Contents of a Complete 
Submission for Threshold 
Analyses and Human 
Factors Submissions to Drug 
and Biologic Applications 
Guidance for Industry and FDA Staff 
 
 
 
 
DRAFT GUIDANCE
 
 
This guidance document is being distributed for comment purposes only. 
 
Comments and suggestions regarding this draft document should be submitted within 60 days of 
publication in the Federal Register of the notice announcing the availability of the draft 
guidance. Submit electronic comments to https://www.regulations.gov. Submit written 
comments to the Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 
Fishers Lane, rm. 1061, Rockville, MD 20852. All comments should be identified with the 
docket number listed in the notice of availability that publishes in the Federal Register. 
 
For questions regarding this draft document, contact Quynh Nhu Nguyen, 301-796- 6273, or 
(CBER) Office of Communication, Outreach and Development, 800-835-4709 or 240-402-8010.  
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
 
September 2018 
Procedural   
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
Contents of a Complete 
Submission for Threshold 
Analyses and Human 
Factors Submissions to Drug 
and Biologic Applications 
Guidance for Industry and FDA Staff 
 
 
Additional copies are available from: 
Office of Communications, Division of Drug Information  
Center for Drug Evaluation and Research 
Food and Drug Administration 
10001 New Hampshire Ave., Hillandale Bldg., 4th Floor  
Silver Spring, MD 20993-0002  
Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353 
Email: druginfo@fda.hhs.gov  
http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm 
and/or 
Office of Communication, Outreach and Development  
Center for Biologics Evaluation and Research 
 Food and Drug Administration 
10903 New Hampshire Ave., Bldg. 71, Room 3128 
Silver Spring, MD 20993-0002 
Phone: 800-835-4709 or 240-402-8010 
Email: ocod@fda.hhs.gov 
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm 
 
 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Drug Evaluation and Research (CDER) 
Center for Biologics Evaluation and Research (CBER) 
 
September 2018 
Procedural  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
TABLE OF CONTENTS 
 
 
I.  INTRODUCTION............................................................................................................. 1 
II.  BACKGROUND ............................................................................................................... 2 
III.  SUBMISSION TYPES, COVER LETTER, AND FDA FORMS................................. 3 
A.  Types of Submissions ..................................................................................................................... 3 
B.  Cover Letter ................................................................................................................................... 3 
C.  Form FDA 1571 or Form FDA 356h ............................................................................................ 3 
IV.  CONTENTS OF THRESHOLD ANALYSES AND HUMAN FACTORS 
SUBMISSIONS ............................................................................................................................. 4 
A.  Use-Related Risk Analysis ............................................................................................................. 4 
B.  Human Factors Validation Study Protocol ................................................................................. 5 
C.  Human Factors Validation Study Report .................................................................................... 7 
D.  Threshold Analyses ........................................................................................................................ 9 
E.  Comparative Use Human Factors Study Protocol .................................................................... 10 
F.  Comparative Use Human Factors Study Results Report ......................................................... 11 
V.  WHERE TO SEND A THRESHOLD ANALYSIS OR HUMAN FACTORS 
SUBMISSION ............................................................................................................................. 12 
A.  Drug Products, Including Biologics, and Combination Products, That Are the Subject of an 
IND Paper Submission ......................................................................................................................... 13 
B.  Drug-Device Combination Products Under Development for Submission Under ANDA .... 13 
C.  Electronic Submissions ................................................................................................................ 14 
VI.   REVIEW TIMELINE .................................................................................................... 14 
VII.   HOW TO OBTAIN ADDITIONAL INFORMATION ............................................... 15 
VIII.   REFERENCES ................................................................................................................ 16 
GLOSSARY................................................................................................................................. 18 
APPENDIX A .............................................................................................................................. 21 
APPENDIX B .............................................................................................................................. 22 
APPENDIX C .............................................................................................................................. 22 
APPENDIX D .............................................................................................................................. 23 
  Contains Nonbinding Recommendations 
Draft  Not for Implementation 
Contents of a Complete Submission for Threshold Analyses and 
1 
Human Factors Submissions to Drug and Biologic Applications 
2 
Draft Guidance for Industry and FDA Staff1 
3 
 
4 
5   
6  This draft guidance, when finalized, will represent the current thinking of the Food and Drug 
7  Administration (FDA or Agency) on this topic. It does not establish any rights for any person and is not 
8  binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the 
9  applicable statutes and regulations. To discuss an alternative approach, contact the FDA staff responsible 
10  for this guidance as listed on the title page.  
11   
12   
13   
14   
15  I.  INTRODUCTION  
16   
17  This document provides guidance to industry and FDA staff on the contents of and submission 
18  procedures for threshold analyses2 and human factors (HF) submissions3 that will support 
19  efficient Agency review, and presents timelines for FDAs review of such submissions.4  
20   
21  This guidance applies to the following types of products5: 
22   
23    Human prescription drug products, including biologics, that are the subject of an 
24  investigational new drug application (IND)6, a new drug application (NDA), a 
25  biologics license application (BLA), or an abbreviated new drug application 
26  (ANDA),7 and supplements to these applications 
27   
28    Human nonprescription drug products that are the subject of an IND, NDA, or ANDA 
29   
                                                 
1 This guidance has been prepared by the Office of Surveillance and Epidemiology in the Center for Drug Evaluation and 
Research (CDER), in cooperation with the Center for Biologics Evaluation and Research (CBER), the Center for Devices and 
Radiological Health, and the Office of Combination Products (OCP) at the Food and Drug Administration.  
2 All terms presented in bold italic at first use in this guidance are defined in the Glossary. 
3 See section III of this guidance for the types of submissions. 
4 This document is one of several documents FDA is issuing to fulfill the performance goals under the sixth authorization of the 
Prescription Drug User Fee Act (PDUFA VI). This document also provides information on what to include in submissions for 
products under other user fee programs.  
5 This includes combination products. See definition of combination product in 21 CFR 3.2. For the purposes of this guidance, we 
are referring to combination products assigned to CDER or CBER as the lead center. 
6 Sponsors can engage FDA on human factors issues as early as the pre-IND phase.  
7 The recommendations in this guidance apply to ANDA submissions covering drug-device combination products.  
 
