QUALITY: ADDING VALUE Marian Mutch MSc. Director Global QA Covance
Agenda History of Covance Central Laboratory Services, CLS What is ISO 15189? Why adopt ISO 15189 in an organisation that is already following GCP & College of American Pathologists, CAP, Laboratory Accreditation Program, LAP ISO 15189 implementation strategy How has Quality added value in a regulated environment case study Data analysis driving action to improve quality 2 Quality: Adding Value November 2016
Covance Overview DISCOVERY DEVELOPMENT COMMERCIALIZATION Research Preclinical Phase l Phase ll Phase lll Phase lv Discovery, Lead Optimization, Research Models Toxicology and Safety Pharmacology Bioanalytical and DMPK Biomarkers Solutions Clinical Pharmacology Clinical Development Central Laboratory Market Access Covance generates more drug development data for the regulatory evaluation of efficacy and safety than any other company in the world 3 Quality: Adding Value November 2016
Covance Central Laboratory Services Indianapolis, Indiana Tokyo, Japan Geneva, Switzerland Shanghai, China Singapore Indianapolis 1986 Geneva 1992 Singapore 2000 Shanghai 2007 Tokyo 2010 4 Quality: Adding Value November 2016
Sample Volume Covance Central Laboratory Services handled more than 14 million samples in 2015 49 of 50 5 Quality: Adding Value November 2016 best-selling products of 2014 were developed in partnership with CLS
What is ISO 15189? Based on ISO 17025 General Requirements for the Competence of Testing and Calibration Laboratories and ISO 9001 Quality Management Systems ISO 15189 applicable to medical laboratories providing Advice to users of the laboratory services Collection of patient samples Interpretation of test results Acceptable turnaround times Lab's role in the education and training of staff Guidance on how to assess your organisation s competency 6 Quality: Adding Value November 2016
What are the Benefits of ISO 15189? Takes into consideration specific requirements of the medical environment and the importance of the medical laboratory to patient care Focus on sustainable quality management processes in all areas of an organisation interacting with laboratory CAP LAP and ISO 15189 complement one another Balances the assurance of accurate patient diagnosis through technical requirements of CAP LAP and confidence in the organisation s QMS ISO 15189 Continuous improvement! Continuous improvement! Continuous improvement! 7 Quality: Adding Value November 2016
Why Adopt ISO 15189? Global organisation Testing specimens for clinical trials Developing custom assays Quality standards followed College of American Pathologists, Laboratory Accreditation Program (CAP LAP) Good Clinical Practice (GCP) Increasing requests to follow international standards: International Organisation for Standardisation (ISO) ISO 15189 Medical Laboratories Requirements for Quality and Competence ISO 15189 journey started in 2010 8 Quality: Adding Value November 2016
ISO 15189 Implementation Strategy Selection of accreditation body Generally independent National Bodies Global CLS presence meant a number of accreditation bodies were available Consistency in approach Assigned a Global Project Lead to manage the global implementation strategy 9 Quality: Adding Value November 2016
ISO 15189 Implementation Strategy Key Activities Project Charter Gap analysis of QMS Manual & global SOPs against the standard Accessibility of tools & documentation Implement structure & procedure for departmental Management Review meetings Assess appropriateness of Quality Cost Delivery metrics Communication plan Training plan Training and Awareness Strategy Purchased ISO 15189 training modules Developed in house ISO 15189 training modules Considered audience specific training content QMS logo contest Developed QMS: Newsletters Posters Table placards Communication Strategy Socialisation Awareness Visibility The Journey Value of another quality standard Buy-in Celebration of successes Communicate, communicate, communicate Maintaining Momentum Each inspection is an opportunity to improve Continuous review and development of training modules Communication of improvement opportunities Awareness of quality indicators and standards Awareness of impact on quality indicators and services Process to collect employee feedback 10 Quality: Adding Value November 2016
How has Quality Added Value? ISO 15189 drives continuous improvement Quality data analysis and trending Management review meetings driving actions to improve quality A process where data and reviews drive discussion and a culture of improvement 11 Quality: Adding Value November 2016
Case Study IMPLEMENTING RISK-BASED CAPA AND EFFECTIVENESS CHECKS USING CO 2 QUALITY CONTROL FAILURE Background Management Review meeting identified that significant number of quality issues were related to QC failures for bicarbonate (CO 2 ) tested in AutoChem laboratory Prompted further investigation on QC failures resulting from CO 2 issues 12 Quality: Adding Value November 2016
