Good Clinical Practice for Clinical Trials - Detailed Guidance - GOV
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21/04/2016 Good clinical practice for clinical trials Detailed guidance GOV.UK https://www.gov.uk/guidance/goodclinicalpracticeforclinicaltrials 1/7 From: First published: Last updated: Part of: GOV.UK Medicines, medical devices and blood regulation and safety (https://www.gov.uk/topic/medicinesmedicaldevicesblood) – guidance Good clinical practice for clinical trials Medicines and Healthcare products Regulatory Agency (https://www.gov.uk/government/organisations/medicinesandhealthcareproductsregulatoryagency) 18 December 2014 24 February 2016, see all updates Good clinical practice: guidance and inspections (https://www.gov.uk/government/collections/goodclinical practiceguidanceandinspections), Good practice, inspections and enforcement (https://www.gov.uk/topic/medicinesmedicaldevicesblood/goodpractice), Medicines, medical devices and blood regulation and safety (https://www.gov.uk/topic/medicinesmedicaldevicesblood) and Patient safety (https://www.gov.uk/government/policies/patientsafety) + others How to show MHRA you're meeting good clinical practice (GCP) standards and what to expect from an inspection. Overview Good clinical practice (GCP) is a set of internationallyrecognised ethical and scientific quality requirements that must be followed when designing, conducting, recording and reporting clinical trials that involve people. Organisations that may have to comply with GCP include: pharmaceutical companies contract research organisations universities NHS hospitals charities GP practices clinical laboratories good laboratory practice Guidance on good clinical practice (http://www.ich.org/products/guidelines/efficacy/efficacysingle/article/good clinicalpractice.html). has been produced by the International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use (ICH). You can also get more information about GCP in the Good Clinical Practice Guide (http://www.tsoshop.co.uk/bookstore.asp?FO=1160007&DI=635071&trackid=000039), produced by MHRA. To ensure compliance with GCP, MHRA: asks trial sites to notify them of serious breaches carries out inspections of trial sites where serious breaches are reported carries out inspections of trial sites that sponsor clinical trials, mostly based on a risk assessment score carries out inspections of sites when companies apply for marketing authorisations
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Good Clinical Practice for Clinical Trials - Detailed Guidance - GOV
Transcript of Good Clinical Practice for Clinical Trials - Detailed Guidance - GOV
21/04/2016 Good clinical practice for clinical trials Detailed guidance GOV.UK
https://www.gov.uk/guidance/goodclinicalpracticeforclinicaltrials 1/7
From:
First published:Last updated:Part of:
GOV.UK Medicines, medical devices and blood regulation and safety(https://www.gov.uk/topic/medicinesmedicaldevicesblood) – guidanceGood clinical practice for clinical trials
Medicines and Healthcare products Regulatory Agency(https://www.gov.uk/government/organisations/medicinesandhealthcareproductsregulatoryagency)18 December 201424 February 2016, see all updatesGood clinical practice: guidance and inspections (https://www.gov.uk/government/collections/goodclinicalpracticeguidanceandinspections), Good practice, inspections and enforcement(https://www.gov.uk/topic/medicinesmedicaldevicesblood/goodpractice), Medicines, medical devices and bloodregulation and safety (https://www.gov.uk/topic/medicinesmedicaldevicesblood) and Patient safety(https://www.gov.uk/government/policies/patientsafety) + others
How to show MHRA you're meeting good clinical practice (GCP) standards and what to expect from aninspection.
OverviewGood clinical practice (GCP) is a set of internationallyrecognised ethical and scientific quality requirementsthat must be followed when designing, conducting, recording and reporting clinical trials that involve people.
Organisations that may have to comply with GCP include:
pharmaceutical companiescontract research organisationsuniversitiesNHS hospitalscharitiesGP practicesclinical laboratories good laboratory practice
Guidance on good clinical practice (http://www.ich.org/products/guidelines/efficacy/efficacysingle/article/goodclinicalpractice.html). has been produced by the International conference on harmonisation of technicalrequirements for registration of pharmaceuticals for human use (ICH).
You can also get more information about GCP in the Good Clinical Practice Guide(http://www.tsoshop.co.uk/bookstore.asp?FO=1160007&DI=635071&trackid=000039), produced by MHRA.
To ensure compliance with GCP, MHRA:
asks trial sites to notify them of serious breachescarries out inspections of trial sites where serious breaches are reportedcarries out inspections of trial sites that sponsor clinical trials, mostly based on a risk assessment scorecarries out inspections of sites when companies apply for marketing authorisations
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Report a serious breachYou must notify MHRA of serious breaches of GCP or the trial protocol. See Guidance for the notification ofserious breaches of GCP or the trial protocol(https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/404588/GCP_serious_breaches_guide.pdf) (PDF, 153KB, 14 pages) .
