© 2017 Illumina, Inc. All rights reserved.

Reflections on Illumina’s MDDAP/VIP AppraisalCase for Quality (CfQ) Pilot Program November 12-16, 2018

Ravi Nabar, Ph.D., MBASenior Director Quality- Head of Global QMS and Compliance, Illumina, Inc. | 02/25/2019

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Why participate in the CfQ VIP pilot?

Illumina MissionImprove human health by unlocking the

power of the genome.

CfQ VIP Benefits- Produce high quality devices- Increase patient safety- Elevate product & process quality

Illumina’s Benefits: Regulatory Relief

- Entry into program via FDA vetting(inspectional history)

- Product moves (Class III PMA device)- Reduce burden & disruption of audits- Accelerate clearance, change

review & approval process; fasterTime To Market (TTM)

30-Day Submission- Simplified & bundled notifications- Positive outcomes- Improved quality and compliance- Increases competitive advantage- Participating in site transfer pilot

Site Changes- Streamlined submission- Accelerated approval 1 week- Enhances growth & site expansion- New B6 Facility

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CONFIDENTIAL – FOR INTERNAL USE ONLY

FDA Inspection CFQ VIP Appraisal

Inspection Requirements

• Facility Inspection (Class III PMA device)

• Anticipated in 2019

• No inspection needed• Waive future surveillance

& risk-based inspections

Interaction• 1-2 Investigators @ 5 Days• Inspectors interrogate SMEs & Process

Owners• Audit and compliance-based

• 1-4 Appraisers @ 5 Days• Appraisers conduct group interviews of the

“doers” (practitioners)• Look at practice of foundational quality

capability elements vs. “best” practices

Effort• Large support team with backroom/front

room, etc.• 150+ SMEs & Support Staff

• Minimal support team with no backroom/front room.

• 60+ SMEs (~2-3 hrs. per week) & Support Staff

Time & Cost• 2,400+ person- hrs. support • 2 weeks inspection• Estimated cost $140k

• 120-180+ person-hrs. support• 1-week appraisal• Estimated cost $74k

30-Day/180-day submissions

• Additional information requirements• Complex communications and

coordination• Missed opportunities due to delays

• Simplified & bundled notifications• Positive outcomes• Improved quality and compliance

CfQ VIP Appraisal Benefits

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CONFIDENTIAL – FOR INTERNAL USE ONLY

Illumina CfQ VIP Pilot Appraisal Preparation

Support:• Absolutely No Backroom• No Procedures• No Records• No Scribing• 2 Conference Rooms

Appraisal Team:• Four CMMI Appraisers

(1 lead @ 2 teams)

Resources Needed:• 40+ Participants• 7 interview sessions

@ 1.5 - 2 hrs./ea.

Intake Meetings:• Three 1-hour meetings• CMMI Mentor session

(Coach Lindsey McGowan)• Defined product scope • Set Schedule & duration• Developed & refined list of

interviewees

How is MDDAP different from a regulatory audit?

Is Is NOT

Confidential dialog Audit (observers, back room)Focus on

“run the business” Compliance

Interviewed practitioners

Verification with process owners

Results are ours Audit responses, CAPAs

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Illumina CfQ VIP Pilot Appraisal Scope

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Illumina CfQ VIP Pilot Appraisal Process

● CMMI Model: CMMI Development v2.0

● CMMI Team:

Evaluated in7 interview

sessions@ 1.5 - 2 hrs/ea.

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CONFIDENTIAL – FOR INTERNAL USE ONLY

Illumina On-Site Appraisal ScheduleFinal Appraisal November 12-16, 2018

Session 7 (Included in all sessions): Implementation Infrastructure

7 interview sessions (minimal impact to interviewees)

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Illumina Pilot AppraisalSite Strengths

Sampling: 3 on-market IVD products

● Proactive improvement vs. Reactive Improvement

● Agility Innovation Staying ahead of the market

● Design Transfer Maturity

● Product Integration & Technical Solution

● Strong Core Values

● Focus of Safety and Quality

● Forward looking through “Factory of the Future” automation & Data Analytics

IlluminaConfiguration Management (CM)Estimating (EST)Governance (GOV)Implementation Infrastructure (II)Monitor and Control (MC)Managing Performance and Measurement (MPM)Product Integration (PI)Planning (PLAN)Process Quality Assurance (PQA)Requirements Development and Management (RDM)Technical Solution (TS)

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© 2019 Illumina, Inc. All rights reserved.

Illumina Design Transfer Maturity Index

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Navigating RUO vs Dx product roadmaps

Transparency and informed decision making at all levels of organization

Removing ambiguity in business and compliance risks

Concrete alignment on “all in” activities and their level of robustness

What good looks like relative to product intended use

Illumina Design Transfer Maturity Index (DTMI)Capability Maturity Levels

Level 1 Level 2 Level 3 Level 4 Level 5

Raw

Mat

eria

ls

Raw Material Critical Parameters

Critical parameters established for < 80% of critical components

Critical parameters established for > 80% of critical components

Critical parameters established for all critical components

Impact to product quality is well understood

Critical parameters established for all critical and most non-critical components

Impact to product quality is well understood

Critical parameters established for all components

Operations alignment tool guides the level of robustness appropriate to project type

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Illumina’s MDDAP/VIP Appraisal ReflectionsFeedback & Learnings● Scope: Some practice areas could additionally be considered core for Level 2

Capability Attainment; Two practice areas were determined to be at Level 3

● Time to enroll was short (++)

● Would benefit from some pre-work on common knowledge with terminology between Illumina & CMMI Appraisers

● Required major re-calibrating internally to undo “audit mindset” (++)- Dialogues to build trust & convey pride in work; not to defend compliance- Open-ended dialogue; not binary answers (yes/no)- No scribing; this violates confidentiality of the process- Ushering audit personnel out of the room

● Understanding of what CMMI really means amongst the interviewees

● Communication between the CMMI Appraisers & Illumina staff was extremely cooperative and clear

● Invested a lot of time to refine the list of interviewees- Require practitioners, not process owners- Ensure that the right level of participation was achieved

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Next Steps

1. Define CMMI Performance Metrics

2. Define glidepath to maturity based on appraisal results - Refine Estimation practice area

3. Determine next practice areas for maturity appraisal- Improvements (“PDCA” based) initiated- Extend to other sites?- CMMI Appraiser Training SD (Feb 26 - Mar 1st)

4. Scheduled first MDDAP quarterly check-Feedback from lead assessor positive

Reflections on Illumina’s MDDAP/VIP Appraisal�Case for Quality (CfQ) Pilot Program November 12-16, 2018Why participate in the CfQ VIP pilot?Slide Number 3Illumina CfQ VIP Pilot Appraisal Preparation�Illumina CfQ VIP Pilot Appraisal ScopeIllumina CfQ VIP Pilot Appraisal �Process�Slide Number 8Illumina Design Transfer Maturity IndexIllumina Design Transfer Maturity Index (DTMI)�Capability Maturity LevelsIllumina’s MDDAP/VIP Appraisal Reflections�Feedback & LearningsNext Steps��