Investigator Site Checklist: A Compendium of Preparatory List-to-do prior/after FDA Inspection

Investigator Site # ________ Protocol: Review Dates of the Investigator Files: ___________________ Number of Patients: Screened _______; Enrolled __________; Randomized __________; Completed: ______; Active: ________; Discontinued: _______; # of SAE reported: _______. Please note: These are questions FDA investigators might potentially ask the site during the audit. Protocol # Investigator Name: _________________________________

General Information:

Investigator/ Location

Satellite Offices (Address) Study Coordinator(s) and contact info: Study Pharmacist Other Staff: 1. 2. 3. Monitor (s) and contact info: Comments: All CV available: Yes No:

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1. General Preparation Logistics: In preparation for any Governmental Inspection After receiving a call from ANY governmental agency, please notify the sponsor without unnecessary delay and all involved personnel about the inspection. when done

Identify one person as an Inspection Coordinator to coordinate preparations. During the Inspection, one staff member (preferably a Quality Assurance personnel) must always accompany/host the Inspection and takes notes during the entire process. In addition, a staff member must be assigned to photocopy the exhibits being subjected to inspection. Exhibit (pages) logs. Designated person to escort FDA personnel: _______________ Designated person to photocopy documents: ________________

Assure that a room is designated for the audit. The area should include a table large enough for the auditor(s) to spread out several documents. The room should be away from the hallway and cleared of all documents relating to trials other than the one that is the subject of the inspection. Identify which room/location is designated: _________________

Assure that a copy machine will be available for use during the audit. Retain a site copy of all documents inspected and requested by the FDA during the inspection for future reference when responding to the inspection findings. Identify location of copy machine: ________________________ Identify copy machine make/model: _______________________ (Photocopies for FDA to be done in 2 sets. One for Exhibit Log and the other copy for the FDA personnel.)

Retrieve all trial records from storage. Ensure all records are retrieved PRIOR to audit: ______________

Obtain and/or assure ready access to all hospital inpatient charts for all SAEs involving hospitalization during the trial. Ensure all hospital charts are retrieved PRIOR to audit: ________ Item/Task Assure that all records related to drug accountability are available, 2 of 15 v 2.0 when done

including records stored in the pharmacy or drug dispensing area, if separate from the site. Ensure all study drug records are available PRIOR to audit._____

When the FDA Inspector arrives at the site, he/she should provide identification (badge) and a Notice of Inspection form (Form 482).

Additional Notes:

2. Regulatory Binder Item/Task Assure that all versions of the protocol provided by the sponsor are available for inspection. Version: _____________ Version: _____________ Version: _____________ Reference(s) 21CFR312.30 ICH GCP 8.2.2, 8.3.2 when done

Assure that each version of the protocol has been signed and dated by the principal investigator and sponsor, if required by the sponsor. _________________________________ _________________________________

ICH GCP 8.2.2

Assure that all versions of the Investigators Brochure (IB) provided by the sponsor are present. A copy of the acknowledgement of receipt sent to the sponsor for each version of the IB should be available for inspection. Version: _____________ Version: _____________ Item/Task Assure that all IND Safety Reports provided by the sponsor are present. Obtain a complete list of IND Safety Reports from the sponsor to assure that they are all present. Assure that the file of Safety 3 of 15

21CFR 312.55; ICH GCP 8.2.1

Reference(s) 21CFR 312.50, 312.32(c)(1)(i), ICH GCP 8.3.18

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Reports is organized and reviewer friendly. IND Safety Report____________________ IND Safety Report____________________ IND Safety Report____________________

Assure that all annual reports and the final report to 21 CFR the IRB/EC are present (including interim reports, if 56.109(f), applicable). ICH GCP 8.3.19 Annual reports: _____________________ Final report: _______________________

Assure that the original IRB/EC approval letters are present for the protocol (all versions and amendments). Protocol approval date(s): ______________ Amendment approval date(s): ___________

21 CFR 56.103(a), 56.109(e), ICH GCP 8.2.7, 8.3.3

Assure that all IRB/EC approved versions of the informed consent form available for inspection. ICF approval date(s): ______________ ICF approval date(s): ______________ ICF approval date(s): ______________ ICF approval date(s): ______________

21 CFR 312.60 ICH GCP 8.2.3, 8.3.2

Assure that the original IRB/EC approval letters are present for the informed consent form including all versions and all translated informed consent forms. Translated ICFs ? : _________________ IRB/EC approval letters: _______________ Item/Task If the informed consent form has been translated from English into another language, assure that all translated versions are available. If applicable: ________________________ ______________________________________ ______________________________________

21 CFR 56.109(c), 50.20, ICH GCP 8.2.7, 8.3.3

Reference(s) 21 CFR 50.20, 50.23 ICH GCP 8.2.3, 8.3.2, FDA Information Sheets, FAQ, #51, 1998 update, and A Guide to Informed consent 1998 update.

