Contains Nonbinding Recommendations 
Developing and Responding to 
Deficiencies in Accordance with 
the Least Burdensome Provisions 
 
Guidance for Industry and  
Food and Drug Administration Staff  
 
 
Document issued on October 26, 2022. 
 
Document originally issued on November 2, 2000. 
 
This document supersedes Developing and Responding to Deficiencies in 
Accordance with the Least Burdensome Provisions issued September 29, 
2017. 
 
 
For questions about this document regarding CDRH-regulated devices, contact ORP: Office of 
Regulatory Programs/DRP1: Division of Regulatory Programs 1 at 301-796-5640 or by email 
at  opeqsubmissionsupport@fda.hhs.gov. 
  
 
For questions about this document regarding CBER-regulated devices, contact the Office of 
Communication, Outreach, and Development (OCOD) at 1-800-835-4709 or 240-402-8010, or 
by email at ocod@fda.hhs.gov.  
 
 
 
 
 
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 Dockets Management Staff, Food 
and Drug Administration, 5630 Fishers Lane, Room 1061, (HFA-305), Rockville, MD 20852-
1740. Identify all comments with the docket number FDA-2017-D-5711. Comments may not 
be acted upon by the Agency until the document is next revised or updated. 
 
Additional Copies 
 
CDRH 
Additional copies are available from the Internet. You may also send an e-mail request to 
CDRH-Guidance@fda.hhs.gov to receive a copy of the guidance. Please use the document 
number 1195 and complete title of the guidance in the request . 
 
CBER 
Additional copies are available from the Center for Biologics Evaluation and Research 
(CBER), Office of Communication, Outreach, and Development (OCOD), 10903 New 
Hampshire Ave., WO71, Room 3128, Silver Spring, MD 20993-0002, or by calling 1-800-
835-4709 or 240-402-8010, by email, ocod@fda.hhs.gov, or from the Internet at  
https://www.fda.gov/vaccines-blood-biologics/guidance-compliance-regulatory-
information-biologics/biologics-guidances. 
   
  Contains Nonbinding Recommendations 
Table of Contents 
 
I.  Introduction ....................................................................................................................... 1 
 
II.  Background ....................................................................................................................... 2 
III.  Scope .............................................................................................................................. 5 
IV.  Deficiency letters in marketing applications .................................................................. 5 
A.  Guiding principles ...................................................................................................... 5 
B.  Suggested content and format for deficiencies .......................................................... 7 
C.  Review of deficiency letters ....................................................................................... 8 
V.  Suggested format for industry responses to FDA deficiencies ......................................... 8 
Appendix A: Deficiency and applicant response examples .................................................... 10 
 
   
  Contains Nonbinding Recommendations 
Developing and Responding to 
Deficiencies in Accordance with 
the Least Burdensome Provisions 
 
 
Guidance for Industry and  
Food and Drug Administration Staff  
 
This guidance represents the current thinking of the Food and Drug Administration (FDA 
or Agency) on this topic. It does not establish any rights for any person and is not binding 
on FDA or the public. You can use an alternative approach if it satisfies the requirements 
of the applicable statutes and regulations. To discuss an alternative approach, contact the 
FDA staff or Office responsible for this guidance as listed on the title page.  
 
I.  Introduction 
This guidance document is intended to help Food and Drug Administration (FDA) staff 
develop a request for additional information needed to make a decision on a medical device 
marketing application in accordance with the Least Burdensome Provisions of the Federal 
Food, Drug, and Cosmetic Act (FD&C Act). Such an FDA request for additional information 
is known as a deficiency. In addition, this guidance describes suggested formats for FDA 
staff to communicate deficiencies, and for industry to use for responses to such requests, in 
order to make efficient use of industry and FDAs time. This guidance includes examples of 
well-constructed deficiencies and industry responses to facilitate an efficient review process. 
This guidance also details supervisory review, major/minor deficiencies, additional 
considerations, and prioritization of deficiencies in FDA deficiency letters.  
 
For the current edition of the FDA-recognized consensus standard(s) referenced in this 
document, see the FDA-Recognized Consensus Standards Database.1 
 
In general, FDAs guidance documents do not establish legally enforceable responsibilities. 
Instead, guidances describe the Agencys current thinking on a topic and should be viewed 
only as recommendations, unless specific regulatory or statutory requirements are cited. The 
 
 
 
1 Available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm. 
1  Contains Nonbinding Recommendations 
use of the word should in Agency guidance means that something is suggested or 
recommended, but not required.  
 
Throughout this guidance document, the terms we, us, and our refer to FDA staff from 
the Center for Devices and Radiological Health (CDRH) or the Center for Biologics 
Evaluation and Research (CBER) involved in the review and decision-making aspects of a 
marketing application. You, your, or applicant refer to the submitter of a premarket 
application. 
 
