FOCUSED. TRUSTED. GLOBAL. Who is a Vendor? Anybody contracted or subcontracted to be involved in a clinical trial • Company • Person • Institution • Organisation
FOCUSED. TRUSTED. GLOBAL. Vendors/ Subcontractors Sponsor bound per contract Vendors CRO bound per contract Vendors Subcontractors ? 1. Who holds the contract? 2. Which tasks are delegated?
FOCUSED. TRUSTED. GLOBAL. Regulatory Background Europe (1) Commission Directive 2005/28/EC “GCP Directive” http://ec.europa.eu/health/files/eudralex/vol-1/dir_2005_28/dir_2005_28_en.pdf Chapter 2, THE SPONSOR, Article 7 A sponsor may delegate any or all of his trial-related functions to an individual, a company, an institution or an organization. However, in such cases, the sponsor shall remain responsible for ensuring that the conduct of the trials and the final data generated by those trials comply with Directive 2001/20/EC as well as this Directive.
FOCUSED. TRUSTED. GLOBAL. Regulatory Background Europe (2) European Commission: Eudralex Volume 10 Chapter IV Guidance Documents for Inspections: Annex IV to Guidance for the conduct of GCP Inspections - Sponsor and CRO“ (28 May 2008): http://ec.europa.eu/health/files/eudralex/vol10/chap4/annex_iv_to_guidance_for_the_conduct_of_gcp_inspections- o 2. SPONSOR OR CRO QUALITY SYSTEM INSPECTION o 3. SPECIFIC CLINICAL TRIAL INSPECTION
FOCUSED. TRUSTED. GLOBAL. Regulatory Background Europe (cont 2) 2. SPONSOR OR CRO QUALITY SYSTEM INSPECTION: The aim of this kind of inspection is to evaluate the quality assurance and quality control systems established by the sponsor/CRO in order to assure that clinical trials are conducted and data are generated, recorded and reported in compliance with the protocol, GCP and applicable regulatory requirements. The following items should be reviewed in a sponsor/CRO system inspection: 2.3.8 Sponsor audit and quality assurance system The aim is to determine if the sponsor/CRO has established an audit system, as part of its own quality assurance system, in order to evaluate its activities related to clinical trials. It should be determined if the procedures include: Audits of key clinical trial processes, including monitoring, data management, safety reporting, clinical study report production, archiving and computer system validation activities Audits of contractors/subcontractors
FOCUSED. TRUSTED. GLOBAL. Regulatory Background Europe (cont 2) The inspectors should also review: The processes for communicating and addressing audit findings, including the format and distribution of audit reports The procedures for dealing with serious and/or persistent GCP non- compliance Audit trails Procedures for generation and implementation of audit program(s)/plan(s) 2.3.9 Delegation of duties The aim is to verify the procedures for contracting/subcontracting of trial-related duties. Inspectors should examine the procedures related with: Pre-selection and ongoing assessment of contractor/subcontractors Documentation of duty delegation and its time recording Handling contract amendments Contracts should be reviewed (either specific ones or a sample)
FOCUSED. TRUSTED. GLOBAL. Regulatory Background Europe (cont 2) 3. SPECIFIC CLINICAL TRIAL INSPECTION 3.1 Implementation and termination of the clinical trial The aim is to determine if all legal and administrative aspects of the clinical trial have been accomplished. Review: Distribution of sponsor’s duties or functions …… 3.8 Audit Determine: If the clinical trial was audited and if audit reports exist Qualifications of the auditors
FOCUSED. TRUSTED. GLOBAL. Consequences Sponsor and CRO: • Need a vendor qualification program » Internal vendors „Affiliates“ » External vendors „Subcontractors“ Risk based approach SOPs needed
FOCUSED. TRUSTED. GLOBAL. Risk based Vendor Qualification 1. High risk: Delegation of critical tasks, e.g. - CROs - CMOs - Depots with QP release Audit mandatory o Medium risk: Delegation of routine tasks, e.g. - Courier - Depots without QP release - Translation companies paper based/ audit on case by case basis o Low risk: e.g. - provider of commercially available material paper based o Freelancers
FOCUSED. TRUSTED. GLOBAL. CROs/ Subcontractors Prequalification (paper based) • by means of questionnaire and supporting documents, e.g. » SOP Index » QM Manual » CVs Qualification: Audit mandatory
FOCUSED. TRUSTED. GLOBAL. Depots with and without QP release
FOCUSED. TRUSTED. GLOBAL. Courier Services Courier Service Companies • Qualification by means of questionnaire and supporting documents, e.g. » ISO certificates, index of quality manual, system description » Transport validation
FOCUSED. TRUSTED. GLOBAL. Freelancers Risk based vs. Realistic approach paper based: CV Training records Personal experience audit of local situation: security
FOCUSED. TRUSTED. GLOBAL. Goals? All Key Service Providers should be qualified. Keep a Qualified Vendor List Only Service Providers from the Qualified Vendor List should be chosen Train the operational functions
FOCUSED. TRUSTED. GLOBAL. Process Internal Vendor Qualification Identification of vendors prior to contracts issued Re-Qualification Audits foreseen every 2 years as per SOP includes "experience criteria" Qualification after contracting only in exceptional cases
FOCUSED. TRUSTED. GLOBAL. How can Operations help? Let QA know which Key Service Providers you plan to work with When selecting a vendor check the Qualified Vendor List Use Vendor Audit Request Form for new vendors Provide feedback on experience with vendors
FOCUSED. TRUSTED. GLOBAL. Request a Vendor Audit!
FOCUSED. TRUSTED. GLOBAL. Inspection/ Audit Questions 1. Are SOPs available? 2. Do you use vendors? 3. What kind of vendors? 4. Which are internal and which are external vendors? 5. How do you qualify them? 6. How often do you re-qualify them? 7. Which vendors have been qualified? 8. Why do you also allow paper-based qualification? 9. Can we get insight in the audit reports? 10. Does QA have GCP/ GLP and GMP experience? 11. Do you audit against Task Allocation?