Briefing on MHRA routine Briefing on MHRA routine inspection of non-inspection of non-

commercial clinical trialscommercial clinical trials

Routine Good Clinical Practice (GCP) Routine Good Clinical Practice (GCP) MHRA Inspection, University of MHRA Inspection, University of

Aberdeen 2011Aberdeen 2011

AimsAims MHRA inspectionsMHRA inspections MHRA inspection at University of AberdeenMHRA inspection at University of Aberdeen How should staff prepare?How should staff prepare? Advice for staff on key areas of weaknessAdvice for staff on key areas of weakness

So that:So that: You can identify and address any actions requiredYou can identify and address any actions required You can participate in the interviews with confidenceYou can participate in the interviews with confidence University of Aberdeen can demonstrate that clinical University of Aberdeen can demonstrate that clinical

trials are following current legislation and are conducted trials are following current legislation and are conducted to high safety and quality standards. to high safety and quality standards.

Why do the MHRA Inspect?Why do the MHRA Inspect?

EU directive 2001/20/EC transposed into UK law EU directive 2001/20/EC transposed into UK law May 2004 as May 2004 as Medicines for Human Use (Clinical Medicines for Human Use (Clinical Trials) Regulations 2004Trials) Regulations 2004

Legal obligation to conduct Clinical Trials of Legal obligation to conduct Clinical Trials of Investigational Medical Products (CTIMPs) to Good Investigational Medical Products (CTIMPs) to Good Clinical Practice (GCP). Clinical Practice (GCP).

MHRA is statutory body responsible for compliance MHRA is statutory body responsible for compliance with UK regulationswith UK regulations

MHRA inspect (CTIMPs) on humans covered by MHRA inspect (CTIMPs) on humans covered by the regulationsthe regulations

3 Types of MHRA Inspection3 Types of MHRA Inspection

RoutineRoutine

TriggeredTriggered

RequestedRequested

University of Aberdeen inspection is University of Aberdeen inspection is routineroutine Provisionally 4 days week of 20 June 2011Provisionally 4 days week of 20 June 2011

Who do the MHRA inspect?Who do the MHRA inspect?

Legally able to inspect all organisations ‘sponsoring’ or ‘hosting’ clinical trials in the UK

Includes commercial and non-commercial organisations

Adapt inspection to organisation type Routine inspections focus on systems

What do the MHRA inspect?What do the MHRA inspect? University has systems in place to support conduct of CTIMPs in University has systems in place to support conduct of CTIMPs in

compliance with regulations (and GCP). compliance with regulations (and GCP). Specific examples of CTIMPs to demonstrate those systemsSpecific examples of CTIMPs to demonstrate those systems Areas of interest include:Areas of interest include:

Approval processes and regulatory submissionsApproval processes and regulatory submissions Contract ManagementContract Management Trial file and data managementTrial file and data management Quality assurance and monitoringQuality assurance and monitoring TrainingTraining IT systemsIT systems PharmacovigilancePharmacovigilance ArchivingArchiving LaboratoriesLaboratories PharmacyPharmacy

What happens before the inspection?What happens before the inspection?

■ University notified by MHRA of inspection 4University notified by MHRA of inspection 4 thth February 2011February 2011

■ Dossier sent to MHRA on Dossier sent to MHRA on 44thth March 2011 March 2011. Including . Including a list of CTIMPs (live and complete) to give an a list of CTIMPs (live and complete) to give an overview of clinical trial activity. overview of clinical trial activity.

MHRA provide draft agenda approx MHRA provide draft agenda approx 6 weeks 6 weeks prior to prior to the inspectionthe inspection

Teleconference to finalise agenda approx 2 weeks Teleconference to finalise agenda approx 2 weeks prior to inspectionprior to inspection

University will coordinate the inspectionUniversity will coordinate the inspection

What are we doing to prepare?What are we doing to prepare?

MHRA Inspection Internal Working GroupMHRA Inspection Internal Working Group

Gap analysis and action planGap analysis and action plan

Monitoring and AuditMonitoring and Audit

Informing staff of the inspection Informing staff of the inspection

Staff training – GCPStaff training – GCP

What are the key areas of weakness?What are the key areas of weakness?

1.1. Qualifications and trainingQualifications and training

2.2. CommunicationCommunication

3.3. Delegation of dutiesDelegation of duties

4.4. Standard Operating ProceduresStandard Operating Procedures

5.5. Evidencing of informationEvidencing of information

6.6. Study file and filingStudy file and filing

7.7. PharmacovigilancePharmacovigilance

8.8. Informed ConsentInformed Consent

9.9. EquipmentEquipment

10.10. Study closure and archivingStudy closure and archiving

PharmacovigilancePharmacovigilance

Sponsor responsibility to ensure events are Sponsor responsibility to ensure events are reported in accordance with regulations.reported in accordance with regulations.

Currently have central reporting (documented Currently have central reporting (documented in CI delegation letter) .in CI delegation letter) .

New SOP to be issued with updated processNew SOP to be issued with updated process

Monitoring/AuditMonitoring/Audit

Sponsored studies will be audited to ensure Sponsored studies will be audited to ensure that essential documents are present in the that essential documents are present in the Trial Maser File. Trial Maser File.

Training record will be required for trial Training record will be required for trial personnel on a study delegation log. personnel on a study delegation log.

What can you do to prepare?What can you do to prepare?