II.  Background 
FDA review staff often identify the need for additional information in order to make a 
premarket approval (PMA) determination of reasonable assurance of safety and effectiveness 
(RASE), a humanitarian device exemption (HDE) determination of safety and probable 
benefit, a 510(k) determination of substantial equivalence (SE), or a classification 
determination for a De Novo request. Throughout this guidance document, PMA, 510(k), 
HDE, and De Novo premarket submissions will be collectively called marketing 
applications. In addition, throughout this guidance document, the FDA decisions made on 
these applications will be collectively called marketing authorization decisions (e.g., PMA 
reasonable assurance of safety and effectiveness determination, 510(k)substantial 
equivalence determination, HDE safety and probable benefit determination, and De Novo 
classification determination). FDAs requests for additional information needed to complete 
the review process are colloquially known as deficiencies. 
 
FDA may convey deficiencies via interactive review or through a deficiency letter. In 
general, FDA uses interactive review to attempt to resolve minor deficiencies and additional 
considerations with the applicant by phone or email without putting the submission officially 
on hold. Deficiency letters are delivered via email and generally include at least one major 
issue and place the marketing application on hold pending FDAs receipt of the requested 
additional information. FDA refers to PMA and HDE deficiency letters as major deficiency 
letters and 510(k) and De Novo deficiency letters as additional information letters or 
requests for additional information. For more information about interactive review and 
when medical device submissions are placed on hold, see the FDA guidance documents 
Types of Communication During the Review of Medical Device Submissions,2 FDA and 
Industry Actions on Premarket Notification (510(k)) Submissions: Effect on FDA Review 
Clock and Goals,3 FDA and Industry Actions on Premarket Approval Applications 
 
 
 
2 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/types-communication-during-
review-medical-device-submissions.  
3 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/fda-and-industry-actions-
premarket-notification-510k-submissions-effect-fda-review-clock-and-goals. 
2  Contains Nonbinding Recommendations 
(PMAs): Effect on FDA Review Clock and Goals,4 and FDA and Industry Actions on De 
Novo Requests: Effect on FDA Review Clock and Goals.5 
 
Minor deficiencies may still be included in deficiency letters when related to the resolution of 
substantive issues (e.g., modification of the proposed Indications for Use may lead to 
revisions in labeling and administrative items), or if they were still unresolved following 
interactive review attempts. Additional considerations may also be included in deficiency 
letters if left unresolved following interactive review attempts, but would not require an 
applicant response. 
 
The Least Burdensome Provisions of the Food and Drug Administration Modernization Act 
(FDAMA) were added to the FD&C Act in 1997. The Least Burdensome Provisions were 
amended by the Food and Drug Administration Safety and Innovation Act (FDASIA) and the 
21st Century Cures Act and state that: 
 
  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.6 
 
  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.7 
 
  In requesting additional information with respect to a PMA application, the 
Secretary shall consider the least burdensome appropriate means necessary to 
demonstrate a reasonable assurance of device safety and effectiveness.8 
 
 
 
 
4 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/fda-and-industry-actions-
premarket-approval-applications-pmas-effect-fda-review-clock-and-goals. 
5 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/fda-and-industry-actions-de-
novo-classification-requests-effect-fda-review-clock-and-goals. 
6 See FD&C Act, Section 513(i)(1)(D)(i). 
7 See FD&C Act, Section 513(a)(3)(D)(ii). 
8 See FD&C Act, Section 515(c)(5)(A). 
3  Contains Nonbinding Recommendations 
  The Secretary shall consider the role of postmarket information in determining the 
least burdensome means of demonstrating a reasonable assurance of device safety and 
effectiveness.9 
 
  The Secretary shall only request the minimum required information necessary to 
support a determination of substantial equivalence or a reasonable assurance of safety 
and effectiveness of the device.10 
 
  The Least Burdensome Provisions do not change the standards for premarket 
approval or substantial equivalence.11 
 
Information about specific approaches to the Least Burdensome Provisions are detailed in the 
FDA guidance document The Least Burdensome Provisions: Concept and Principles.12 
Additionally, the Agencys approach to least burdensome principles in 510(k) submissions is 
discussed in the FDA guidance document The 510(k) Program: Evaluating Substantial 
Equivalence in Premarket Notifications [510(k)].13 
 
Under section 513(a)(2) of the FD&C Act, FDA determines the safety and effectiveness of a 
device 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.14  The least 
burdensome principles are also consistent with FDAs approach to evaluating the benefit-risk 
profile in marketing authorization decisions for medical devices.  Further, marketing 
authorization decisions may involve some degree of uncertainty about the benefits and risks 
of a medical device. In some circumstances, greater uncertainty may be appropriate, such as 
when the probable benefits are high or the probable risks of the device are low.  As part of 
considering and applying the tenets of least burdensome principles, the factors of benefit, risk 
and uncertainty are also considered as appropriate.  For additional information and a fuller 
explanation of how FDA may consider these factors in marketing authorization decisions, 
please see FDAs guidance documents entitled Benefit-Risk Factors to Consider When 
Determining Substantial Equivalence in Premarket Notifications (510(k)) with Different 
Technological Characteristics,15 Factors to Consider When Making Benefit-Risk 
 
