FDA eCTD Validation Criteria: Every Rule, Explained (v3.2.2 and v4.0)


eCTD validation criteria · United States

FDA eCTD validation criteria, every rule explained

All 294 criteria FDA applies to eCTD v3.2.2 and v4.0 sequences, in plain language: what each rule checks, how severe it is, and how to fix it before you submit.

Search the criteria →See DnXT validate a sequence
150v3.2.2 criteria
144v4.0 criteria
45v3.2.2 high-severity
How FDA validates

What happens to a sequence before anyone reads it

When a sequence reaches FDA through the Electronic Submissions Gateway, it is checked automatically against FDA’s published eCTD validation criteria before it is routed to a review division. The check covers the backbone files, the Module 1 envelope, file names and checksums, lifecycle operations, PDF properties and study tagging files.

For eCTD v3.2.2, every criterion has a severity. A high finding means FDA will reject the submission on technical grounds and the review clock does not start. A medium finding may require corrective action, and FDA will contact you if it does. A low finding should be corrected in future submissions.

For eCTD v4.0, criteria are graded as High Error or Warning. A High Error stops the submission; a Warning is reported but does not. FDA publishes the v4.0 criteria separately because the message format, controlled vocabularies and lifecycle model are different.

Study data has its own technical rejection criteria, applied alongside these. Both apply to the same transmission.

Reference

Search all FDA criteria

Open any rule to see what it checks, how to fix it, and the specification it comes from. Filter by severity to see only the rules that cause rejection.

150 criteria · 45 high · 74 medium · 31 low · source: FDA Specifications for eCTD Validation Criteria

Schema Error

2002XML didn't pass validation with the schema (DTD) and attribute filesHigh

What it checks. You provided an index.xml, us-regional.xml or stf.xml file which does not conform to the schema (DTD) and/or attribute files.

How to fix it. Resubmit your submission ensuring that you use xml files valid with the schema (DTD) and attribute files as applicable. You may resubmit using the original sequence number of the submission.

Reference. ICH eCTD Specification V3.2.2; The eCTD Backbone Files Specification for Module 1; General good practice to ensure reviewability

3001STF doc-content title usedMedium

What it checks. You have included a STF doc-content title. This title is not visible to the reviewer and should not be used. The leaf title is visible to reviewers.

How to fix it. Corrective action may be necessary. In future submissions, ensure that doc-content titles for each document referenced in the STF XML are not included.

Reference. The eCTD Backbone File Specification for Study Tagging Files V2.6.1

3015The element 'file-tag' preceded the element 'property'Medium

What it checks. In the STF XML the 'property' element should come before its sibling element 'file-tag'.

How to fix it. Modify your SOPs to ensure your STF is in conformance with the ordering as described in the specification and the DTD.

Reference. The eCTD Backbone File Specification for Study Tagging Files V2.6.1

3029Use of content-block is not recommendedMedium

What it checks. Although content block is in both DTD versions, the specification does not refer to it; it is recommended that you do not use it.

How to fix it. Remove the content block element in the identified stf-xxxxxxxx.xml and resubmit at time of next planned submission.

Reference. The eCTD Backbone File Specification for Study Tagging Files V2.6.1

General

6Submission is not in eCTD formatHigh

What it checks. You are required to submit in eCTD format

How to fix it. Resubmit using eCTD format

Reference. Providing Regulatory Submissions in Electronic Format - Certain Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specification

7Fillable form not includedHigh

What it checks. You have submitted without including the appropriate fillable form 356h, 2252, or 1571

How to fix it. Resubmit with the appropriate fillable form 356h, 2252, or 1571

Reference. Providing Regulatory Submissions in Electronic Format - Certain Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specification

1344Attribute value leads or ends with a spaceLow

What it checks. Attribute value leads or ends with a space.

How to fix it. No corrective action is necessary. Modify your SOPs to ensure that attribute values do not lead or end with a space.

Reference. General good practice to ensure reviewability.

1357Required attribute value omitted in M2 - M5Medium

What it checks. You did not specify a required attribute in a heading element or STF XML file in m2 through m5, e.g. 'indication' in the section 5.3.5 element or 'type of control' in the STF XML file for a study in section 5.3.5.1.

How to fix it. Corrective action may be necessary. If corrective action is necessary, you will be contacted by FDA. Modify your SOPs to ensure that attributes are used as described in the eCTD Specification.

Reference. DTDs; The eCTD Backbone File Specification for Study Tagging Files V2.6.1

1362An attribute appears multiple times in the stf.xml fileMedium

What it checks. You have duplicated an attribute, e.g., two 'type-of-control' attributes in a STF XML file. Viewer will ignore duplicate attributes and display only the first attribute.

How to fix it. Corrective action may be necessary. If corrective action is necessary, you will be contacted by FDA. Modify your SOPs to ensure that attributes are used as described in the eCTD Specification.

Reference. DTDs; The eCTD Backbone File Specification for Study Tagging Files V2.6.1

1368Extraneous attributeLow

What it checks. You have submitted an attribute that is not called for in the specification, e.g. 'manufacturer' in a Module 4 or Module 5 heading element or 'species' in a Module 5 STF.

How to fix it. No corrective action is currently possible. Modify your SOPs to ensure that attributes are used as described in the eCTD Specification.

Reference. DTDs; The eCTD Backbone File Specification for Study Tagging Files V2.6.1

1374Checksum value must match the actual checksumLow

What it checks. Your checksum value does not match the actual checksum.

How to fix it. Corrective action is based on the underlying reason for the error. You should determine if the issue is simply a miscalculation or misapplication of a checksum; if so, no corrective action is necessary. If you determine that the incorrect file was submitted you should submit the corrected file in a future submissions with a leaf element referencing the original leaf with an operation attribute of 'Replace'. If you believe that an error has occurred and that the file you have submitted may have become corrupt you should contact your appropriate Center representative.

Reference. ICH eCTD Specification V3.2.2

1391Invalid checksum formatting in index-md5.txtLow

What it checks. You are using an invalid checksum format, i.e., you have not specified the 32 characters produced as part of generating the MD5 checksum, or you have included trailing spaces or carriage returns.

How to fix it. No corrective action is necessary. Modify your SOPs to ensure the proper MD5 checksum format is used.

Reference. ICH eCTD Specification V3.2.2

1408Invalid checksum typeLow

What it checks. You have used an invalid checksum type.

How to fix it. No corrective action is necessary. Modify your SOPs to ensure the use of MD5 checksums.

Reference. ICH eCTD Specification V3.2.2

1425Omitted checksum valueLow

What it checks. You have omitted the checksum value.

How to fix it. No corrective action is necessary. Modify your SOPs to ensure that the MD5 checksums are specified.

Reference. ICH eCTD Specification V3.2.2

1426Unexpected checksum valueLow

What it checks. You have provided a checksum when the leaf operation is 'Delete'.

How to fix it. No corrective action is necessary. Modify your SOPs to ensure that the checksums are not specified for delete operations.

Reference. ICH eCTD Specification V3.2.2

1442Omitted DTD version in index.xmlMedium

What it checks. You have omitted the DTD version in the index.xml file.

How to fix it. No corrective action is necessary unless FDA notifies you that it is unable to process your submission. Modify your SOPs to ensure that the DTD version is specified in the index.xml file.

Reference. The eCTD Backbone File Specification for Study Tagging Files V2.6.1

1445Omitted DTD version in us-regional.xml fileMedium

What it checks. You have omitted the DTD version in the us-regional.xml file.

