inspection readiness · inspection readiness informed consent process • subject must write date...

INSPECTION READINESS

EMORY UNIVERSITY

OFFICE OF COMPLIANCE

Margaret Huber, RN, CHRCCompliance ManagerOffice of Compliance Emory University

Emory University Office of Compliance

Inspection Readiness

Objectives

List common audit findings

Outline steps that promote

readiness

Review FDA inspection process

EMORY UNIVERSITY



Inspection readiness should be a

state of being rather than an

activity

EMORY UNIVERSITY


Good Clinical Practice

GCP (Good Clinical Practice) ICH-E6

provides standards for the design, conduct,

recording, and reporting of clinical trials.

GCP standards delineate documentation

required to demonstrate compliance with

regulatory requirements.

EMORY UNIVERSITY


Good Clinical Practice

Why is Good Clinical Practice (GCP) important?

Guidance documents represent the FDA's

current thinking on how regulations should be

met for a particular subject.

GCP is current FDA guidance that outlines the

roles and responsibilities of clinical

investigators and all key personnel involved in

the Research Protocol.

EMORY UNIVERSITY



By following GCP, you will

capture quality data

maintain inspection

readiness

BE PREPARED!

EMORY UNIVERSITY


Clinical Trial Audit Finding

Common Areas

Informed Consent Process

Study Records

Protocol Adherence

Eligibility Criteria Determination and Documentation

Adverse Event Review and Reporting

Drug/Device Accountability

Regulatory Site Documentation

Monitoring Findings

Sponsor-Investigator Responsibilities

Emory University Office of Compliance


Poor Protection of Subjects

Common Findings:

Incorrect consent version

No source documentation of consent process

Consent not dated by subject

Check boxes left blank; pages not initialed by subject where required

No HIPAA Authorization

Original consent missing

Not re-consented when required

EMORY UNIVERSITY




• Make sure you use the latest IRB approved version

• Document the consent process

• Include a note in the research record regarding consent

process -- how it was conducted; whether questions

were asked/answered; and fact that subject was

provided a copy of consent

• Provide the subject time to consider options–

Not too much, not too little – Just Right!

EMORY UNIVERSITY



Informed Consent Process• Subject must write date (and time if required) when

signing

• Make sure consent is signed by each of the proper

parties on all required lines & all check boxes are

completed

• Obtain a HIPAA Authorization

• Keep all original informed consent documents

• Re-consent when sponsor or IRB requires and keep track

EMORY UNIVERSITY


Study Records

Inadequate recordkeeping

Common Findings:

Data not entered on case report forms (CRFs) or incomplete CRFs

Discrepancies between CRFs and medical records/source documents

Data queries not completed

No documentation of investigator review of CRFs

Improper error correction

EMORY UNIVERSITY



Study Records• Read the protocol and CRF forms carefully before

starting the study to make sure:

– CRF captures necessary study data

– Source document captures necessary study data

• Complete study forms in real time – not just before

the next monitoring visit

• Keep study documents organized & current

EMORY UNIVERSITY



Study Records

• Set up a regular research team meeting time to

communicate & review study data

• Document real time investigator review

• Maintain logs to assist in tracking

• Correct any errors appropriately

• Ensure an audit trail exists

• NO WHITE OUT; NO PENCIL

EMORY UNIVERSITY


Protocol Adherence

Failure to Follow the approved protocol

Common Findings:

Protocol not followed

Changes made in protocol without first

obtaining IRB approval for reasons other than

immediate patient safety

Missed tests, schedule changes, etc.

EMORY UNIVERSITY



Protocol Adherence

• Read protocol BEFORE starting the trial to make sure it

is realistic and to identify differences between what

protocol requires and what would typically be done in a

treatment situation

• Read/compare the protocol & consent for consistency

• Be the protocol expert

EMORY UNIVERSITY



Protocol adherence

• Avoid Protocol Deviations

– Follow time frames for visits/procedures

– Know inclusion/exclusion criteria

• Document deviations including any reasons

• If a protocol deviation occurs more than once, determine root

cause and if protocol modification is appropriate

• Keep the investigator informed

• Follow reporting requirements

• IRB

• Sponsor

• FDA EMORY UNIVERSITY


Eligibility Determination and

Documentation

Common Findings:

Subjects enrolled who are not eligible

Eligibility checklists incomplete

No source documentation confirming eligibility criteria

Failure to conduct all tests needed to satisfy eligibility

criteria

No documentation that investigator has reviewed

eligibility

Waiver of eligibility requirement

EMORY UNIVERSITY



Eligibility Determination & Documentation• Confirm source documentation for eligibility

• Set up a process for investigator review/signature of eligibility checklist

• Do not waive subject eligibility requirements without documentation from sponsor

• REMEMBER – you are working with research subjects; don’t confuse treatment with research

– Protocol may call for tests within a certain window for eligibility determination even though in a treatment context those tests might not be required

EMORY UNIVERSITY


Adverse Event Review and

Reporting

Common Findings:

Conflict between CRFs and source documentation,

e.g., Adverse Event (AE) noted in medical record

but not on CRF, or vice versa

AEs not signed/graded/attributed in a

timely manner by qualified personnel

Failure to follow reporting requirements

EMORY UNIVERSITY



Adverse Event Review & Reporting

• Set up process for evaluation of AEs in real time

• Make sure AEs are evaluated by qualified

individual

• Report AEs in timely manner

• Review the reporting requirements

• IRB Policy & Procedures

• Clinical Trial Agreement

EMORY UNIVERSITY


Drug/Device Accountability

Inadequate accountability of investigational product

Common Findings:

Incomplete device records

No documentation that oral drug was provided to subject and/or returned by subject with pill count

Poor documentation regarding drug diaries

Poor prescription practices

EMORY UNIVERSITY



Drug/device accountability

• maintain a drug/device accountability log

• document each time a drug or device is

dispensed or retrieved

• document pill diaries

• record events contemporaneously

EMORY UNIVERSITY



Drug/device accountability

• Document reminders to subjects

– Phone call before visit and after visit

– Letter seeking return of drug

• Improve prescription practices

– Make sure all are signed by authorized prescriber

– Print name, phone number and date under signature

EMORY UNIVERSITY



Inadequate recordkeeping

Common Findings:

No delegation of duties log

CVs, licensing info, etc. not up-to-date

No SOPs – lack of process documentation

Missing records and poor record storage

EMORY UNIVERSITY



Regulatory Site Documentation• Create and maintain a delegation of duties log

• Review with all study team members to ensure

accuracy

• Update as new staff are added or deleted

• Update as new responsibilities are assigned

• Ensure documentation of study specific training

prior to listing on delegation log.

EMORY UNIVERSITY




• Using a laptop or flash drive?

• Protect study data

• Encryption is the key!

• Maintain study documentation in

regulatory binder.

• Ensure all study close-out activities are

completed and all required documents

are stored according to regulations &

institutional policy.EMORY UNIVERSITY


Monitoring Findings

Common Findings:

Failure to address findings

Failure to document a response

EMORY UNIVERSITY



Monitor Findings

• Review monitoring reports and address findings.

• Don’t let it wait – set rigid timetable for addressing all monitor findings

• Document how findings were addressed

• PI should review & sign off

REMEMBER –

If it’s not recorded, it didn’t happen

EMORY UNIVERSITY


Sponsor-Investigator Trials

Investigator assumes the role and all

responsibilities of a sponsor in addition to those

of an investigator

Sponsor-Investigator (S-I) must fully comply with all

sponsor & investigator regulations

Usually receive the study drug/device

but limited financial support for

monitoring

EMORY UNIVERSITY



Common Findings:

Investigator does not have processes to

meet BOTH Investigator and Sponsor (S-I)

FDA Responsibilities

S-I does not have processes to meet Sponsor

Responsibilities for multi-site trials

EMORY UNIVERSITY


Re-Sponsor-bilities Checklist

IND/IDE submission

Annual Reports

Protocol Amendments

Regulatory documents:

CV, 1572, financial

disclosures

Investigator Brochure

Monitoring Trial

Training

Safety reports on AEs/risks to all investigators and FDA

Ensure FDA compliance by all investigators

Evaluate safety and effectiveness data

Drug/device accountability records

EMORY UNIVERSITY




• Evaluate before starting the trial:

• Do the S-I and study team have the experience to do this?

• Are there resources to complete the additional responsibilities?

• Watch out for multi-site trials

• Monitoring is required, not optional

• Use available resources (Compliance Office may be available to answer questions & provide assistance with investigator-initiated trials)

EMORY UNIVERSITY



EMORY UNIVERSITY



FDA Inspections

Inspectors require strict adherence to

GCP.

EMORY UNIVERSITY



FDA InspectionsImmediately notify:

• PI/Coordinator

• Sponsor

• Compliance Office

• IRB

EMORY UNIVERSITY



Inspection may be ‘for cause’ or ‘not

for cause’

Use checklists to help you prepare

Goal is to spot weaknesses, gaps or

anything that can be corrected

before inspection.

EMORY UNIVERSITY



Usual order of document review

General study documents, regulatory

binders

Consent documents

Specific subjects’ charts

EMORY UNIVERSITY



Exit Interview/Close-out

• Ensure that PI, coordinator are present

• Best case scenario:

• No findings of serious deficiencies

• No Form 483 issued

• Otherwise: Inspector will give the PI a Form 483

recording the Inspector’s observations of serious

deficiencies

EMORY UNIVERSITY



If Form 483 is issued:

15 working days to respond in writing

Include corrective and preventive action (CAPA)

PI is responsible for content and delivery to FDA

Institution may also require review of draft

Submit a copy of the Form 483 and PI response with

CAPA to the IRB as a reportable event

EMORY UNIVERSITY



EMORY UNIVERSITY


Questions ?

Margaret Huber

Emory University

Office of Compliance

(404) 727-2233

[email protected]

inspection readiness · inspection readiness informed consent process • subject must write date...

Documents