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30  All such products in this guidance are jointly referred to as products,8 and persons responsible 
31  for making submissions are referred to as sponsors. 
32   
33  This guidance does not describe when threshold analyses or HF submissions are warranted for 
34  any particular application pathway, the processes or procedures associated with their review, or 
35  the methods used by the Agency for evaluation. Furthermore, this guidance does not describe the 
36  methods used to design, conduct, or analyze HF studies. In addition to the information described 
37  in this guidance, FDA recommends that sponsors refer to other relevant guidance documents 
38  related to product design and human factors (see section VIII).  
39   
40  In general, FDAs guidance documents do not establish legally enforceable responsibilities. 
41  Instead, guidances describe the Agencys current thinking on a topic and should be viewed only 
42  as recommendations, unless specific regulatory or statutory requirements are cited. The use of 
43  the word should in Agency guidances means that something is suggested or recommended, but 
44  not required.  
45   
46   
47  II.  BACKGROUND 
48   
49  The Federal Food, Drug, and Cosmetic Act (FD&C Act) requires that drug products submitted 
50  for approval under section 505(b) be proven safe and demonstrate substantial evidence of 
51  effectiveness for the product's intended use (21 U.S.C. 355(b)). Under section 351 of the Public 
52  Health Service Act, FDA licenses a biological product based on a demonstration that it is safe, 
53  pure, potent, and it is manufactured in a facility designed to ensure that the product continues to 
54  be safe, pure, and potent.  
55   
56  As part of evaluating drug and biologic products for safety and effectiveness, FDA will evaluate 
57  HF data submitted by sponsors in support of the product user interface when submission of such 
58  data is warranted. For products that sponsors intend to submit as an ANDA, the sponsor can rely 
59  on the Agencys previous finding that its listed drug is safe and effective so long as the sponsor 
60  can demonstrate certain findings.9 Certain products, including drug-device combination products, 
61  may warrant threshold analyses and additional data, such as data from comparative HF studies.10  
62     
                                                 
8 For purposes of this guidance, unless otherwise specified, references to products include drugs submitted for approval or 
approved under sections 505(b) or 505(j) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 355(b) or 355(j)) 
and biological products licensed under section 351 of the PHS Act. 
9 See Section 505(j)(2)(A), 505(j)(4) of the FD&C Act (21 U.S.C. 355(j)(2)(a), 355(j)(4)); 21 CFR 314.127. 
10 See draft guidance for industry and FDA staff Comparative Analyses and Related Comparative Use Human Factors Studies for 
a Drug-Device Combination Product Submitted in an ANDA (Comparative Analyses Draft Guidance), available at 
https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM536959.pdf.  When final, 
this guidance will represent the FDAs current thinking on this topic. For the most recent version of a guidance, check the FDA 
Drugs guidance web page at https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm. 
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63  III.  SUBMISSION TYPES, COVER LETTER, AND FDA FORMS  
64   
65  A.  Types of Submissions 
66   
67  Listed below are the different threshold analysis and human factors submission types:  
68   
69  1)  Use-Related Risk Analysis 
70   
71  2)  HF Validation Study Protocol  
72   
73  3)  HF Validation Study Results Report 
74   
75  4)  Threshold Analyses 
76   
77  5)  Comparative Use HF Study Protocol  
78   
79  6)  Comparative Use HF Study Results Report 
80   
81  See section IV for information regarding the content of each submission type listed in this 
82  section: 
83   
84  B.  Cover Letter 
85   
86  Each submission should include a cover letter that includes the statement REQUEST FOR 
87  [Type of Submission] REVIEW in bolded capital letters.  
88   
89  For submission amendments, the cover letter should include the statement AMENDMENT TO 
90  REQUEST FOR [Type of Submission] REVIEW in bolded capital letters.11 
91   
92  See Appendix A for examples.  
93   
94  C.  Form FDA 1571 or Form FDA 356h  
95   
96  All electronic submissions should include only fillable forms and electronic signatures to enable 
97  automated processing. A submission that is the subject of an active IND should include Form 
98  FDA 1571, Investigational New Drug Application (IND). A submission that is the subject of a 
99  marketing application should include Form FDA 356h, Application to Market a New or 
100  Abbreviated New Drug or Biologic for Human Use. Refer to the FDA Forms website for the 
101  latest versions of these forms and their corresponding instruction files.12  
102   
103   
                                                 
11 See section VI for additional considerations for amendments. 
12 See the FDA Forms website for latest versions of forms and instruction files at: 
http://www.fda.gov/aboutfda/reportsmanualsforms/forms/default.htm.  
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104  IV.  CONTENTS OF THRESHOLD ANALYSES AND HUMAN FACTORS 
105  SUBMISSIONS 
106   
107  This section describes the information that a sponsor should include for each respective 
108  submission type.  
109   
110  A.  Use-Related Risk Analysis13  
111   
112  A comprehensive use-related risk analysis may be a separate submission or may be included as 
113  part of another submission (e.g. with the HF validation study protocol (see section IV.B) or 
114  Human Factors Engineering (HFE) Report (see section IV.C).14 The risk analysis submission 
115  should include:  
116   
117    A comprehensive and systematic evaluation of all the steps involved in using the 
118  proposed product (e.g., based on a task analysis)  
119   
120    The errors that intended product users might commit or the tasks they might fail 
121  to perform, taking into consideration known problems with similar products 
122   
123    The potential negative clinical consequences of use errors and task failures 
124  including the severity of the resulting harm 
125   
126    User task description and categorization (e.g., critical)  
127   
128    The mitigation strategies employed to reduce identified risks or eliminate hazards  
129   
130    The proposed methods used to validate these mitigation strategies 
131   
132    Description of intended product users, uses, use environments, and training (if 
133  applicable) 
134   
135    Graphical depiction and written description of product user interface (see 
136  Appendix C for example)  
137   
138    Summary of known use problems with previous or similar products15 
                                                 
13 ANSI/AAMI/ISO 14971, Medical Devices  Application of risk management to medical devices, defines risk as the 
combination of the probability of occurrence of harm and the severity of the potential harm. However, because probability is very 
difficult to determine for use errors, and in fact many use errors cannot be anticipated until product use is simulated and 
observed, the severity of the potential harm may be more meaningful for determining the need to eliminate (design out) or reduce 
resulting harm. Therefore, it may be appropriate when conducting the use-related risk analysis to focus on the resulting harm, and 
including estimated occurrence rates may not be needed. 
14 See guidance Applying Human Factors and Usability Engineering to Medical Devices available at 
https://www.fda.gov/downloads/medicaldevices/.../ucm259760.pdf 
 
