Penn Medicine Clinical Research

Essential Documents

Essential documents which include regulatory binders (also known as Study Admin File, Investigator Binder, Investigational Site File (ISF), or Study Binder) contain the study specific information and regulatory documentation in a centralized location. It organizes essential study documents and should be easy to access and auditable.  

Site Regulatory Binder Essentials

  • Correspondence

    • IRB
    • Penn Reviewing Entities
    • Sponsor/CRO
    • General
  • Study Documents
    • Protocol/Protocol Amendments and supporting documents
    • Informed Consent & HIPAA Authorization  
    • Case Report Form Sample
    • Investigator’s Brochure /Device Manual 
    • FDA Forms as applicable – 1572, sample of labels, FDA correspondence, financial disclosures  
    • Lab Documents (CLIA/CAP)  
  • Study Tracking Logs
    • Subject Logs (Screening/Enrollment)
    • Adverse Event Reports
    • Investigational Product
    • Monitoring Visits and Logs
  • Research Personnel
    • Study personnel (CV, licenses, training, etc.) 
    • Delegation of Authority Log
  • Other
    • Unmasking Procedures for Blinded Trials
    • Certificates of Confidentiality
    • Other study documents as needed

It is preferable that the essential documents are maintained electronically, either through Penn Box or Veeva Vault, which both serve as options for electronic Regulatory Binders. Contact OCR for an eTemplate for maintaining the Regulatory Binder in PennBox.

OCR offers downloadable templates with instructions for maintaining regulatory binders on paper.

There are three different templates available within our forms, tools and templates library depending on the study type:

The sponsor essential documents are filed in what is known as the Trial Master File (TMF).  It should begin at first inception of a trial and should be maintained current and complete during the life cycle of the investigation until its completion.

For some studies, an individual might be both the PI and the (Regulatory) Sponsor. In this case, both sets of responsibilities mentioned apply.

The table below lists examples of essential documents maintained exclusively by the Sponsor in the TMF, maintained exclusively by the PI in the Reg. Binder and maintained by both.

Examples of Sponsor Docs for Sponsor TMF only Examples of Docs Shared by Both Examples of PI Docs for Reg Binder only
Sample of Label(s) Investigator's Brochure and updates Ad(s) for Subject Recruitment
Certificate(s) of Analysis of Investigational Products(s) Shipped Signed Protocol and Amendments and Sample Case Report Form (CRF) Signed Informed Consent Forms
Master Randomization List

Original document and Any Revision To:

  • Protocol/Amendment(s) and CRF
  • Informed Consent Form
  • Any Other Written Information Provided To Subjects
  • Advertisement For Subject Recruitment (If Used)
 Source Documents

Pre-Trial Monitoring Report

Insurance Statement (Where Required)

Subject Identification Code List

Certificate(s) of Analysis

Signed Agreement Between Involved Parties

Subject Enrolment Log

Monitoring Visit Reports

IRB approvals/acknowledgements

Completed Subject Identification Code List
     

Audit Certificate (If Available)

Institutional Review Board/Independent Ethics Committee Composition

Final Report By Investigator To IRB/IEC Where Required, and Where Applicable, To The Regulatory Authority(ies)

Final Trial Close-Out Monitoring Report

Regulatory Authority(ies) Authorization/Approval/Notification of Protocol (Where Required), Protocol Amendment(s) and Other Documents

 

Treatment Allocation and Decoding Documentation

CV and/or Other Relevant Documents Evidencing Qualifications of Investigator(s) and Subinvestigator(s)

 
  Normal Value(s)/Range(s) and Updates For Medical/Laboratory/Technical Procedures(s) and/or Test(s) Included In The Protocol  
 

Medical/Laboratory/Technical Procedures/Tests and Updates

  • Certification/Accreditation
  • Established and/or External Quality Control/Assessment
  • Other Validation (Where Required)
  
 

Instructions For Handling of Investigational Product(s) and Trial-Related Materials

  
 

Shipping Records For Investigational Product(s) and Trial-Related Materials

  
 

Decoding Procedures For Blinded Trials

  
 

Instructions For Handling of Investigational Product(s) and Trial-Related Materials

  
 

Shipping Records For Investigational Product(s) and Trial-Related Materials

  
 

Decoding Procedures For Blinded Trials

  
 

Trial Initiation Monitoring Report

  
 

Documentation of Investigational Product(s) and Trial-Related Materials Shipment

  
 

Relevant Communications Other Than Site Visits

  • Letters, Meeting Notes, Notes of Telephone Calls
  
 

Signed, Dated, and Completed Case Report Forms (CRF)

  
 

Documentation of CRF Corrections

  
 

Notification By Originating Investigator To Sponsor of Serious Adverse Events and Related Reports

  
 

Notification By Sponsor and/or Investigator To Regulatory Authority(ies) and IRB(s)/IEC(s) of Unexpected Serious Adverse Drug Reactions and of Other Safety Information

  
 

Notification By Sponsor To Investigators of Safety Information

  
 

Interim Or Annual Reports To IRB/IEC and Authority(ies)

  
 

Subject Screening Log

  
 

Signature Sheet

  
 

Record of Retained Body Fluids/Tissue Samples (If Any)

  
 

Investigational Product(s) Accountability At Site

  
 

Documentation of Investigational Product Destruction

  
 

Clinical Study Report

  

 

Additionally,

  • If the study data supports a marketing application, the records must be maintained for 2 years after a marketing application is approved by the FDA.
  • If the study data does not support a marketing application, the records must be maintained for 2 years after shipment and delivery of the drug for the investigational use is discontinued and the FDA has been so notified.
  • Certain documents might need to be retained for a longer period of time based on the Penn’s Research Administration Records Policy.  

Access to the TMF must be controlled and limited to only to the study sponsor and sponsor-authorized individuals.

Standard procedures and naming conventions should be developed to ensure an easy location of the records.

OCR has adopted the CDISC TMF Reference Model, endorsed by the Drug Information Association (DIA), to organize the TMF documents and recommends Penn Box or Veeva eTMF as the platforms for maintaining your TMF. Additional information about using the Veeva eTMF (including access and training) may be found here.

TMF Zones

This structure organizes the essential documents in eleven zones (categories). Each TMF zone is represented with the following graphics:

  • The purple graphics represent zones containing documents generated by the Sponsor when setting up a trial.
  • The gray graphics represent zones containing core documents necessary for the conduct of the study.
  • The orange graphics represent zones containing documents generated by PI activities.
Image with shapes representing components of eTMF zone 01 Trial Management
eTMF zone representing the sponsor’s oversight documents for a clinical trial

 

 

Image with shapes representing components of eTMF zone 08 Central and Local Testing
eTMF zone representing the sponsor’s documents for laboratories used

 

 

Image with shapes representing components of eTMF zone 02 Central Trial Documents
eTMF zone representing the sponsor’s repository of the central documents for a trial

 

 

 

image with shapes representing components of eTMF zone 04 IRB or IEC and other Approvals
eTMF zone representing the sponsor’s repository of documents related to IRB, IEC or other local approvals

 

 

image with shapes representing components of eTMF zone 06 IP and Trial Supplies
eTMF zone representing the sponsor’s repository of documents related to all investigational products in the trial

Contact OCR Regulatory for questions or assistance at PSOM-IND-IDE@pobox.upenn.edu