote 2.  
13 21 CFR 814.82 states that FDA may impose postapproval requirements in a PMA approval order or by 
regulation at the time of approval of the PMA or by regulation subsequent to approval.  In addition, under section 
522 of the FD&C Act, and FDAs implementing regulations at 21 CFR Part 822, FDA may order postmarket 
surveillance for certain Class III devices.   
  7  Contains Nonbinding Recommendations 
 
In addition, FDA believes that the implementation of our 2012 strategy for a National Medical 
Device Postmarket Surveillance System entitled Strengthening Our National System for 
Medical Device Postmarket Surveillance could address certain limitations with the current 
medical device surveillance program and allow for a greater shift of premarket data collection to 
the postmarket setting for appropriate devices.14  
III.  Postmarket Data 
As provided in the Benefit-Risk Guidance,15 postmarket data collection is a factor FDA 
considers as a part of making benefit-risk determinations.  We state in the Benefit-Risk 
Guidance: 
FDA may consider the collection of postmarket data as a way to clarify the magnitude 
and effect of mitigations or as a way to develop additional information regarding benefits 
or risks for certain device types or in specific patient populations when making a benefit-
risk determination. . . .  In addition, pursuant to section 513(a)(3)(C) of the FD&C Act, in 
certain cases, such as if a device is likely to be denied approval due to uncertainty about 
its effectiveness, FDA will consider whether postmarket data collection or other 
conditions might be structured so as to permit approval subject to those conditions.16 
As part of FDAs benefit-risk determination, one of the factors that FDA considers is the degree 
of certainty of the probable benefits and probable risks of a device in the Agencys review of a 
PMA. As part of the uncertainty factor discussed in the Benefit-Risk Guidance, FDA states that:  
there is never 100% certainty when determining reasonable assurance of safety and 
effectiveness of a device. However, the degree of certainty of the benefits and risks of a 
device is a factor we consider when making benefit-risk determinations.17 
FDA recognizes that medical device approvals are not made with absolute certainty due to 
significant obstacles, such as the time and cost involved to address possible rare adverse events 
or long-term safety and because clinical studies do not fully represent how a device will be used 
in clinical practice. 
                                                           
 
14 In September 2012, FDA released an initial report, Strengthening Our National System for Medical Device 
Postmarket Surveillance, providing an overview of FDA's medical device postmarket authorities and the current 
U.S. medical device postmarket surveillance system and also proposed four specific actions, using existing resources 
and under current authorities, to strengthen the medical device postmarket surveillance system in the U.S. This 
report is available at: 
http://www.fda.gov/downloads/AboutFDA/CentersOffices/CDRH/CDRHReports/UCM301924.pdf.  The update to 
the report, published in April, 2013, detailed the concrete steps that the FDA intends to complete to more efficiently 
collect better and more timely data, helping to identify issues more quickly.  This update is available at: 
http://www.fda.gov/downloads/MedicalDevices/Safety/CDRHPostmarketSurveillance/UCM348845.pdf. 
15 See footnote 2. 
16 See footnote 2. 
17 See footnote 2. 
  8  Contains Nonbinding Recommendations 
 