15 In certain circumstances, there may be post-marketing experience that is relevant to the product under consideration. Such 
information might include known use problems with previous models of the subject product or known use problems with similar 
products. 
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139   
140    Summary of preliminary analyses and evaluations, including formative 
141  evaluation 
142   
143  See Appendix B for an example of how to present some of the key information for a use-related 
144  risk analysis.  
145   
146  A sponsor can employ the use-related risk analysis to identify the need for risk mitigation 
147  strategies and to design an HF validation study that adequately evaluates the risk mitigation 
148  strategies. In circumstances where, based on the use-related risk analysis and other information, a 
149  sponsor determines that an HF validation study is not needed, the sponsor may submit the use-
150  related risk analysis and other information, together with the justification for not conducting a 
151  HF validation study, for review under the IND.  
152   
153  B.  Human Factors Validation Study Protocol 
154   
155  Sponsors should include the following elements in the submission:  
156   
157  1.  Background 
158   
159    Description of intended product users, uses, use environments, and training 
160  (if applicable) 
161   
162    Graphical depiction and written description of product user interface (see 
163  Appendix C for example), including the intend-to-market labels and labeling 
164  that will be evaluated in the HF validation study 
165   
166    For Instructions for Use (IFUs), in addition to an intended 
167  commercial printed layout version, sponsors should provide a Word 
168  version to facilitate the exchange of labeling comments and revisions 
169  between the sponsor and FDA.16 
170   
171    Summary of known use problems with previous or similar products17 
172   
173    Summary of preliminary analyses and evaluations, including formative 
174  evaluations; a discussion of key findings; and any changes made to the user 
175  interface (e.g., device constituent part design change, labeling changes), as 
176  well as a discussion of how the sponsor used the formative evaluation results 
177  and findings to update the product user interface and use-related risk analysis 
                                                 
16 Submitting the IFU document in a Word version is consistent with recommendations to submit labeling content to FDA as part 
of a marketing application; see draft guidance SPL Standard for Content of Labeling Technical Qs & As. When final, this 
guidance will represent the FDAs current thinking on this topic. For the most recent version of a guidance, check the FDA Drugs 
guidance web page at https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm. 
17 In certain circumstances, there may be post-marketing experience that is relevant to the product under consideration. Such 
information might include known use problems with previous models of the subject product or known use problems with similar 
products. 
5  Contains Nonbinding Recommendations 
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178   
179  2.  Analysis of hazards and risks associated with use of the product in a use-related 
180  risk analysis 
181   
182  3.  HF validation testing details 
183   
184  a.  Study objective(s) 
185   
186  b.  Type of testing (simulated-use vs. actual use)18  
187   
188  c.  Test environment and conditions19 
189   
190  d.  Training provided to participants and rationale for how it corresponds to 
191  real-world training and training decay (if applicable) 
192   
193  e.  Distinct user groups by number and type of test participants20 
194   
195  f.  User task description and categorization (e.g., critical)21 and a description of 
196  use scenarios that include critical tasks 
197   
198  g.  Definition of successful performance or failure of each test task  
199   
200  h.  Description of data (e.g., data collected from observational tasks, knowledge 
201  tasks, and subjective interview) to be collected and methods for documenting  
202   
203  i.  Methods for root cause analysis of all use errors, difficulties, and close 
204  calls22  
205   
206  j.  Moderator script 
                                                 
18 See draft guidance for industry and FDA staff Human Factors Studies and Related Clinical Study Considerations in 
Combination Product Design and Development (Combination Products Human Factors Draft Guidance), available at 
https://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM484345.pdf, for further discussion of simulated vs. 
actual use studies. When final, this guidance will represent the FDAs current thinking on this topic. 
19 A rationale for how the testing environment and conditions of testing is representative of real-world use is helpful. In 
identifying conditions of testing, sponsors should consider aspects of use that can be reasonably anticipated, such as use with 
gloves or wet fingers, in dim lighting, or in noisy situations.  
20 When describing study participants and how they represent distinct user populations (groups), it is helpful to describe the 
characteristics that distinguish the groups and that can affect user interaction with the product (e.g., limited hand dexterity, 
cognitive deficit). 
21 The selection of user tasks can be derived from the comprehensive use-related risk analysis. Tasks that could lead to harm 
(e.g., underdose or overdose), including those requiring the user to respond to alerts or alarms, should be categorized as critical 
and prioritized for testing. A task requiring comprehension of warnings, caution statements, or contraindications in the product 
labels or labeling would generally be considered a critical knowledge task. See Combination Products Human Factors Draft 
Guidance), available at https://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM484345.pdf, for definition of 
critical tasks.  
22 While close calls and difficulties may not manifest into use errors/task failures, they are good sources of data in terms of 
providing potential user interface inadequacies that should be further evaluated. 
 
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207   
208  4.  Product samples (5 samples of product that will be tested in the HF validation)23 
209   
210  C.  Human Factors Validation Study Report24 
211   
212  Sponsors should include the following elements in their submission: 
213   
214  1.  Summary of findings and conclusions 
215   
216  a.  Conclusions based on HFE process25   
217   
218  b.  Brief summary of validation study results  
219   
220  c.  Discussion of whether additional risk mitigation measures are necessary 
221   
222  i.  If additional mitigation measures are needed, the study report should 
223  include a description of the additional mitigation measures and justify 
224  whether additional validation testing is not warranted.  However, if 
225  additional validation testing is needed, the results should be submitted 
226  within the report.  
227   
228  d.  Discussion of residual use-related risks versus benefits of the product 
229   
230  2.  Background26  
231   
232  a.  Brief summary of Human Factors Engineering processes applied throughout 
233  the development of the product 
234   
235  b.  Descriptions of intended product users, uses, use environments, and training 
236  (if applicable) 
237   
238  c.  Graphical depiction and written description of user interface (see Appendix 
239  C), including the intend-to-market labels and labeling that were evaluated in 
240  the HF validation study 
241   
                                                 
23 FDA recognizes that in some circumstances, the ability to provide the requested quantity of samples may not be feasible.  In 
this instance, we recommend you contact FDA for further guidance. 
 
24 The contents of the HF validation study report are intended to be equivalent to the contents outlined in Appendix A of the 
guidance Applying Human Factors and Usability Engineering to Medical Devices.  
 