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Assure that the original IRB/EC approval letters are present for advertising, including patient information sheets, if applicable. Ad approval date(s): ___________________ Ad approval date(s): ___________________

21 CFR 56.109(a), FDA Information Sheet, Recruiting Study Subjects, December 1999; ICH GCP 8.2.3 21 CFR 312.53 (c)(1)(vii), ICH GCP 8.3.17

Assure that a copy of all letters from the investigator to the IRB/EC are present, including submission of all versions of the protocol (including protocol amendments), informed consent form, Investigators Brochure, advertising, annual reports, final report, interim reports if applicable, notification of premature discontinuation from the trial, clinical hold(s), and if a comparator drug was used in the trial, the package insert for that drug; all IND safety reports provided to the investigator by the sponsor, all site serious adverse events and any other adverse events submitted to the IRB/EC. Memos to file, if applicable: ____________ ______________________________________ ______________________________________

Assure that the original IRB/EC letters are present, acknowledging receipt of the Investigators Brochure, IND safety reports, site serious adverse events, and any other adverse event information submitted to the IRB/EC, annual reports, periodic reports if applicable, and the final report. Memos to file, if applicable: ____________ ______________________________________ Item/Task Assure that documentation of the IRB/EC membership list is present, over the time period of the trial. IRB/EC Roster (date): ____________________ IRB/EC Roster (date): ____________________

21 CFR 56.109(e), ICH GCP 8.2.7

Reference(s) 21 CFR 56.107 ICH GCP 8.2.8

when done

If the principal investigator, a subinvestigator, or a 5 of 15

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staff member involved in the trial was a member of ICH GCP 3.2.5 the IRB/EC, assure that documentation is present from the IRB/EC stating that the person abstained from initial and continuing review of the trial and abstained from voting on any part of the trial. Documentation present, if applicable: _____ _______________________________________

If there is more than one IRB/EC, all approval and As noted above for notification documentation as noted above is IRB/EC required in regard to all involved IRBs/ECs for the documentation. site for this trial. Specify name(s) of IRBs/ECs: ____________________________________ _______________________________________

Assure that all financial disclosure documentation is present for the principal investigator and all subinvestigators as listed on Form FDA 1572 in section 6, if applicable. Disclosure(s) for PI: ___________________ Disclosure(s) for Sub-I(s): ______________ Disclosure(s) for Sub-I(s): ______________ Disclosure(s) for Sub-I(s): ______________ Disclosure(s) for Sub-I(s): ______________

21 CFR 54.1(b). 54.4(3)(b), 312.53(c)(4), ICH GCP 8.2.4

Assure that all signed agreements between involved parties are available, i.e., - Investigator/Institution and sponsor - Investigator/Institution and CRO Item/Task

ICH GCP 8.2.6

Reference(s)

when done

Assure that a signed and dated Curriculum Vitae are 21 CFR 312.53(2), available for the principal investigator and each ICH GCP 8.2.10 subinvestigator listed on Form FDA 1572 evidencing their qualifications. Signed CV for PI: __________________ Signed CV for Sub-I: _______________ Signed CV for Sub-I: _______________

Assure that a signed and dated Curriculum Vitae is present for the study coordinator(s) and 6 of 15

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pharmacist(s) involved in the trial evidencing their qualifications. Signed CV for SC: ____________________ Signed CV for SC: ____________________ Signed CV for pharmacist: ______________ Signed CV for other: __________________

Assure that a copy of all versions of Form FDA 1572 signed and dated by the principal investigator is present (two-sided). 1572(s) present: ______________________ 1572(s) present: ______________________