When making a determination whether it is appropriate to collect certain data in the postmarket 
setting, rather than premarket, FDA considers, among other factors, the devices potential impact 
on public health.  FDA may approve a device with a greater degree of uncertainty regarding the 
benefits and risks of the device if this uncertainty is sufficiently balanced by other factors, 
including the probable benefits of the device and the extent of postmarket controls.  For example, 
as discussed in FDAs Expedited Access for Premarket Approval and De Novo Medical Devices 
Intended for Unmet Medical Need for Life Threatening or Irreversibly Debilitating Diseases or 
Conditions Guidance,18 as part of FDAs Expedited Access Pathway program, FDA may accept 
greater pre-approval uncertainty regarding specific benefits and risks of devices demonstrating 
the potential to address unmet medical needs, as long as the premarket data still support a 
reasonable assurance of safety and effectiveness.  For example, FDA may be willing to allow 
smaller clinical trials, or nonrandomized trials. In addition, the extent to which FDA will accept 
certain data to be collected in the postmarket setting, rather than premarket, is impacted by the 
Agencys current authority to mandate completion of post-approval studies, and to withdraw 
PMA approval for the marketed device should FDA later determine that there is a lack of a 
showing of reasonable assurance that the device is safe or effective under the conditions of use 
prescribed. 
As discussed in more detail below, FDA may consider it acceptable to collect certain data in the 
postmarket setting under certain circumstances.  In these circumstances, in accordance with 
existing statutory requirements under the FD&C Act, including section 513(a)(3)(C) of the 
FD&C Act, its implementing regulations, and consistent with current guidance, FDA intends to 
appropriately balance the submission of premarket and postmarket data.  For example, 
uncommon or minor risks raised prior to PMA approval may, in appropriate instances, be 
addressed postmarket; assessing the long-term benefit-risk profile of the device may also be 
deferred to the postmarket phase.  In addition, in cases where FDA has robust experience with 
the device type, typically a more mature technology, there may be less uncertainty about 
probable risks and benefits of the device, and it may be appropriate for some data collection to 
occur in the postmarket setting. FDA appreciates that experience using a device in real-world 
settings helps healthcare providers learn about ways to improve a device as well as which 
patients are the best candidates for a device.  
IV.  When Post-Approval Studies May Be Appropriate at 
the Time of PMA Approval 
FDA may consider it acceptable to collect certain data in the postmarket setting, rather than 
premarket under certain circumstances when FDA has uncertainty regarding certain benefits or 
risks of the device, but the degree of uncertainty is acceptable in the context of the overall 
benefit-risk profile of the device at the time of premarket approval.19 
                                                           
 
18 See footnote 3.   
19 While the focus of this guidance is on original PMAs and new medical devices, the concepts and principles 
discussed in this document can be applied to appropriate PMA supplements supporting a change to a previously 
approved device if the change addresses an unmet medical need for patients with a life-threatening or irreversibly 
debilitating disease. 
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Examples:   
  Mature technology.  A mature technology is a device type that is well understood and the 
benefits and risks are well-characterized because of a robust history of testing and clinical 
use.  Therefore, it may be appropriate for some of the data collection that might 
ordinarily occur in the premarket setting to occur in the postmarket setting, such as when 
postmarket studies are likely to produce similar results to previously conducted similar 
studies for the same type of device). 
o  Example: Safety and effectiveness of pacing and defibrillation leads requires 
electrical and mechanical integrity over the life of the implant. While short-term 
clinical studies are adequately predictive of chronic electrical performance, many 
mechanical failures are time-dependent and appear years after implant. To 
demonstrate that short-term benefits outweigh short-term risks, the efficacy of 
leads can be demonstrated with measures of electrical performance (like pacing 
capture threshold) and limited longer-term data on mechanical reliability (1 or 2 
years compared to an implant life of 10 years). The collection of a more complete 
data set characterizing the long-term mechanical integrity over the longer life of 
the implant can be deferred to the postmarket setting.  
o  Example: A subcutaneous implantable cardioverter defibrillator (S-ICD) has the 
same basic elements of an ICD, which have been used for decades. Clinical and 
preclinical evaluations in the premarket setting for the subcutaneous ICD were 
tailored to collect data on the new aspects and to evaluate functionality of the 
device, while more detailed safety data is collected in a postmarket study. 
  Urgent public health need. Diagnostics with a public health impact can address unmet 
medical needs for both individual patients through early diagnosis, as well as informing 
the public health response by providing more detailed, timely information on disease 
incidence.  These types of diagnostic assays can provide information on timing of 
infections (e.g., whether infection occurred within the last 6 months or further into the 
past).  Individuals in the early stage of disease are at highest risk of transmission to their 
partners, and treatment and contact tracing can be effective in lowering risk.  However, in 
the past, significant barriers existed for properly evaluating the performance of these tests 
in clinical cohorts.  By allowing postmarket data collection to better confirm these tests 
medical benefits, uncertainties in the timing of infection can be validated while 
significantly streamlining the review process for devices with such a public health design 
scope.   
  Migration. Migration is an approach used for approval of Class III in vitro diagnostic 
devices when a previously approved, licensed, or cleared assay is migrated to another 
system for which FDA has not evaluated assay performance. The paradigm is suitable in 
cases when sufficient knowledge can be derived for the documentation of design 
controls, risk analyses, and prior performance studies on an already marketed system. 
This paradigm uses smaller and more focused analytical and clinical data sets, along with 
prior knowledge of device design and performance. For more information, see Assay 
Migration Studies for In Vitro Diagnostic Devices: Guidance for Industry and FDA Staff, 
  10  Contains Nonbinding Recommendations 
 