 
 
9 See FD&C Act, Section 515(c)(5)(C). 
10 See FD&C Act, Sections 513(i)(1)(D)(ii), 513(a)(3)(D)(iii), and 515(c)(5)(B). 
11 See FD&C Act, Sections 513(i)(1)(D)(iii), 513(a)(3)(D)(iv), and 515(c)(5)(D). 
12 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/least-burdensome-provisions-
concept-and-principles. 
13 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/510k-program-evaluating-
substantial-equivalence-premarket-notifications-510k. 
14 The criteria for establishing safety and effectiveness of a device are set forth in 21 CFR 860.7. Subsection (b) 
notes, [i]n determining the safety and effectiveness of a device...the Commissioner and the classification 
panels will consider the following, among other relevant factors... (3) The probable benefit to health from the 
use of the device weighed against any probable injury or illness from such use. (21 CFR 860.7(b)). For 
additional information on FDAs safety and effectiveness review, see 21 CFR 860.7(d) and (e).    
15 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/benefit-risk-factors-consider-
when-determining-substantial-equivalence-premarket-notifications-510k. 
4  Contains Nonbinding Recommendations 
Determinations in Medical Device Premarket Approval and De Novo Classifications,16 and 
Consideration of Uncertainty in Making Benefit-Risk Determinations in Medical Device 
Premarket Approvals, De Novo Classifications, and Humanitarian Device Exemptions.17 
 
In the Medical Device User Fee Amendments of 2022 (MDUFA V) Commitment Letter 
from the Secretary of Health and Human Services to Congress,18 FDA committed to update 
this guidance document to clarify what constitutes a statement of basis for the deficiency 
and continue alignment with the following:   
 
Deficiency letters should include a statement of the basis for the deficiencies (e.g., a 
specific reference to applicable section(s) of a rule, final guidance, recognized 
standard unless the entire or most of document is applicable). In the instance when 
the deficiency cannot be traced in the manner above and relates to a scientific or  
regulatory issue pertinent to the determination, FDA will cite the specific scientific 
issue and the information to support its position.  
 
Deficiency letters will undergo supervisory review prior to issuance to ensure the 
deficiencies cited are relevant to a marketing authorization decision (e.g., 510(k) 
clearance, PMA approval, and [D]e [N]ovo classification). 
 
III.  Scope 
This guidance is intended to help FDA review staff and supervisors develop deficiencies for 
inclusion in deficiency letters for medical device marketing applications. While FDA review 
staff may use a similar deficiency format for interactive review, investigational device 
exemption applications (IDEs), 513(g) requests for information, and Q-Submissions, this 
guidance document only applies to deficiency letters sent during the review of marketing 
applications. This guidance will also aid industry in preparing responses to deficiency letters. 
Examples of different types of FDA deficiencies along with rationales to support such 
requests for information, as well as examples of different approaches to respond to FDA 
deficiencies, are included in Appendix A.  
 
IV.  Deficiency letters in marketing applications 
A.  Guiding principles 
 
 
 
16 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/factors-consider-when-making-
benefit-risk-determinations-medical-device-premarket-approval-and-de.  
17 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/consideration-uncertainty-
making-benefit-risk-determinations-medical-device-premarket-approvals-de.  
18 See 168 CONG. REC. S5194-S5203 (daily ed. September 28, 2022) (Food and Drug Administration User Fee 
Reauthorization). The MDUFA V Commitment Letter is also available at 
https://www.fda.gov/media/158308/download. 
5  Contains Nonbinding Recommendations 
In using this guidance document, FDA review staff should follow these guiding 
principles regarding the development of deficiency letters: 
 
1.  Information unrelated to the marketing authorization decision should not be 
part of the decision-making process. 
2.  Alternative approaches to resolving regulatory issues should be considered to 
optimize the necessary time, effort, and resources involved in developing a 
response. 
3.  Deficiencies should request the minimum (i.e., least burdensome) amount of 
information necessary to adequately address the identified issue in the most 
efficient manner at the right time. The balance between premarket and 
postmarket should be considered to determine when information should be 
provided to address the identified issue.19   
4.  The totality of the information necessary for evaluating the benefit-risk profile 
of the device20 as well as uncertainty in making benefit-risk determinations 
for PMAs and De Novos should be considered.21 
5.  Major deficiencies are those based on least burdensome principles that, if not 
resolved, will preclude a favorable marketing authorization decision. Major 
deficiencies should only be included if their resolution is necessary in order to 
reach a final decision. 
6.  If the Agency is including minor deficiencies identified during the review in 
the deficiency letter, the Agency should identify these requests separately 
from major issues, and whenever possible, attempt to resolve minor 
questions/issues interactively. Minor deficiencies are FDA requests that can 
be resolved in a straightforward manner, but that need to be addressed to meet 
regulatory requirements or to prevent potential misbranding or adulteration. In 
 