How to fix it. No corrective action is necessary unless FDA notifies you that it is unable to process your submission. Modify your SOPs to ensure that the DTD version is specified in the us-regional.xml file.

Reference. The eCTD Backbone Files Specification for Module 1

1459Unsupported DTD version in index.xml fileHigh

What it checks. You are using an unsupported DTD version in the index.xml file.

How to fix it. Resubmit your submission using a version of the DTD that is supported. You may resubmit using the original sequence number of the submission.

Reference. ICH eCTD Specification V3.2.2; FDA eCTD Website

1463Unsupported DTD version in us-regional.xml fileHigh

What it checks. You are using an unsupported DTD version in the us-regional.xml file.

How to fix it. Resubmit your submission using a version of the DTD that is supported. You may resubmit using the original sequence number of the submission.

Reference. The eCTD Backbone Files Specification for Module 1; FDA eCTD and Module 1 Website

1476Node-extension existsMedium

What it checks. You have included node extensions in your submissions. Node extensions are strongly discouraged by FDA.

How to fix it. Modify your SOPs to ensure that node extensions are not used in future submissions.

Reference. FDA Presentations

1478Node-extension does not have a titleMedium

What it checks. Node extension is supplied without a title.

How to fix it. In a future submission, a leaf should be provided that references the original node-extension leaf specifying the 'Delete' operation. A new leaf using an existing eCTD heading should be also submitted specifying the operation attribute of 'New' taking care to include all required elements and attributes. The use of node extensions is strongly discouraged.

Reference. ICH eCTD Specification V3.2.2; General good practice to ensure reviewability.

1482Node-extension title leads or ends with a spaceLow

What it checks. The node-extension title begins or ends with a space

How to fix it. No corrective action is necessary. Modify your SOPs to ensure that node extensions are not used in future submissions. The use of node extensions is strongly discouraged.

Reference. eneral good practice to ensure reviewability.

1500Text data was truncatedLow

What it checks. You have submitted data that exceed the maximum limits.

How to fix it. No corrective action is necessary. This is a warning to examine your naming conventions to reduce the size of the data values. Titles and keywords are limited to 512 characters.

Reference. ICH eCTD Specification V3.2.2

3078eCTD element does not contain any leaf elementsLow

What it checks. You have included a lowest level element that does not contain any leaf elements.

How to fix it. No corrective action is necessary. Modify your SOPs to ensure lowest level elements contain leaf elements.

Reference. FDA Presentations

1734A dataset named ts.xpt with information on study start date must be present for each study in Module 4, sections 4.2.3.1, 4.2.3.2, 4.2.3.4, and in Module 5, sections 5.3.1.1, 5.3.1.2, 5.3.3.1, 5.3.3.2, 5.3.3.3, 5.3.3.4, 5.3.4, 5.3.5.1, 5.3.5.2High

What it checks. You have not submitted a dataset named ts.xpt with information on study start date for each study in Module 4, section 4.2, or in Module 5, section 5.3

How to fix it. Resubmit, including a dataset named ts.xpt with information on study start date for each study in Module 4, section 4.2, and Module 5, section 5.3

Reference. Providing Regulatory Submissions in Electronic Format - Standardized Study Data; Study Data Technical Conformance Guide.

1736For Standard for Exchange of Nonclinical Data (SEND) data, a Demographic (DM) dataset and define.xml must be submitted in Module 4. For Study Data Tabulation Model (SDTM) data, a DM dataset and define.xml must be submitted in Module 5. For Analysis Data Model (ADaM) data, an ADaM Subject level analysis dataset (ADSL) and define.xml must be submitted in Module 5.High

What it checks. You have not submitted SEND DM and corresponding define.xml for each study in Module 4, section 4.2. You have not submitted SDTM DM and corresponding define.xml for each study in Module 5, section 5.3. You have not submitted ADSL, and corresponding define.xml for each study in Module 5, section 5.3.

How to fix it. Resubmit the submission with the SEND DM and corresponding define.xml in Module 4, section 4.2. Resubmit including SDTM DM and corresponding define.xml for each study in Module 5, section 5.3. Resubmit including ADSL and corresponding define.xml for each study in Module 5, section 5.3.

Reference. Providing Regulatory Submissions in Electronic Format - Standardized Study Data; Study Data Technical Conformance Guide.

M1

5Application MismatchHigh

What it checks. Application Type/Number in the FDA Form does not match Application Type/Number in us-regional.xml

How to fix it. Resubmit using consistent Application Type/Number between FDA Form and us-regional.xml

Reference. FDA Presentations

1454Company name is missingLow

What it checks. You have omitted the company name in the us-regional.xml file.

How to fix it. No corrective action is necessary unless FDA notifies you that it is unable to process your submission.

Reference. DTDs; The eCTD Backbone Files Specification for Module 1

1496Application type is invalidHigh

What it checks. The application type must match a valid, supported application type from the specification and/or attribute xml file if applicable.

How to fix it. Resubmit your application specifying a valid application type. Certain application types in the attribute file are used only for cross-referenced applications, and it's noted in the attribute file. You may resubmit using the original sequence number of the submission.

Reference. DTDs; The eCTD Backbone Files Specification for Module 1

1519Application number does not match the folder nameMedium

What it checks. Your application number in the us-regional.xml file does not match the folder name or the application number referenced for application-containing-files='true' does not match the folder name.

How to fix it. Your application number and folder name must match; please correct one of them.

Reference. General good practice to ensure reviewability.

1544Company name must remain constantLow

What it checks. The company name has changed.

How to fix it. No corrective action is necessary since company names do change from time to time. Modify your SOPs to ensure that company name is used consistently from submission to submission. The company name should only change when there is an actual name change.

Reference. General good practice to ensure reviewability.

1545Promotional labeling and advertising regulatory contact is missingMedium

What it checks. You did not provide the promotional labeling and advertising regulatory contact for a Promotional Labeling Advertising submission (submission-type=Promotional Labeling Advertising).

How to fix it. Ensure that a promotional labeling and advertising regulatory contact is provided for all future promotional labeling and advertising submissions.

Reference. The eCTD Backbone Files Specification for Module 1

1550Material-id exceeds 30 charactersMedium

What it checks. You provided a material-id that exceeds the 30 character limitation.

How to fix it. Ensure each material-id is within character limitations in future submissions.

Reference. The eCTD Backbone Files Specification for Module 1

15512253 submission does not include Product LabelingHigh

What it checks. Your 2253 submission did not include Product Labeling. Firms must submit the most current product labeling to section 1.14.6

How to fix it. Resubmit the 2253 submission with most current product labeling

Reference. FDA Form 2253 instructions; Firms must submit the most current product labeling, as required in 21 CFR 314.81(b)(3)(i), to section 1.14.6; Providing Regulatory Submissions in Electronic and Non-Electronic Format - Promotional Labeling and Advertising Materials for Human Prescription Drugs, Guidance for Industry

1553The only valid FDA Form to include in a 2253 submission is FDA Form 2253High

What it checks. You have submitted an eCTD submission with an eCTD Submission Type of Promotional Labeling and included a Form which is not a 2253. Only 2253 Forms are allowed with a submission of this type.