25 If the HFE process identifies no use errors or problems that could result in harm, the sponsor should discuss how the validation 
study results supports a conclusion of safe and effective use by the end user. Otherwise, the sponsor should include a discussion 
of why the existing mitigations are effective and why the Agency should find the residual risks acceptable in the report. The 
discussion should incorporate findings from the entire HFE process. 
26 If previously submitted, cross-reference the prior submission and include the eCTD sequence number and date of submission. 
Sponsors should not resubmit the electronic files when referencing that document. 
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242  d.  Summary of known use problems with previous products or similar products  
243   
244  e.  Summary of preliminary analyses and evaluations, including formative 
245  evaluations 
246   
247  i.  The summary should include a discussion of key findings and any 
248  changes made to the product design and its labeling based on key 
249  findings, and should explain how the sponsor used the formative 
250  results and findings to update the product user interface and risk 
251  analysis. 
252   
253  f.  Reference to previous HF validation study protocol submission, description 
254  of changes made to the protocol after prior feedback from the FDA, and 
255  description of any protocol deviations that occurred during the study 
256   
257  3.  Analysis of hazards and risks associated with use of the product in a use-related 
258  risk analysis27  
259   
260  4.  HF validation testing details 
261   
262  a.  Study objective(s) 
263   
264  b.  Rationale for test type selected (simulated-use or actual use)28  
265   
266  c.  Test environment and conditions of use  
267   
268  d.  Training provided to test participants and how it will correspond to real-world 
269  training levels and training decay (if applicable) 
270   
271  e.  Distinct user groups broken out by number and type of test participants  
272   
273  f.  User tasks description and categorization and a description of use scenarios 
274  that include critical tasks  
275   
276  g.  Definition of successful performance or failure of each test task  
277   
278  h.  Test results and analysis (see example in Appendix D) 
279   
280  i.  Observations of task performance, including occurrences and 
281  description of use errors, close calls, and use difficulties 
                                                 
27 If previously submitted, cross-reference the prior submission and include the eCTD sequence number and date of submission. 
Sponsors should not resubmit the electronic files when referencing that document. 
28 See Combination Products Human Factors Draft Guidance for further discussion of simulated vs. actual use studies. When 
final, this guidance will represent the FDAs current thinking on this topic 
 
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282  ii.  Documentation of subjective data from study participants regarding 
283  product use, use errors, close calls and use difficulties.   
284  iii. Root cause analysis of all use errors, difficulties, and close calls and 
285  discussion of risk mitigation strategies  
286   
287  5.  Product samples (5 samples of intend-to-market product) 29 
288   
289  D.  Threshold Analyses 
290   
291  Threshold analyses generally are utilized in comparing two drug products.  For these analyses, 
292  sponsors should include the following elements in their submission: 
293   
294  1.  Labeling comparison (a side-by-side, line-by-line comparison between the 
295  proposed product and the product it references that includes the full prescribing 
296  information, instructions for use, container labels and carton labeling, and 
297  descriptions of the products) 
298   
299  2.  Comparative task analysis30 (a comparative task analysis of the proposed product 
300  and the product it references) 
301   
302  3.  Physical comparison of the device constituent part(s) (e.g., examine, through a 
303  visual or tactile examination, the physical features of the product that it plans to 
304  reference and compare them to those of the proposed product) 
305   
306  4.  Sponsors determination of whether design differences exist and, if so, whether 
307  they are characterized as minor design differences or other design differences,31 
308  and the rationale for each characterization 
309   
                                                 
29 FDA recognizes that in some circumstances, the ability to provide the requested quantity of samples may not be feasible.  In 
this instance, we recommend you contact FDA for further guidance. 
 
30 To conduct a comparative task analysis, sponsors should systematically dissect the use process for each product (i.e., for both 
the proposed product and the product it references) and analyze and compare the sequential and simultaneous manual and 
cognitive activities for end-users interacting with each product. FDA recommends that sponsors analyze the differences with the 
goal of characterizing the potential for use error. See the Association for the Advancement of Medical Instrumentation/American 
National Standards Institute HE75: 2009-Human factors engineeringDesign of medical devices, available at: 
http://my.aami.org/aamiresources/previewfiles/HE75_1311_preview.pdf.  Presenting this information in a side-by-side 
comparison table can help to facilitate FDA evaluation of this information. 
31 For further discussion on identifying design differences and characterizing design difference(s), see Comparative Analyses 
Draft Guidance, available at 
https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM536959.pdf and draft 
guidance for industry Considerations in Demonstrating Interchangeability With a Reference Product, available at 
https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM537135.pdf. When final, 
these guidance will represent the FDAs current thinking on this topic. For the most recent version of a guidance, check the FDA 
Drugs guidance web page at https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm. 
 
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310  5.  Product samples (5 samples each of the proposed product and the product it 
311  references)32 
312   
313  E.  Comparative Use Human Factors Study Protocol33  
314   
315  Sponsors should include the following elements in their submission: 
316   
317  1.  Background, including description of the intended product users, uses, and use 
318  environments 
319   
320  2.  Threshold analyses (see section IV.D, above)34 
321    
322  3.  Comparative use HF testing details 
323   
324  a.  Study objective(s) 
325   
326  b.  Type of testing (simulated-use vs. actual use)35  
327   
328  c.  Statistical analysis plan (SAP) and sample size considerations (including 
329  proposed analyses and all assumptions, as well as literature references or other 
330  justification supporting the methods or assumptions) 
331   
332  d.  Test environment and conditions of testing  
333   
334  e.  Distinct user groups broken out by number and type of test participants  
335   
336  f.  User task description and categorization (e.g., critical)36 and a description of 
337  use scenarios that include critical tasks 
338   
339  g.  Definition of successful performance or failure of each test task  
340   
341  h.  Description of data (e.g., data collected from observational tasks, knowledge 
342  tasks, and subjective interview) to be collected and methods for documenting  
343   
                                                 
32 FDA recognizes that in some circumstances, the ability to provide the requested quantity of samples may not be feasible.  In 
this instance, we recommend you contact FDA for further guidance. 
 
33 Potential applicants intending to submit a drug-device combination product under an ANDA are strongly encouraged to discuss 
the results of the threshold analyses with the Agency via the controlled correspondence or pre-ANDA submission pathways, or 
both, prior to conducting comparative use human factors studies.  
34 If previously submitted, cross-reference the prior submission and include the eCTD sequence number and date of submission. 
Sponsors should not resubmit the electronic files when referencing that document. 
35 See Combination Products Human Factors Draft Guidance for further discussion of simulated vs. actual use studies. 
36 In some instances, it may be appropriate to focus the selection of user tasks on the critical tasks related to the external critical 
design attributes found to be different between the proposed product and the product it references.   
 