 
 
19 See also The Least Burdensome Provisions: Concept and Principles, available at 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/least-burdensome-provisions-
concept-and-principles. 
20 See Benefit-Risk Factors to Consider When Determining Substantial Equivalence in Premarket Notifications 
(510(k)) with Different Technologial Characteristics, available at https://www.fda.gov/regulatory-
information/search-fda-guidance-documents/benefit-risk-factors-consider-when-determining-substantial-
equivalence-premarket-notifications-510k and Factors to Consider When Making Benefit-Risk Determinations 
in Medical Device Premarket Approval and De Novo Classifications, available at 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/factors-consider-when-making-
benefit-risk-determinations-medical-device-premarket-approval-and-de. 
21 See Consideration of Uncertainty in Making Benefit-Risk Determinations in Medical Device Premarket 
Approvals, De Novo Classifications, and Humanitarian Device Exemptions, available at 
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/consideration-uncertainty-making-
benefit-risk-determinations-medical-device-premarket-approvals-de. 
6  Contains Nonbinding Recommendations 
general, the Agency should not issue a formal deficiency letter if only minor 
deficiencies remain, but instead should attempt to resolve them interactively. 
7.  FDA may also include additional considerations that are suggestions, 
recommendations, or requests that are not expected to preclude a favorable 
marketing authorization decision. Because additional considerations are not 
expected to preclude a favorable decision, they do not require an applicant 
response. 
B.  Suggested content and format for deficiencies 
An effective deficiency should concisely include the following four elements: 
 
1.  What was submitted: Acknowledgment of the information submitted by the 
applicant, including references to sections, page numbers, or tables where 
appropriate. 
 
2.  Identification of a specific issue or concern22 with information that was 
submitted, is missing, or is inadequate. 
 
3.  Statement of basis for the deficiency23 that includes the effect or impact of 
the specific issue or concern on the marketing authorization decision,24 and, 
when available, applicable, and relevant, a specific reference.25  
 
4.  Explicit request for the additional information needed to address the issue 
and potential alternate ways of satisfying the issue, if applicable. 
 
 
 
 
22 A specific issue or concern can be scientific, clinical, and/or regulatory in nature. 
23 The commitment letter states that FDA will clarify what constitutes a statement of the basis for the deficiency 
and continue alignment with the following principle: Deficiency letters should include a statement of the basis 
for the deficiencies (e.g., a specific reference to applicable section of a rule, final guidance, recognized standard 
unless the entire or most of document is applicable). In the instance when the deficiency cannot be traced in the 
manner above and relates to a scientific or regulatory issue pertinent to the determination, FDA will cite the 
specific scientific issue and the information to support its position. FDAs definition of the statement of basis 
for the deficiency in this guidance clarifies that an effective deficiency should include the specific scientific 
issue and the information to support its position (i.e., effect or impact of the specific issue on the marketing 
authorization decision) regardless of whether or not a specific reference is available, applicable, and relevant.  
This is also consistent with FDAs long-standing policy, as described in previous versions of this guidance. 
24 The effect or impact of the specific issue or concern on the marketing authorization decision encompasses the 
elements of the statutory standard for each submission type, including but not limited to, the impact on device 
safety or effectiveness, the devices benefit-risk profile, and/or the uncertainty in making the benefit-risk 
determination of a device. 
25 A specific reference is an applicable section of a final rule or statute, or a recommendation provided through 
an applicable section of a final guidance or FDA-recognized consensus standard (unless the entire or most of 
the reference is applicable).   
7  Contains Nonbinding Recommendations 
FDA review staff may include more than one statement for each element or alter the 
order of the elements listed above to represent a logical thought flow or because the 
concepts may be intertwined. Additionally, FDA review staff may include an 
introductory paragraph to the deficiency letter, or a preface for multiple deficiencies 
on a single topic, to improve clarity and reduce redundant language. Examples of 
deficiencies with different structures are included in Appendix A for reference. 
C.  Review of deficiency letters 
As stated in the MDUFA V Commitment Letter, deficiency letters will undergo 
supervisory review prior to issuance to ensure the deficiencies cited are relevant to 
the marketing authorization decision.  Supervisory review should also ensure 
deficiencies include the four elements described above in Section IV.B of this 
guidance. This supervisory review should ensure that specific references are 
included in deficiencies (when such references are available, applicable, and 
relevant), and if any deficiencies do not include specific references, verify such 
exclusions are appropriate. FDA staff and managers should ensure that deficiencies 
are prioritized according to the Agencys view of their significance. The most 
significant deficiencies should be listed first in deficiency letters. During their review, 
FDA managers should also consider the totality of all deficiencies to determine 
whether each individual request is still appropriate. 
 
