Implementing A Cross-Functional Quality Culture to Ensure Product

Safety & Effectiveness

Lisa A. Sykes

VBF Quality Operations Director

Merck

Agenda

• Introduction

• Compliance Mindset – Why is it important?

• Case Study – The Red Zone

• Identify, Remediate and Sustain

• Questions and Answers

Introduction

• Lisa A. Sykes

– 20 years of experience in the pharmaceutical industry

– BS. Biology and MBA in Management

– Certified Quality Auditor by ASQ

– Certified Qualified Person Liaison by David Beck and Associates

We are in the business to save lives.

• http://innovationsaves.life/index.php

These innovations are going to be needed by all of us — our sons and daughters, your mother, your father, neighbors, friends, yourself.Ron Cohen, M.D.President & CEO of Acorda TherapeuticsChair, BIO

The Red Zone • Product was not being shipped to the customer.

Unreleased Batches in que were over 800 days old. Target is 270 days for release. A huge number of investigations were being generated and were overdue. Discards were steadily increasing. The Quality Testing Group was not meeting their lead time. Temporary workers were being hired, but the backlog continued and increased. The Quality Staff worked in silos. Colleagues were leaving to go to other roles. Nothing was getting completed. Unprocessed work was piling up. We were in the RED ZONE.

Group Discussion

• What may be some possible root causes?

– People, Process, Equipment, Methods, Systems

• Do you see similar concerns at your company?

• What would you do first?

The Red Zone

• The Targets are not being met.

• Metrics are not recoverable.

• The customer is not getting their product on time.

• The batch has numerous defects.

• Waste is in your process.

• Compliance is at risk.

Quality State of Union

• The Batch Record Review group was not meeting their target. 28 day Cycle Time

• No one was cross trained.

• 35% of the staff was a temporary workforce.

• A high number of employees had temporary work agreements.

• The Batch Release Group were not releasing batches.

• The Quality Approvers for investigations had unrealistic expectations.

• No one was accountable.

Process Monitoring Assessment

• Process Monitoring Assessment– Determine the Critical Quality Attributes. . – KPI Monitoring

• Execution • Raw Materials – Link Raw material attributes and process

parameters to CQAs • Process Sampling

– Feedback/React Plan

• Pay attention to time and temperature• Engage the operators• When decisions are needed on the floor, consider

processing impact.

The manufacturing process

• The manufacturing process is biological and involves cells. Two (2) inputs. – Input 1 – Growing and harvesting the cells.

• 39 days to manufacture

• 150 lead time = number of days to manufacture + the number of days to release

– Input 2 – Utilize Input 1 to create Input 2. Pooling and filtering the product. Final outcome is Bulk Product. • 2 days to manufacture

• 120 lead time = number days to manufacture + the number of days to release. CBER submit on day 90.

Phase 1

• Enhancing the communication tool. – Forecast - weekly notifications detailing the lots that

the are due for release. • List the batches

• List the hold ups – investigations, testing, batch record review, change controls, etc.

• Sent to stakeholders

– Daily Release Meetings• Whiteboard

• Accountable contributors – Lab, QA reviewers, Investigation writers, Operation’s batch record reviewers

Phase 1 – Continue

– Moved towards a Matrix Organization• Cross training – example, Batch Record Reviewers were

trained to review and approve investigations. Learned how to use Root Cause Analysis Tools.

– Focused on Teamwork and Collaboration • Implemented QA Shop Floor

– Improved Comment Resolution • Implemented a comment decision tool

• Coached QA on Risk Based Decisions

– Proactively worked on WIP(Work In Progress)

Phase 1 – Continue Waste Identification

– INPUT 1 – The QA Batch Record Reviewers were not meeting their target of 28 days. A backlog of records was steadily increasing.

– 19 Training Requirements for INPUT 1

– 1 fully trained colleague

– 6 month onboarding process

– No accountability

Phase 1 – Continue Waste Removal

– Kaizen Results

• Only 2 TQRs from 19– Grouped into skill sets not process orders

• 1 month onboarding process

• Clear Goals and Objectives

• 89% Reduction in Work Content

• Simplified and Streamlined the training process

• Capacity Improvement with decrease in Batch Record Review cycle time.

Phase 1 results

• Elimination of Batch Record Review Backlog.

• Target Cycle time was achieved.

• Lots Release On time was achieved.

• A fully utilized and capable work force was created.

Phase 2 - Sustain and Improve Batch Cycle Time

Risk Processing

Before:

Input 1 and 2 end-to-end Lead Time

After:

Input 1 and 2 end-to-end Lead Time

Approach/Methodology:

Daily visual management

Early identification of investigations

Collaborations with QA, Operations and the laboratory

Standard work

Real Time Batch Record Review

Timely Comment Resolution

Business Benefits:

Lab results known earlier. Health of the batch is assessed.

Deviations identified sooner

Lead time reduced by 45%

Decreased batch record review cycle time.

120 daysInput 2

150 daysInput 1

270 days

114 daysInput 1

120 daysInput 2

149 days

Risk Processing • Can we process at risk?

– Should we have completed and passing Sterility Results?

– Should all batch requirements be met?

Figure 1: ICH Q9 QRM Process Overview

Initiating a QRM process

• QRM activities should be performed using systematic processes designed to coordinate, facilitate and improve science-based decision-making with respect to risk.

• Possible steps used to initiate and plan a QRM process might include the following (Ref. ICH Q9):– define the problem and/or risk question, including pertinent

assumptions identifying the potential for risk;– assemble background information and/or data on the potential

hazard, harm or human health impact relevant to the risk assessment;– identify a leader and necessary resources; and– specify a timeline, deliverables and appropriate level of decision-

making for the risk management process.

http://www.who.int/medicines/areas/quality_safety/quality_assurance/QualityRiskManagement_QAS10-376Rev2_27082012.pdf

Things to Consider

• Did this scenario sound familiar?

• Is your product at risk?

• Do you think more is better?

• Speed, Quality and Cost.

– Does speed and cost, matter?

• Is your Quality team in a Silo?

References

• Guidance for Industry: QP Quality Risk Management 2006 – U.S. Food and Drug Administration

• ISO 14971:2007 Medical Devices – Application of risk management to medical devices.

• WHO GUIDELINE ON QUALITY RISK MANAGEMENT

Quality Mindset

• Look for continuous improvements.

• Improve your process and identify waste.

• Base Decisions on data and facts.

• Align Quality around customer needs.

• See as a team, work as team, act as a team, improve as a team.

As leaders

• Promote teamwork and collaboration.

• Utilize and promote Quality Risk Management

– QRM does allow for process efficiencies that lead to compliance improvements.

• Quality is everyone’s responsibility.

• Drive Change!!!!!

• Communicate, Communicate, Communicate

Questions