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344  i.  Methods for evaluating error rates  
345   
346  j.  Moderator script 
347  4.  Product samples (5 samples each of the proposed product and the product it 
348  references that will be tested in the comparative use HF study) 37 
349   
350  F.  Comparative Use Human Factors Study Results Report  
351   
352  Sponsors should include the following elements in the submission: 
353   
354  1.  Summary of study findings and conclusions 
355   
356    Conclusions38  
357   
358    Brief summary of study results  
359   
360  2.  Background39  
361   
362  a.  Descriptions of intended product users, uses, and use environments  
363   
364  b.  Reference to previous protocol submission, description of changes made to 
365  the protocol after prior feedback from the FDA, and description of any 
366  protocol deviations that occurred during the study 
367   
368  3.  Threshold analyses (see section IV.D, above)40  
369   
370  4.  Comparative use HF testing details 
371   
372  a.  Study objective(s) 
373   
374  b.  Rationale for test type selected (simulated-use or actual use) 41   
375   
                                                 
37 FDA recognizes that in some circumstances, the ability to provide the requested quantity of samples may not be feasible.  In 
this instance, we recommend you contact FDA for further guidance. 
 
38 A comparative use human factors study should be designed to provide sufficient data to confirm that the use error rate for the 
critical task(s), as impacted by the differing external critical design attribute of the device constituent part(s) for the proposed 
generic combination product, is not worse than the corresponding use error rate for the RLD when used by patients and 
caregivers in representative use scenarios and use environments consistent with the labeled conditions of use. See Comparative 
Analyses Draft Guidance for further discussion. 
 
39 If previously submitted, cross-reference the prior submission and include the eCTD sequence number and date of submission. 
Sponsors should not resubmit the electronic files when referencing that document. 
40 If previously submitted, cross-reference the prior submission and include the eCTD sequence number and date of submission. 
Sponsors should not resubmit the electronic files when referencing that document. 
41 See Combination Products Human Factors Draft Guidance for further discussion of simulated vs. actual use studies. 
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376  c.  SAP and sample size considerations (including analyses and all assumptions, 
377  as well as literature references or other justifications supporting the methods 
378  or assumptions)  
379   
380  d.  Test environment and conditions of use  
381   
382  e.  Distinct user groups broken out by number and type of test participants 
383   
384  f.  Critical tasks and use scenarios included in testing  
385   
386  g.  Definition of successful performance or failure of each test task  
387   
388  h.  Test results and analysis 
389   
390  i.  Use error rates and analysis  
391   
392  ii.  Observations of task performance, including occurrences of use errors 
393   
394   
395  V.  WHERE TO SEND A THRESHOLD ANALYSIS OR HUMAN FACTORS 
396  SUBMISSION  
397   
398  Generally, FDA expects that sponsors will submit threshold analyses or HF submissions 
399  consistent with the respective regulatory pathway. Sponsors should submit an HF validation 
400  study protocol and questions regarding the protocol to the IND.  For proposed generic products, 
401  sponsors should submit threshold analyses, device assessments, and questions via the controlled 
402  correspondence or pre-ANDA submission pathways, or both, as appropriate.  Comparative use 
403  HF study protocols should be submitted within a specific pre-ANDA meeting request. 
404  It is recommended that all sponsors plan their development timelines to allow for Agency 
405  feedback on protocols prior to initiation and conduct of the appropriate HF study. In addition, 
406  sponsors should submit HF validation study results reports or comparative use HF study results 
407  reports in their application for FDA review (i.e., NDA, BLA, or ANDA).  
408   
409  Submissions to a Commercial IND, NDA, BLA, or ANDA must be made in Electronic Common 
410  Technical Document (eCTD) format.42 Submissions to a Research IND43 may be in paper or 
411  electronic format. For paper submissions, sponsors should submit 3 copies to the appropriate 
412  address below. 
                                                 
42 See guidance for industry Providing Regulatory Submissions in Electronic Format  Certain Human Pharmaceutical Product 
Applications and Related Submissions Using the eCTD Specifications (Using eCTD Specifications Guidance); see also section 
745A(a) of the FD&C Act (21 U.S.C. 379k-1(a)).  
43 See FDAs web page on Investigational New Drug (IND) Application at 
https://www.fda.gov/drugs/developmentapprovalprocess/howdrugsaredevelopedandapproved/approvalapplications/investigationa
lnewdrugindapplication/default.htm.  
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413    
414  A.  Drug Products, Including Biologics, and Combination Products, That Are 
415  the Subject of an IND Paper Submission 
416   
417  1.  Human Factors Submissions for Prescription or Nonprescription Drugs, 
418  Including Biologics, That Are the Subject of an IND Reviewed by CDER 
419   
420  Food and Drug Administration 
421  Center for Drug Evaluation and Research 
422  Central Document Room 
423  5901-B Ammendale Rd. 
424  Beltsville, MD 20705-1266 
425   
426  2.  Human Factors Submissions for Prescription or Nonprescription Biologics That 
427  Are the Subject of an IND Reviewed by CBER 
428   
429  Food and Drug Administration 
430  Center for Biologics Evaluation and Research 
431  Document Control Center 
432  10903 New Hampshire Ave. 
433  Bldg. 71, Rm. G112 
434  Silver Spring, MD 20993-0002 
435     
436  B.  Drug-Device Combination Products Under Development for Submission 
437  Under ANDA 
438   
439  1.  Controlled Correspondence 
440   
441  Sponsors seeking FDAs feedback on a specific element in the development of a drug-device 
442  combination product (e.g., identification and assessment of identified differences between the 
443  user interface of a proposed generic combination product and its reference listed drug) should 
444  submit the correspondence through the process outlined in FDAs draft guidance Controlled 
445  Correspondence Related to Generic Drug Development.44 This will facilitate prompt 
446  consideration of and response to the controlled correspondence by the appropriate discipline.  
447   
448  2.  Pre-ANDA Meeting 
449   
450  A request for a product development or pre-submission meeting for complex products that may 
451  be submitted in an ANDA should be sent through the process outlined in FDAs draft guidance 
452  for industry Formal Meetings Between FDA and ANDA Applicants of Complex Products Under 
453  GDUFA (Generic Drug User Fee Act). The meeting request should clearly identify in the subject 
454  line that the prospective applicant is requesting a product development or pre-submission 
                                                 
