The document presents information on Quality by Design (QbD), a systematic approach to pharmaceutical development that emphasizes product and process understanding. It defines key QbD concepts like target product profile, quality target product profile, critical quality attributes, critical material attributes, and critical process parameters. The benefits of QbD for industry include eliminating batch failures and empowering technical staff. Design space, design of experiments, and process analytical techniques are important tools in QbD. Regulatory agencies support the QbD approach for developing scientific understanding and continuous improvement.

1. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721
Quality-by-Design in
Pharmaceutical development
A Seminar as a part of curricular requirement
for M. Pharm I year II semester
Presented by
V.NABI RASOOL. (20L81S0401).
Department of Pharmaceutical Quality Assurance.
1

2. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 2
DEFINITION
•Quality by design (QbD) is a systematic approach to
product development that begins with predefined objectives
and emphasizes product and process understanding and
controls based on sound science and quality risk
management (ICH Q8).
Quality-by-design

3. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 3
•The main objective of QbD is to achieve the quality
products.
•To achieve positive performance testing.
•Ensures combination of product and process
knowledge gained during development.
•From knowledge of data process, desired attributes
may be constructed.
Objectives :

4. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721
Benefits of QbD for Industry :
•Eliminate batch failures.
•Minimize deviations and costly investigations.
•Empowerment of technical staff.
•Better understanding of the process.
•Continuous improvement.
•Ensure better design of product with less problem.
4

5. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 5
Aspects Traditional QbD
Pharmaceutical development Empirical (Experimental) Systematic and multivariate
experiments.
Manufacturing process Fixed Adjustable with experiment
design space.
Process control Offline and has wide or slow
response
PAT (Process Analytical
Technique) utilized for feed
back.
Product specification Based on batch data Based on the desired product
performance.
Control strategy By end product testing Risk based, controlled shifted
up stream, real time release.
Life cycle management Post approval changes
needed
Continual improvement
enable within design space.
Approaches to Pharmaceutical Development

6. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 6
Define Target product profile (TPP) and Quality Target Product profile (QTPP)
Identify critical quality attributes (CQA)
Carry out risk assessments, linking material attributes and process parameters CQA
Establish the design space
Describe control strategy
Life cycle management and continuous improvement
Flow of QbD :

7. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 7
• “A prospective summary of the quality characteristics of drug
product that ideally will be achieved to ensure the desired quality,
taking into account safety & efficacy of drug product.”(ICH Q8)
Target product profile should includes-
• Dosage form
• Route of administration
• Dosage strength
• Pharmacokinetics
• Stability
Target Product Profile(TPP)

8. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 8
• QTPP is a quantitative substitute for aspects of scientific safety &
efficacy that can be used to design and optimize a formulation and
manufacturing process.
• QTPP should only include patient relevant product performance.
• The Quality Target product profile is a term that is an ordinary
addition of TPP for product quality.
• QTPP is related to identity, assay, dosage form, purity, stability in the
label.
Quality Target Product Profile (QTPP)

9. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 9
• A CQA has been defined as “a physical, chemical, biological or
microbiological property or characteristics that should be within an
appropriate limit, range, or distribution to ensure the desired product
quality”.
• Critical Quality Attributes are generally associated with the drug
substance, excipients, intermediates and drug product.
Critical Quality Attributes(CQAs)

10. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 10
• The quality attributes of a drug product may include identity, assay,
content uniformity, degradation products, residual solvents, drug
release, moisture content, microbial limits.
• Physical attributes such as color, shape, size, odor, and friability.
• These attributes can be critical or not critical.

11. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 11
• A CMA of a drug substance, excipient, and in-process materials is a
physical, chemical, biological, or microbiological characteristic of an
input material that should be consistently ,
• The CMA is likely to have an impact on CQA of the drug product.
• A material attributes can be an excipients, raw material, drug
substances, reagents, solvents, packaging & labeling materials.
Critical Material Attributes(CMA)

12. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 12
• A CPP of manufacturing process are the parameters which, when
changed, can potentially impact product CQA and may result in
failure to meet the limit of the CQA.
Critical Process Parameters(CPP)
Operations during tableting CPP
Wet granulation Mixing time, temperature, method of binder addition
Drying Drying time, Inert air flow
Milling Milling speed, screen size, feeding rate
Compression Pre compression force, main compression force, dwell time,
hopper design, ejection force
Coating Inert air flow, time, temperature, spray pattern and rate

13. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 13
Design Space As per ICH Q8-
• This is the multidimensional combination and interaction of
input variables (e.g., material attributes) and process
parameters that have been demonstrated to provide assurance
of quality.
• A design space may be built for a single unit operation or for
the ensure process.
Design Space :

14. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 14
Design of Experiment (DoE):
• This is a systematic approach applied to conduct experiments
to obtain maximum output.
• We have capability and expertize to perform DoE in product
development using software like Minitab and Statistica.
Tools applied in QbD approach

15. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 15
Design of experiments done by 2 methods-
1. Screening:
• Designs applied to screen large number of factors in minimal number
of experiments to identify the significant ones.
• Main purpose of these designs is to identify main effects and not the
interaction effects.
• For such studies common designs used are-
Placket-Burman design
Fractional factorial design.

16. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 16
2. Optimization:
• Experimental designs considered to carry out optimization are
mainly full factorial design, surface response methodology .
e.g. Central composite
Box-Behnken and
Mixture designs.
• These designs include main effects and interactions and may also
have quadratic and cubic terms require to obtain curvature.

17. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721
17
Process Analytical Techniques :
Assurance of product quality during intermittent steps using Process
Analytical Technology (PAT) is recommended by regulatory
authorities, which is yet to be extensively accepted by the
pharmaceutical industry over conservative methodologies.
It involves advanced online monitoring systems like NIR (Near IR),
Handheld Raman Spectrometer, Online Particle Size Analyzer etc.,
These technologies further make assurance of continuous
improvement in process and product quality through its life cycle.

18. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 18
• As defined by an FDA official (Woodcock, 2004),
• “The QbD concept represents product and process performance characteristics
scientifically designed to meet specific objectives, not merely empirically
derived from performance of test batches.”
• Another FDA representative (Shah, 2009) states that “introduction of the QbD
concept can lead to cost savings and efficiency improvements for both
industry and regulators.”
Regulatory views on QbD

19. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 19
• Pfizer was one of the first companies to implement QbD and PAT
concepts.
• Through these concepts, the company gained enhanced process
understanding, higher process capability, better product quality, and
increased flexibility to implement continuous improvement change.
Industry views on QbD

20. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 20
Industry Regulatory agency
Development of scientific understanding
of critical process and product attributes.
Scientifically based assessment of
product and manufacturing process
design and development.
Controls and testing are designed based
on limits of scientific understanding at
development stage.
Evaluation and approval of product
quality specifications in light of
established standards (e.g: purity,
stability, content uniformity, etc.,)
Utilization of knowledge gained over the
product’s lifecycle for continuous
improvement.
Evaluation of post-approval changes
based on risk and sciences.
QbD for industry and regulatory bodies

21. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 21
• Quality by Design is intended to enhance process knowledge and is based on existing
guidance and reference documents.
• QbD can be viewed as a process defined by series of document requirements as per
process knowledge and understanding.
• The goals of implementing pharmaceutical QbD are to reduce product variability and
defects, thereby enhancing product development and manufacturing efficiencies and post
approval change management.
• Finally, QbD is challenge & the current challenges to QbD implementation from an
industry perspective are numerous because industry has yet to fully embrace its
application to pharmaceutical product development.
Conclusion

22. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 22
i. Lan Zhang, Shirui Mao (2016 ). Application of quality by design in
the current drug development: Asian journal of pharmaceutical
sciences 12 (2017) 1–8.
ii. Sushila D. Chavan, Nayana V. Pimpodkar, Amruta S. Kadam, Puja
S.Gaikwad. Quality by Design : Research and Reviews: Journal of
Pharmaceutical Quality Assurance|Volume 1 | Issue 2 | October-
December, 2015.
iii. D. M. Patwardhan, S. S. Amrutkar , T. S. Kotwal and M. P. Wagh ,
APPLICATION OF QUALITY BY DESIGN TO DIFFERENT
ASPECTS OF PHARMACEUTICAL TECHNOLOGIES : IJPSR,
2017; Vol. 8(9): 3649-3662.
References

23. RIPER
AUTONOMOUS
NAAC &
NBA (UG)
SIRO- DSIR
Raghavendra Institute of Pharmaceutical Education and Research - Autonomous
K.R.Palli Cross, Chiyyedu, Anantapuramu, A. P- 515721 23