V.  Suggested format for industry responses to FDA 
deficiencies  
Applicants should provide complete responses to all deficiencies within the timeframe 
indicated in FDAs deficiency letter. For more information about deficiency letter responses 
and their impact on the FDA review clock, see FDA and Industry Actions on Premarket 
Notification (510(k)) Submissions: Effect on FDA Review Clock and Goals,26 FDA and 
Industry Actions on Premarket Approval Applications (PMAs): Effect on FDA Review 
Clock and Goals,27 and FDA and Industry Actions on De Novo Requests: Effect on FDA 
Review Clock and Goals. 28 
 
FDA recommends the following format for applicants when responding to deficiencies: 
 
1.  Restate the identified Agency issue; and 
 
 
 
26 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/fda-and-industry-actions-
premarket-notification-510k-submissions-effect-fda-review-clock-and-goals. 
27 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/fda-and-industry-actions-
premarket-approval-applications-pmas-effect-fda-review-clock-and-goals. 
28 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/fda-and-industry-actions-de-
novo-classification-requests-effect-fda-review-clock-and-goals. 
8  Contains Nonbinding Recommendations 
2.  Provide one of the following: 
a.  the information or data requested; 
b.  an explanation why the issue does not affect or impact the marketing 
authorization decision; or 
c.  alternative information and an explanation describing why the information 
adequately addresses the issue. 
 
FDA recommends that applicants provide the deficiency number and an identical restatement 
of the Agencys question when responding to a particular deficiency. If you are responding to 
a follow-up question from a previous deficiency, FDA recommends that you include both the 
original deficiency and follow-up question in advance of providing your response to such 
deficiency. If your response is extensive, we recommend that you organize the information 
with a table of contents, list of figures, and/or list of tables, as necessary to facilitate ease of 
review. In your response to deficiencies, you should include a description or justification of 
how the information adequately addresses the Agencys concern(s). When providing a 
declaration of conformity to FDA-recognized consensus standards in lieu of data, you 
should identify the standard, its revision date, applicable sections, and any deviations from 
the standard. For more information about consensus standards in regulatory submissions, 
please refer to the FDA guidance titled Appropriate Use of Voluntary Consensus Standards 
in Premarket Submissions for Medical Devices29 and Standards Development and the Use 
of Standards in Regulatory Submissions Reviewed in the Center for Biologics Evaluation 
and Research.30 
 
As stated in 2b of FDAs recommendations on how to respond to a deficiency above, if you 
believe that the Agencys request is not relevant to the marketing authorization decision, 
you should provide a justification in your response to FDAs deficiency letter. For 510(k) 
submissions, if a legally marketed predicate is available to support your response, you 
should also reference the relevant 510(k) number. 
 
As stated in 2c above, in formulating your response, you may consider suggesting alternate 
approaches to optimize the time, effort, and cost of resolving the issue within the applicable 
statutory and regulatory criteria for the marketing authorization decision. This alternate 
approach could include different types of bench testing, proposing non-clinical testing in 
lieu of clinical testing, or conformance to FDA-recognized consensus standards. If an 
alternative approach is taken, you should discuss how the included information satisfies 
applicable statutory and regulatory criteria for the marketing authorization decision. 
   
 
 
 
29 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/appropriate-use-voluntary-
consensus-standards-premarket-submissions-medical-devices. 
30 https://www.fda.gov/regulatory-information/search-fda-guidance-documents/standards-development-and-use-
standards-regulatory-submissions-reviewed-center-biologics-evaluation. 
9  Contains Nonbinding Recommendations 
 
Appendix A: Deficiency and applicant response examples 
The following example deficiencies and applicant responses are only intended to illustrate 
the principles and recommendations discussed in this guidance document. For illustrative 
purposes, we have enumerated each portion of the deficiencies below in brackets to 
demonstrate how each example includes the four elements described in Section IV. B above. 
FDA does not intend to enumerate each element of the deficiency format in deficiency 
letters.  Additionally, we have indicated the type(s) of marketing application(s) for which the 
example deficiency and applicant response may be relevant.   
 
As noted in Section V, FDA recommends that applicants provide the deficiency number and 
an identical restatement of the Agencys question when responding to a particular deficiency. 
However, in the examples below, we have omitted the restatement of the Agencys question 
for purposes of simplicity.  Some examples also include justifications in lieu of the requested 
information. Although justifications are provided to demonstrate potential alternative 
approaches, it should not be inferred that such responses would necessarily be considered to 
be adequate to support a particular marketing authorization.   
 
