Quality by Design (QbD)

FDA Session

What is QbD?
Systematic, holistic and proactive approach to
pharmaceutical development.
Begins with predefined objectives
Emphasizes product and process understanding and
process control
Based on sound science and quality risk management
Ref.: ICH Q8
(R2)

What is going on?

File first, learn later
Major amendments during review process
Exhibit batch stability failure, formulation revision
Longer time for generic product approval
Approved product may not be marketed
Post approval changes prior approval supplements

How QbD will help improve?

Ensure higher level of assurance of product quality
Improved product and process design & understanding
Monitoring, tracking & trending of product & process

More efficient regulatory oversight

Efficiency and cost saving for industry
Increase efficiency of manufacturing process
Minimize / eliminate potential compliance actions

A QbD workflow

QbD: Required or Optional?

Required
Quality target product profile (QTPP) including critical quality attributes (CQAs) of the
drug product and including Product design and understanding
Product design and understanding
Critical material attributes (CMAs) of the drug substance and excipients
Process design and understanding
Critical process parameters (CPPs)
Control strategy, including justification

Optional
Design Space
Process Analytical Technology

Current vs. QbD Approach to

Pharmaceutical Development

QbD example
A:Elution pH B:Conductivity C:Cleavage D:Load Mass E:Wash pH Recovery % Purity %
-1
-1
-1
-1
1
112.6
96.3
1
-1
-1
-1
-1
90.7
96.9
-1
1
-1
-1
-1
104.9
97.1
1
1
-1
-1
1
72.8
97.3
-1
-1
1
-1
-1
99.6
96.1
1
-1
1
-1
1
84.2
97.1
-1
1
1
-1
1
98.4
97.3
1
1
1
-1
-1
104.2
97.8
-1
-1
-1
1
-1
104.3
91.8
1
-1
-1
1
1
79.0
94.9
-1
1
-1
1
1
94.8
96.6
1
1
-1
1
-1
93.7
96.0
-1
-1
1
1
1
95.5
94.4
1
-1
1
1
-1
88.5
93.9
-1
1
1
1
-1
78.7
96.5
1
1
1
1
1
58.7
98.4

Des ign -Ex pert S of tware

Purit y
9 8. 4
9 1. 8
X1 = A : E lut ion pH
X2 = B : Conduc ti vi ty
Ac tual Fac to r s
C: C leava ge = -1. 00
D: Load Mas s = 0. 00
E: W as h pH = 0.00

QbD example
Purity

1.00

96.6333

0.50

B: Conductivity

96.1792
D es ign-E xpert Sof tw are
Ov erlay P lot
R ec ov ery
P uri ty
X 1 = A : E lut ion pH
X 2 = B : C onduct ivi ty
A c tual F actors
C : C leav age = -1. 00
D : Load Mas s = 0.0 0
E : Was h pH = 0. 00

Overlay Plot

0.00

1.00

95.725

-0.50

95.2708

0.50

-1.00
-1.00

-0.50

0.00

0.50

1.00

A: Elution pH
Des ign-E xpert So ftware
Rec over y
112 .6
58. 7
X1 = A: Elution p H
X2 = B: Conduc t ivit y
Ac t ual F ac tors
C: Cle avage = -1 .0 0
D: Lo ad Mas s = 0.0 0
E: W ash pH = 0. 00

Recovery

1.00

B: Conductivity

94.8167

Recovery: 100

0.00

Recovery: 90

-0.50

B: Conductivity

0.50

-1.00
-1.00
99.8417

95.4875

91.1333

-0.50

0.00

86.7792

0.00

A: Elution pH
104.196

-0.50

-1.00
-1.00

-0.50

0.00

A: Elution pH

0.50

1.00

0.50

1.00

QbD for dietary supplements?

FDA regulates as foods
Do not need FDA approval for market
Manufacturers are required to follow GMP but what
about growing, harvest, processing and even naming the
plants?
How to complete botanical characterization,
authentication and safety evaluation
One of the key difficulties lies in their vast diversity

QbD for dietary supplements?

Establishing a QbD model to evaluate as many of the
key aspects that identify each botanical is imperative
since there is no single method that can authenticate
every

plant

sample

or

characterize

each

dietary

supplement. For each botanical, there needs to be a full

understanding of the constituents being considered and
the capabilities of the techniques specifically suited for
authentication purposes

References for QbD

Guidance for Industry: Q8(R2) Pharmaceutical Development
Guidance for Industry: Q9 Quality Risk Management
Guidance for Industry: Q10 Pharmaceutical Quality System
Guidance for Industry PAT: A Framework for Innovative
Pharmaceutical Development, Manufacturing, and Quality Assurance
Quality by Design for ANDAs: An Example for Modified Release
Dosage Forms
Quality by Design for ANDAs: An Example for Immediate Release
Dosage Forms