Complete the notification of serious breaches of GCP or the trial protocol form(https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/275216/Notification_of_serious_breaches_of_GCP_or_the_trial_protocol_form__1_.doc) (MS Word Document, 227KB) and send it [email protected]
See the annual summary of MHRA GCP referrals (https://www.gov.uk/government/statistics/annualreviewofgoodclinicalpracticereferrals2011and2012).
Triggered inspections for serious breachesMHRA may contact you to arrange an inspection if they suspect the law has been broken. This informationmight come from:
a serious breach notificationa whistleblowerother MHRA departmentsthe health research authority (HRA)
In rare circumstances, MHRA may give little or no notice of these inspections.
Inspections under the riskbased compliance programmeThe majority of MHRA GCP inspections are carried out under the riskbased compliance programme. Thesecan be either systemsbased or trial specific.
GCP systems inspections examine the systems used by your organisation to conduct clinical trial research.The inspectors will select a number of your clinical trials to examine how your organisation’s trial proceduresare applied. One or two investigator sites involved in the selected trials may also be inspected.
Trialspecific GCP inspections assess clinical trials that have been completed and reported.
Currently phase I units that are part of the phase I accreditation scheme (https://www.gov.uk/guidance/mhraphaseiaccreditationscheme) are not part of the riskbased programme but they are inspected every 2 years.
The riskbased compliance programme uses information available to MHRA to determine an organisation’srisk. This information includes:
internal information about previous inspection historyorganisational changes
Each organisation is given a risk assessment score and inspections are prioritised for the organisations withthe highest risk assessment score.
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This will be used with the output from the inspectorate riskbased progamme. A small number of theorganisations in the medium and lowrisk categories will be randomly selected for routine riskbasedinspections.
See the flowchart of the inspection process(https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/420781/GCPflowchart.pdf) (PDF,92.8KB, 1 page) .
Compliance report requirements
There have been updates to requirements for completing a compliance report in 2016.
Over the last seven years the MHRA GCP Inspectorate has requested organisations involved in the conductof clinical trials to complete and submit GCP compliance reports. We have used the data provided in thesereports to support our inspection scheduling and planning activities. In addition, we have used the reports toenhance the information that we maintain on our inspection universe by looking at the numbers and types oftrials that have been conducted by the various clinical trials organisations operating in the UK.
As of 2016, we no longer require routine compliance reports to be submitted unless your organisation isspecifically requested to provide information in relation to the number and/or types of trials being undertaken.You will be contacted directly by the GCP Inspectorate should this information be required (as someorganisations have been already). We would like to take this opportunity to thank you for the information thathas been provided to date.
Preinspection documentationYou will be notified if your organisation is chosen for inspection under the routine riskbased inspectionprogramme.
The notification includes a request for information, in the form of a GCP inspection dossier and a clinical trialsspreadsheet to MHRA within 30 days.
This dossier should include:
a list of clinical trialsorganisation chartsstandard operating procedure (SOP) listscontact detailsoverview of facilitiesservice providersclinical trials activities
Use the GCP inspection dossier template(https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/269334/GCP_inspection_dossier.doc)(MS Word Document, 416KB) and the GCP inspection dossier clinical trial spreadsheet(https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/269336/Clinical_trial_spreadsheet_for_GCP_inspection_dossier.xls) (MS Excel Spreadsheet, 110KB) to help you prepare your dossier. Use the GCP
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inspection dossier checklist(https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/269335/GCP_inspection_dossier_checklist.doc) (MS Word Document, 352KB) to ensure your dossier is complete.
MHRA will agree an inspection date and give you information on the inspection team and the practicallogistical aspects of the inspection.
Occasionally, after reviewing the dossier, the lead inspector may decide not to proceed with the inspection.
The trial master file (TMF)A number of clinical trials are usually selected for Trial Master File (TMF) review, although the inspection maynot be limited to these.
The complete TMF is the basis for inspection and all the documents in it must be made available to theinspectors. This includes any electronic documents and emails. You’ll need to provide any equipment andsoftware needed to access any electronic documents.
You can discuss with the lead inspector beforehand on how to make the TMF available during the inspection.
If you are a sponsor and have subcontracted some activities to a contract research organisation (CRO), thenyou will have to provide the TMF and/or other documents.
If you have problems meeting these requirements, you should tell the lead inspector before the inspection.
Failure to provide the TMF can affect the results of your inspection.
Inspections
The inspection planThe inspection plan is based on discussions with you and the information provided in your GCP inspectiondossier, to ensure all activities are covered. Appropriate people should be available for interview either inperson or by teleconference.
