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If you’re new to Quality by Design (QbD) or Process Analytical Technology (PAT) — Welcome to QbDWorks!

I’m Sun Kim, PhD — the Experimenter of Quality by Design (QbD) — testing and sharing what works (and what doesn’t).

There’s hype in any initiative . QbD is no exception. My goal for this website is to take out the fluff and get to the core essence of QbD — and share it with others along the way. As a QbD practitioner myself, I personally strive to push beyond theory and seek results.

This page contains the information you need to get up to speed quickly and start your organization’s QbD initiative.

Feel free to read top-to-bottom or jump around the articles.

What is Quality by Design?

Let’s first cover the basics. “Quality-by-Design is a systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management.” (Ref: ICH Q8(R2)-Pharmaceutical-Development 2009)

What does this mean to a scientist (click for a 2-min Video of QbD Framework)? 

Confused about QbD jargons (click for QbD Glossary)?

This sounds all great but where do I start? If you are planning on launching a QbD program, I strongly recommend securing an executive sponsor to support your initiative. Otherwise, prepare for a steep uphill battle.

So…How do I Justify QbD to my Executives?

This is a tough one. There are no silver bullets but here are some business justification articles that you can reference.

Selling QbD to Executive

How do I measure the progress of QbD? – KPI or metric to continue to justify QbD program (click)

Why quality-by-design should be on the executive team’s agenda (2009, Ted Fuhr, Michele Holcomb, Paul Ruttenb_McKinsey&Co.)

Building a Business Case for Biopharmaceutical QbD Implementation (2012, Junker, BioPharma International)

Now that you have the “License to Implement QbD,” what’s the next step?

How to Implement QbD?

In essence, QbD is successfully connecting the 3 core elements — 1. Risk Assessment – 2. Design Space – 3. Control Strategy — in order to understand the link of QTPP – CQA – CPP and control them.

Risk Assessment is the tool to determine the link of QTPP – CQA – CPP. This is the first step and therefore a critical one.

DOE – Design of Experiments is the common approach to characterize Design Space.

Are there any examples or case studies? Yes!

QbD Case Studies

Large Molecules, Biologics case studies

A-Mab: QbD for Monoclonal Antibody Case Study (2009, CMC Antibody WG, PDA)

Gazyva – the First QbD Design Space Approval from  Biologics

Perjeta-Lessons from Failure and Success

A-VAX: QbD in Vaccines (2012, CMC Vaccines WG, PDA)

Quality by Design Approaches to Formulation Robustness – Antibody Case Study

Small Molecules, Generics case studies:

Quality by Design for ANDAs: An Example for Immediate-Release Dosage Forms

Quality by Design for ANDAs: An Example for Modified Release Dosage Forms

Question-Based Review for CMC Evaluations of ANDAsQbD for

Pharmaceutical Development  Case Study: “ACE Tablets” (2009, CMC-IM WG, PDA)

QbD in Generics (courtesy: Inna Ben-Anat of Teva, IFPAC 2013)

Quality by Design for Orally Inhaled Drug Products (Lawrence X. Yu, FDA)

QbD Approaches for Orally Inhaled and Nasal Drug Products (OINDPs) (Peri, FDA)

Korea QbD 식약처 품질심사

Design Space

Q&A on Normal Operating Range, Proven Acceptable Range, Design Space and Process Parameters (EMA, 2017)

Design Space Considerations (FDA, 2012)

Design Space – Process Models with Monte Carlo Simulation (FDA, 2012)

Questions and Answers on Design Space Verification (FDA, 2013)

Analytical Methods

QbD Considerations for Analytical Methods – FDA Perspective

Nano-Formulations

Adaptation of the quality by design concept in early pharmaceutical development of an intranasal nanosized formulation (Pallagi, 2015)

Medical Devices  (Combination Products)

QbD for Devices – Drug Eluting Stents(Mcdermott & Chatterjee of FDA)

Process Variability

Using Control Chart to Evaluate Process Variability (Peng, FDA)

FDA Process Validation (FDA)

Biosimilars

Labeling for Biosimilar Products (FDA, 2016)

CELLTRION Infliximab Biosimilar (FDA, 2016)

Continuous Manufacturing

FDA Perspective on Continuous Manufacturing (Chatterjee, 2012)

FDA on Continuous Manufacturing (Lee, 2016)

Knowledge Management

FDA Perspective on Continuous Manufacturing (Yu, 2019)

Submission Tips from CMC and Regulatory Agency Reviewers

Regulatory Assessment of Applications Containing QbD Elements – Reviewer Experience (Miksinski, 2014)

Regulatory Assessment of QbD Elements in NDA Submissions – Experience and Considerations (Miksinski, 2014)

CMC Considerations for a Successful Regulatory Submission (Madurawe, FDA)

Advancement of Emerging Technology Applications To Modernize the Pharmaceutical Manufacturing Base (FDA, 2015)

Best Practices for Communication Between IND Sponsors and FDA During Drug Development (FDA, 2015)

FDA Reflections on EMA Joint Regulator Industry Workshop (FDA, 2014)

ICH Q8, Q9, Q10 Questions and Answers – R4 (FDA, 2011)

ICH Q8, Q9, Q10 Q&A (FDA, 2012)

Questions and Answers on Level of Detail in the Regulatory Submissions (FDA, 2014)

FDA Applying ICH Q8(R2), Q9, and Q10 (FDA, 2016)

Good ANDA Submission Practices (FDA, 2018)

MAPP-Good ANDA Assessment Practices (FDA, 2018)

Clinical Trials

Quality by Design Clinical Studies

Books:

Recommended Books

Tools:

Lean QbD:  The Smartest Risk Assessment Software for QbD. 

I will continue to add to this page. Please contact me if you have any suggestions!

Related Topics:

EU Guidelines for Good Manufacturing Practice for Medicinal Products for Human and Veterinary Use

FDA Guidance on Data Integrity cGMP (FDA 2016)

Quality in the Pharmaceutical Industry – Brief Literature Review

FDA Guidance On Data Integrity