How to fix it. Resubmit without the non-2253 Form

Reference. Providing Regulatory Submissions in Electronic and Non- Electronic Format - Promotional Labeling and Advertising Materials for Human Prescription Drugs, Guidance for Industry

1554Promotional Material Issue Date Format is incorrectLow

What it checks. The Promotional Material Issue Date in the submission does not match the proper format of YYYYMMDD

How to fix it. Resubmit following the date format YYYYMMDD

Reference. Providing Regulatory Submissions in Electronic and Non- Electronic Format - Promotional Labeling and Advertising Materials for Human Prescription Drugs, Guidance for Industry

1636The submission-id referenced has not been received and/or processedHigh

What it checks. The submission-id referenced has not been received and/or processed.

How to fix it. Submit the referenced submission-id sequence first before using it as a submission-id in future submissions.

Reference. DTDs; The eCTD Backbone Files Specification for Module 1; General good practice to ensure reviewability.

1681Issue-date attribute value is missingMedium

What it checks. You did not provide the issue-date for one or more promotional materials in a 2253 submission (promotional-material-doc-type=promotional 2253).

How to fix it. Ensure that an issue date is provided for each promotional material in future 2253 submissions.

Reference. The eCTD Backbone Files Specification for Module 1

1697Sequence number was previously submittedHigh

What it checks. The sequence number used in your submission has already been submitted to the application.

How to fix it. Resubmit your submission ensuring that you use a 4 numeric digit sequence number that is unique within the application.

Reference. The eCTD Backbone Files Specification for Module 1

1714Sequence number does not match the folder nameHigh

What it checks. The sequence number used in your submission does not match the folder name or for DTD V3.2 the sequence number for the application containing files (application-containing-files='true') does not match the folder name

How to fix it. Resubmit your submission ensuring that the sequence number used in your submission matches the folder name for DTD V2.01 or that the sequence number for the application containing files (application-containing-files='true') matches the folder name for DTD V3.2

Reference. ICH Q&A 36 #19

2001An older version of the DTD has been used after a submission to the application used a higher version.High

What it checks. You referenced a version of the DTD that can no longer be used for the application because a previous submission(s) to the same application referenced a higher, more recent version.

How to fix it. Resubmit your submission using the same or higher version of the DTD referenced in previous submissions. You may resubmit using the original sequence number of the submission.

Reference. DTDs; The eCTD Backbone Files Specification for Module 1

2003us-regional.xml is not referencing the DTD and stylesheet at an approved valid locationHigh

What it checks. You submitted a submission with its us-regional.xml referencing incorrect DTD and stylesheet file locations.

How to fix it. Resubmit your submission that contains a us-regional.xml that references the valid, correct versions of the DTD and stylesheet. You may resubmit using the original sequence number of the submission.

Reference. The eCTD Backbone Files Specification for Module 1

2012A required attribute value in M1 is missingHigh

What it checks. You have failed to provide a required attribute value for an M1 element.

How to fix it. Resubmit the submission and ensure all required attribute values are provided. You may resubmit using the original sequence number of the submission.

Reference. The eCTD Backbone Files Specification for Module 1

2013Invalid M1 attribute valueHigh

What it checks. You submitted a submission that refers to an M1 attribute value that has a status of invalid or the value itself is not allowed according to the corresponding referenced attribute type list.

How to fix it. Resubmit the submission and ensure all provided M1 attributes are valid. You may resubmit using the original sequence number of the submission.

Reference. The eCTD Backbone Files Specification for Module 1

2021A submission sub-type error occurred because this particular submission sub-type is only allowed once for each regulatory activity.Medium

What it checks. You used a submission sub-type that was provided in a previous submission to the same regulatory activity. Certain submission sub-types (application, original, report) can only be submitted once for each regulatory activity. (e.g., original-application should only have one submission with a sub-type value 'application').

How to fix it. You will be contacted if corrective action is necessary. Modify your SOPs to ensure that the submission sub-types which should only be used once for each regulatory activity, are not used again for subsequent submissions to the same regulatory activity.

Reference. General good practice to ensure reviewability.

2022Submission-sub-type is invalid for submission-typeHigh

What it checks. You have used a submission-sub-type which is not allowed for the submission-type and/or type of application.

How to fix it. Resubmit the submission using a valid submission-sub-type. You may resubmit using the original sequence number of the submission.

Reference. The eCTD Backbone Files Specification for Module 1

2023All grouped submission submission-sub-type values must be the sameHigh

What it checks. You have referenced more than one application and the submission sub-type values are not the same.

How to fix it. Resubmit the submission and provide the same submission sub-type for all applications referenced in the us-regional.xml. You may resubmit using the original sequence number of the submission.

Reference. The eCTD Backbone Files Specification for Module 1

2024For all sequences for a regulatory activity the submission type must be consistent.High

What it checks. You have used a submission type that is different than the submission type of the parent regulatory activity.

How to fix it. Resubmit the submission with a submission type that matches the parent regulatory activity type.

Reference. The eCTD Backbone Files Specification for Module 1

2025The eCTD sequence number of the submission sub-type that starts a new regulatory activity and the submission-id must match.High

What it checks. You have used a submission sub-type that begins a new regulatory activity and the eCTD sequence number does not match the submission-id.

How to fix it. Resubmit the submission where the eCTD sequence number matches the submission-id for the new regulatory activity.

Reference. The eCTD Backbone Files Specification for Module 1

2026The submission-id must reference the eCTD sequence number for the parent regulatory activityMedium

What it checks. You have used a submission-id that matches the eCTD sequence number and the submission sub-type does not start a new regulatory activity.

How to fix it. You will be contacted if corrective action is necessary. Modify your SOPs to ensure that the submission-id references the sequence number that begins the regulatory activity.

Reference. The eCTD Backbone Files Specification for Module 1

2031All grouped submission application-type values must be the sameHigh

What it checks. You have referenced more than one application and the application-type values are not the same.

How to fix it. Resubmit the submission and provide the same application-type for all applications referenced in the us-regional.xml. You may resubmit using the original sequence number of the submission.

Reference. The eCTD Backbone Files Specification for Module 1

2032All grouped submission submission-type values must be the sameHigh

What it checks. You have referenced more than one application and the submission-type values are not the same.

How to fix it. Resubmit the submission and provide the same submission-type for all applications referenced in the us-regional.xml. You may resubmit using the original sequence number of the submission.

Reference. The eCTD Backbone Files Specification for Module 1

2033Different sequence numbers are referenced for the same application numberHigh

What it checks. You referenced different sequence numbers to the same application in a grouped submission. When submitting to different regulatory activities in the same application, use the same sequence number for each submission.

How to fix it. Reference the same sequence number for all regulatory activities to the same application number.

Reference. The eCTD Backbone Files Specification for Module 1

2034Submission-type is invalid for application-typeHigh

What it checks. You have used a submission-type which is not allowed for the application type.

How to fix it. Resubmit the submission using a valid submission-type. You may resubmit using the original sequence number of the submission.

Reference. The eCTD Backbone Files Specification for Module 1

2035Submission description exceeds 128 charactersLow

What it checks. You provided a submission description that exceeds the 128 character limit.

How to fix it. Ensure future submissions do not have a submission-description that exceeds 128 characters.

Reference. The eCTD Backbone Files Specification for Module 1

2036No application element with application-containing-files value of 'true'High

What it checks. You did not provide an application-containing-files value='true' for any applications referenced in the us-regional.xml.

How to fix it. Resubmit the submission indicating which application contains the files by ensuring the application's application-containing-files element has a value='true'. You may resubmit using the original sequence number of the submission.