available at 
http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/Guidanc
eDocuments/ucm092752.pdf.    
o  Example: The migration paradigm is often used on Class III devices for hepatitis 
to support device performance when the previously approved assay is transferred 
to a new instrument platform. 
  Confirm mitigation effectiveness for a known risk in a post-approval study.  Mitigations 
may be necessary for known safety risks associated with use of the device.  Confirmation 
of the adequacy of the mitigation may be evaluated post-approval if mitigation of the risk 
is not fundamental to FDAs determination at the time of approval that the probable 
benefits outweigh the probable risks of the device.   
o  Example:  After a permanent implant was recalled due to failures that could lead 
to death, a firm developed a novel software feature aimed at predicting those 
failures.   The firm intends to incorporate that feature into its submission for a 
permanent implant intended for the same use as the recalled implant, which was 
marketed by a different company. The ability to predict failures would alert at-
risk patients to see their clinician (and address the concern) prior to a life-
threatening event.  FDA might typically expect clinical data in a PMA to support 
this type of feature before approval.  However, due to the public health need, 
FDA worked with the firm to use modeling on the novel software feature coupled 
with evaluation of published data to support premarket approval of the PMA. 
Clinical data on devices with the software feature were collected postmarket in a 
post-approval study, which was completed in a timely fashion after approval of 
the PMA. 
o  Example: For pacing and defibrillation leads, the degree of the changes in the 
products themselves and the potential impact to patient safety of those changes 
can affect the collection of data premarket and postmarket. For major changes 
(e.g., a completely new design, including new materials, new arrangement of 
those materials, and/or new connections) there will likely be more questions about 
impacts to patient safety, and thus a more rigorous set of premarket data (and a 
smaller degree of uncertainty) would be required before approval as compared to 
a lead with only minor changes. For example, even when a lead is new or 
significantly modified, FDA generally only requires 6 months to 2 years of data 
with a longer post-approval study to demonstrate long-term performance since the 
safety risks are well known. 
  Modify warnings, contraindications, precautions in approved labeling.  Post-approval 
studies may be designed to collect further data on specific adverse events or event types 
for which there was limited knowledge during premarket review (e.g., small number of 
adverse events that occur within a subpopulation or uncertainty relating to the probability 
of minor adverse events), and the review of the postmarket data may result in revision of 
the warning, contraindications and/or precautions in the labeling. 
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o  Example:  FDA generally requires that the labeling of certain device types contain 
warnings and precautions when the device has not been tested in the magnetic 
resonance imaging (MRI) environment for practitioners to use the device safely 
and effectively.  However, FDA determined that the results from a limited clinical 
study, modeling, and bench testing, when assessed together, provided assurance 
that a new device was safe under certain MRI scanning conditions [i.e., Magnetic 
Resonance (MR) Conditional]. The device could be approved without a 
contraindication or precaution regarding MRI; instead it only had a labeling 
limitation regarding the conditions under which an MRI could be done safely. In 
this scenario, additional clinical data collection to further confirm the safety of 
multiple scans and demonstrate chronic device durability occurred in the 
postmarket setting. 
  Approve for an intended population beyond what was fully evaluated in the pivotal trial, 
with a confirmatory post-approval study.  In some cases, a device may be approved for a 
patient population that has not been fully evaluated in the premarket clinical studies, if 
the approval is conditioned on a post-approval confirmatory trial in the indicated patient 
population and other data support a reasonable assurance of safety and effectiveness for 
the intended population at the time of approval.  If the device is being studied postmarket 
in accordance with its approval, there are no 21 CFR Part 812 investigational device 
exemption (IDE) requirements for the post-approval confirmatory study, as long as the 
device is studied in accordance with its approved labeling, including the indications for 
use.   
o  Example:  Human papillomavirus (HPV) testing devices have two distinct 
intended use populations with inherently different risk levels for cervical pre-
cancer and cancer.  Approval for both populations was based on full analytical 
data and agreement of clinical samples against a valid comparator, and clinical 
evidence of safety and effectiveness for the high risk population.  A post-approval 
study assessed the longitudinal risk of cervical cancer in the population with 
lower risk. 
  Assess long-term performance in a post-approval study.  Long-term performance of a 
specific aspect of a device may be difficult to assess in a premarket study as it may be 
necessary to collect data over a number of years in order to fully establish the 
performance of the device.  Shifting the collection and evaluation of long-term 
performance of a specific aspect of a device to a post-approval study allows FDA to 
approve the device based on a reasonable assurance of safety and effectiveness 
demonstrated in the premarket study, with uncertainty regarding the long-term 
performance to be addressed postmarket.   
o  Example:  Long-term chronic performance and mechanical integrity of new 
pacemaker leads is established through a standard post-approval study design 
requiring 1000 patients out to 5 years.  This postmarket study is in lieu of 
requiring chronic/long term data prior to premarket approval, which FDA 
  12  Contains Nonbinding Recommendations 
 