1.  Statement of basis for the deficiency with specific reference to final rule or statute 
 
FDA deficiency: 
[1] In your device description on page 5, you stated that the oscillation frequency of the 
device is 8  12 Hz, and you provided results from performance testing of the handpiece 
in a test report (in Appendix A). [2] However, the test results you provided did not 
include an evaluation of puncture rate [3] as required by the special control specified in 
21 CFR 878.4430(b)(2)(i). [4] Please provide bench performance data to demonstrate 
that the puncture rate is within the specified operating frequency of 8  12 Hz across the 
devices operating parameters. We recommend that your puncture rate testing be 
conducted using a test set-up that is representative of a clinically relevant worst-case 
scenario. Please also include a rationale in your test report for the test parameters you 
have chosen, including the test set-up, clinically relevant substrate, and acceptance 
criteria. [Relevant to 510(k)s only]  
 
Applicant response: 
We did not include the requested testing because the proposed device only includes 
modifications from our own predicate that did not affect the puncture rate of the device. 
Since we have not changed the puncture rate nor would any of the device changes since the 
last 510(k) clearance impact the devices puncture rate performance, the test results from 
our predicate device to demonstrate the puncture rate is within the specified operating 
frequency (of 8  12 Hz) are still applicable (Reference Kxxxxxx). [Relevant to 510(k)s 
only] 
 
 
10  Contains Nonbinding Recommendations 
2.  Statement of basis for the deficiency with specific reference to final rule or statute 
and final guidance document 
 
FDA deficiency: 
[1] Based on information in your submission (Section 1), your device is supplied sterile 
and requires the user to reprocess after the initial use and prior to subsequent patient use. 
[2] However, your provided labeling (in Section 10) did not include reprocessing 
instructions. Instructions on how to adequately reprocess a device of this type are critical 
to ensuring that it is appropriately prepared for its subsequent use [3] and to reduce the 
risk of infection in patients from an improperly reprocessed device. Further, as stated in 
Section II of FDAs guidance document Reprocessing Medical Devices in Health Care 
Settings: Validation Methods and Labeling (https://www.fda.gov/regulatory-
information/search-fda-guidance-documents/reprocessing-medical-devices-health-care-
settings-validation-methods-and-labeling), for reprocessed devices, FDA interprets 
adequate reprocessing instructions to be important to comply with labeling requirements 
for prescription use devices per 21 CFR 801.109(c) and section 502(f) of the Federal 
Food, Drug, and Cosmetic Act. [4] Therefore, please add validated reprocessing 
instructions to your device labeling to sufficiently mitigate the risks associated with 
multiple uses of your device for the intended patient population. Additional 
recommendations regarding the content of reprocessing instructions may be found [3] in 
Section V and VI of FDAs guidance document Reprocessing Medical Devices in 
Health Care Settings: Validation Methods and Labeling. [Relevant to all marketing 
applications]  
 
Applicant response: 
We have added validated reprocessing instructions to our device labeling, consistent with 
the recommendations outlined in the FDA guidance Reprocessing Medical Devices in 
Health Care Settings: Validation Methods and Labeling. The updated labeling is in 
Section 5 of this response. [Relevant to all marketing applications] 
 
3.  Statement of basis for the deficiency with specific reference to FDA-recognized 
consensus standard 
 
FDA deficiency: 
[1] You provided irritation test results in Appendix C that you stated are in accordance 
with FDA-recognized consensus standard ISO 10993-23 Biological evaluation of 
medical devices  Part 23: Tests for irritation. [2] However, the results from your polar 
extract failed to meet the acceptance criteria of this test [3] as described in ISO 10993-
23:2021, Clause 7.3.7 and [2] you have not provided a corresponding justification to 
support why this failure does not raise safety concerns regarding your devices 
biocompatibility profile. These results raise concerns about the irritation risk from your 
device, [3] because exposure to the device (if it includes even a small amount of an 
irritant) can result in a localized non-specific inflammatory response, which can lead to 
redness, swelling, itching, dryness, cracking of the skin, blistering or pain. [4] 
Therefore, please provide a justification for acceptance of the failed irritation testing 
including an explanation of how you determined that your device demonstrates 
11  Contains Nonbinding Recommendations 
acceptable biocompatibility. Please note that depending on the justification provided, 
information from a root cause analysis and/or additional testing (e.g., comparison to a 
legally US-marketed device with similar materials and the same intended use) may be 
necessary to demonstrate the safety of your product. [Relevant to all marketing 
applications] 
 
