FDA Compliance:

FDA Inspections

FDA Compliance:

FDA Inspections

A Practical GuideA Practical Guide

byby

Compliance Insight, Inc.Compliance Insight, Inc.513-860-3512513-860-3512

www.Compliance-Insight.comwww.Compliance-Insight.com

Preparing for the AuditPreparing for the Audit

You should always be prepared for an You should always be prepared for an audit!audit! If you only prepare things just prior to an audit, If you only prepare things just prior to an audit,

it is very apparentit is very apparent fresh paint over poorly prepared materialfresh paint over poorly prepared material all documents just signed or signed very recentlyall documents just signed or signed very recently very apparent that hurried work was performedvery apparent that hurried work was performed

Last minute general cleaning and organizing is Last minute general cleaning and organizing is expectedexpected

Preparing for the auditPreparing for the audit

Most inspections are not announcedMost inspections are not announced General GMP inspections are performed approximately General GMP inspections are performed approximately

every two yearsevery two years Pre-Approval Inspections (PAIs) are performed Pre-Approval Inspections (PAIs) are performed

following submission of filings with the FDAfollowing submission of filings with the FDA ANDAANDA NDANDA

For Cause Inspections performed following an issueFor Cause Inspections performed following an issue recallrecall complaintscomplaints

Preparing for the AuditPreparing for the Audit

Some general things to Some general things to keep in mindkeep in mind A place for everything A place for everything

and everything in its and everything in its placeplace

First impressions are First impressions are very importantvery important

Have documents readily Have documents readily availableavailable

Preparing for the AuditPreparing for the Audit

Make sure any prior observations from Make sure any prior observations from auditors are completedauditors are completed Were they completed on time?Were they completed on time? Were they effective in resolving the problem?Were they effective in resolving the problem? If there were any issues, make sure they were If there were any issues, make sure they were

explained.explained. If things are not done, make sure you have a good If things are not done, make sure you have a good

excuse!!!excuse!!! What have you done in the interim???What have you done in the interim???

Preparing for the AuditPreparing for the Audit

Conduct mock inspectionsConduct mock inspections internal personnelinternal personnel corporate personnelcorporate personnel consultantsconsultants

Evaluate your quality systemEvaluate your quality system prepare for a systemic inspectionprepare for a systemic inspection

Preparing for the AuditPreparing for the Audit

PAIPAI Prepare a “war room”Prepare a “war room” Pull all documents relevant to the filingPull all documents relevant to the filing

batch recordsbatch records stabilitystability validationvalidation raw material receiptsraw material receipts testing datatesting data cleaning validationcleaning validation raw material supplier auditsraw material supplier audits

PM recordsPM recordscalibration recordscalibration recordschange control fileschange control filesFiling (final)Filing (final)water/HVAC datawater/HVAC datainvestigationsinvestigationsuse/cleaning logsuse/cleaning logs

During the AuditDuring the Audit

Receive FDA Form 482Receive FDA Form 482 Notify all partiesNotify all parties Retrieve information as requestedRetrieve information as requested

PAI - Don’t drop off the FDA in your “war room” PAI - Don’t drop off the FDA in your “war room” and let them look through everything.and let them look through everything.

Gather data quicklyGather data quickly evaluate data prior to giving it to the inspectorevaluate data prior to giving it to the inspector

Train people how to communicate with the FDATrain people how to communicate with the FDA

During the AuditDuring the Audit

Be prepared to walk through the facilityBe prepared to walk through the facility Have someone there to take notesHave someone there to take notes Keep copies of whatever copies you give to Keep copies of whatever copies you give to

the inspectorsthe inspectors Be aware that the inspector is looking at Be aware that the inspector is looking at

previous commitments and has read the EIRprevious commitments and has read the EIR FDA should approach issues systemicallyFDA should approach issues systemically

During the AuditDuring the Audit

General items evaluatedGeneral items evaluated Returned goodsReturned goods

reason why and dispositionreason why and disposition

CompliantsCompliants InvestigationsInvestigations Batch RecordsBatch Records Validation ProtocolsValidation Protocols

During the AuditDuring the Audit

Ask as the day progresses or at the end of Ask as the day progresses or at the end of the day about observations or questionsthe day about observations or questions This give you a chance to make corrections or This give you a chance to make corrections or

clarify misunderstandingsclarify misunderstandings Keep on top of thingsKeep on top of things