recognizes would be difficult to obtain in a timely fashion.  Current premarket 
clinical trials for this device require data out to one or two years.  
  Assess rare adverse events in a post-approval study.  It may be more appropriate to 
assess rare anticipated adverse events in the postmarket setting when FDA has a low 
degree of uncertainty regarding the positive benefit-risk balance at the time of premarket 
approval. 
o  Example:  In the 1980s, some contact lenses had been approved for up to 30 days 
of continuous wear. After some market experience, an epidemiologic study was 
published showing significant risk of microbial keratitis (severe corneal infection) 
in the extended wear modality that was correlated to length of continuous wear.  
Discussion between FDA and industry resulted in companies with extended wear 
approvals voluntarily changing their indications to a maximum of 7-days of 
continuous wear.  In the late 1990s, a new class of soft contact lens material 
(silicone hydrogel) was developed that permitted much higher oxygen flow to the 
cornea, which was widely expected to result in lower risk of microbial keratitis.  
Sponsors sought indications from FDA for 30 days of continuous wear for these 
new contact lenses.  However, microbial keratitis occurs at such a low rate that 
improved safety could not be adequately characterized in a conventional contact 
lens PMA study. FDA proposed a premarket study that, though large, could only 
assess related, less severe corneal adverse events, which was followed by a much 
larger post-approval cohort study accumulating approximately 5,000 patient-years 
of device exposure.  This provided a practical way for the rate of microbial 
keratitis to be adequately evaluated, while allowing the new technology to come 
to the market in a timely manner, with an indication for 30 days of continuous 
wear. 
o  Example:  Meta-analyses revealed that patients treated with first generation drug-
eluting stents had a higher rate of stent thrombosis than patients treated with bare 
metal stents.  While the overall rates of stent thrombosis were very low, stent 
thrombosis often results in heart attack, stroke, or death.  Dual antiplatelet therapy 
provides some protection from stent thrombosis, but it carries risks of bleeding, 
preventing patients from having even minor surgeries or dental procedures.  There 
was great debate in the scientific community regarding the optimal duration of 
dual antiplatelet therapy that would provide the needed protection against stent 
thrombosis without unduly prolonging a therapy with such substantial associated 
risks.  FDA proceeded with approval of second-generation drug-eluting stents 
with no change to premarket requirements, but required additional post-approval 
studies to determine stent thrombosis rates and the optimal duration of dual anti-
platelet therapy.     
  Confirm bench data with clinical data collected in a post-approval study.  It may be 
possible to approve a new device or a change to an existing device based on bench data 
with postmarket confirmatory clinical data.   
  13  Contains Nonbinding Recommendations 
 
