Quality Assurance : Quality Assurance : Audit & InspectionAudit & Inspection

Prashanth Babu. MPrashanth Babu. M

Principal ConsultantPrincipal Consultant

Topics to be discussedTopics to be discussed

• Why do we need quality assurance ?Why do we need quality assurance ?

• Who should be involved in the QA process ?Who should be involved in the QA process ?

• Audit & InspectionAudit & Inspection

• How to prepare for an audit ?How to prepare for an audit ?

Quality Assurance is mentioned Quality Assurance is mentioned in ICH-GCPin ICH-GCP

• Chapter 5 : Sponsor Chapter 5 : Sponsor

• Section 5.1 Quality assurance & quality controlSection 5.1 Quality assurance & quality control

• ‘‘The sponsor is The sponsor is responsibleresponsible for implementing & for implementing &

maintaining quality assurance & quality control maintaining quality assurance & quality control

systems with systems with written SOPswritten SOPs to ensure that trials to ensure that trials

are are conductedconducted & & data are generateddata are generated, ,

documented (recorded)documented (recorded) in compliance with in compliance with

protocolprotocol, , GCP GCP & & applicable regulatory applicable regulatory

requirement(s)requirement(s) ICH GCP 1997ICH GCP 1997

Quality Assurance is Quality Assurance is responsibility responsibility of sponsorof sponsor • ‘‘The sponsor is responsible for The sponsor is responsible for securing securing

agreementagreement from from all involved partiesall involved parties to to

ensure ensure direct accessdirect access to all to all trial related sitestrial related sites, ,

source data/ documentssource data/ documents & & reportsreports for the for the

purpose of purpose of monitoring monitoring & & auditingauditing by the by the

sponsor & sponsor & inspectioninspection by domestic & foreign by domestic & foreign

regulatory authorities’regulatory authorities’ ICH GCP 1997ICH GCP 1997

Who should be involved in QA Who should be involved in QA processprocess

Quality of the studyQuality of the study

Investigators/ team Investigators/ team SponsorSponsor

Ethics CommitteeEthics Committee

InstitutionInstitution

Health AuthorityHealth Authority

Monitor/ study Monitor/ study operation teamoperation team

Biometrics teamBiometrics team

Patients Patients

QA teamQA team

The Quality Assurance Procedure ?The Quality Assurance Procedure ?

• Audit Audit

• The iThe independent,ndependent, systematic systematic action to action to

ensure the quality of study, data generated, ensure the quality of study, data generated,

is accurate, reliable, patient’s safety and is accurate, reliable, patient’s safety and

right is protected and followed right is protected and followed GCP, GCP, SOPsSOPs & &

applicable regulationsapplicable regulations in the country in the country

ICH-GCP 1997

InspectionInspection

• The act by a The act by a regulatory authority(ies)regulatory authority(ies) of of

conducting an official review of conducting an official review of documentsdocuments, ,

facilitiesfacilities, , recordsrecords and and any other resourcesany other resources

that are deemed by the authority(ies) to be that are deemed by the authority(ies) to be

related to the clinical trial and that may be related to the clinical trial and that may be

located located at the site of theat the site of the trialtrial,, at the at the

sponsor’ssponsor’s and/ or CRO’s facilitiesand/ or CRO’s facilities or at other or at other

establishments deemed appropriate by the establishments deemed appropriate by the

regulatory authority(ies)regulatory authority(ies)ICH-GCP 1997 ICH-GCP 1997

Why do the authority inspect ?Why do the authority inspect ?

• Support regulatory authority decisionSupport regulatory authority decision

Base uponBase upon

– SafetySafety

– Validity of dataValidity of data

– Regulatory complianceRegulatory compliance

– Subject’s right protectionSubject’s right protection

– Law enforcementLaw enforcement

• When the data from the trial will be used for When the data from the trial will be used for

authority approvalauthority approval

How to Prepare for AuditHow to Prepare for Audit

What are the areas concerned by What are the areas concerned by auditorauditor

Patient’s safety Patient’s safety

• Has the study approved Has the study approved

• Did patient agree to join Did patient agree to join the studythe study

• Does the investigator Does the investigator follow protocolfollow protocol

• Does the investigator Does the investigator report the adverse event report the adverse event (on time) (on time)

• Does Ethics Committee Does Ethics Committee be informed on safetybe informed on safety

• Does the patient be Does the patient be informed on new informed on new informationinformation

Study credibility Study credibility

• Does the patient exist Does the patient exist

• How can we ensure that How can we ensure that

the procedure is followedthe procedure is followed

• Human, machine variationHuman, machine variation

• We have to document all We have to document all

the activity the activity

• Does the facilities meet Does the facilities meet

the standardthe standard

• How can we ensure the How can we ensure the

equipment work properlyequipment work properly

Preparation for AuditPreparation for Audit

• Should start from the beginning of the studyShould start from the beginning of the study

• Ensure that we have the documents to prove Ensure that we have the documents to prove that study has been conducted properlythat study has been conducted properly– According to ICH-GCP, Local regulation, Institution According to ICH-GCP, Local regulation, Institution

SOPSOP

• All party understand the protocol, procedureAll party understand the protocol, procedure

• Any concern raised by any party should be Any concern raised by any party should be documenteddocumented

• Aware of the chronology of the event, version Aware of the chronology of the event, version of documentsof documents

Essential Documents (1)Essential Documents (1)

• Study protocol, Study protocol, patient information sheet,patient information sheet, informed informed

consent,consent, questionnaire,questionnaire, investigator brochureinvestigator brochure etc. etc.

