Quality System Deployment in a Clinical Trials Vendor Environment Jeffrey Brandt Quality Assurance Manager Rocky Mountain Poison and Drug Center First Annual Clinical Trial Summit June 4 – June 7 Boston, MA USA

History of Quality Management Systems Guilds of Medieval Europe (13 th Century – 19 th Century) Industrial Revolution –Craftsmanship –Factory System –Taylor System (productivity) More with less Negative effect on quality QC inspection – not root cause Early 20 th Century –Processes Takes input, adds value and provides output 2

History of Quality Management Systems (cont.) First QMS standards – companies supplying the military A famous example: –During WWI and WWII, bullets and bombs would blow up –United Kingdom’s ministry of defense appointed inspectors –Lack of Quality was a safety issue MIL STDs 3

History of Quality Management Systems (cont.) Military found that suppliers (vendors) had inferior quality –Lack of management system –Lack of identification and traceability –Poor record keeping and document control ISO 9000 series of quality management standards –

History of Quality Management Systems (cont.) Manufacturing Quality Management Systems – Manufacturing PRODUCTS (GMPs) Services (call centers, clinical trials vendors) DATA (GCPs) 5

History of Quality Management Systems (cont.) In 2000, ISO standard was rewritten Focused on continuous improvement Measurable objectives Competencies Customer satisfaction Limited documentation of quality procedures Much more service oriented 6

Why a QMS in Clinical Trials Environment? Growing regulatory expectations for a QMS approach to GCP compliance Makes clients comfortable Imperative that vendor partners are inspection ready Quality Assurance of data Continual improvement Internal Audits (Gap Analysis) 7

Why a QMS in Clinical Trials Environment (cont.)? Processes are optimized when best practices are DOCUMENTED Written changes in procedures and policies reduce ambiguity Better understanding = improved service delivery (both quality and efficiency) 8

Effective QMS Attributes Structure and Framework Procedures Processes Dedication of Resources Audit mechanism CAPA system in place Continuous improvement cycle QA vs. QC 9

Organizational Chart (Why?) Foundational Defines responsibilities Outlines the support structure Provides clients visibility of organization Brings value and clarity to your quality system Helpful auditing tool (external and internal) 10

Overview PLAN Establish the objectives and processes necessary. DO Implement the new processes to test possible effects. CHECK Measure the new processes and compare the results against the expected results. ACT Analyze the differences to determine their cause. Determine where to apply changes that will include improvement.

Management Responsibility Quality Policy Document Control System Training System Business Continuity Plan

Management Responsibility Quality Policy Quality Objectives Management Review Resources

Drives business Communicated and understood Suitability Quality Manual –Excerpt from RMPDC’s Quality Policy: Quality Policy The Rocky Mountain Poison and Drug Center will strive to achieve total quality performance by understanding what our Clients service requirements are. This is accomplished through a total quality commitment of our people, involvement of our Sub-Contractors, suppliers and clients…

Document Control System Revision Control Ensure current instructions to staff Review (Annual) –Paper or Electronic

Training System Resources for Training Electronic/Paper/Hybrid Auditable

Business Continuity Disaster Recovery Redundancy Drills –Records (auditable) Back up systems are in place

Business Continuity (cont.)

Do SOPs Work Instructions Train Staff Document Control CAPA System

SOPs What High Level Version Control Auditable Proof of competency

Examples of SOPs in a QMS Quality Manual SOP on SOPs Handling Adverse Events Internal, External and Supplier(Vendor) Audits Training Change Control Data Privacy (Physical and Electronic Safeguards) Deviations, Non-Conformances, and CAPA 21

Work Instructions How Desktop Daily Tasks Detailed

Training of Staff Evaluation of Training needs –Training Matrix Provision of training –LMS or Paper Validated Evaluation of the effectiveness –Competency Exams Documentation of training and/or retraining –Electronic or Paper

Document Control Only most current version of information Paper or electronic Control what needs to be controlled Obsolete previous versions

CAPA Most auditable areas Problem Identified –Remedial corrections of a problem –Root cause analysis –Preventive Action Closeout in timely manner Preventive action to avert recurrence Don’t overburden your CAPA system…..

CAPA VS.

Check Quality Metrics Internal Audits 3 rd Party Audits

Internal Audits Monitor Gap Analysis Process Improvement Management Review Input CAPA system Input

Third Party Audits Client Audits Objective Eyes Review Quality System Learn Something New

Act Management Review Top Management –Inputs Audits Customer Feedback CAPA Changes –Outputs Improve Effectiveness Resources Personnel or Technology

Active process, not passive Continual cycle Leads to process improvement PDCA Recap 31

Jeffrey Brandt, Quality Assurance Manager