Additional supporting documentation such as line listings, database extracts, floor plans etc. might beneeded. All documentation requested should be provided within the time agreed with the lead inspector.
Inspectors will be flexible with the inspection plan to accommodate working patterns of individuals andimmediate issues if they arise.
An inspection plan will be given to you in advance and any comments or questions relating to it can bediscussed with the lead inspector.
During the inspectionThe inspection includes interviews with relevant people and a review of the documentation, such as the TMF.The inspector may visit:
data management unitsarchives
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pharmacylaboratories
You should be prepared to provide additional documentation to the inspectors on request.
Inspection findingsAt the end of the inspection the inspector will give you a verbal summary of the inspection findings and allowyou the opportunity to correct any misunderstandings.The grading of the findings are provisional and may bechanged by the inspector for the report.
Grading of inspections findingsDeficiencies found during inspections are graded at 3 levels critical, major and other.
The inspection reportThe inspection report is emailed to you. You must respond to the report, see Guidance for formulatingresponses to GCP inspection findings(https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/269339/Guidance_for_formulating_responses_to_GCP_inspection_findings.pdf) (PDF, 42.4KB, 4 pages) . Your organisation must provide a response tothe inspection report in the form of a corrective action and preventative action (CAPA) plan. For someinspections, you may need to provide periodic reports on the progress of proposed CAPA actions.
The lead inspector may ask you for additional clarification from the responses you provided. Usually, you willbe given one opportunity to provide additional information or clarification.
Once adequate responses are received, a GCP inspection statement will be issued to you by email.
Information from previous MHRA inspections.
Fees for GCP inspectionsFees for inspections (https://www.gov.uk/government/publications/mhrafees/currentmhrafees#inspectionfees)
Make payment to MHRA (https://www.gov.uk/makeapaymenttomhra)
Feedback from GCP inspectionsMHRA GCP inspectorate sent surveys to get feedback from inspected organisations and investigators.Organisations and investigators were asked to score their response to questions on the inspection process.
To help you understand the areas where GCP inspectors have found compliance problems during GCPinspections in the UK, the GCP inspectorate produces metrics reports(https://www.gov.uk/government/statistics/goodclinicalpracticeinspectionmetrics2007topresent).
GCP discussion forum
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MHRA GCP forum MHRA GCP forum (http://forums.mhra.gov.uk/forumdisplay.php?1GoodClinicalPractice(GCP)) can help you comply with the clinical trials regulations and GCP requirements by. The forum gives youan opportunity to discuss clinical trials and GCP requirements with other researchers.
European and UK law and for GCPYou can find the European Union directives, GCP and other guidance in Volume 10 of the rules governingmedicinal products in the European Union (http://ec.europa.eu/health/documents/eudralex/vol10/)
The key UK legislation and guidance which covers GCP inspections includes:
The Medicines for Human Use (Clinical Trials) Regulations 2004(http://www.legislation.gov.uk/uksi/2004/1031/contents/made)The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006(http://www.legislation.gov.uk/uksi/2006/1928/pdfs/uksi_20061928_en.pdf)The Medicines(Advisory Bodies)(No. 2)Regulations 2005(http://www.legislation.gov.uk/uksi/2005/2754/pdfs/uksi_20052754_en.pdf)The Medicines for Human Use (Clinical Trials) Amendment (No.2) Regulations 2006(http://www.legislation.gov.uk/uksi/2005/2759/pdfs/uksi_20052759_en.pdf)The Medicines for Human Use (Clinical Trials) Amendment (No.2) Regulations 2006(http://www.legislation.gov.uk/uksi/2006/2984/pdfs/uksi_20062984_en.pdf)The Pharmacists and Pharmacy Technicians Order 2007(http://www.legislation.gov.uk/uksi/2007/289/pdfs/uksi_20070289_en.pdf)The Medicines for Human Use (Clinical Trials) and Blood Safety and Quality (Amendment) Regulations2008 (http://www.legislation.gov.uk/uksi/2008/941/contents/made)The Medicines for Human Use (Miscellaneous Amendments) Regulations 2009(http://www.legislation.gov.uk/uksi/2009/1164/contents/made)The Medicines for Human Use (Advanced Therapy Medicinal Products and MiscellaneousAmendments) Regulations 2010 (http://www.legislation.gov.uk/uksi/2010/1882/contents/made)MHRA’s guidance for clinical trial sponsors and host organisations on electronic health records(https://www.gov.uk/government/publications/clinicaltrialshownhstrustsandhealthboardscanmaintaincompliantelectronichealthrecordsystems)
ContactFor further information on GCP inspections, email [email protected] or [email protected]
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