44 We update guidances periodically.  For the most recent version of a guidance, check the FDA guidance web page at 
https://www.fda.gov/RegulatoryInformation/Guidances/default.htm. 
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455  meeting and should include adequate information for FDA to assess the potential utility of the 
456  meeting and identify the appropriate staff that should attend the meeting.  
457   
458  C.  Electronic Submissions 
459   
460  The sponsor should place the request for HF submission review in Module 1.2 and associated 
461  documents (e.g. use-related risk analysis, protocols, reports) in Module 5, section 5.3.5.4  Other 
462  Study Reports and Related Information in eCTD.  
463   
464  The eCTD leaf title of the document should be clear, concise, and indicative of the content. 
465  Examples include: 
466   
467    HF - REQUEST FOR HUMAN FACTORS VALIDATION STUDY PROTOCOL 
468  REVIEW 
469   
470    HF - AMENDMENT TO REQUEST FOR HUMAN FACTORS VALIDATION STUDY 
471  PROTOCOL REVIEW 
472   
473    HF - REQUEST FOR HUMAN FACTORS VALIDATION STUDY REPORT REVIEW 
474   
475    HF - AMENDMENT TO REQUEST FOR HUMAN FACTORS VALIDATION STUDY 
476  REPORT REVIEW 
477   
478    HF-REQUEST FOR HUMAN FACTORS VALIDATION OTHER REVIEW45 
479   
480    HF-AMENDMENT TO REQUEST FOR HUMAN FACTORS VALIDATION OTHER 
481  REVIEW 
482   
483  The sponsor should also provide the eCTD location of the contents of the HF submission on the 
484  cover letter and, if possible, include cross-document links or external bookmarks to the 
485  information. This approach will help ensure that the information can be accessed quickly and 
486  easily. For further information on providing leaf titles and study results reports (including file-
487  tags) in eCTD, see the eCTD Technical Conformance Guide.46 
488   
489   
490  VI.   REVIEW TIMELINE 
491   
                                                 
45 For the purposes of the eCTD, there are three options: protocols, reports, or other. Other includes use-related risk analyses 
and threshold analyses.  
46 The eCTD Technical Conformance Guide is available at: 
http://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/ElectronicSubmissions/ucm153574.ht
m. 
 
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492  The Agency intends to review and comment on HF validation study protocol submissions in 
493  accordance with PDUFA VI performance goals.47 The review clock for the performance review 
494  goals begins when the Agency receives a complete submission. FDA will: 
495   
496    By fiscal year (FY) 2019, review 50% of HF protocol submissions and provide the 
497  sponsor with written comments within 60 days 
498   
499    By FY 2020, review 70% of HF protocol submissions and provide the sponsor with 
500  written comments within 60 days 
501   
502    By FY 2021, review 90% of HF protocol submissions and provide the sponsor with 
503  written comments within 60 days  
504   
505  If, after submitting an HF validation study protocol, a sponsor submits additional questions, 
506  unsolicited revisions to the protocol, or a lengthy or complex response to an FDA question, or 
507  amends original submission materials with new information for any reason, FDA ordinarily will 
508  not respond to the original questions and will consider the original protocol submission 
509  withdrawn. FDA will consider submission of a revised protocol, or revised or additional 
510  supporting materials, to be a new submission with a new 60-day timeline for response. 
511   
512  FDA will review all threshold analyses or comparative use HF submissions consistent with good 
513  review management principles and practices, as applicable, and in a timeframe to support any 
514  applicable performance goals under FDAs various user fee programs, taking into consideration 
515  the specific circumstances (e.g. breakthrough designation) surrounding the individual 
516  application.  
517   
518   
519  VII.   HOW TO OBTAIN ADDITIONAL INFORMATION 
520    
521  FDA encourages industry to meet with the Agency when appropriate48 to obtain Agency advice 
522  during product development. Meetings should not be used to obtain Agency review of HF 
523  validation study protocols or reports.  
524   
525  Prior to submitting an ANDA for a generic combination product, sponsors are encouraged to 
526  submit a controlled correspondence49 or pre-ANDA meeting package, or both,50 when 
527  appropriate.  
                                                 
47 PDUFA VI reauthorization performance goals and procedures for fiscal years 2018 through 2022, Section I.1.5.e, available at: 
http://www.fda.gov/downloads/ForIndustry/UserFees/PrescriptionDrugUserFee/UCM511438.pdf. 
48 Please refer to Guidance for Industry Formal Meetings between FDA and Sponsors or Applicants, available at: 
https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM590547.pdf.  
49 Draft guidance for industry, Controlled Correspondence Related to Generic Drug Development, available at: 
https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm583436.pdf. When final, this 
guidance will represent the FDAs current thinking on this topic. For the most recent version of a guidance, check the FDA Drugs 
guidance web page at https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm. 
50 Please refer to draft guidance for industry, Formal Meetings Between FDA and ANDA Applicants of Complex Products Under 
GDUFA, available at 
 
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528   
529   
530  VIII.   REFERENCES 
531   
532  Applicable guidance documents relating to HF, product design, requesting meetings with the 
533  Agency, and providing electronic submissions include those listed below: 
534   
535  A.  Guidance documents related to HF   
536    
537    Draft Guidance on Human Factors Studies and Related Clinical Study Considerations 
538  in Combination Product Design and Development  
539   
540    Draft guidance for industry Comparative Analyses and Related Comparative Use 
541  Human Factors Studies for a Drug-Device Combination Product Submitted in an 
542  ANDA 
543   
544    Draft guidance for industry Considerations in Demonstrating Interchangeability With 
545  a Reference Product 
546   
547    Guidance for industry and FDA staff Applying Human Factors and Usability 
548  Engineering to Medical Devices 
549   
550  B.  Guidance documents related to product design 
551   
552    Guidance for industry Safety Considerations for Product Design to Minimize 
553  Medication Errors 
554   
555    Draft guidance for industry Safety Considerations for Container Labels and Carton 
556  Labeling Design to Minimize Medication Errors  
557   
558  C.  Guidance on requesting meetings with Agency 
559   
560    Draft guidance for industry Formal Meetings Between the FDA and Sponsors or 
561  Applicants of PDUFA Products  
562   
563    Draft guidance for industry, Controlled Correspondence Related to Generic Drug 
564  Development   
565   
566    Draft guidance for industry, Formal Meetings Between FDA and ANDA Applicants of 
567  Complex Products Under GDUFA 
568   
                                                 
