STF-Study tagging file Study Tagging Files contain descriptive information on nonclinical and clinical studies in Modules 4 and 5. In FDA- It is used. for EU-not applicable and for CA- It can be used but optional.

Need for STF The eCTD is amazing because it allows reviewers to find the same information in the same place for any type of application. E.g.: cover letter is always under section 1.2 Confusion of a reviewer searching for case report forms for a particular study who, instead of finding them in their assigned spot, locates them scattered all throughout Module 4 0r 5.

Satisfying needs = Role of the STF Organizes study information into meaningful , standardized headings . Provides capability to group documents in a logical order Allows reviewer to quickly understand what has been submitted, what has not. Helps guide reviewer to specific documents they are looking for. Provides consistency over the lifecycle of the regulatory application.

Good Representation of STF in M5

Bad Representation of STF in M5

Understanding the STF and its correct usage is “vital”. when the STF is not used, the submission in many cases, pass technical validation. The review team, as it examines the submission- entity detecting the errors – in review tool display. The simple solution is always to use an STF when you are submitting any type of study file. Always take the time to construct the appropriate STF file, apply the correct tags and make sure your leaf titles are succinct and meaningful—that is, they tell the reader what the file is in as few words as possible.

STUDY-IDENTIFIER ELEMENT Title Element - Title of the study, not the title of each individual document. study-id Element – It is the internal alphanumeric code used by the sponsor to unambiguously identify this study. Category Element - Additional level of study organization not currently provided by the eCTD DTD. This element is only relevant for studies provided in the specific CTD sections cited below. 1) Single dose toxicity (grouped by species and route of administration) 2) Repeat dose toxicity (grouped by species, route of administration, and duration if applicable) 3) Long term [carcinogenicity] studies (grouped by species) 4) Study reports of controlled clinical studies pertinent to the claimed indication (grouped by type of control)

STUDY-DOCUMENT AND DOC-CONTENT ELEMENTS Property element -The property element is appropriate when files might need to be grouped by an applicant provided value. Currently, this element should only be used for site identification within a study. For example, [us] site-identifier 2 ( [i.e] info-type="us" ; name="site-identifier“ ) File-tag element - The file-tag element contains the attributes name and info-type . For example, [ich ] Study report body ( [i.e] info-type ; name)

ASASSSSAsaanmxMNXBgenda Creating STF Files STF (Study Tagging Files) Created under M5.3.1 Section ASASSSSAsaanmxMNXBgenda

ASASSSSAsaanmxMNXBgenda SAS in eCTD SAS files are added along with the other clinical documents ASASSSSAsaanmxMNXBgenda

Example: STF in XMl view

LCM The Study name of the stf will be always APPEND when making any changes. The Stf files under the study category will have New, Replace and Append Doc operations to be performed. We cannot perform continues append in sequences. When the original document is deleted, any appended documents must be deleted. So Operations to the sequence of appended document will fail.

When to use replace vs. append Don’t use append to replace things For incremental appends – instead use replace Safety reports – follow-up to initial safety report – use replace draft labels – use replace, not append Replace doesn’t mean “mistake” . Use append when you are adding a little more information to an existing document, not resubmitting all the same info, plus a little more

Changes to STF Study Document Information Adding New Files to an Existing STF – use append . Deleting Files Cited by an Existing STF - use delete operation so leaf element for the file will be flagged as deleted. Correcting File-tag Values : “Replace" the incorrectly tagged leaf element and use Replace operation to create a new file with tag values changed.

ASASSSSAsaanmxMNXBgenda SAS files in Module 2 Clinical Efficacy and Clinical Safety SAS files will also be added in M2.7.3 and M2.7.4 ASASSSSAsaanmxMNXBgenda

Example : Issue Problem: You placed a pivotal study under 5.3.1.1, and now you realize it needs to be under 5.3.5.1 Solution: Delete out all the leaf IDs that were referenced in the STF under the wrong heading element. This deletes the STF. Create a new STF referencing all the same files, but use new leaf IDs and Submit in new submission sequence.

5.3.7 and 5.3.5.4 FDA does not use 5.3.7 for CRFs Reviewers can’t tell which CRFs go to a study Instead, CRFs should be referenced in each study’s STF and tagged “case report form” ---------------- Create an STF, under 5.3.5.4 – call it “Non-IND Safety Reports” Safety reports related to the drug but not that specific IND

References http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/AbbreviatedNewDrugApplicationANDAGenerics/UCM204900.pdf http://estri.ich.org/STF/STFV2-6-1.pdf http://www.raps.org/personifyebusiness/Portals/0/Documents/focus_june10_tagging.pdf