Applicant response: 
As the results of testing with polar extract of the device were inconsistent between the 
animals, we repeated the test with the polar extract of the device using three additional 
rabbits according to the recommendation provided in clause 7.3.7 in ISO 10993-23. The 
repeat test results met the test acceptance criteria of this standard, demonstrating 
mitigated irritation risk and acceptable biocompatibility.  Please see Attachment II for 
the results. [Relevant to all marketing applications] 
 
4.  Statement of basis for the deficiency with specific reference to final guidance 
document  
 
FDA deficiency: 
[1] You stated on page 5 that, based on the coating integrity testing and results provided 
in Section 18, your device is equivalent to the predicate device and therefore additional 
particulate testing is not needed. [2] Although your coating integrity testing has not 
shown any flaking or coating defects, the dimensional and coating changes that you made 
to your device (as compared to the predicate) could still result in increased particulate 
generation. This is a concern [3] as particulate generation during clinical use may result 
in serious adverse events including pulmonary embolism, pulmonary infarction, 
myocardial embolism, myocardial infarction, embolic stroke, tissue necrosis and death. 
[4] Therefore, please provide the results of particulate testing conducted on your device at 
baseline and at the end of your labeled shelf life (T = 12 months) in a simulated use 
model that is reflective of a sufficiently challenging case in order to capture an estimation 
of particulates that could be released during clinical use. [3] Consistent with the 
recommendations in Section IV.G.11 of FDA Guidance Coronary, Peripheral, and 
Neurovascular Guidewires  Performance Tests and Recommended Labeling 
(https://www.fda.gov/regulatory-information/search-fda-guidance-documents/coronary-
peripheral-and-neurovascular-guidewires-performance-tests-and-recommended-labeling), 
[4] we also recommend that as part of this testing, the number of particulates generated at 
each evaluation be quantified and characterized by size and count using a validated 
method (e.g., light obscuration, light refraction) under continuous flow conditions to 
simulate blood flow. Specifically, we recommend that the total number of particulates be 
reported in the following size ranges:  10m,  25m, and at the largest size for which 
validation yields  75% recovery. We also recommend that appropriate precautions be 
implemented to ensure that particulates are suspended during particulate counting and 
sizing to minimize the risk of undercounting. [Relevant to 510(k)s only] 
 
Applicant response: 
We have included study results for particulate generation testing (in Section V) to address 
the Agencys concern regarding the modifications to the coating and the dimensional 
12  Contains Nonbinding Recommendations 
changes to the subject device. These results are presented with a direct comparison, in the 
same simulated use model, to the predicate device to better demonstrate substantial 
equivalence. [Relevant to 510(k)s only] 
 
5.  Statement of basis for the deficiency with specific reference to final guidance 
document and FDA-recognized consensus standard  
 
FDA deficiency: 
[1] You indicated that your home use device includes smart lithium-ion battery packs 
(batteries hereafter) that the user needs to detach from the host device to recharge (page 
13). [2] However, you have not provided electrostatic discharge (ESD) immunity testing 
for the batteries separately from the evaluations for the complete device. [3] As 
described in Section IV.E of the FDA Guidance Electromagnetic Compatibility (EMC) 
of Medical Devices (https://www.fda.gov/regulatory-information/search-fda-guidance-
documents/electromagnetic-compatibility-emc-medical-devices), [2] this is a concern as 
ESD can damage the batterys electronic components, [3] which can lead directly to 
patient harm (e.g., burn from overcharge). [2] Damaged battery electronic components 
can also lead to premature battery depletion, [3] which can interrupt patient treatment 
and result in adverse clinical impacts. [4] Therefore, please provide an ESD test protocol 
and test report for the batteries independently after removal from the device. We 
recommend using test methods [3] consistent with the current FDA-recognized version 
of IEC 60601-1-2 Medical electrical equipment  Part 1-2: General requirements for 
basic safety and essential performance  Collateral Standard: Electromagnetic 
disturbances  Requirements and tests (Clause 8), as well as the test criteria specified in 
Table 4 or Table 8 from the same standard. [Relevant to all marketing applications]  
 
Applicant response: 
We have included an ESD test report for the devices smart lithium-ion battery pack, 
removed from the device and tested separately (see Section 2).  The ESD protocol used 
is the same as the one we used for another one of our devices in a separate, recently 
authorized marketing submission (see [specific submission number]).  The ESD 
protocol from that previously authorized device is applicable to this device because they 
both have a similar intended use and both use a similar smart, removable, rechargeable 
battery pack.  The ESD protocol is also consistent with the test methods and criteria 
specified in the current FDA-recognized version of IEC 60601-1-2. [Relevant to all 
marketing applications] 
 
6.  Statement of basis for the deficiency without specific reference to final rule, statute, 
FDA-recognized consensus standard, or final guidance document 
 