Reference. The eCTD Backbone Files Specification for Module 1

2037More than one application-containing-files element has a value of 'true'High

What it checks. You have reference more than one application with an application-containing-files value= 'true'.

How to fix it. Resubmit the submission indicating which application contains the files by ensuring the application's application-containing-files element has a value='true'. You may resubmit using the original sequence number of the submission.

Reference. The eCTD Backbone Files Specification for Module 1

2038Cross-reference-application-number must contain 6 numeric digits onlyLow

What it checks. Your cross-reference-application-number must be 6 numeric digits in length.

How to fix it. In a future submission, reference the correct six (6) digit application number.

Reference. The eCTD Backbone Files Specification for Module 1

2041Supplement-effective-date-type attribute value is missingMedium

What it checks. You did not provide the supplement-effective-date-type for this first submission to the supplement.

How to fix it. Include a supplement-effective-date-type in the first submission to a new supplement.

Reference. The eCTD Backbone Files Specification for Module 1

2042Email address exceeds 64 charactersLow

What it checks. You provided an email address that exceeds the 64 character limitation.

How to fix it. Ensure email addresses are within character limitations in future submissions.

Reference. The eCTD Backbone Files Specification for Module 1

2043id element has changedLow

What it checks. You are using an company id element that is different than the id used in previous submissions to the application.

How to fix it. No corrective action is necessary since id can change from time to time. Modify your SOPs to ensure that same id is used consistently in future submissions to the application. The id should change only when there is a change in ownership of the application.

Reference. General good practice to ensure reviewability.

2044id element must contain 9 digits onlyMedium

What it checks. You provided an id that is not 9 numeric digits.

How to fix it. Ensure future submissions include an id that is 9 numeric digits.

Reference. The eCTD Backbone Files Specification for Module 1

2045Invalid form type for eCTD locationMedium

What it checks. You have included an invalid form-type attribute value in the submission-information section.

How to fix it. Reference the form in the m1-1-forms section and not in submission-information in the admin section of the us-regional.xml.

Reference. The eCTD Backbone Files Specification for Module 1

3036Application number must contain 6 numeric digits onlyHigh

What it checks. The application number must be 6 numeric digits in length.

How to fix it. Resubmit your submission specifying a properly formatted application number. You may resubmit using the original sequence number of the submission.

Reference. The eCTD Backbone Files Specification for Module 1

3050Submission sequence number must contain 4 numeric digits onlyHigh

What it checks. Your submission's sequence number must be 4 numeric digits in length.

How to fix it. Resubmit your submission specifying a properly formatted sequence number.

Reference. The eCTD Backbone Files Specification for Module 1

3065Submission-id element must contain 4 numeric digits onlyHigh

What it checks. Your submission-id must be 4 numeric digits in length.

How to fix it. Resubmit your submission specifying a properly formatted submission-id number. You may resubmit using the original sequence number of the submission.

Reference. The eCTD Backbone Files Specification for Module 1

5029Misnamed formLow

What it checks. You may have submitted an application form that is not named correctly (a 1571 form missing 1571 in its filename or 356 form with missing 356h in its file name). If so, this will prevent automated processing of the form.

How to fix it. n the future, ensure that your application form is named 356h.pdf or 1571.pdf. It is also good practice to follow a similar approach when submitting other FDA forms (e.g., 2252, 3674, etc.).

Reference. FDA Presentations

5030Application number in form does not match application number in us-regional.xmlHigh

What it checks. The application number in your application form does not match the application number supplied in your us-regional.xml file. Note: This error can be ignored for trans BLAs.

How to fix it. In future submissions, ensure that these numbers match. You may need to resubmit with consistent information.

Reference. FDA Presentations

5032Multiple application forms present for the same applicationLow

What it checks. You have submitted more than one application form for the same application. Note: This error can be ignored for trans-BLAs submitted with DTD version 2.01.

How to fix it. In future submissions, include only one file with the form number as part of the file name. For example, only include one file named 356h.pdf for an NDA, and do not include 356h in the file names of other ancillary documents.

Reference. FDA Presentations

5034Application form placed in wrong TOC locationLow

What it checks. You have submitted an application form that was not placed in the correct TOC location.

How to fix it. If corrective action is necessary, you will be contacted. You should provide forms in the correct Module 1 location as specified in the applicable eCTD Backbone Files Specification for Module 1.

Reference. FDA Presentations; The eCTD Backbone Files Specification for Module 1

5038Wrong application formHigh

What it checks. You have submitted the wrong application form based on your application type, that is, you have submitted a form named 1571.pdf for an NDA/ANDA/BLA, a form named 356h.pdf for an IND or a form named 2252.pdf for a sequence that is not an annual report.

How to fix it. Resubmit your submission with the correct application form. You may resubmit using the original sequence number of the submission. Modify your SOPs to ensure that your submission has a the correct type of form correctly named 356h.pdf or 1571.pdf and referenced in the correct eCTD location.

Reference. FDA Presentations; FDA Form Instructions

5039Promotional material audience type is missingMedium

What it checks. The promotional-material-audience-type attribute is required on m1-15-promotional-material but was not provided or is empty.

How to fix it. Include a promotional-material-audience-type attribute value (Consumer or Professional) on the m1-15-promotional-material element in future submissions.

Reference. The eCTD Backbone Files Specification for Module 1

File Check

2eCTD submission missing us-regional.xml fileHigh

What it checks. You have submitted an eCTD submission without the required us-regional.xml file.

How to fix it. Resubmit with us-regional.xml file.

Reference. The eCTD Backbone Files Specification for Module 1, ICH eCTD Specification V3.2.2

3Single file submissionHigh

What it checks. You have a submitted a single file.

How to fix it. Resubmit folder containing file(s)/subfolders.

Reference. FDA Presentations

4Submission containing no filesHigh

What it checks. Submission does not contain files.

How to fix it. Resubmit folder containing file(s)/subfolders.

Reference. The eCTD Backbone Files Specification for Module 1, ICH eCTD Specification V3.2.2

1034Invalid leaf element operationMedium

What it checks. You have submitted a leaf and did not include the operation attribute. The system substituted 'New'.

How to fix it. If the operation attribute should not have been 'New', submit two new leaves. The first leaf should delete the leaf submitted without the operation attribute. The second should associate the file referenced by the first leaf to the leaf you had originally intended to modify.

Reference. DTDs; ICH eCTD Specification V3.2.2

1038Application form and cover letter should be 'New'Low

What it checks. You have submitted a form or cover letter using an operator other than 'New'.

How to fix it. No corrective action is necessary as occasionally there is a need to replace an incorrect document. Modify your SOPs to ensure the 'New' operator is used with forms and cover letters except for exception cases.

Reference. FDA Presentations

1051Extraneous leaf element pathMedium

What it checks. You have specified a xlink:href path for an operation that does not require one, e.g., 'Delete'.

How to fix it. Modify your SOPs to ensure extraneous information is not submitted.

Reference. ICH eCTD Specification V3.2.2

1068Extraneous modified leaf element pathMedium

What it checks. You have specified a modified-file path for an operation that does not require one, e.g., 'New'.

How to fix it. Modify your SOPs to ensure extraneous information is not submitted.

Reference. ICH Q&A 36 #4

1085Leaf element path length exceeds maximum (230 characters)Medium

What it checks. There is a maximum path length of 230 characters. Internal processing adds additional characters to your paths which may invalidate your links.