o  Example: When an in vitro diagnostic device is capable of detecting both 
common and rare targets (e.g., mutations or pathogens), the rare targets may be 
challenging to evaluate clinically in a timely manner. Such tests may be approved 
based on robust pre-clinical and clinical data for the common target(s) with 
masking of the rare target(s) not adequately supported by the data. Masking 
involves software programming that prevents the user from viewing results for 
specific targets, and allows the test to reach the market before adequate data on 
rare targets are available. Sponsors may continue to evaluate the rare targets 
postmarket to support unmasking. This process thus allows collection of 
additional clinical data to support the final approval of the device for all targets. 
o  Example: When quadripolar lead connectors were introduced, FDA worked with 
sponsors to capture clinical data in both the premarket and postmarket settings in 
combination with premarket animal study data and bench testing. 
  Where the performance of a particular device type is well-studied, documented, and 
understood. It may be possible to approve a new device or a new indication for an 
existing device based on safety and effectiveness information already known about the 
device or device type. 
o  Clinical data that may be sufficient in cases like this include Objective 
Performance Criteria (OPC), Performance Goals (PG), Patient Reported 
Outcomes (PROs), or other data in lieu of a randomized controlled clinical trial. 
o  Example: A sponsor is seeking approval of a 7-day extended wear lens. The same 
lens was approved for daily wear and the sponsor has a substantial marketing 
history in the U.S. for the daily wear lens. If the 7-day lens is made of the same 
material as the daily wear lens, FDA may consider transferring a clinical study to 
assess most aspects of device safety to the postmarket setting. 
  Where long-term outside the U.S. (OUS) clinical performance data is available but not 
sufficient. It may be possible to defer to postmarket or otherwise limit the collection of 
clinical data from patients in the U.S. followed by a post-approval study if data from 
outside the U.S. is available and provides reasonable assurance of safety and 
effectiveness. 
FDAs Expedited Access for Devices Guidance20 also describes circumstances under which FDA 
may consider it acceptable to collect certain data in the postmarket setting, rather than premarket, 
while still ensuring that the statutory standard for premarket approval of reasonable assurance of 
safety and effectiveness is met.  As part of the Expedited Access Pathway program described in 
the Expedited Access for Devices Guidance, in order to facilitate earlier patient access to devices 
that demonstrate the potential to address an unmet medical need, FDA may accept a higher 
degree of uncertainty about the benefit-risk profile of the device at the time of approval by 
                                                           
