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QRTI Newsline --- Wednesday September 8, 2010

Preparing Investigators for an FDA Inspection

by Phyllis B. Kent

When an investigator has been notified that FDA plans to conduct a pre-approved inspection of the investigator sites, there are a number of steps that can be taken to prepare for a successful inspection. Usually if a site participates in the pivotal protocol, you can anticipate that the site may be inspected.

The following are some suggestions to facilitate the potential FDA inspections. Routinely, FDA calls the sites to schedule their inspections with only a one week notice. Therefore, sites should be prepared in advance. When an audit request call from the FDA is received, the Principal Investigator should contact the sponsor as soon as possible. The clinical team will then be able to assist the site with the planning for the inspection and assure that the sponsor's staff is standing by to answer any questions that may arise during the inspection.

It is suggested that sites take the following steps to prepare in advance of the inspection.

Request all medical charts from the hospital medical records for the time period in which the study was conducted.
Assemble all worksheets, binders and supporting documents that were used to capture the source documentation for the study.
Assure that every original informed consent form for the subjects in the study has been retrieved. Although copies may be acceptable, the original forms should be requested prior to the FDA visit.
For electronic data capture studies, assure that the site personnel can access the eCRFs either through a web portal or on the CD provided by the sponsor.
Assure that all pertinent documents are filed in the regulatory binder. FDA will focus on the protocol and amendments, the IRB approvals and correspondence, Serious Adverse Event reports, FDA 1572 forms and corresponding study staff CVs. Documentation of the study staff delegation of responsibilities and signatures, as well as the monitoring visit sign-in log will also be inspected. Correspondence with the monitor, CRO, sponsor, and the IRB will also be reviewed.
The Principal Investigator and study coordinator should be prepared to describe exactly how the study was conducted at their site. It is especially important to describe how the study specific procedures were accomplished. The site may wish to write down this process and place it in the regulatory binder. Keep in mind that the FDA inspector will be reviewing office charts, hospital records (e.g. operative notes) and the study worksheets to assess compliance with the protocol. The inspector will be comparing the names of those in the regulatory documentation with the names on the source documents to assure that all who participated in the study were properly qualified.
The Principal Investigator must be available at the beginning of the inspection to receive the Notice of Inspection and to provide the description of the study to the FDA inspector. The inspector will conduct an interview with the PI, using the questions from their inspection program CPGM7348.811, Clinical Investigators, which can be found at www.fda.gov/ora/compliance_ref/bimo/7348_811.
It is best for the principal investigator and study coordinator to review these questions in advance, to be sure that all of the appropriate information for the interview has been gathered.
The staff should refer to the records when answering study specific questions to assure accurate responses, since it is usually more that a year since the study was completed.
The study coordinator should remain with the FDA inspector at all times, especially to obtain information from the electronic hospital charts. Although some inspectors may request to be left alone, FDA inspectors should not be given passwords or left unsupervised when electronic charts are being reviewed. The coordinator should locate the specific documents requested for the inspector to save time and assure that the correct records are reviewed. The coordinator should continually assure that the inspector is finding what is needed for review.
At the end of each day, the PI and coordinator should meet with the inspector and ask if she/he has found any objectionable items, which might appear on a form FDA 483, List of Observations. This will provide an opportunity to give additional information, if needed, and to clarify any possible misunderstandings.
At the conclusion of the inspection (usually 3-5 days in length), the FDA inspector will issue a form FDA 483, List of Observations, to the Principal Investigator, listing any violations of regulations or the protocol which they have noted. The inspector will discuss this form with the principal investigator and study coordinator, who will have the opportunity to clarify and respond to the items noted. They should report to the inspector any corrective action which has already been taken. It is important to assure that the form FDA 483 accurately represents the findings, as it is releasable to the public under the Freedom of Information Act.
If the observations are substantial in either quantity or significance, a written response should be sent to the FDA immediately following the inspection.

It is the sponsor's goal to assist clinical sites to have a successful FDA inspection. Clinical site staff should not hesitate to contact the study sponsor with any questions about the inspection process.

The entire research team looks forward to the successful completion of the FDA inspection since it is the final milestone in the FDA approval process.