How to fix it. Corrective action may be necessary. Examine your naming conventions to reduce the length of path statements.

Reference. ICH eCTD Specification V3.2.2

1102Leaf element path contains invalid characters:tilde(~), forward slash, backslash, colon, asterisk, question mark, single quote, double quote, less than, greater than, pipe, or spaceMedium

What it checks. Your path statement contains invalid characters. Since the restriction on characters in the path is an operating system constraint there is likely to be an orphaned file caused by a mismatch between the path specified for the leaf and the actual path of the file referenced by the leaf.

How to fix it. Resubmit a corrected leaf in a future submission with the operation attribute of 'Replace' to replace the original erroneous leaf.

Reference. ICH eCTD Specification V3.2.2; FDA Portable Document Format Specifications

1111More than one version of the us-regional.xml file existsHigh

What it checks. More than one us-regional.xml was found in the same sequence; the M1 element contains two leafs for regional files.

How to fix it. Resubmit with only one us-regional.xml and only one reference to a regional file per submission sequence.

Reference. General good practice to ensure reviewability.

1119Missing required fileMedium

What it checks. A required file in the UTIL folder is missing.

How to fix it. Corrective action may be necessary. Modify your SOPs to prevent this in the future.

Reference. ICH eCTD Specification V3.2.2; ICH Q&A 36 #2, 6, and 8

1130Required file checksum value in the util folder must match the expected checksumLow

What it checks. You have submitted a required file which has been altered (DTD or stylesheet in the UTIL folder).

How to fix it. No corrective action is necessary. Modify your SOPs to prevent this in the future and ensure the required file is not altered.

Reference. ICH Q&A 36 #2, 6, and 8

1136Omitted leaf element pathMedium

What it checks. You have not provided the path to the file that should be referenced by the leaf.

How to fix it. Resubmit the leaf specifying the file path to the original document in a later submission. Use the operational attribute of 'Replace' to replace the original incorrect leaf.

Reference. ICH eCTD Specification V3.2.2; ICH Q&A 36 #13

1153Missing modified fileMedium

What it checks. The leaf referenced in the modified-file element cannot be found.

How to fix it. In your next submission submit a leaf modifying the leaf that generated this error using the operation attribute of 'Delete'.In the same submission resubmit the leaf that generated this error correcting the modified-file reference.

Reference. ICH eCTD Specification V3.2.2

1154A leaf referenced in the modified-file element was not originally submitted to all applications in the grouped submissionMedium

What it checks. You are using an operator attribute on a leaf that has been found in a different application, but has not been submitted to this application.

How to fix it. n your next submission, submit a leaf modifying the leaf that generated this error using the operation attribute of 'Delete'. In the same submission, resubmit the leaf that generated this error correcting the modified-file reference.

Reference. General good practice to ensure reviewability.

1170Omitted leaf element modified file pathMedium

What it checks. The file path is not specified.

How to fix it. Resubmit the missing file path in a later submission referencing the original document using the operation attribute of 'Replace'.

Reference. ICH Q&A 36 #4; ICH eCTD Specification V3.2.2

1204File name contains invalid characters: tilde(~), forward slash, backslash, colon, asterisk, question mark, single quote, double quote, less than, greater than, pipe, or spaceLow

What it checks. The file name contains invalid characters.

How to fix it. Modify your SOPs to ensure file names do not contain invalid characters.

Reference. ICH eCTD Specification V3.2.2

1221File name exceeds maximum length (64 characters) per eCTDLow

What it checks. The file name exceeds maximum length (64 characters).

How to fix it. Modify your SOPs to ensure files names do not exceed the maximum length (64 characters) per the eCTD Specification.

Reference. ICH eCTD Specification V3.2.2

1238File size exceeds maximum limit (400 MB) per eCTD specificationLow

What it checks. The file size exceeds the maximum limit (400 MB). Note: This limit may not be applicable if your file is a dataset. Please refer to the FDA Study Data Specifications document for current information regarding dataset file sizes.

How to fix it. No corrective action is necessary. You should generally avoid sending files with sizes that exceed the eCTD Specification.

Reference. ICH eCTD Specification V3.2.2

1255Invalid file extensionMedium

What it checks. You provided a file extension that is not allowed in this section.

How to fix it. Only certain file extensions are valid in certain sections, therefore it is important to submit extensions only in the sections in which they are allowed. Corrective action may be necessary based on where the file with the invalid extension appears in the submission. You will be contacted if corrective action is necessary.

Reference. ICH eCTD Specification V3.2.2; Specifications for File Format Types Using eCTD Specifications

1276Leaf element title leads or ends with a spaceLow

What it checks. Leaf element title leads or ends with a space.

How to fix it. No corrective action is necessary. Modify your SOPs to ensure that leaf element titles do not lead or end with a space.

Reference. General good practice to ensure reviewability.

1290Leaf element title contains the eCTD section numberLow

What it checks. A leaf title begins with the eCTD section number (for example '2.5 Clinical Overview'). The section is already shown by the position of the leaf in the table of contents, so repeating it in the title costs the reviewer space without adding information.

How to fix it. No corrective action is necessary for an already-submitted sequence. Modify your SOPs so leaf titles describe the document rather than repeat the section heading.

Reference. FDA eCTD Technical Conformance Guide, Section 2.4

1291Leaf element title exceeds 512 charactersLow

What it checks. A leaf title exceeds the 512-character limit on the title field.

How to fix it. Shorten the leaf title. Titles should be short, meaningful, and indicative of the document's content.

Reference. FDA eCTD Technical Conformance Guide, Section 2.4

1289Omitted leaf element titleMedium

What it checks. You have omitted the title of a leaf element.

How to fix it. Resubmit a replacement leaf element in a later submission referencing the original leaf using the operation attribute of 'Replace'.

Reference. ICH Q&A 36 #20; ICH eCTD Specification V3.2.2

1298File does not contain a file extensionMedium

What it checks. You have provided a file that does not have a file extension such as .pdf, .xpt, etc.

How to fix it. Resubmit a replacement leaf element in a later submission referencing the original leaf using the operation attribute of 'Replace'.

Reference. General good practice to ensure reviewability.

1306No leaf element for fileHigh

What it checks. You have submitted the file(s) listed in the validation report without a corresponding reference in the backbone.

How to fix it. Corrective action is based on the underlying reason for the error. If the error is the result of a simple omission of a leaf element then you should submit a leaf element referencing the file in a future submission using the operation attribute of 'Replace'. If the error occurred due to a difference between the name of the file in a leaf reference and the actual name of the file then submit a corrected leaf element in a future submission that references the original leaf with an operation attribute of 'Replace'.

Reference. ICH Q&A 36 #13; ICH eCTD Specification V3.2.2; eCTD Comprehensive Table of Contents Headings and Hierarchy

1314Non-required file existsMedium

What it checks. You have submitted files in the UTIL folder that are not required.

How to fix it. Modify your SOPs to ensure that only required files are placed in the UTIL folder.

Reference. ICH Q&A #51

1322Folder contains no files or sub foldersLow

What it checks. Your submission includes a file folder that contains no files or sub folders.

How to fix it. Modify your SOPs so that you do not submit empty folders in the future.

Reference. ICH Q&A #54

1323No file for leaf elementHigh

What it checks. You have referenced the file(s) listed in the validation report from the us-regional.xml or index.xml files without providing the actual file(s).