 
20 See footnote 3.   
  14  Contains Nonbinding Recommendations 
 
collecting certain data in the postmarket setting rather than premarket.  Please reference the 
Expedited Access Pathway guidance for more information about how FDA may be willing to 
accept greater uncertainty. 
FDA believes it is important to routinely reassess whether data that the Agency receives in a 
premarket submission for a device type may instead be collected postmarket or if the data are no 
longer necessary for FDA to determine that there is a reasonable assurance of safety and 
effectiveness for the device type.  Sponsors who believe that the extent of data FDA previously 
expected in a premarket submission for the device type for which they plan to submit a PMA 
should be collected postmarket or should no longer be required, should submit a Pre-Submission 
(Pre-Sub),21 as described in FDAs guidance, Requests for Feedback on Medical Device 
Submissions: The Pre-Submission Program and Meetings with Food and Drug Administration 
Staff22 (Pre-Sub Guidance).23   
V.  Conditions of Approval  
As discussed above, the extent to which FDA will accept certain data to be collected in the 
postmarket setting, rather than premarket, is affected by the Agencys current authority to 
mandate completion of post-approval studies and to withdraw PMA approval for marketed 
devices for which FDA later determines that there is insufficient data demonstrating reasonable 
assurance that the device is safe or effective under the conditions of use prescribed.  Therefore, 
FDA may impose postmarket requirements at the time of approval of the device, including 
conditioning the device approval on continuing evaluation and periodic reporting on the safety, 
effectiveness, and reliability of these devices for their intended uses, in accordance with 21 CFR 
814.82(a)(2).  These postmarket data will enable the Agency to assess the risks and benefits of 
these devices with a higher degree of certainty and take action where this information raises 
concerns regarding the safety or effectiveness of these devices.   
FDA may also impose conditions of approval on the labeling of the devices under 21 CFR 
814.82(a)(3) if important for the devices safe and effective use (e.g., in order to ensure that 
patients and healthcare providers have complete and accurate information regarding the benefits 
and risks of the device).  In addition, if necessary to provide for a reasonable assurance of the 
                                                           
 
21 Section 745A(b) of the FD&C Act, added by section 1136 of FDASIA, requires applicants to include an 
electronic copy of certain submission types, including PMA submissions and Pre-Subs, after issuance of final 
guidance implementing that provision.  FDA issued the guidance eCopy Program for Medical Devices Submissions 
(available at 
http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM313794.
pdf), on December 31, 2012.  Sponsors are therefore required to include an eCopy for all PMA submission types and 
Pre-Subs.   
22 For more information on the Pre-Sub Program, see FDAs guidance Requests for Feedback on Medical Device 
Submissions: The Pre-Submission Program and Meetings with Food and Drug Administration Staff 
(http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM311176.
pdf).  FDAs draft guidance represents FDAs proposed approach on this topic.    
23 As another option, for devices that have been automatically classified into class III under Section 513(f)(1) of the 
FD&C Act, if there is an approved PMA for a device of that type, sponsors may seek reclassification under Section 
513(f)(3) of the FD&C Act. If there is no approved PMA for a device of that type, a de novo request may be an 
appropriate option for such a device. 
  15  Contains Nonbinding Recommendations 
 
safety and effectiveness of these devices, FDA may restrict the device as a condition of approval 
under 21 CFR 814.82(a)(1).   
FDA intends to work with sponsors regarding the conditions of approval that may be imposed, 
including discussing post-approval study type and size, the types of follow-up necessary, and 
other details to ensure postmarket activities meet requirements for data collection. Further, FDA 
recognizes that postmarket studies should not be limited to repeating or conducting variations of 
premarket studies. FDA intends to work with sponsors to identify the best way to collect the 
 