Handout available with Handout available with recommendations for recommendations for addressing key areas of addressing key areas of weakness. weakness.

SOPs for SOPs for maintaining a Trial maintaining a Trial Master File, Master File, Investigator Site File, Investigator Site File, Pharmacovigilance Pharmacovigilance will be available soon will be available soon

What happens during the inspection?What happens during the inspection?

Opening meeting – inspectors present Opening meeting – inspectors present inspection planinspection plan

Document review – including medical Document review – including medical notesnotes

Interviews with selected staffInterviews with selected staff Tour of facilitiesTour of facilities Additional requestsAdditional requests Closing meeting – summary of findings Closing meeting – summary of findings

and provisional gradingand provisional grading

Interviews with study personnel on Interviews with study personnel on study conductstudy conduct

These assess knowledge of GCP and These assess knowledge of GCP and regulatory requirements, and probe for regulatory requirements, and probe for evidence of robust processes for ensuring evidence of robust processes for ensuring compliance with GCPcompliance with GCP

You should read through the example You should read through the example questions and answers provided. questions and answers provided.

Common Themes During Interview:Common Themes During Interview:

TrainingTraining CommunicationCommunication Safety reportingSafety reporting Protocol procedures & Protocol procedures &

adherenceadherence Investigational medicinal Investigational medicinal

product handlingproduct handling Informed consentInformed consent Approval process Approval process

including amendmentsincluding amendments

Annual reports to Annual reports to ethics/MHRAethics/MHRA

Statistics and data Statistics and data handlinghandling

Out of hours/leave coverOut of hours/leave cover Randomisation & Randomisation & un-un-

blindingblinding procedures procedures End of trial & archiving End of trial & archiving

proceduresprocedures

Dos and Don’ts during InterviewDos and Don’ts during Interview

Be honest - we know we have some gaps and are Be honest - we know we have some gaps and are addressing them - failure to recognize the gaps is addressing them - failure to recognize the gaps is more problematic than acknowledging the gapsmore problematic than acknowledging the gaps

Avoid being confrontational - esp. avoid giving the Avoid being confrontational - esp. avoid giving the impression that this is ‘bureaucratic detail’impression that this is ‘bureaucratic detail’

Be ‘alert’ to areas of improvementBe ‘alert’ to areas of improvement Avoid being defensive.Avoid being defensive.

Dos and Don’ts during InterviewDos and Don’ts during Interview

Only answer the question askedOnly answer the question asked

If mistakes are made or wrong answers given, correct If mistakes are made or wrong answers given, correct them at an appropriate time, or ensure somebody else them at an appropriate time, or ensure somebody else does so.does so.

Try your best to correct any deficiencies noted by the Try your best to correct any deficiencies noted by the inspectors before they leaveinspectors before they leave

Demonstrate confidence in your trial systems and data – Demonstrate confidence in your trial systems and data – you know it best. you know it best. Be positiveBe positive. .

Dos and Don’ts during InterviewDos and Don’ts during Interview

Should inspection findings be made, make sure Should inspection findings be made, make sure that you understand them completely – it is that you understand them completely – it is easier to ask the inspector for clarification during easier to ask the inspector for clarification during the inspection rather than after the report is the inspection rather than after the report is issued.issued.

Don’t volunteer informationDon’t volunteer information

It is appropriate to challenge a finding made by It is appropriate to challenge a finding made by an inspector if you are certain they are incorrect, an inspector if you are certain they are incorrect, but do not persist in your objection. but do not persist in your objection.

What happens after the inspection?What happens after the inspection?

MHRA to report issues within 30 days of the inspection, MHRA to report issues within 30 days of the inspection, summarising findings.summarising findings.

University response will include an action plan, timelines to University response will include an action plan, timelines to address any findings. address any findings.

MHRA receive response - will issue a closing letter and MHRA receive response - will issue a closing letter and GCP Inspection Statement.GCP Inspection Statement.

Future inspections will be performed at a frequency Future inspections will be performed at a frequency determined by the MHRA. determined by the MHRA. Possible routine GCP inspection of NHS GrampianPossible routine GCP inspection of NHS Grampian

SummarySummary

■ Review your trial documentation and training files Review your trial documentation and training files for staff. for staff.

■ Have evidence of training (GCP certificate, CV)Have evidence of training (GCP certificate, CV)■ Ensure you can explain your role in the trialEnsure you can explain your role in the trial

■ Review the typical questions and answers Review the typical questions and answers providedprovided

■ Familiarise yourself with new SOPs when Familiarise yourself with new SOPs when availableavailable

■ Be confident of your trial and processes. Be confident of your trial and processes. Remember that you know your trial better than Remember that you know your trial better than anyone else.anyone else.

Any Questions?Any Questions?

Main Contacts: Main Contacts: Prof Phil Hannaford – p.hannaford@abdn.ac.ukProf Phil Hannaford – p.hannaford@abdn.ac.uk Prof Alison MacLeod – mmd175@abdn.ac.ukProf Alison MacLeod – mmd175@abdn.ac.uk Dr Gail Holland – g.holland@abdn.ac.ukDr Gail Holland – g.holland@abdn.ac.uk

Tel: 01224 - 555076Tel: 01224 - 555076 Lynda Sime – lynda.sime@nhs.netLynda Sime – lynda.sime@nhs.net

Tel: 01224 -554656Tel: 01224 -554656