https://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm578366.pdf.  When final, this 
guidance will represent the FDAs current thinking on this topic. For the most recent version of a guidance, check the FDA Drugs 
guidance web page at https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm. 
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569    Guidance for industry and review staff Best Practices for Communication Between 
570  IND Sponsors and FDA During Drug Development 
571   
572  D.  Guidance on providing electronic submissions 
573   
574    Guidance for industry Providing Regulatory Submissions in Electronic Format  
575  Certain Human Pharmaceutical Product Applications and Related Submissions 
576  Using the eCTD Specifications 
577   
578     
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579  GLOSSARY 
580   
581  Applicant or sponsor: The entity that submits proposed Threshold Analyses or HF submissions
 
582  for the following types of products: 
583   
584    Prescription drug products (including biologics) that are the subject of an NDA (21 CFR 
585  314.3(b)), a BLA (21 CFR 601.2), or an ANDA (21 CFR 314.92), or that are currently 
586  the subject of an IND (21 CFR 312.3(b)) in anticipation of the submission of a marketing 
587  application 
588   
589    Nonprescription drug products that are the subject of an IND, NDA, or ANDA 
590   
591  Close calls: Instances in which a user almost makes a use error that could result in harm, but the 
592  user takes an action to recover and prevent the use error from occurring. 
593   
594  Comparative Use Human Factors Study Protocol: A study protocol for a proposed 
595  combination product that describes the design and methodology for a comparative use human 
596  factors study. 
597   
598  Comparative Use Human Factors Study Results Report: A study report that provides the 
599  results of a comparative use human factors study.  
600   
601  Complete submission: The information FDA identifies for a sponsor to include to ensure that 
602  the Agency can conduct a complete review of a proposed Human Factors Validation Study 
603  Protocol. 
604   
605  Critical task: A user task which, if performed incorrectly or not performed at all, may cause 
606  harm to the patient or user, where harm includes compromised medical care. 
607   
608  Formative evaluation: The process of assessing, at one or more stages during the product 
609  development process, a user interface or user interactions with the user interface in order to 
610  identify the interfaces strengths and weaknesses and to identify potential use errors that would 
611  or could result in harm to the patient or user. 
612   
613  Hazard: A potential source of harm. 
614   
615  Human Factors Engineering: The application of knowledge about human behavior, abilities, 
616  limitations, and other characteristics of medical device users when designing medical devices, 
617  including mechanical and software-driven user interfaces, systems, tasks, user documentation, 
618  and user training, to demonstrate and enhance safe and effective use. HF engineering and 
619  usability engineering can be considered synonymous. 
620   
621  Human Factors Validation Study Protocol: A study protocol that describes the design and 
622  methodology for a human factors validation study.  
623   
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624  Human Factors Validation Study Results Report: A study report that provides the results of a 
625  human factors validation study.  
626   
627  Human factors validation testing: Testing conducted at the end of the product development 
628  process to assess user interactions with a product user interface and to identify use errors that 
629  may result in serious harm to the patient or user. Human factors validation testing is also used to 
630  assess the effectiveness of risk management measures. Human factors validation testing 
631  represents one portion of design validation. 
632   
633  Label: As defined in section 201(k) of the FD&C Act (21 U.S.C. 321(k)), the term label means 
634  a display of written, printed, or graphic matter upon the immediate container of any article.  
635   
636  Labeling: As defined in section 201(m) of the FD&C Act (21 U.S.C. 321(m)), the term labeling 
637  means all labels and other written, printed, or graphic matter (1) upon any article or any of its 
638  containers or wrappers, or (2) accompanying such article. Labeling includes outside containers 
639  or wrappers and package liners.  
640   
641  Medication error: The National Coordinating Council for Medication Error Reporting and 
642  Prevention describes medication error as any preventable event that may cause or lead to 
643  inappropriate medication use or patient harm while the medication is in the control of the health 
644  care professional, patient, or consumer. Such events may be related to professional practice, 
645  health care products, procedures, and systems, including prescribing; order communication; 
646  product labeling, packaging, and nomenclature; compounding; dispensing; distribution; 
647  administration; education; monitoring; and use.51  
648   
649  Residual use-related risks: The risks that remain after risk control measures have been taken.  
650   
651  Simulated-use testing: Testing of a product under conditions of use that mimic real-world use 
652  conditions without administering the actual therapy to patients.  
653   
654  Task: An action or set of actions performed by a user to achieve a specific goal. 
655   
656  Task Analyses: A systematic breakdown of device use process into discrete sequences of 
657  tasks.52  
658   
659  Threshold analyses: Conducted to identify differences (if any) that may exist between the 
660  proposed combination products user interface and the product it references. Consist of labeling 
661  comparison, comparative task analysis, and physical comparison of the device constituent 
662  part(s).53 
663     
                                                 
51 National Coordinating Council for Medication Error Reporting and Prevention web page, available at: 
http://www.nccmerp.org/aboutMedErrors.html. 
52 See an example of a task analysis in Guidance for Industry and FDA Staff titled Applying Human Factors and Usability 
Engineering to Medical Devices, available at https://www.fda.gov/downloads/MedicalDevices/.../UCM259760.pdf.  
 
