Multi - Site Studies Non-Clinical Multi-Site studies and GLPqualitynano.eu/uploads/QNano_Knowledge_Hub/GLP2012/15 Multi Site... · Multi - Site Studies •Multi Site Study: One where

Multi - Site Studies

Non-Clinical

Multi-Site studies

and GLP


•Multi Site Study: One where phases are conducted on more than one site

•Phase : A defined activity or set of activities

•Test Facility : Location of Study Director

•Test Site : Location of other phases


Principles

• Separation of phases from Test Facility • Geographical

• Organisational

• Single study • One protocol

• One report

• One Study Director

• One PI for each test site

• Planning

• Communication


SPONSOR

TEST FACILITY

TEST SITE TEST SITE

TEST SITE


• Sponsor • Management

• Monitor

• Test Facility • Management

• Study Director

• QA

• Test Site(s) • Management

• Principal Investigator

• QA


• Management - Test Facility: • Appoint SD

• Approve Test Sites (including rationale if not part of National GLP programme)

• Facilitate good communications

• Designate “lead QA site”

• Management - Test Site • Provide resource

• Selection of Principal Investigator

• Replacement of PI if necessary


• Study Director: • Ensure sites are acceptable (how?)

• Authorize protocol including contributions from PIs

• Establish good communications

• Liaise with PI on all aspects including QA

• Include PI contributions in report

• Sign Compliance Statement for whole study


• Principal Investigator • Act on behalf of SD for phase of study

• Agree to GLP principles

• Report deviations from protocol or SOPs to

• Provide report sections

• Provide written assurance of GLP compliance for phase

• Archive data and specimens as protocol


• QA - “Lead Site”:

• Liaise with test site QA to ensure coverage

• Pay attention to operation and documentation of interfaces and communication

• Ensure protocol checked and final report reviewed

• Prepare QA statement


• QA - “Test Site”: • Review section of protocol relevant to

test site activities

• Inspect work carried out

• Review PIs contribution to report

• Prepare QA statement relative to their activities


AUDIT FEEDBACK

TEST FACILITY

Management

Study Director QA

Principal Investigator QA

Management

TEST SITE


• Protocol • Should identify PI and test sites and phases

carried out

• How data generated at test sites will be included in report

• Where data/specs are archived

• Should be available to test sites/PIs and staff


• Report • One report for study

• Include PI contribution

• Include evidence of QA involvement

• Archive location

• Indicate degree of GLP compliance of all phases


• SOPs should be established to: • Cover select and monitoring of test sites • Appointment and replacement of PIs • Transfer of data and samples - Chain of

Custody • QA reporting and action procedures • Verification of Translation of test facility

SOPs if required

• Test sites will normally have their own SOPs

• If Test Facility’s SOPs are used by test site, updates should also be circulated


• Practical issues

• Communication

• Understanding responsibilities

• Assessment of test sites

• Monitoring and reporting of findings

• Chain of Custody of samples and specimens


Contracting work out


• Referring to studies conducted by another party - e.g. contract laboratory

• Each party has responsibilities

• Sponsor : Contract Placer

• Laboratory : Contractee


• Sponsor should • Understand GLP responsibilities

• Must be sure that test facility can carry out work to GLP

• Responsible for integrity of submitted package of work

Multi - Site Studies Sponsor has explicit and implicit responsibilities

•Explicit • Inform Test Facility that work must comply

with GLP

• Ensure mechanism to identify test item

• Approve protocol (in many countries)

• Identified in protocol

• Identified in report

• Take on archiving responsibility if test facility discontinues operation


Sponsor has explicit and implicit responsibilities

•Implicit • Inform test facility of safety issues

• If responsible for test item characterisation carry out to standards required (eg GLP, GCP, GMP, GCLP, QPBR…..)

• Assure themselves of GLP compliance and scientific reliability

NB it remains the responsibility of the SD to ensure GLP compliance

Multi - Site Studies Contractor has responsibilities for

• Maintaining proper resources facilities / equipment/staff (qualifications & training)

• Ensuring materials received are suitable

• Informing contract giver of problems or deviations.

• Not passing to a third party work entrusted to him under contract.

• Refraining from any activity likely to have adverse effect on quality of product / service.

• Conducting and reporting work to GLP

.

Multi - Site Studies How does Sponsor fulfil responsibilities and maintain assurance?

•Communication and documentation • Correspondence

• Records of meetings

• Contract

•Give assurance

• Before study

• During study

• At reporting

.


Before placing contract

• Ask Around • National QA Societies • Company Brochures • National Compliance status,

Certification / Accreditation • Questionnaire • Initial Site Visit


Initial Site Visit before placing contract

Purpose • To gain confidence in lab • To confirm capabilities - scientific and GLP • To establish communication

• Who? • Monitor • Key scientists? • QAU


Initial Site Visit before placing contract

Items to review (GLP)

• Organisational structure • C.V., Training records of some key persons (

QA, Study Director ) • Talk to key staff • Facility audit ( select key areas ) • Look at typical SOPs, maintenance logs • Ask about any past inspections • Careful examination of QA activities

Monitor assures scientific capabilities/resources


Items to include in contract?

• Standard work will be performed to

• Specifications of any supplied materials

• Contract giver has right to inspect at any time

• Contract giver has right to see data, QA / QC reports, etc

• Specify what changes (if any) may be made without contract giver's consent

• No work to be subcontracted without contract giver's consent

• Inform contract giver of adverse inspections


Other items to agree?

• Communication

• Frequency

• Medium

• Reports ; progress - formal

• Who to/between?


Periodic Inspections during study • Who? Monitor (scientific issues) and/or QA*

• Purpose? To assure maintenance of quality

• What to look for? • Confirm that raw data exists including specimens

• Ask to see where " your data " are archived

• Ask to see documents relating to receipt / storage of test item

• Review QA activities

• Go to where your work was / is being conducted

• Request to see retention samples of your compound

• On rotating basis select zones for more in depth audits

*Supplement but try not to duplicate activities*


Report Issues (GLP)

• Purpose: To assure QA review has been effective • May not have raw data so often review for

internal consistency

• Confirm issues raised during study have been addressed

• Confirm information supplied by Sponsor is correct


Contract situation works best if true partnership with trust and openness

on both sides

Multi - Site Studies Non-Clinical Multi-Site studies and GLPqualitynano.eu/uploads/QNano_Knowledge_Hub/GLP2012/15 Multi Site... · Multi - Site Studies •Multi Site Study: One where

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