21 CFR 312.53(c)(1)

Assure that all correspondence between the investigator and the sponsor (and CRO, if applicable) is available, especially notification to the sponsor of site serious adverse events (SAEs), and including documentation of telephone conversations regarding the trial, hard copies of emails pertinent to the conduct of the study, notes to file, memoranda, documentation of transmittal of case report forms, letters from the monitor describing items to be addressed resulting from monitoring visits. Correspondence section complete or not: __ ______________________________________ ______________________________________ Item/Task

21 CFR 312.64(b) ICH GCP 8.3.11 and 8.3.16

Reference(s)

when done

ICH GCP 8.3.24 Assure that a completed site personnel log is present, including the name and signature of all staff authorized to make entries in case report forms Industry standard and other trial related activities. Updated site personnel log present: _______ _______________________________________ __________________________________________ Assure that the completed subject screening log is available for inspection. Updated/accurate Screening Log: ________ Updated/accurate Screening Log: ________ ICH GCP 8.3.20

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Assure that the completed subject enrollment log is available for inspection. Updated/accurate Patient Log: ___________ Updated/accurate Patient Log: ___________

ICH GCP 8.3.22

Assure that the completed monitor signature log is available for inspection. Updated/accurate Monitoring Log: _______ Updated/accurate Monitoring Log: _______

21 CFR 312.53(d)

Assure that the trial initiation monitoring visit report is available for inspection. Initiation Visit Report on site: ___________ Date of visit(s): ______________________

ICH GCP 8.2.20

Assure that all, other than noted above, relevant ICH GCP 8.3.11 correspondence regarding the trial is available. ____________________________________ _______________________________________ Item/Task Reference(s) when done

Identify all the labs used during the course of the ICH GCP 8.2.11 study. Assure that dated laboratory normal ranges are present for all laboratory tests done and all laboratories used by the site for the trial. Lab(s) name: ________________________ Other lab(s) name: ____________________ Reference Ranges present: ______________ _______________________________________

Assure that documentation of CAP, CLIA, or State laboratory certification is present, for the entire period of the trial for each lab used. CAP (expiration dates): ________________ CLIA (expiration dates ) : ______________ Other certifications : __________________

ICH GCP 8.2.12

Assure that the Curriculum Vitae of the laboratory 8 of 15

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director are available for inspection. CV from Central Lab: Yes_____No______ CV from local lab, if applicable: Yes_____No______

Assure that documentation of drug accountability is available, including shipment invoice copies, completed acknowledgement of receipt forms, retained drug documentation if any, and individual subject drug accountability, over the time period of the trial. ___________________________________

21 CFR 312.61, 312.62(a), ICH GCP 8.2.15, 8.3.8, 8.4.1

Item/Task

Reference(s)

when done

Assure that documentation of final disposition of 21 CFR 312.62(a), study drug is present. If drug was destroyed at the ICH GCP 8.4.2 site, assure that documentation of the sponsors approval for site destruction of study drug is present, as well as documentation of compliance with any local requirements for disposal of medical waste. Study drug destroyed on site: Yes___No___ Documentation present: ________________ Study drug shipped off site: Yes____No___ Documentation present: ________________ _______________________________________

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Assure that a copy of the study drug label is 21 CFR 312.6, available for inspection. Note that this copy can be ICH GCP 8.2.13 from a tear-off label from dispensed study drug, a copy of the label retained in the pharmacy records, or a facsimile of the label if in the protocol. Drug label(s) available on site? __________ _______________________________________

Assure that the instruction for handling the investigational product(s) and trial-related materials (if not included in the Protocol or Investigators Brochure). Confirm all available at the site for inspection.

ICH GCP 8.2.14

Assure that it is clear how the investigator could ICH GCP 8.2.17 unblind study drug in the event of a medical emergency, if the study drug was blinded. Review the procedure w/the PI: __________ Are randomization code envelopes on site?: ____________________________________ Item/Task If subjects were provided with any money related to their participation in the trial, assure that documentation of all payments is present. Note that provision of money to subjects should be clearly described in the IRB/EC approved informed consent/ PIS form(s). Information may be found in the patient information sheets. Ensure documentation of all payments are easily available. _______________________ _______________________________________ Reference(s) FDA Information Sheet, Payment to Research Subjects, December 1999 when done

Additional Notes:

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3. Case Report Forms and Source Documents Item/Task Assure that all blank, annotated and subjects case report forms and any other written information/instruction are available for inspection. Ensure that the subjects CRFs are complete, signed by the principal investigator, pulled, and in order. Ensure complete review of CRFs. Provide a memo to file, if applicable. ______________ _______________________________________ Reference(s) 21 CFR 312.62(b), ICH GCP 8.3.14; 8.2.2; 8.2.3 when done