– Version, date submitted, approved, implementedVersion, date submitted, approved, implemented

• Safety report : AE, SAE, SUSARSafety report : AE, SAE, SUSAR

– Submitted to EC, FDASubmitted to EC, FDA

• Agreements : clinical, financialAgreements : clinical, financial

• Study personnel : CV, authorised letter, sample of Study personnel : CV, authorised letter, sample of

signaturesignature

• Enrollment logEnrollment log

• CorrespondenceCorrespondence

Essential Documents (II)Essential Documents (II)

• Case record form : CRFCase record form : CRF

– Signed & dated informed consent Signed & dated informed consent

– Completeness of CRFCompleteness of CRF

– Investigator signed & dated in the assigned pagesInvestigator signed & dated in the assigned pages

– Accuracy of data compared with source dataAccuracy of data compared with source data

– Black ball point pen Black ball point pen

– Logical date according to protocol !Logical date according to protocol !

– Source data has to be availableSource data has to be available

Essential Documents (III)Essential Documents (III)

• Source dataSource data

– Patient note (OPD card) : should document the Patient note (OPD card) : should document the

information required by the protocol (monitor can information required by the protocol (monitor can

prepare the check list page & attach to the OPD prepare the check list page & attach to the OPD

card)card)

– Other documents : lab test, ECG, X-rays, CT scan, Other documents : lab test, ECG, X-rays, CT scan,

– Translator is required in case local language is Translator is required in case local language is

not English (FDA inspection might ask for an not English (FDA inspection might ask for an

independent translator)independent translator)

Essential Documents (IV)Essential Documents (IV)

• Standardisation, maintenance of equipmentStandardisation, maintenance of equipment

– Document to prove that all procedure is followedDocument to prove that all procedure is followed

• Logistics, accountability of the test kits, study Logistics, accountability of the test kits, study

medicationmedication

– Temperature controlled requiredTemperature controlled required

• Study personnel who operate the machineStudy personnel who operate the machine

– Well trained; training record, CVWell trained; training record, CV

• Sample handling procedure Sample handling procedure

– Tissue block, blood, serum, etcTissue block, blood, serum, etc

Major MistakesMajor Mistakes

• Misconduct of the studyMisconduct of the study

– Study not being approvedStudy not being approved

– Major protocol violationMajor protocol violation

– Patient safety : SAEPatient safety : SAE

– Fraud dataFraud data

• Cause loss of reputation of investigator/ Cause loss of reputation of investigator/

instituteinstitute

• Loss of reputation of sponsorLoss of reputation of sponsor

• Withdrawal, termination of product licenseWithdrawal, termination of product license

Problems/ MistakesProblems/ Mistakes

Things to be rememberedThings to be remembered

• Problems/ mistakes are common thingsProblems/ mistakes are common things

• Auditor’s job is to find mistake !Auditor’s job is to find mistake !

• Don’t arrange or make up, he/she will find Don’t arrange or make up, he/she will find

anywayanyway

• Too good to be true when everything is perfectToo good to be true when everything is perfect

• As long as the mistake is minor & acceptableAs long as the mistake is minor & acceptable

What needs to be done to prevent What needs to be done to prevent mistakemistake

• Understands the principle of GCPUnderstands the principle of GCP– Patient safetyPatient safety– Data validityData validity

• Proactive approachProactive approach– Foresee the problems might happenForesee the problems might happen

• Good communication with monitorGood communication with monitor– Inform monitor if there is anything unclearInform monitor if there is anything unclear

• Positive attitudePositive attitude– Mistake does happen, nothing to hideMistake does happen, nothing to hide

SummarySummary

• QA is the key responsibility of sponsorQA is the key responsibility of sponsor

• QA involved all parties in the clinical studyQA involved all parties in the clinical study

• QA should be started from the beginning of the QA should be started from the beginning of the

study (planning process)study (planning process)

• QA should be placed in every step of the studyQA should be placed in every step of the study

• Standard should be defined & comply to GCP/ Standard should be defined & comply to GCP/

regulationregulation

• QA can not be achieved without the cooperation QA can not be achieved without the cooperation

of all partiesof all parties

Thank you for your attentionThank you for your attention

Any questions ????????????Any questions ????????????