information necessary to demonstrate safety and effectiveness in the postmarket setting.
A.  Post-Approval Studies  
In circumstances where post-approval data collection is appropriate, FDA may require post-
approval studies as a condition of approval.  These studies may include both clinical and non-
clinical testing.  The post-approval study design should take into account possible sample size 
implications for conduct of interim analyses to the extent such analyses are required by FDA. 
FDA also recommends post-approval study designs consider market conditions and potential 
recruitment challenges with respect to the risk level of the device, among other factors. The 
approval order will specify the agreed upon timeframe for the sponsor to complete the post-
approval study, conduct analyses and submit the data to FDA.   
In appropriate instances, FDA may order the sponsor to conduct postmarket surveillance under 
section 522 of the FD&C Act in lieu of a post-approval study.  Note that the failure or refusal of 
a manufacturer to comply with section 522 is a prohibited act under section 301(q)(1)(C) of the 
FD&C Act, 21 U.S.C. 331(q)(1)(C). Further, under section 502(t)(3) of the act, 21 U.S.C. 
352(t)(3), a device is misbranded if there is a failure or refusal to comply with any requirement 
under section 522 of the FD&C Act.  Please note that violations of sections 301(q)(1)(C) or 
502(t)(3) may lead to enforcement action including seizure, injunction, prosecution, or civil 
money penalties. 
B.  Reporting Requirements for Post-Approval Studies 
FDA may impose continuing periodic reporting on the safety, effectiveness, and reliability of the 
device for its intended use under 21 CFR 814.82(a)(2) (e.g., periodic reporting of the status and 
interim data or analyses of the required postmarket data collection).  The reports required to be 
submitted will be included in the post-approval order. 
C.  Labeling 
FDA may impose certain labeling requirements as a condition to PMA approval, under 21 CFR 
814.82(a)(3) that are important for the devices safe and effective use (e.g., information on the 
risks and benefits of the use of the device).  Any labeling requirements will be included in the 
approval order.   
The labeling of an approved device should include a succinct description of the uncertainty about 
anticipated benefits and risks and the extent of data that supported approval, including the 
required post-approval study or studies. 
  16  Contains Nonbinding Recommendations 
 
D.  Registries 
 
In some cases, it may be appropriate to use data from a registry to meet the requirements of the 
condition of approval study.  Maintenance of registry data may help provide further information 
about the safety and effectiveness of the device, or to verify records, reports, or information 
submitted to the agency [21 CFR 814.82(a)]. 
VI.  Postmarket Actions  
There are several actions that the sponsor or the FDA may, as appropriate, take in the postmarket 
setting as a result of the required conditions of approval, depending on whether the sponsor 
conducts and completes the required post-approval study and submits, in a timely manner, the 
data from the study to FDA as specified in the approval order, as well as the studys results.  
FDA may take enforcement action if the sponsor has not met the required conditions of approval, 
including failure to initiate or complete a post-approval study specified in the approval order for 
the device. 
In addition, as provided in the FDA guidance entitled, Procedures for Handling Post-Approval 
Studies Imposed by PMA Order, issued June 15, 2009 (post-approval guidance),24 FDA posts 
certain information about the post-approval studies for devices on FDAs website at: 
http://www.accessdata.fda.gov/scripts/ cdrh/cfdocs/cfPMA/PMA_pas.cfm.   
The actions that the sponsor or FDA may take in the postmarket setting include, but are not 
limited to, the following: 
(1)  Submission of a PMA Supplement 
The results from the post-approval study may trigger the need for the sponsor to submit a PMA 
supplement to FDA in accordance with 21 CFR 814.39(a) if the sponsor makes a change 
affecting the safety or effectiveness of the device.  Examples include, but are not limited to, 
narrowing or expanding the indication for use of the device, labeling changes, and changes in the 
performance or design specifications.   
Labeling Changes 
Information learned about a device from postmarket use may result in changes in the information 
required in the devices approved labeling. Depending on the results of the post-approval study, 
the sponsor could revise the devices labeling, with the approval of FDA, to reflect the 
population and condition for which a clinical benefit was directly established in the post-
approval study or studies, including expanding or narrowing the indication for use, or removing 
or revising language in the labeling regarding the level of uncertainty about the approved 
indication for use. 
                                                           
 
24 Available at:  
http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm070974.htm.   
  17  Contains Nonbinding Recommendations 
 
