First Step in QbD:How to get it Right

ISPE 2014Sun Kim, PhD

Are You ...

1. Starting a QbD project & want to skip common pitfalls?

2. Tried QbD but management and colleagues were skeptical?

3. undecided if QbD is for your organization?

QbD in 3 Steps

1. Risk Assessment: Build Relationships from QTPP, CQA to CPP

(CMA)

2. Design Space

3. Control Strategy

You Are Not Alone.

17 Likes47 Comments

Sampling of LinkedIn Comments

“It is like a loop I always have to dealt with, everytime!” - S of Angelini

“The first part of your blog literally had me laughing out loud. This is so true and relevant.” -I of Teva

“I completely agree with you that FMEA, especially in the early development, is not the ideal tool” - F of PTM Consulting”

Sampling of LinkedIn Comments

“How refreshing to see this. Thank you so much for noting that the FMEA emperor may be missing some clothing.” - D, Statistician

“The formality of risk assessment should align with the level of product and process understanding. FMEA definitely has its place, but later in the development process.” - S of UpsherSmith

Agenda

0. Story1. Why Risk Assessment is Critical to QbD

2. Why You shouldn’t blindly apply FMEA for QbD development projects.

3. A Smarter Risk Assessment Approach

Why Risk Assessment determines success and failure of QbD

1. 1st step & planning stage of QbD

2. Output is Control Strategy

3. Precursor to Design Space studies

Why Risk Assessment determines success and failure of QbD

1. 1st step & planning stage of QbD

a. Scientists dread these types of meetingsb. If this doesn’t go well, the momentum fizzlesc. Links QTPP-CQA-CPP-CS

Why Risk Assessment determines success and failure of QbD

1. 1st step & planning stage of QbDa. Scientists hate these types of meetingsb. If this doesn’t go well, the momentum fizzlesc. Links QTPP-CQA-CPP-CS

2. Output: Control Strategya. Prioritized list of projects or experiments

Why Risk Assessment determines success and failure of QbD

1. 1st step & planning stage of QbDa. Scientists hate these types of meetingsb. If this doesn’t go well, the momentum fizzlesc. Links QTPP-CQA-CPP-CS

2. Output Control Strategya. Prioritized list of projects

3. Precursor to Design Space studiesa. Links to Design Space

FMEA (Failure Mode Effects and Analysis)

Goal: “Identify all possible failures...prevent…”

Ref: ASQ

1. Most attributes become “Critical.”

A. FMEA’s definition:RPN (Risk Priority Number) = Severity x Occurrence x Detectability( or Controllability)

B. Classic definition Risk Index = Severity x P(Occurrence)

http://plato.stanford.edu/archives/win2012/entries/risk/#DefRis

W. Gilchrist, ?Modelling Failure Modes and Effects Analysis,? International Journal of Quality and Reliability Management 10 (5), 16-23, 1993.

S. Kmenta, Scenario-based FMEA Using Expected Cost, A new perspective on evaluatng risk in FMEA, IIE Workshop,January 22, 2002.

S. Kmenta and K. Ishill, Scenario-Based Failure Modes and Effects Analysis using Expected Costs, Journal of Mechanical Design 126, 1027-1036, 2004.

D. Wheeler, ?Problems with Risk Priority Numbers,Quality Digest, 2011 Available at: http://www.qualitydigest.com/inside/quality-insider-article/problems-risk-priority-numbers.html

2. Inappropriate ordinal scale

At the development stage where scale-up details are not available, scientist do not yet understand the manufacturing process well enough to list realistic failure modes.

Recommendation: Use Low-Med-High or better yet, 0-1-3-9 scale

http://plato.stanford.edu/archives/win2012/entries/risk/#DefRis

W. Gilchrist, ?Modelling Failure Modes and Effects Analysis,? International Journal of Quality and Reliability Management 10 (5), 16-23, 1993.

S. Kmenta, Scenario-based FMEA Using Expected Cost, A new perspective on evaluatng risk in FMEA, IIE Workshop,January 22, 2002.

S. Kmenta and K. Ishill, Scenario-Based Failure Modes and Effects Analysis using Expected Costs, Journal of Mechanical Design 126, 1027-1036, 2004.

D. Wheeler, ?Problems with Risk Priority Numbers,Quality Digest, 2011 Available at: http://www.qualitydigest.com/inside/quality-insider-article/problems-risk-priority-numbers.html

3. Mediocre Control Strategy

Typical Examples:equipment maintenance, training or monitoring- feed control valves, steam traps, tank, flange, piping leaks- pH, DO, backpressure monitoring

Ref: Pharmaceutical Engineering, May/June 2010, Vol. 30, No. 3, P.1-11

Smarter Approach

1. Scientist-driven: Y=f(X), QFD=C&E + FMEA

2. Process Map: TRD (Technical Requirements Document), IMPD (Investigational medicinal product dossier)

3. Link how a CPP matters to the Patient (QTPP)

4. Risk = Impact x P(Occurrence)

Yoji Akao, Quality Function Deployment: Integrating Customer Requirements Into Product Design, Productivity Press, 1990.

How will a Process Parameter affect a Patient?

Linking QTPP-CQA-CPP/CMA

Linear Approach

QTPP (C)QA

(C)PP(C)QA

Occurrence(C)PP

Link: from QTPP to (C)QA

QTPP

(C)QA

Impact

Link: from (C)QA to (C)PP

(C)QA

(C)PP

Impact

Occurrence

(C)PP

Probability

Occurrence

Linking it Together

QTPP (C)QA

(C)QA (C)PP

(C)PP Occurrence

Control Strategy

Control Strategy: CQA Pareto

Control Strategy: CPP Pareto

(HD) Control Strategy: Impact x Occurrence

Lean QbD Software Demo

LeanQbD.com

The First Step in QbD

1. Risk Assessment is the Blueprint of QbD.

2. Focus on building Y=f(x) for QTPP-CQA-CPP/CPP

3. Save time by using Templates and a simple rating system

Recommendation:

● Use LeanQbD approach - Get it at LeanQbD.com

● More Tips from QbDWorks.com

More Tips from QbD Practitioners

QbDWorks.com