1. Sponsor-Investigator (SI) FDA Inspections
Christiana Provencal, M.A.
Quality Assurance / Quality Improvement Administrator
April 13, 2018

2. Inspection types
Inspection assignments are issued by the FDA Center to the District Office. There are two types of inspections:
Routine/Surveillance
The purpose may be to verify data submitted to the FDA or the FDA may be generally interested in what you’re doing.
For Cause
The FDA may have received information that calls into question study conduct. These types of inspections can be
limited to one area of concern or cover the entire study.

3. What information should I record if I receive a call from the FDA?
The FDA will typically notify the PI (Sponsor-Investigator) about its intention to inspect via phone. Below are the questions you should ask and information you should record during this initial call:
What type of inspection will this be? (Routine/surveillance or for- cause?)
Which study(ies) do they plan on inspecting?
What is the date/time of inspection and the expected duration? (Note that the FDA typically provides only a few days’ advanced notice for inspections and expects you to accommodate the proposed inspection dates.)
Who will be conducting the inspection?
What is the inspector(s)’ contact information?
The details of any documents/information the inspector asks you to provide in advance of or at the inspection*

4. Who do I notify about the inspection?
Brown’s Office of Research Integrity (ORI)
The ORI, through its QA/QI program, will assist you with preparing for the FDA inspection. Christiana Provencal with a copy to Keri Godin, or call (The ORI typically sends a representative to support you during the intake session.)
Any co/sub-study investigators and any other study staff that will play a role in the inspection procedures
Your Program Officer (sponsor) for the study(ies) that will be inspected.

5. Inspection logistics
As much as is feasible, clear your schedule for the duration of the visit. Typical routine inspections at Brown have lasted 3-5 business days.
As much as is feasible, clear the schedules of critical team members, which may include research assistants and project managers/coordinators; the FDA may also ask to speak data analysts/data managers, study nurses / other study clinicians
Reserve a conference room for the duration of the inspection to provide work space and interview space for the inspectors. Ensure the space has wifi connectivity
In advance of the inspection, designate who will take notes during the inspection, who will retrieve requested study files, and who will prepare any documentation requested by the inspector
Ensure that no documents that are required for the inspection are person- dependent (only accessible by one person) in the event that someone is running late, out sick, etc.
Ensure any data security scans or other data security measures referenced in your IRB protocol are performed before they inspector arrives

6. Preparation of Study Documentation*
Review and organize paper copies of the following documentation:
A single, complete, current IRB-approved study protocol. This protocol should include all IRB-approved study procedures, informed consent procedures, data storage and security procedures. It should incorporate into the IRB-approved study protocol any changes (amendments/mods) made to the protocol
All IRB-related study documentation, including approval memos, protocol deviations, serious adverse events, progress reports and any other IRB correspondence
All FDA documentation and correspondence
Records of study drugs, inventory, storage, dispensing and disposal
Study instrument maintenance/calibration logs and records
Study personnel training records
*ORI’s QA/QI Administrator, Christiana Provencal, is available to consult with / meet with your study team prior to the inspection to review the prepared documentation, highlight and missing information or red flags, and ensure congruency with the IRB office’s records

7. Preparation for Intake Meeting (Day 1 of inspection)
Have a document ready for the inspector containing a list of personnel present for the intake meeting, their study roles and responsibilities, and their complete contact information
Ensure that all individuals present for the intake meeting have reviewed beforehand the IRB-approved protocol and are well-versed in study procedures and amendments
Each individual present should be prepared to answer an open-ended question about his/her role on the study. Study personnel should be prepared to describe specific responsibilities, qualifications and training.
Be prepared to answer questions about methods for cross-checking data / ensuring data integrity (i.e., secondary review of data entry, etc.)

8. Communicating with the FDA Inspector
Listen carefully to questions. Repeat and/or clarify any questions as needed before responding.
Ask the inspector to define or explain a term or phrase if needed.
Only answer the question that is asked. Resist the urge to elaborate or speculate (don’t try to fill the silence as the FDA inspector records his/her notes!)
Answer honestly. You are encouraged to review the protocol itself or any study records in real time to ensure the accuracy of your answers.
Answer with “one voice.” Avoid contradictory answers among study personnel; if the PI (SI) doesn’t have the most direct knowledge, encourage a study coordinator or others to speak up.
The inspectors do not need your assistance to identify problems. Don’t raise any proactively. Do not bring up past deviations for the study in question or reference other issues or deviations in other research studies.

9. Communicating with the FDA Inspector (cont.)
If the inspector identifies an issue, it is appropriate to ask for the rationale and associated FDA regulation.
Avoid responses that may sound like stonewalling, blaming or pointing to adversarial relationships.
The FDA inspector is not always right. If the inspector asks for documentation you don’t have (and don’t believe is required) and/or is unable to cite a regulatory reason for an identified problem, it is appropriate to note the issue and follow-up with the QA/QI Administrator for clarification / to do some research behind-the-scenes regarding the regulations.
If, at any point during the inspection, the FDA inspector indicates that the inspection has shifted to a “For Cause” inspection, immediately contact the QA/QI Administrator and the Director of ORI.

10. Exit Meeting
The Inspector will summarize his/her observations at this meeting
Attendees general mirror those at the intake meeting
Ensure that someone is assigned to take detailed notes
A Form 483 may be issued if there are deficiencies
Make copies for all attendees.
The Form 483 will categorize deficiencies as “observations.” You will have 15 business days to respond in writing.
Reserve rebuttals for your written response.
You may also receive verbal suggestions or discussion items. These will not be on the Form 483, but they will be part of the report the inspector issues to headquarters. Take notes.
When necessary, ask for clarification to ensure you understand each suggestion/item and the reason why it’s being cited.
If you receive a Form 483, inform the QA/QI Administrator. The ORI can provide assistance with reviewing your written response and interpreting regulatory requirements.

11. Additional Resources
ORI’s QA/QI Administrator, Christiana Provencal, is available to consult with / meet with your study team at any time to assist with a Best Practices review of study files. FDA Guidance: FDA Inspections of Clinical Investigators BIMO Guide For Clinical Investigators/Sponsor-Investigations