53 See Comparative Analyses Draft Guidance.  
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664  Training decay: The time elapsed between receiving training and first product use.  
665   
666  Use environment: The environment(s) in which the product will be used. This may include a 
667  variety of settings, such as clinical settings or home settings.  
668   
669  Use error: A user action, or lack of action, that was different from that expected by the 
670  manufacturer and that caused an outcome that (1) was different from the result expected by the 
671  user, (2) was not caused solely by product failure, and (3) did or could result in harm. 
672   
673  Use-related risk analysis: An analytical method to identify use errors associated with each use 
674  step, and then the hazards/risks and clinical significance of those hazards/risks. The use-related 
675  risk analysis includes a comprehensive and systematic evaluation of all the steps involved in 
676  using the product (e.g., based on a task analysis), the errors that users might commit or the tasks 
677  they might fail to perform (considering known problems for similar products), the potential 
678  negative clinical consequences of use errors and task failures, the mitigation strategies, and 
679  methods for validating the risk mitigation strategies. 
680   
681  User: A person who interacts with (i.e., operates or handles) the product. 
682   
683  User interface: All components of the product with which the user interacts, including the 
684  device constituent part(s) of the product and any associated controls and displays, as well as 
685  product labels, labeling, and packaging.  
686     
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687  APPENDIX A 
688   
689  EXAMPLE OF STATEMENTS TO INCLUDE IN THE COVER LETTER 
690   
691  1)  For use-related risk analysis reviews, include the statement REQUEST FOR 
692  USE-RELATED RISK ANALYSIS REVIEW in bold capital letters. 
693   
694  2)  For amendments to use-related risk analysis reviews, include the statement 
695  AMENDMENT TO REQUEST FOR USE-RELATED RISK ANALYSIS 
696  REVIEW in bold capital letters. 
697   
698  3)  For HF protocol reviews, include the statement REQUEST FOR HUMAN 
699  FACTORS VALIDATION STUDY PROTOCOL REVIEW in bold capital 
700  letters. 
701       
702  4)  For amendments to HF protocols, include the statement AMENDMENT TO 
703  REQUEST FOR HUMAN FACTORS VALIDATION STUDY PROTOCOL 
704  REVIEW in bold capital letters. 
705   
706  5)  For HF study results reports, include the statement REQUEST FOR HUMAN 
707  FACTORS VALIDATION STUDY REPORT REVIEW in bold capital 
708  letters. 
709   
710  6)  For amendments to HF study results reports, include the statement 
711  AMENDMENT TO REQUEST FOR HUMAN FACTORS VALIDATION 
712  STUDY REPORT REVIEW in bold capital letters. 
713   
714  7)  For comparative use HF threshold analyses reviews, include the statement 
715  REQUEST FOR THRESHOLD ANALYSES REVIEW in bold capital 
716  letters. 
717   
718  8)  For amendments to comparative use HF threshold analyses reviews, include the 
719  statement AMENDMENT TO REQUEST FOR THRESHOLD ANALYSES 
720  REVIEW in bold capital letters. 
721       
722  9)  For comparative use HF protocol reviews, include the statement REQUEST 
723  FOR COMPARATIVE USE HUMAN FACTORS PROTOCOL REVIEW 
724  in bold capital letters. 
725   
726  10)  For amendments to comparative use HF protocol reviews, include the statement 
727  AMENDMENT TO REQUEST FOR COMPARATIVE USE HUMAN 
728  FACTORS PROTOCOL REVIEW in bold capital letters. 
729   
730  11)  For comparative use HF study results report reviews, include the statement 
731  REQUEST FOR COMPARATIVE USE HUMAN FACTORS REPORT 
732  REVIEW in bold capital letters. 
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733   
734  12)  For amendments to comparative use HF study results report review, include the 
735  statement AMENDMENT TO REQUEST FOR COMPARATIVE USE 
736  HUMAN FACTORS REPORT REVIEW in bold capital letters. 
737   
738   
739  APPENDIX B 
740   
741  EXAMPLE OF USE-RELATED RISK ANALYSIS 
742   
Task  Use task  Description  Potential  Critical  Risk  Evaluation 
No.   description  of potential  hazards/harm  task  mitigation  method in HF 
use errors  and severity54   (Yes/  measure for  validation study 
No)  each use 
error 
4  Press green  Button is  Full dose is  Yes  Redesign  Evaluated in HF 
button and  held for less  not injected;  product to  validation study 
hold for 10  than 10  leads to  eliminate  in use scenario 1: 
seconds  seconds  patient death   the need to  Administration 
hold for 10  of Drug, task 4 
seconds 
743   
744   
745  APPENDIX C 
746   
747  EXAMPLE OF DESCRIPTION OF USER INTERFACE 
748   
Interface  Written description of the user interface  Graphical depiction of the 
Item  user interface 
Inspection  The user inspects the window to ensure that 
Window  the drug color is clear and drug solution does 
not have any particulates 
 
749   
750     
                                                 
54 Describe potential hazard/harm and severity for each potential use error. 
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751  APPENDIX D 
752   
753  HYPOTHETICAL EXAMPLE OF HF VALIDATION DATA 
754   
755  A hypothetical example of the results of analyzing human factors validation study data are 
756  shown in the table below.  Analysis of human factors validation study data should focus on any 
757  problems found during the testing. The study data should be analyzed to determine which part of the 
758  user interface was involved and how the user interaction could have resulted in the use error or 
759  problem.  
760   
Description  Number of  Number of  Study  Sponsors Root  Sponsors 
of Tasks  use errors  close calls and  participan cause analysis57  Discussion of 
(denote C  and  use  ts  Mitigation 
for critical)  description  difficulties55  subjective  strategies58 
of use  and  feedback
errors  description of  56 
close calls and 
use difficulties  
Task 4:  1 use error.  0 close calls or  The user  Root cause  Product was 
    use difficulties  heard a  analysis  redesigned to align 
Press green  The user  second  showed that the  the audible cues to 
button and  did not  click and  user interface  the hold time 
hold for 10  press the  stopped  has audible  needed to deliver the 
seconds  green  pressing  cues that do not  drug. This change 
(C)  button for  the button  coincide with  impacts a critical 
10  because  the labeled  task for drug 
seconds,  he  hold time and  delivery. Thus, the 
he only  thought  contribute to  change was 
held it for  the  confusion.  evaluated in another 
5 seconds.  injection  validation study 
was  conducted to 
complete  demonstrate the 
based on  effectiveness of this 
the click.   change to the user 
interface.  
761   
                                                 
55 While close calls and difficulties may not manifest into actual use errors/failures, they are good source of data in terms of 
providing potential user interface inadequacies that should be further evaluated. 
56 What the participant(s) say about the use errors/close calls/use difficulties from their perspective.  
57 This should incorporate the sponsors analysis of the subjective data obtained from study participants clarifying why or how 
the use errors and failures occurred from the participants perspective. Some questions to consider: What did study participants 
say about the errors/failures? Did they say how/why the errors/failures occurred? Did they comment on any aspect of the user 
interface that may have influenced their behavior/action while they were performing the task? Did they note any suggested user 
interface improvements? 
58 This should address whether additional product modifications, risk mitigations, or risk mitigation validation should be 
implemented as necessary. 
23