Don’t become overconfidentDon’t become overconfident Many small observations can lead to “the straw Many small observations can lead to “the straw

that broke the camel’s back”that broke the camel’s back”

Following the AuditFollowing the Audit

Make sure you return ALL information Make sure you return ALL information pulled for the inspectionpulled for the inspection

Don’t dispose of any documents until you Don’t dispose of any documents until you have accounted for everythinghave accounted for everything

You may want to have a master list of You may want to have a master list of documents pulled to reference when you documents pulled to reference when you start returning thingsstart returning things

Following the AuditFollowing the Audit

Corrective Action Plans (CAP) Corrective Action Plans (CAP) Direct response to investigator Direct response to investigator

findingsfindings Initiated by and based on the 483 or Initiated by and based on the 483 or

Warning LetterWarning Letter Limited in scope to the systems that Limited in scope to the systems that

FDA reviewedFDA reviewed Corrective Actions to be performed as Corrective Actions to be performed as

committed in time frame committedcommitted in time frame committed Response to FDA is public recordResponse to FDA is public record

Following the AuditFollowing the Audit

GMP Enhancement Master Plans GMP Enhancement Master Plans (GEM) (GEM) Preparation may be unrelated to the Preparation may be unrelated to the

FDA inspectionFDA inspection Initiated and controlled internallyInitiated and controlled internally An overall comprehensive assessment An overall comprehensive assessment

of the firms Quality Systemsof the firms Quality Systems Corrective Actions can be planned Corrective Actions can be planned

and modified as necessaryand modified as necessary May be held as Confidential and May be held as Confidential and

Proprietary InformationProprietary Information

The Close Out MeetingThe Close Out Meeting

Who should attendWho should attend Regulatory AffairsRegulatory Affairs Quality AssuranceQuality Assurance ProductionProduction Upper ManagementUpper Management Any other pertinent Any other pertinent

individualsindividuals

The Close Out MeetingThe Close Out Meeting

Decide in advance on response Decide in advance on response strategystrategy

Go through each itemGo through each item If errors are present, commentIf errors are present, comment Corrections made during the Corrections made during the

inspectioninspection Corrected and verifiedCorrected and verified Corrected and not verifiedCorrected and not verified Correction promised by ___Correction promised by ___ No commentNo comment

Commit to a written response within Commit to a written response within a given time perioda given time period

Re-establish CredibilityRe-establish Credibility

Evaluate the current state of Evaluate the current state of compliance in light of the FDA compliance in light of the FDA inspectioninspection

Collectively analyze each citationCollectively analyze each citation Review prior FD-483s to determine Review prior FD-483s to determine

if all commitments were indeed metif all commitments were indeed met Note any repeat observationsNote any repeat observations Identify the Root CauseIdentify the Root Cause Relate each issue to the appropriateRelate each issue to the appropriate

Compliance and Quality SystemsCompliance and Quality Systems

Re-establish CredibilityRe-establish Credibility

Develop a corrective action Develop a corrective action plan (CAP) around the plan (CAP) around the entire scopeentire scope

Secure required resources – Secure required resources – financial and personnelfinancial and personnel

Assign responsibilities and Assign responsibilities and accountabilityaccountability

Do not make commitments Do not make commitments that can not be honored.that can not be honored.

Notify FDA of any set backs Notify FDA of any set backs or missed timelinesor missed timelines

Prepare to be ReinspectedPrepare to be Reinspected

Assure that the firm met Assure that the firm met their commitmentstheir commitments

Assure that the resolution Assure that the resolution encompassed the root encompassed the root cause and that it was cause and that it was comprehensivecomprehensive

Monitor warnings to other Monitor warnings to other companies, regulatory companies, regulatory actions, and GMP trendsactions, and GMP trends

Root Cause of the 483Root Cause of the 483

With the FDA’s new systemic approach the FDA wants a systemic review of all your

systems don’t just “fix” the issue, determine the root cause,

evaluate the solution and implement corrective actions

evaluate across the board are there other systems with the same or similar problems

The End?The End?

Any Questions???Any Questions??? www.Compliance-Insight.com 513-860-3512 513-860-3512 Call us for a free consultation Call us for a free consultation