The sponsor may decide to revise other sections of labeling (e.g., contraindications, warnings, 
precautions, adverse events and clinical studies), with FDAs approval, to ensure that, based on 
the new data, the labeling adequately describes the safety and effectiveness of the device. For 
example, new information about an adverse event may require labeling changes to device 
instructions for use or to warnings or precautions to ensure the device complies with section 
502(f) of the FD&C Act and 21 CFR Part 801.  During its review of post-approval study reports, 
FDA may discuss changes to the labeling based on the study findings to ensure the device 
labeling has adequate directions for use. 
(2)  Safety Communications 
In some instances, it may be in the best interest of public health for FDA to issue a safety 
communication, such as if the post-approval study raises new safety concerns, but FDA believes 
there is still a reasonable assurance of safety and effectiveness. 
(3)  Panel Meeting 
As described in the post-approval guidance, FDA may seek the advice of panels when 
considering the progress of, or data from the post-approval study, such as when the results of the 
study may be difficult to interpret.25   
(4)  Administrative and Enforcement Actions 
FDA may take a variety of administrative or enforcement actions if the Agency concludes that, 
based on the data from the required post-approval study or other source, there is a lack of 
reasonable assurance that the device is safe or effective under the conditions of use, or if the 
sponsor has not met the required conditions of approval under 21 CFR 814.82, including failure 
to initiate or complete a post-approval study specified in the approval order.  For example, 
failure to comply with post-approval requirements under 21 CFR 814.82(a)(2) when conducting 
postmarket surveillance may cause the device to be misbranded under section 502(t)(2) of the 
FD&C Act and constitute a prohibited act under section 301(q)(1)(B) of the FD&C Act, which 
could result in seizure, injunction, or civil money penalties.  Also, failure to comply with post-
approval labeling and advertising requirements under 21 CFR 814.82(a)(3) may cause the device 
to be misbranded under section 502 of the FD&C Act.   
FDA recognizes that circumstances may arise outside of the sponsors control that may adversely 
affect the ability of the sponsor to complete the post-approval study on time.  Therefore, 
although FDA expects sponsors to undertake efforts to complete the study on time, when 
appropriate, FDA intends to be reasonably flexible about the timeframe for completing a post-
approval study and submitting data to the Agency. 
In accordance with section 515(e) of the FD&C Act and 21 CFR 814.46, FDA may also 
withdraw PMA approval of a device if, for example:  
  On the basis of the data from the required post-approval study(ies), or other new 
information with respect to such device, evaluated together with the evidence available to 
                                                           
 
25 See footnote 23. 
  18  Contains Nonbinding Recommendations 
 
FDA when the PMA was approved, FDA finds that there is a lack of a showing of 
reasonable assurance that the device is safe or effective under the conditions of use 
prescribed, recommended or suggested in the labeling; 
  The sponsor fails to meet any post-approval requirement imposed by the PMA approval 
order, which includes failure to complete a post-approval requirement within the 
timeframe established in the approval order; or 
  On the basis of new information, evaluated together with the evidence available to FDA 
when the PMA was approved, FDA finds that the labeling, based on a fair evaluation of 
all material facts, is false or misleading in any particular, and such labeling is not 
corrected within a reasonable time after receipt of written notice from FDA. 
If FDA determines there are grounds for withdrawal, the Agency may ask the sponsor if they 
would like to voluntarily request withdrawal of approval under 21 CFR 814.37(d).  If the sponsor 
does not voluntarily request the Agency to withdraw approval, FDA will notify the sponsor of 
FDAs proposal to withdraw approval in a notice of opportunity for an informal hearing under 21 
CFR Part 16.26  If the sponsor does not request a hearing or if after the part 16 hearing, FDA 
decides to proceed with the withdrawal, FDA will issue the sponsor an order withdrawing 
approval of the application.27  The order will be issued under 21 CFR 814.17, will state each 
ground for withdrawing approval, and will include a notice of an opportunity for administrative 
review under section 515(e)(2) of the FD&C Act. FDA will give the public notice of an order 
 
withdrawing approval of a PMA, in accordance with 21 CFR 814.46(e).
                                                           
 
26 21 CFR 814.46(c) 
27 21 CFR 814.46(d).  
  19