Assure that all original signed and dated informed consent forms (ICFs/PISs) are present, including all versions signed by each subject, including enrolled subjects and screen failures. Assure that subjects signed and dated the informed consent forms themselves. Note to file, if applicable: _______________ _______________________________________

21 CFR 312.62(b), ICH GCP 8.3.12

Item/Task Assure that it is clear in source documentation that subjects signed the informed consent form prior to study specific procedures being done. Review source documentation of the informed consent form process and ensure procedures were done after patients were properly consented. ____________________

Reference(s) 21 CFR 312.62(b)

when done

Assure that all queries are resolved, signed by the principal investigator/SC, and are complete, and in order. Ensure all queries have been resolved, signed, dated and easily available._________

21 CFR 312.62(b), ICH GCP 8.3.15

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Assure that all source documents are present for all case report forms. In the event that any source documentation is written directly on the case report forms, assure that documentation is present describing what source documentation has been directly recorded on case report forms. Review sites sequence of capturing data and source documentation. Generate a memo to file, if applicable. _____ _______________________________________

21 CFR 312.62(b) ICH GCP 8.3.13

Assure that source documentation is available for all 21 CFR 312.60 screen failures and premature withdrawals, including documentation of the reason for screen failure and withdrawals. Review Screen Log and ensure documentation available for screen failures as well as for early withdraws. ___________ _______________________________________ Additional Notes:

4. Miscellaneous Regulatory and Quality Items Item/Task If there were non-English speaking subjects, or subjects with any potential communication impairment such as deafness or blindness, assure that there is documentation of who, at the site, assisted with translation as needed to answer subject questions and provide information throughout the trial. Non-English speaking subjects at this site: ___________________________________ Did any subjects need assistance with translations? _________________________ Supporting documentation available: ______ _______________________________________ Reference(s) Industry standard. when done

If the site had standard operating procedures during 12 of 15

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the trial, assure they are available, complete and up to date. Sites SOPs present: ___________________ Pharmacys SOPs present: ______________ IRB/ECs SOPs present: ___________________

Assure that the delegation of responsibility was documented, and properly delegated so that the Investigator retained control of the study. Confirm Delegation of Authority is complete and accurate: _________________________

FDA Compliance Program Guidance Manual 7348.811

Assure that documentation is present of any staff training provided and training provided by the sponsor or external GCP classes that have been completed. Investigator Meeting Date(s): ____________ Other training date(s): __________________ _______________________________________ Additional Notes:

21 CFR 312.60 ICH GCP 4.2.4

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Item/Task

Reference(s)

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If the CRO/Investigator has been inspected N/A previously, review past findings and how deficiencies were resolved. Has site been inspected previously?________ Were all discrepancies resolved? _________ How were discrepancies resolved? ________ _______________________________________

If electronic systems were used for the trial at the 21 CFR 11 site, to create electronic records and/or electronic signatures, assure that documentation is present for system security, validation, and controls in place during the trial. The site should discuss requirements with the sponsor to ascertain what documentation should be present for the FDA inspection. If case report forms for the trial are electronic, assure that signed certified as true hard copies, signed by the principal investigator, and are present, if required by the sponsor. Comments: __________________________ _______________________________________ _______________________________________ Additional Notes:

5. Logistics At the conclusion of the Audit: If the FDA Inspector issues a Form FDA 483 (Inspectional Findings) at the end of the audit, during the exit interview, the principal investigator should state his/her intention to respond/correct the deficiencies at the earliest opportunity, and must refrain from arguing about the observations being presented at the conclusion of the audit. Discuss this with the PI: _________________________________ Ensure PI is clear on actions needed to resolve deficiencies: ____ ________________________________________________________ ________________________________________________________ Item/Task when done v 2.0 when done

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In the event of issuance of a Form FDA 483, the investigator/CRO should notify the sponsor immediately and work with the sponsor on corrective actions in response to the inspection findings. Ensure the PI understands requirement to contact ____________ ASAP if FDA 483 is issued:_________________________ Ensure the PI understands follow-up by the site will be needed after the inspection to correct deficiencies: __________________ ________________________________________________________ Additional Notes:

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