How to fix it. Corrective action is based on the underlying reason for the error. If the error is the result of a simple omission of the file then you should submit the file and a leaf element referencing the original leaf using the operation attribute of 'Replace' in a future submission. If the error occurred due to a difference between the name of the file in a leaf reference and the actual name of a file then submitted, you should submit a corrected leaf element in a future submission that references the original leaf with an operation attribute of 'Replace'.

Reference. ICH Q&A 36 #12; ICH eCTD Specification V3.2.2; eCTD Comprehensive Table of Contents Headings and Hierarchy

PDF

3102Failed to process PDF contentsMedium

What it checks. You have submitted a document with contents that cannot be processed, e.g. a corrupted or invalid PDF document.

How to fix it. Resubmit a corrected leaf in a future submission with the operation attribute of 'Replace' and an updated valid PDF file.

Reference. General good practice to ensure reviewability.

5005Non standard font (not embedded)Medium

What it checks. You have used a non-standard font and failed to fully embed the font. You should limit fonts to standard fonts. If you use non-standard fonts you should fully embed them in the PDF file.

How to fix it. Resubmit a corrected leaf in a future submission with the operation attribute of 'Replace' and an updated PDF file with all non standard fonts embedded.

Reference. ICH eCTD Specification V3.2.2; FDA Portable Document Format Specifications

5020PDF security usedMedium

What it checks. You have submitted a PDF file with security settings that limit the ability to select text or graphics, or make other changes. This prevents agencies from copying text and taking other actions with submitted documents. (Not applicable for FDA Forms)

How to fix it. Resubmit a corrected leaf in a future submission with the operation attribute of 'Replace' and an updated PDF file without restrictions.

Reference. ICH eCTD Specification V3.2.2

5035PDF version of document is incorrectLow

What it checks. You have submitted a document using a PDF version that is not consistent with ICH / regional guidance.

How to fix it. No corrective action is necessary. Modify your SOPs to ensure that documents in future submissions conform to the published standards.

Reference. ICH eCTD Specification V3.2.2; FDA Portable Document Format Specifications

5040PDF does not have 'Fast Web Access' activeMedium

What it checks. You have submitted a PDF that has been created without 'Fast Web Access' active.

How to fix it. Ensure that documents in future submissions are created with the 'Fast Web Access' option.

Reference. ICH eCTD Specification V3.2.2; ICH Q&A 36 #23

5045PDF opening settings not optimalMedium

What it checks. You have submitted a PDF that does not open in the desired view.

How to fix it. Ensure that PDF Opening settings are correct for all future submissions. The initial view of the PDF files should be set as Bookmarks and Pages in the Navigation Panel. If there are no bookmarks, the initial view should be set to Pages only. PDFs should open in 'most recent view' (i.e. 'inherit zoom' for bookmarks and links, and 'default' in open dialogue box).

Reference. ICH eCTD Specification V3.2.2; FDA Portable Document Format Specifications

5050Document has password protectionMedium

What it checks. You have submitted a document that has password protection and cannot be opened. (Not applicable for FDA Forms)

How to fix it. Resubmit the protected file in a later submission referencing the original leaf using the operation attribute of 'Replace'.

Reference. ICH eCTD Specification V3.2.2; ICH Q&A 36 #21

5055Document has annotations, only PDFs in module 1, section 1.15 are permitted to have annotations.Medium

What it checks. You have submitted a document that has PDF annotations, only PDFs in module 1, section 1.15 are permitted to have annotations.

How to fix it. Ensure that documents in future submissions do not have annotations, only PDFs in module 1, section 1.15 are permitted to have annotations.

Reference. General good practice to ensure reviewability.

5057Document contains no textMedium

What it checks. You have submitted a document that is a scanned image only and is not text searchable.

How to fix it. Ensure that documents in future submissions are text searchable whenever possible (minimize the use of scanned documents).

Reference. FDA Portable Document Format Specifications

5100Broken bookmarkMedium

What it checks. You have submitted a document with one or more bookmarks pointing to a file that does not exist.

How to fix it. Corrective action may be necessary and you will be contacted if it is necessary. Ensure that documents in future submissions do not have broken bookmarks.

Reference. General good practice to ensure reviewability.

5101Corrupt bookmarkMedium

What it checks. You have submitted a document with one or more bookmarks pointing to a file that cannot be opened.

How to fix it. Corrective action may be necessary and you will be contacted if it is necessary. Ensure that documents in future submissions do not have corrupt bookmarks.

Reference. General good practice to ensure reviewability.

5102Bookmark has non-existent named destination or pageMedium

What it checks. You have submitted a document with one or more bookmarks pointing to a named destination or page that does not exist.

How to fix it. Corrective action may be necessary and you will be contacted if it is necessary. Ensure that documents in future submissions do not have bookmarks linking to non-existent pages or named destinations.

Reference. General good practice to ensure reviewability.

5103Multiple action bookmarkMedium

What it checks. You have submitted a document with one or more bookmarks containing multiple actions.

How to fix it. Corrective action may be necessary and you will be contacted if it is necessary. Ensure that documents in future submissions do not have bookmarks triggering multiple actions.

Reference. General good practice to ensure reviewability.

5105External bookmarkMedium

What it checks. You have submitted a document that makes reference to one or more external bookmarks (e.g. web links, email links).

How to fix it. Ensure that documents in future submissions do not have bookmarks that are external to the application.

Reference. ICH Q&A 64

5110Inactive bookmarkMedium

What it checks. You have submitted a document that has one or more inactive bookmarks.

How to fix it. Corrective action may be necessary and you will be contacted if it is necessary. Ensure that documents in future submissions do not have inactive bookmarks.

Reference. General good practice to ensure reviewability.

5115Non-relative bookmarkMedium

What it checks. You have submitted a document that has one or more non-relative (absolute) bookmarks.

How to fix it. Corrective action may be necessary and you will be contacted if it is necessary. Ensure that documents in future submissions have only relative bookmarks.

Reference. ICH eCTD Specification V3.2.2; FDA Portable Document Format Specifications; ICH Q&A 36 #23

5117Bookmark does not 'Inherit Zoom'Medium

What it checks. You have submitted a document with one or more bookmarks that are not set to 'Inherit Zoom'.

How to fix it. Ensure that all bookmarks are set to 'Inherit Zoom'.

Reference. ICH eCTD Specification V3.2.2; FDA Portable Document Format Specifications; Final Guidance for Industry: Providing Regulatory Submissions in Electronic Format--Human Pharmaceutical Applications and Related Submissions Using the eCTD Specifications

5200Broken hyperlinkMedium

What it checks. You have submitted a document with one or more hyperlinks pointing to a file that does not exist.

How to fix it. Corrective action may be necessary and you will be contacted if it is necessary. Ensure that documents in future submissions do not have broken hyperlinks.

Reference. General good practice to ensure reviewability.

5201Corrupt linkMedium

What it checks. You have submitted a document with one or more links pointing to a file that cannot be opened.

How to fix it. Corrective action may be necessary and you will be contacted if it is necessary. Ensure that documents in future submissions do not have corrupt links.

Reference. General good practice to ensure reviewability.

5202Link has non-existent named destination or pageMedium

What it checks. You have submitted a document with one or more hyperlinks pointing to a named destination or page that does not exist.

