Tips for successful Audit

Tips for Successful Auditor/Monitor VisitsCRMO September 2015

Outline Objectives Role of Auditors/Monitors Explore auditing and monitoring

Differences between the visit types Purpose of visits

Common Deficiencies Preparation Response

Objectives Be familiar with difference between

auditing and monitoring Know what to expect during either an

audit or monitor visit Understand ways to prepare and

respond to auditing and monitoring visits

Role and Responsibilities: Auditor/Monitor Assure rights, safety and well being of

subjects are protected Review trial data for accuracy, verifiable Oversee study activities for protocol,

GCP and regulatory compliance

Monitoring vs AuditingMonitoring AuditingContinuous process Done either during the trial

or after the completion of trial

Controls quality of trial Assures quality of trialDone by monitor who is a part of trial

Done by independent personnel of trial

Monitor Visits:Type and Purpose

Purpose of Monitoring Visits Review progress of clinical trial and

ensure protocol adherence and regulatory compliance while maintaining the rights, safety, and well-being of subjects

Frequency of visits dictated by complexity and Sponsor requirements

Types of Monitor Visits Site Initiation Visit

Interim Monitoring Visit

Close Out Visit

Site Initiation Visit The purpose of this visit is to ensure the

study team is familiar and understands Protocol procedures CRF completion Drug handling requirements Adverse Event Reporting Patient recruitment resources

Identify potential problems and concerns

Interim Monitoring Visits Purpose of visit is to:

Review progress of study Ensure protocol adherence Assure data accuracy and patient safety Regulatory compliance

Occur at various frequency depending on sponsor requirements

Close Out Visit Purpose is to review:

All regulatory documents DARFs Review record retention guideline

Occurs when all subjects have completed the study and all necessary data has been collected

Audits: Type and Purpose

Purpose of Auditing Evaluate the trial conduct and

compliance with: Quality systems SOPs Protocol GCP & other applicable regulatory

requirements

Types of Audits 2 types

Sponsor audit of site Routine For cause

IRB audit

Sponsor Audit of Site Aim to assess:

Have subject’s rights and safety been maintained?

Company procedures satisfactorily implemented

Accurate, reliable and verifiable data has been obtained from the trial

Provides assurance to both the sponsor and investigator that if a regulatory inspection occurs, no major problems have remained undetected and unresolved

Routine vs For CauseRoutine For CauseTo ensure that a site is complying with Protocol, SOP, GCP, and applicable regulatory requirements

If the site is out of compliance and the sponsors want to either verify the problem or be reassured that no problem exists.

“study-oriented audit” “investigator- oriented audit”

IRB Audit To ensure ethical conduct of trial Ensure subjects enrolled are well

informed about the trial and enrolled through a proper informed consent procedure

Can be either for cause or routine

Preparing for Auditor/Monitor Visits

Be Prepared… Best preparation is to know and

understand regulations and GCP guidance documents

Review protocol and associated documents

Learn from monitoring visits Ask questions

…Be Prepared Review agenda or monitoring letter

Ensure all records and documentation will be available

Monitor letters- check for any long outstanding deficiencies Have issues from previous visit been

resolved?

Preparing for Monitoring/Auditing Visits Prepare regulatory files

Ensure DOA is up to date A copy should be kept in binder if out for

signature so monitor can review Training

exists for all staff on DOA Training for protocol amendments

CVs/MLs up to date Lab documents are up to date SAE reports

Preparing Cont. Current 1572 is filed All protocol and IB versions are filed FDFs for all investigators on 1572 IRB Approvals

Current stamped consents Current patient materials

Correspondence IMV letters Email Newsletters

Preparing Cont. Study documentation to have readily

available: Regulatory binder Original signed ICFs CRFs Source documentation

During Audit/Monitor Visit Respond to questions asked with simple,

honest, and complete answers Listen actively Don’t rely on memory alone “I don’t know; we will review and get back to

you by the end of the day” is an acceptable answer, if applicable

Deferring to and locating appropriate person to answer the question within a specified time frame is acceptable.

At the End of the Visit Audit

Exit interview to review observations and findings

Monitor Meet to share findings, answer questions,

and identify any corrections needed

Responding to Auditor/Monitor Reports

Audit/Monitor Reports Audits:

Findings are rated as critical, major, and minor May include recommendations

Monitor: Summary of what was reviewed & significant

findings/facts, deviations & deficiencies, actions to take/recommended to ensure compliance

Common Deficiencies Failure to follow investigational plan Protocol deviations Inadequate recordkeeping Inadequate IP accountability Inadequate Adverse Event reporting Inadequate subject protection (includes

IFC issues)

Response to Findings… Answer queries or clarifications

May be done during the visit, but don’t need to correct all findings prior to monitor/auditor’s departure from site

Follow up with monitor to provide any documents or corrections to address issues on report

…Response to Findings When a mistake or incident of non-

compliance occurs, evaluate why What was the actual mistake? Under what circumstances did it occur? Who was involved? When was the error detected and how? What were the consequences?

Responding to Audit: CAP CAPA Answers should be S.M.A.R.T.

Specific, Measurable, Attainable, Relevant, Time-bound/Trackable

Be clear and precise Back up statements with fact (documents,

data)

Notes to File Effective NTFs correct, clarify, or add to

the existing source documentation and are: Well-written Relevant Infrequent Timely

Questions

References ICH GCP guidelines E6 www.fda.gov.in ICH 5.1.8.4 21 CFR 312 21 CFR 56