Case Study Root cause analysis using Cause-Effect Analysis diagram Materials Dry ice used for sample preservation. CO 2 released in the lab environment Why CO 2 accumulated and did not go away? The SD/CV used to evaluate the acceptability of QC results is too stringent What is the industry standard? Measurements Specimen exposed to CO 2 in the environment How much is the CO 2 level? How to protect specimens? Mother Nature (Environment) Larger number of specimens analysed at one go cause long run times. Uncapped specimens exposed to environment for too long Methods Manpower (People) Humans release CO 2 when breathing HVAC system not able to remove CO 2 accumulated in the lab Is air exchange rate sufficient? Is air recycling back to the lab? Is air ventilation shared? Machines CO 2 QC Failures 13 Quality: Adding Value November 2016
Case Study CO 2 levels mapped in the laboratory areas as a base reference High CO 2 levels observed in pre-analytical area. Top 5 8 4 contributors were identified as; 7 6 3 2 1 Dry ice used in pre-analytical area Shared ventilation with other areas where lots of dry ice used HVAC system not coping 1 2 3 3100 ppm 3225 ppm 2775 ppm 5 6 7 975 ppm 875 ppm 875 ppm Specimens exposed to CO 2 before, during and after testing causing QC failures 4 2825 ppm 8 875 ppm 14 Quality: Adding Value November 2016
Case Study CAPA Plan created to address the top contributing factors by; Removing CO 2 contamination at source Limiting CO 2 exposure to specimens Solutions identified in four main areas; Facilities Pre-analytical Analytical Post-analytical 15 Quality: Adding Value November 2016
Case Study Facilities Action & Control Autochem area walled off creating a positive pressure environment to control the CO 2 levels coming into the lab HVAC replaced with a more powerful unit CO 2 monitored via three wall sensors in the lab linked to software that automatically regulates the HVAC power according to levels detected Boxplot of CO2 level at Box Opening Boxplot of Covance AC rdg-before, Covance AC rdg-after 8000 2000 7000 1750 6000 5000 1500 Data 4000 Data 1250 3000 1000 2000 750 1000 500 0 Before After Covance AC rdg-before Covance AC rdg-after 16
Case Study PRE-ANALYTICAL SOLUTION Dry ice removed from area Decapping automation introduced to allow uncapping of specimen container directly before testing Specimens wrapped with parafilm if not immediately tested following decapping 17 Quality: Adding Value November 2016
Case Study ANALYTICAL SOLUTION Input/output queues to the instrument closed to eliminate airflow over the specimens Specimens tested in smaller batches Increased the frequency of QC runs to help trend the assays performance Close monitoring of QC trending to allow action to be taken before CO 2 QC failures occur 18 Quality: Adding Value November 2016
Case Study POST ANALYTICAL SOLUTION Specimens are parafilmed immediately after testing as they await automated recapping Robust spot check process in place in the event of a QC failure in order to assess the impact to the data 19 Quality: Adding Value November 2016
Case Study EFFECTIVENESS CHECK Purpose was to verify if the CAPA plan was addressing the root cause of the CO 2 QC failures The CO 2 QC performance trending data was collected at three levels over a six-month period of time Three months before the CAPA implementation Three months after the CAPA implementation 20 Quality: Adding Value November 2016
Case Study EFFECTIVENESS CHECK POST CAPA IMPLEMENTATION The trending showed that the CO 2 QC failure rate had reduced significantly QC warning rates had reduced from 12.06% to 5.93% QC rejection rate had decreased from 2.40% to 1.29% Conclusion: CAPA plan implemented reduced the CO 2 QC failure issue effectively 21 Quality: Adding Value November 2016
Case Study Summary Quality issues in a Central Laboratory can cause delays in releasing the clinical data to investigators CAPA is a risk mitigating approach, which fulfills the promise of continuous improvement Quality issues are a source of input to CAPA programmes CAPA risk definition, provides the means for rationalising the scope and extent of the investigation and actions necessary to mitigate the risk CAPA tracking, review and monitoring of actions to mitigate the risk to ensure closure Effectiveness checks help to ensure actions are effective and did not introduce new risks Risk and science-based CAPA and effectiveness checks help to prevent reoccurrence of quality issues 22 Quality: Adding Value November 2016
Summary Indianapolis, Indiana, USA Kawagoe, Japan Shanghai, China Singapore Geneva, Switzerland Benefits of implementing a voluntary international standard, ISO 15189 Implementation in a GCP, CAP LAP environment globally Analysing and trending data in a way that drives action and improves quality Reduces risk Drives a culture of continuous improvement Journey that continues 23 Quality: Adding Value November 2016
About Covance Covance Inc., headquartered in Princeton, NJ, USA, is the drug development business of Laboratory Corporation of America Holdings (LabCorp). COVANCE is a registered trademark and the marketing name for Covance Inc. and its subsidiaries around the world. 24 Quality: Adding Value November 2016