How to fix it. Corrective action may be necessary and you will be contacted if it is necessary. Ensure that documents in future submissions do not have links pointing to non-existent pages or named destinations.

Reference. General good practice to ensure reviewability.

5203Multiple action hyperlinkMedium

What it checks. You have submitted a document with one or more hyperlinks containing multiple actions.

How to fix it. Corrective action may be necessary and you will be contacted if it is necessary. Ensure that documents in future submissions do not have links triggering multiple actions.

Reference. General good practice to ensure reviewability.

5205External hyperlinkMedium

What it checks. You have submitted a document that makes reference to one or more web references in a hyperlink (e.g. web links, email links).

How to fix it. Ensure that documents in future submissions do not have hyperlinks that are external to the application.

Reference. ICH Q&A 64

5210Inactive hyperlinkMedium

What it checks. You have submitted a document that has one or more inactive hyperlinks.

How to fix it. Corrective action may be necessary and you will be contacted if it is necessary. Ensure that documents in future submissions do not have inactive hyperlinks.

Reference. General good practice to ensure reviewability.

5215Non-relative hyperlinkMedium

What it checks. You have submitted a document that has one or more non-relative (absolute) hyperlinks.

How to fix it. Corrective action may be necessary and you will be contacted if it is necessary. Ensure that documents in future submissions do not have non-relative hyperlinks.

Reference. ICH eCTD Specification V3.2.2; FDA Portable Document Format Specifications; ICH Q&A 36 #23

5217Link does not 'Inherit Zoom'Medium

What it checks. You have submitted a document with one or more links that are not set to 'Inherit Zoom'.

How to fix it. Ensure that all links in future submissions are set to 'Inherit Zoom'.

Reference. ICH eCTD Specification V3.2.2; FDA Portable Document Format Specifications; Final Guidance for Industry: Providing Regulatory Submissions in Electronic Format--Human Pharmaceutical Applications and Related Submissions Using the eCTD Specifications

STF

1731Cumulative STF files are not allowedHigh

What it checks. FDA only accepts the accumulative approach to STF.

How to fix it. Resubmit your submission ensuring that the STF files created follow the accumulative approach.

Reference. The eCTD Backbone File Specification for Study Tagging Files V2.6.1

1735The correct STF file-tags must be used for all standardized datasets and corresponding define.xml files in Module 4, sections 4.2.3.1, 4.2.3.2, 4.2.3.4, and in Module 5, sections 5.3.1.1, 5.3.1.2, 5.3.3.1, 5.3.3.2, 5.3.3.3, 5.3.3.4, 5.3.4, 5.3.5.1, 5.3.5.2High

What it checks. You have submitted XPT files or define.xml files without correct file tag. Valid file tags for XPT files are: data-tabulation-dataset-sdtm data-tabulation-dataset-send analysis-dataset-adam Valid file tags for corresponding define.xml files are: data-tabulation-data-definition analysis-data-definition.

How to fix it. Resubmit using one of the valid file tags for all submitted datasets.

Reference. Providing Regulatory Submissions in Electronic Format - Certain Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specification; Providing Regulatory Submissions in Electronic Format - Standardized Study Data; Study Data Technical Conformance Guide.

1737For each study referenced by an STF file in Module 4 and Module 5, no more than one dataset of the same file name and leaf title should be submitted using the lifecycle operator new. STFs are not required for 4.3 Literature references, 5.2 Tabular listings, 5.4 Literature references and 5.3.6 Postmarketing reportsMedium

What it checks. You have submitted more than one dataset of the same type using the lifecycle operator new for a study.

How to fix it. In future submissions, ensure that only one dataset of each type is marked using the lifecycle operator new.

Reference. Providing Regulatory Submissions in Electronic Format - Certain Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specification; eCTD Technical Conformance Guide; Study Data Technical Conformance Guide.

1738STF Study ID should match STUDYID or SPREFID listed in the referenced Trial Summary (ts.xpt) file. STFs are not required for 4.3 Literature references, 5.2 Tabular listings, 5.4 Literature references and 5.3.6 Postmarketing reportsMedium

What it checks. The STF Study ID does not match the STUDYID or SPREFID listed in the referenced ts.xpt file (not an exact match).

How to fix it. Ensure ts.xpt is referenced under the correct STF. If ts.xpt is under the correct STF, update the STUDYID or SPREFID in the ts.xpt and other referenced study data files. Modify your SOPs to ensure that a consistent Study ID (exact match) is used.

Reference. The eCTD Backbone File Specification for Study Tagging Files; Providing Regulatory Submissions in Electronic Format - Standardized Study Data; Study Data Technical Conformance Guide; General good practice to ensure reviewability.

1748Omitted STF DTD version in leaf elementMedium

What it checks. Omitted STF DTD version in leaf element.

How to fix it. No corrective action is necessary unless FDA notifies you that it is unable to process your submission. Modify your SOPs to ensure that the DTD version is in the leaf element.

Reference. The eCTD Backbone File Specification for Study Tagging Files V2.6.1

1752Omitted STF DTD version in STF XML fileMedium

What it checks. Omitted STF DTD version in the STF XML file.

How to fix it. No corrective action is necessary unless FDA notifies you that it is unable to process your submission. Modify your SOPs to ensure that the DTD version is specified in the STF XML file.

Reference. The eCTD Backbone File Specification for Study Tagging Files V2.6.1

1765STF DTD version must match the XML fileMedium

What it checks. Your STF DTD version listed in the leaf element does not match the DTD version in the STF XML file.

How to fix it. No corrective action is necessary unless FDA notifies you that it is unable to process your submission. Modify your SOPs to ensure that the DTD version specified in the leaf matches that specified in the STF XML file.

Reference. The eCTD Backbone File Specification for Study Tagging Files V2.6.1

1782Unsupported STF DTD version in leaf elementHigh

What it checks. You are using an unsupported STF DTD version in a leaf element.

How to fix it. Resubmit your submission using a version of the DTD that is supported. For STF Version 2.2 references, the version value should be indicated as 'STF Version 2.2' exactly. You may resubmit using the original sequence number of the submission.

Reference. The eCTD Backbone File Specification for Study Tagging Files V2.6.1

1786Unsupported STF DTD version in STF XML fileHigh

What it checks. You are using an unsupported STF DTD version in a STF XML file.

How to fix it. Resubmit your submission using a version of the DTD that is supported. You may resubmit using the original sequence number of the submission.

Reference. The eCTD Backbone File Specification for Study Tagging Files V2.6.1

1789A file has been submitted in a study section without providing an STF file. STFs are not required for 4.3 Literature references, 5.2 Tabular listings, 5.4 Literature references and 5.3.6 Postmarketing reportsHigh

What it checks. All files in a study section must be referenced by an STF file.

How to fix it. In a new submission include an STF and use the 'Replace' operator to replace previously submitted documents which were not referenced in an STF.

Reference. Providing Regulatory Submissions in Electronic Format - Certain Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specification; the eCTD Backbone File Specification for Study Tagging Files V2.6.1

1799STF cannot reference another STFHigh

What it checks. The STF may not reference another STF.

How to fix it. Resubmit your submission ensuring that STFs do not reference other STFs. You may resubmit using the original sequence number of the submission.

Reference. General good practice to ensure reviewability.

1816STF does not relate to any leaf elementMedium

What it checks. STF does not relate to any leaf elements.

How to fix it. In a future submission, you should include an STF that includes references to appropriate leaf elements. Modify your SOPs to ensure that all STFs submitted reference leaf elements.

