how to prepare for a fda inspections

7/27/2019 How to Prepare for a FDA Inspections

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FDA Inspections

How to Prepare for a FDAInspection

Sreeraj


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Table of Contents

1. Overview of Bioresearch Monitoring (BIMO)Program

2. Preparing for the Inspection

3. The FDA Inspection

4. Post-Inspection

5. Most Common Findings

6. TIPS


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Bioresearch Monitoring (BIMO)Program

FDA developed BIMO to ensure:

The protection of the rights, safety, and welfare ofhuman research subjects

The quality and integrity of data submitted to theAgency

BIMO Program involves site visits to clinicalinvestigators, IRBs, and nonclinical (animal)

laboratories.


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Types of BIMO Inspections

FDA conducts inspections of clinicalinvestigators: Routinely to verify data that has been submitted to

the Agency

As a result of a complaint to the Agency about theconduct of the study at the site

In response to sponsor concerns or termination of theclinical site

Related to certain classes of investigational productsthat FDA has identified as products of special interestin its current work plan


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Routine Inspection

VS

For-Cause Inspection


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Routine inspection:

Routine inspections account for over 80% of theinspections performed each year

Clinical Investigators who enroll the most subjects inthe trial are the most likely to be inspected.


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For Cause Inspection:

Conducting a large volume of clinical trials

Conducting clinical studies outside of onesfield of specialization

Reporting significantly better efficacy, feweradverse effects, or different laboratory results

than other investigators studying the samedrug


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For-Cause Inspections (contd)

Complaints from a patient or sponsor of analleged violation of the regulations, protocol,or human rights


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Preparing for the Inspection

When FDA calls to schedule an inspection,obtain the following information:

The name of the PI being inspected

What studies are being inspected The reason for the inspection

Does the FDA want specific personnel available

Does the FDA want specific documents available


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Document any telephone conversation(s) thatoccurs between the FDA inspector and the studystaff

Notify study team, Sponsor (is the only way thesponsor will know the site is being audited),Ethics Committee

The FDA inspector will usually request theinspection take place within 10 days

Collect the medical records for all subjectsenrolled in the study


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Reserve a room in a private area for theinspection

The room should contain no other files or records

A copy machine should be located next to the room Prepare a general overview of the study for the

PI and study staff


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Update the Principal Investigators CV. Thisshould include a list of all current studies.

Review study documentation for:

Accuracy, and compliance Weakness/gaps; correct those that can be corrected

(i.e. notes-to-file, locate missing documents, etc.)


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During the Inspection

The PI or his/her representatives should meetthe inspector and receive and sign the FDA form482 Notice of Inspection.

Write down the inspectors identificationinformationyou cannot make a copy of theinspectors badge!!


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FDA inspector may request a tour of thefacility where research took place.

Escort should accompany the inspector atall times.

Upon request, provide the inspector onlythe files that have been requested.


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If the inspector requests copies of documents:

Remove subject identifiers from the copies given tothe inspector

Make a copy for yourself The inspectors copies should be stampedConfidential and your copies should be stampedCopy.

The PI should set aside time each day to talkwith the inspector


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How to answer questions from the inspector:

Be concise; answer only the question that is asked

Always be clear with answers to questions

Answer honestly and openly DO NOT volunteer information

DO NOT guess

DO NOT argue

If you dont know the answer, write down thequestion and refer it to the appropriate person

Keep a log of questions asked by the inspector


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FDA Inspector will verify: Who performed various aspects of the protocol

(eligibility, consenting, etc.)

The degree of delegation of authority

Where specific aspects of the investigation wereperformed

How and where data were recorded

How were study staff oriented/trained on the protocol

and investigational product That the PI followed the study protocol approved by

the IRB


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In addition, the inspector will record thefollowing information:

Dates of IRB approvals (original, continuing

review, etc.)

When the first subject was screened

When the first subject was consented

First administration of the investigationalproduct

Last follow-up for any study subject


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Inspected Documents

The following items are routinely examined:

Adequacy of communication with the IRB, includingthe initial submission, continuing reviews, adverseevent reporting, progress reports, etc.

Completeness of accountability documentation for thereceipt, storage, administration and return of theinvestigational product

Compliance with the study protocol anddocumentation that each deviation notified to IRB andsponsor approval


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Inspected Documents

Inspected documents (cont)

Appropriateness of the informed consent process

Prompt and complete reporting of adverse events to

the IRB and sponsor Compliance with record retention requirements

Adequate monitoring of the site and communicationof the sponsor (monitoring reports)

Consent Forms (including the consent process)


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Inspected Documents The inspector will review subject data to verify that:

Data entered on the CRF is has been accurately andcompletely recorded (matches source documents)

Subjects meet inclusion/exclusion criteria

Clinical laboratory testing was documented by laboratoryrecords

All adverse events were documented and appropriatelyreported

The PI assessed the severity of the adverse event and

documented the relationship of the event to theinvestigational product

All concomitant therapies and/or inter-current illnesseswere documented and reported


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After the Inspection

The FDA inspector will hold an exit interview atthe conclusion of the audit to discuss findingsand deficiencies

Study staff should document the interview,specifically noting observations, comments, andcommitments

Any deficiencies will be noted on the FDA form483 and given to the PI

PI can respond to the 483 verbally during the exitinterview and/or in writing


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FDA Form 483

Written response should:

Address each specific finding, point by point

Describe corrective action plan The response should be sent to the FDA within 30

days


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Post-Inspection

After the inspection, the inspector will write anEstablishment Inspection Report (EIR) andsubmit it to FDA headquarters

After the report has been evaluated you willreceive one of three letters:

No action indicated (NAI): No objectionableconditions or practices were found during the

inspection, or the conditions does not justify furtherFDA action


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Post-Inspection

Post-inspection letters (cont)

Voluntary Action Indicated (VAI): Objectionableconditions were found and documented, but the FDAis not prepared to take or recommend furtherregulatory action because the objectionableconditions are few and do not seriously impactsubject safety or data integrity

Official Action Indicated (OAI): Regulatory violations

uncovered during the inspection are repeated ordeliberate and/or involve submission of falseinformation to FDA or to the sponsor


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Post-Inspection

OAI may result in:

Warning letter (WL)

Violations can be corrected through specific action(s) by theinvestigator and adherence to the corrective action plan has

a high probability of preventing similar or other violations inthe future

Notice of Initiation of Disqualification Proceedings andOpportunity to Explain (NIDPOE)

Repeatedly or deliberately failed to comply with therequirements for conducting clinical trials

Repeatedly or deliberately submitted false information toFDA or to the sponsor


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Most Common Findings

Failure to ensure that informed consent wasobtained

Failure to maintain accurate, complete, and

current records Inadequate device/drug accountability

Failure to obtain IRB approval

Different handwriting in subject diary


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TIPS

Train all the staff before the inspection

SOPs: Standard Operating Procedures to achieve

consistency Source Documentation: Maintain all the applicable

original documents, data, and records thatcorrespond with the CRFs

Checklists/Logs: A way to verify completion of study-related procedures

Note-to-file


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