FDA deficiency: 
[1] You provided a test report (Appendix C) where you assessed the ability of your bone 
cement and the predicate to be injected through screws in the spine.  In the Specimen 
Information section of provided test report, you stated the cadaver had non-osteoporotic 
bone. [2] However, this is not worst-case for your proposed indication, which includes 
use in osteoporotic bone. Osteoporotic bone is more porous than non-osteoporotic bone 
13  Contains Nonbinding Recommendations 
and so is more susceptible to cement extravasation beyond the site of intended 
administration. [3] Cement extravasation in the spine can cause several safety and 
effectiveness concerns, including but not limited to, nerve root compression and 
pulmonary embolisms. [4] If you intend to market your device with indications for use in 
osteoporotic bone, please provide performance data to support this indication. We 
recommend that you provide a complete test report describing successful delivery of your 
device through the ABC Spinal System into a void space using cadaveric and/or foam test 
blocks that are representative of worst-case osteoporotic bone, and that you provide a 
comparison to the predicate. Results of your testing should include an adequate rationale 
for how the cadaveric and/or foam block testing represents worst-case osteoporotic bone, 
as defined by the proposed indications for use statement. Alternatively, if you do not 
intend to market your device in osteoporotic bone, we recommend that you remove the 
indications that refer to use in osteoporotic bone. [Relevant to 510(k)s only] 
 
Applicant response: 
We have updated the indications for use to remove reference to use in osteoporotic bone.  
See Appendices 1, 2, and 3 for the updated Indications for Use Statement, 510(k) 
Summary, and labeling. [Relevant to 510(k)s only] 
 
7.  Statement of basis for the deficiency without specific reference to final rule, statute, 
FDA-recognized consensus standard, or final guidance document 
 
FDA deficiency: 
[1] In Section 8 of your premarket submission, you provided results from a precision 
study for your in vitro test. [2] However, this study design did not include a sufficient 
number of replicates or distribution of hCG concentrations around (and at) the devices 
designed cutoff. A higher number of replicates and more adequate analyte distribution 
around (and at) the cutoff are necessary to validate your devices precision performance 
and [3] to demonstrate your device is substantially equivalent to the predicate, which had 
a more comprehensive precision study design (with more replicates and better analyte 
distribution per its publicly-available Decision Summary).  [2] Imprecision around your 
devices designed cutoff increases the risk of erroneous test results (i.e., false positive 
and/or false negative results) [3] which, in your intended use population, could place 
mothers or their fetuses at increased risk due to incorrect patient management. [4] 
Therefore, please provide results from a new precision study where you evaluate a 
sufficient number of replicates and distribution of hCG concentrations (while 
incorporating other relevant contributors to imprecision such as lots and operators), 
equivalent to what was provided to support performance of the predicate. If the precision 
performance of your device is different than that of other legally marketed devices, such 
that your device could have an increased risk of false positive or false negative results, 
please provide information to show that you have adequately mitigated this risk.  
[Relevant to in vitro diagnostic 510(k)s only] 
 
Applicant response: 
We have included updated precision study results (Section B) and updated labeling 
(Section E) to address the Agencys concern about a sufficient number of replicates and 
14  Contains Nonbinding Recommendations 
adequate distribution of hCG concentrations around (and at) the cutoff. We have also 
included a comparison of these results to the predicate and other legally marketed hCG 
devices (in Table 2 below). [Relevant to in vitro diagnostic 510(k)s only] 
 
8.  Statement of basis for the deficiency without specific reference to final rule, statute, 
FDA-recognized consensus standard, or final guidance document 
 
FDA deficiency: 
[1] For the primary safety and effectiveness endpoints in your submitted study (Appendix 
D), you presented subgroup analyses according to several characteristics such as clinical 
severity, physiologic location, and sex of the subject. [2] However, you did not present 
subgroup analyses according to comorbid conditions (e.g., history of hypertension, 
smoking) or concomitant medication use (e.g., steroids). It is important to stratify the data 
according to these heterogeneous characteristics [3] in order to understand whether the 
safety and effectiveness of your device and treatment is comparable between these different 
subgroups. For example, if the risks of treatment with your device are increased for one 
specific comorbid condition, then this information would be valuable to the physician in 
assessing whether to treat that patient or not, or to properly inform the patient of these 
increased risks. [4] Therefore, please perform additional subgroup analyses of your primary 
safety and effectiveness endpoints according to comorbid conditions and concomitant 
clinically relevant medications.  [Relevant to all marketing applications] 
 
Applicant response: 
In response to FDAs request, we have reanalyzed our primary endpoint based on the 
comorbidities observed in our trial in Section 3 of this response. This analysis evaluated the 
most frequently observed comorbidities and their relative impact on the primary safety and 
effectiveness endpoints. Additionally, this subgroup analysis has been added to the draft 
labeling to help better inform clinicians when using this device. Please refer to Section 3 of 
our response for additional details regarding this analysis. [Relevant to all marketing 
applications] 
 
 
 
 
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