Reference. The eCTD Backbone File Specification for Study Tagging Files V2.6.1

1833STF relates to a non-existent leaf elementMedium

What it checks. STF relates to a non-existent leaf element

How to fix it. In a future submission, you should include an STF that includes references to existing leaf elements. Modify your SOPs to ensure that all STFs submitted reference leaf elements.

Reference. The eCTD Backbone File Specification for Study Tagging Files V2.6.1

1850Study ID for STF must remain constantMedium

What it checks. You have appended an STF with a second STF and the two Study IDs are different (not an exact match). The reviewer will see two studies instead of one.

How to fix it. 'Delete' leaf references in the index.xml for the files with incorrect Study IDs and then add the leaf references as 'New' to the index.xml and STF for the study that should remain. Modify your SOPs to ensure that a consistent Study ID (exact match) is used.

Reference. General good practice to ensure reviewability.

1867Invalid STF file extensionMedium

What it checks. You have included an invalid STF file extension.

How to fix it. Corrective action may be necessary. If corrective action is necessary, you will be contacted. Modify your SOPs to ensure that the name for the STF XML file starts with the term 'stf-' followed by the alphanumeric code used by the sponsor to unambiguously identify the study (i.e., study-id) and followed by '.xml' to complete the file name.

Reference. The eCTD Backbone File Specification for Study Tagging Files V2.6.1

1884Invalid STF file nameMedium

What it checks. You have included an invalid STF file name.

How to fix it. Modify your SOPs to ensure that the name for the STF XML file starts with the term 'stf-' followed by the alphanumeric code used by the sponsor to unambiguously identify the study (i.e., study-id) and followed by '.xml' as the file extension to complete the file name.

Reference. The eCTD Backbone File Specification for Study Tagging Files V2.6.1

1901Invalid STF TOC locationMedium

What it checks. Your leaf that points to the STF is under an invalid heading area or invalid module. For example, STFs can only be associated with certain headings under Modules 4 or 5.

How to fix it. In a future submission, place the STF under the correct module and heading element. Modify your SOPs to ensure that STFs are included only in Modules 4 and 5.

Reference. The eCTD Backbone File Specification for Study Tagging Files V2.6.1

1918Omitted STF doc-content file tagMedium

What it checks. You have omitted the STF doc-content file tag which prevents the proper classification of the file within the submission.

How to fix it. In a future submission you should include an updated STF file that reflects the proper doc-content file tag using the 'Replace' operator.

Reference. The eCTD Backbone File Specification for Study Tagging Files V2.6.1

1935Multiple STF doc-content file tagsMedium

What it checks. You have multiple STF doc-content file tags; processor will process the first tag but will ignore any additional tags.

How to fix it. No corrective action is possible due to current STF limitations. Modify your SOPs to ensure that only a single doc-content file tag is used.

Reference. DTDs; General good practice to ensure reviewability.

1953STF XML title and leaf element title do not matchLow

What it checks. Your STF study title and leaf element title do not match; viewer will show the title in the stf.xml file only.

How to fix it. No corrective action is necessary. Modify your SOPs to ensure that STF titles match the provided leaf title.

Reference. General good practice to ensure reviewability.

1969Invalid STF XML fileMedium

What it checks. You have submitted an invalid stf-xxxxxxxx.xml file. This error will occur when: no Study ID is defined, there are no child nodes in the XML document, or the XML document fails to load.

How to fix it. In a future submission, delete the leaves which were referenced in the previous invalid stf-xxxxxxx.xml file. Submit a new valid stf-xxxxxxxx.xml files and use the 'new' operator attribute to re-reference the previously submitted leaves in the STF files.

Reference. DTDs; The eCTD Backbone File Specification for Study Tagging Files V2.6.1

1981STF XML file is missingMedium

What it checks. You have referenced an STF XML file in the hlink:xref attribute of a leaf and the system is unable to locate the file.

How to fix it. Resubmit the missing STF XML file in a new submission sequence and re-reference the appropriate leaves using the operation attribute of 'Replace'.

Reference. ICH eCTD Specification V3.2.2; The eCTD Backbone File Specification for Study Tagging Files V2.6.1

1985The study title for the STF is missingMedium

What it checks. You have omitted the title within the STF XML file. The title is required for STFs submitted using the version 2 specification.

How to fix it. In a new submission sequence, resubmit the STF file which includes the corrected study title (it is not necessary to resubmit files or regenerate leaves). Ensure that your Study ID is identical to what you previously submitted.

Reference. The eCTD Backbone File Specification for Study Tagging Files V2.6.1

1990The same STF XML is referenced more than once.Medium

What it checks. You have submitted one STF XML file and referenced that STF XML file in more than one section.

How to fix it. Only the first study will appear when an STF XML file is referenced more than once. Add a new study STF XML file and one PDF file that states the study is located in another section and provides a link to the study.

Reference. ICH Q&A 60

Where rejections come from

The high-severity rules that catch most teams

Envelope

Application number, submission type and sub-type, sequence number and contacts must be consistent with each other and with FDA’s controlled vocabularies. Typed envelopes are the most common source of high-severity findings.

Checksums and file references

Every file in the sequence must be in the backbone with a matching checksum, and every backbone entry must point to a file that exists. Edits made after the backbone is built break both.

Lifecycle

A replace, append or delete must point at a document that exists in the application, in the same section. Choosing operations from memory instead of the cumulative view causes these.

Specification files

The DTDs and stylesheets in the util folder must be the versions FDA expects, unaltered.

PDF properties

No passwords or security settings, fonts embedded, a supported PDF version, and searchable text.

Validate early

Run the criteria while the sequence is being built

A validation report run the evening before a deadline tells you what is wrong when there is no time left to fix it. The same check run every time the sequence changes turns each finding into a few minutes of work for the person who just made the change.

DnXT Publisher runs FDA’s criteria for both v3.2.2 and v4.0 — at FDA’s own severity — continuously while a sequence is assembled, and on sequences you import from partners or previous vendors. The same engine covers 16 eCTD regions and more than 2,500 criteria.

Questions

Frequently asked

What does a high-severity FDA eCTD validation error mean?

For eCTD v3.2.2, a high-severity finding means FDA will reject the submission on technical grounds. The submission is not filed and the review clock does not start until a corrected sequence is received. For v4.0 the equivalent grade is High Error.

Are the v3.2.2 and v4.0 criteria the same?

No. eCTD v4.0 uses a different message format, controlled vocabularies and lifecycle model, so FDA publishes a separate set of v4.0 criteria. Some concepts carry over — checksums, file references, PDF properties — but the rule numbers and wording are different.

Can I resubmit with the same sequence number after a technical rejection?

For many v3.2.2 schema and file errors FDA states that you may resubmit using the original sequence number. Check the correction text for the specific criterion above.

How do I validate a sequence before sending it to FDA?

Run it through a validator that applies FDA’s current criteria at FDA’s severity levels, fix every high-severity finding, review the medium ones, and keep the validation report with the sequence you transmit.

How current is this list?

It is generated from the criteria DnXT runs in production, which track FDA’s published specifications. Always confirm against FDA’s current specification documents before relying on a single rule.

Catch every FDA finding before FDA does

See DnXT Publisher validate a sequence against FDA’s criteria while it is being built.

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Criteria are summarised from FDA’s published specifications for information. FDA’s own documents are authoritative.