Wake Forest University Health Sciences

Wake Forest University Health Sciences

Guidance Document on Set-up and Maintenance of a Regulatory Binder

Federal and state regulations, institutional policy, and GCPs require investigators to maintain documents related to human subjects research. This guidance document was developed to assist study teams in organizing research-related documents. It details what documents may be stored in each section of a study-specific regulatory binder. Some of the sections or documents are not applicable to certain studies. Additionally, researchers may choose to store certain documents in places other than the regulatory binder. Finally, some sponsors may require that investigators keep documents that are not specifically referenced in this guidance.

General Guidance for Maintaining a Regulatory Binder:

·  Delegate a study team member to oversee the maintenance and storage of the Regulator Binder.

·  Tailor the binder to meet the specific needs of your protocol

o  Include only those sections that are applicable to your protocol and omit unused sections. (See “Applicable sections” below for more information.

o  Organize your binder for easy reference, e.g. file most used sections in the front, file documents in reverse chronological order, etc.

o  Add additional sections to your binder as needed, e.g. any forms submitted to any federal agency related to human subject research, all communications from any regulatory authorities or government agencies, all signed agreements, etc.

·  Store the binder in a safe and secure location that is easily accessible to all members of the study team.

·  Utilize signed and dated notes-to-file :

o  To note that certain documents are stored in places other than the regulatory binder( i.e. a note to file indicating that all CVs are maintained in one central location)

o  To record missing documentation or incomplete data

o  To clarify any discrepancies

·  If documents are maintained electronically, then a note to file indicating the location should be included.

Applicable Sections of the Regulatory Binder

The tabs or sections to be included in the Regulatory Binder are determined by the nature of the research. For questions, please contact the Monitoring and Oversight Specialist.

1.  Human Research

a.  Protocol (GCP 8.2.2; 8.3.2)

A copy of the original protocol and all amended versions should be retained in the binder. Protocols should contain a version date and/or number

b.  IRB

A copy of all IRB approvals/acknowledgements, IRB approved documents, and any revisions to the documents should be retained in the Regulatory Binder. Examples of documents that must be retained in the binder include:

·  Initial IRB approval letter

·  IRB approved study information distributed to subjects (i.e., diaries, pain scales, questionnaires, educational booklets)

·  IRB approved recruitment materials

·  Safety reports (includes deviations) submitted via e-IRB

·  Continuing review approvals

·  Amendments and IRB approval of amendments

·  Final Report to IRB

c.  Consent Forms (HHS 45 CFR 46; FDA 21 CFR 50 and 21 CFR 56; GCP 8.2.3; 8.3.2; 8.3.12)

Original copies of the IRB approved consent forms, marked by the IRB approval stamp, should be retained in the binder.

d.  NIH

A copy of the NIH grant application, all progress reports, and any correspondence with the NIH and collaborators should be retained in the binder.

e.  Sponsor

All correspondence with the sponsor (letters, e-mails, signed agreements, etc.) should be retained in the Regulatory Binder.

·  Documentation of where the clinical trial agreement and study budget between the investigator/institution and the sponsor for the trial is kept.

·  Safety information from the sponsor

·  Notification to the sponsor of SAEs

f.  DSMB (GCP 8.3.10; 5.19.3)

A copy of all DSMB reports and audit reports should be retained in the binder.

g.  Logs

Logs should be updated in a timely manner to ensure accuracy.

·  Subject Screening Log

·  Subject ID Log

·  Subject Enrollment Log

·  Site Responsibility/Delegation Log

·  Protocol Deviation Log

·  Monitoring Log

·  Record of retained body fluids/tissues samples Log

·  Lab Shipment Log

·  SAE Tracking Log

h.  Data Collection

·  Master randomization list

·  Decoding procedures in blinded trials for emergency situation

·  Sample of the Case Report Forms (CRF)

2.  FDA Regulated Human Research

In addition to #1 above (Human Research), the following sections should

be included in the Regulatory Binder

a. Product Information (FDA 21 CFR 312.55; GCP 8.2.1; 8.3.1)

All versions of the investigator’s brochure and device manuals should be submitted to the IRB for review. If the investigational product is already marketed, then a package insert or basic product information brochure may be appropriate to use.

·  Investigator brochure and updates

·  Package insert

·  Device manual

·  Sample of product label

·  Certificates of analysis for investigational products

·  Instructions for handling investigational product(S) and trial-related materials

b. Drug/Device Accountability (FDA 21 CFR 312.57; 312.62; 812.140)

The PI is ultimately responsible for the accountability of all investigational product(s). The following records should be retained in the Regulatory Binder:

·  Shipment and receipt records for investigational products and study related supplies, including documented shipment dates, batch numbers, and methods of shipping the investigational product.

·  Drug/Device Accountability Log

·  Drug/Device Dispensing Log

·  Documentation of investigational product return, disposal, or destruction as specified by the sponsor

c. FDA (FDA 21 CFR 54; 312.30; 312.32; 312.33; 812.150(b)(1); 812.150(b)(5); 812.35; 812.43(c) GCP: 4.11; 5.16.2; 5.17.1; 8.3.16; 8.3.17; 8.3.18; 8.3.19)

Clinical Investigator:

·  Copy of all versions of FDA Form 1572 (for investigational drugs)

·  Copy of all version of Investigator Agreement (for investigational devices)

·  IND safety reports

·  FDA Financial Disclosure Form (FDA Form 3455)

Sponsor-Investigator:

·  IND application FDA Form 1571

·  Investigator-initiated IND or IDE application

·  All correspondence with the FDA

·  Annual Progress Reports

·  Form 3674, certification of registration to ClinicalTrials.gov

3. Good Clinical Practice

In addition to #1 above (Human Research), the following sections should be included in the Regulatory Binder:

a. CVs (GCP 4.1.1; 8.2.10; 8.3.5)

CVs for all investigator(s) and key study staff should be

signed, dated, and updated every 2 years.

b. Licensure (GCP 4.1.1)

Current and valid licenses/certifications should be maintained for all

professional staff.

c. Training

A copy of all study specific training and human subjects training certification for study team members should be retained in the binder. CITI is maintained electronically in e-IRB, so a note to file indicating such is adequate

d. Laboratory Documents (GCP: 8.2.11; 8.2.12; 8.2.14; 8.3.6; 8.3.7)

Research labs typically do not have lab certifications, and may not have “normal” established lab values.

·  Laboratory certifications (e.g. CLIA) and updates of laboratory certifications

·  Normal value(s)/reference values(s) for procedure(s) and test(s) included in the protocol

·  Copy of the laboratory director’s CV

Version 12/30/10