Pharmaceutical Quality by Design (QBD) is a concept introduced by the International Conference on Harmonization (ICH) Q8 guideline, as a systematic approach to development that begins with predetermined objectives and emphasizes the understanding of production and processes and process control, based on sound science and quality risk management. The basic concept of QBD is “The Quality cannot be tested into the product, but it should be built into it.”

1. Kushal Saha
MPH/10008/19
Pharmaceutics
Birla Institute Of Technology
Quality by Design

2. Introduction
Pharmaceutical Quality by Design (QBD) is a concept introduced
by the International Conference on Harmonization (ICH) Q8
guideline, as a systematic approach to development that begins
with predetermined objectives and emphasizes the
understanding of production and processes and process control,
based on sound science and quality risk management.
The basic concept of QBD is “The Quality cannot be tested into the
product, but it should be built into it.”
QBD, also known as quality purchasing design is emerging to
increase the promise of providing safe and effective medicines to
customers and promises to improve the efficiency of product
quality.

3. QBD DEVELOPMENT PROCESS INCLUDE
• Begin with a target product profile that describes the use,
safety and efficacy of the product
• Define a target product quality profile that will be used by
formulators and process engineers as a quantitative surrogate
for aspects of clinical safety and efficacy during product
development
• Gather relevant prior knowledge about the drug substance,
potential excipients and process operations into a knowledge
space.
• Design a formulation and identify the critical material (quality)
attributes of the final product that must be controlled to meet
the target product quality profile.
• Design a manufacturing process to produce a final product
having these critical materials attributes.

4. Cont..
• Identify the critical process parameters and input (raw) material
attributes that must be controlled to achieve these critical
material attributes of the final product. Use risk assessment to
prioritize process parameters and material attributes for
experimental verification. Combine prior knowledge with
experiments to establish a design space or other representation
of process understanding.
• Establish a control strategy for the entire process that may
include input material controls, process controls and monitors,
design spaces around individual or multiple unit operations,
and/or final product tests. The control strategy should encompass
expected changes in scale and can be guided by a risk
assessment.
• Continually monitor and update the process to assure consistent
quality.

5. LAY OUT OF QUALITY BY DESIGN

6. Opportunities
• Efficient, agile, flexible system
• Increase manufacturing efficiency, reduce costs and project
rejections and waste
• Build scientific knowledge base for all products
• Better interact with industry on science issues
• Ensure consistent information
• Incorporate risk management
FDA report “Pharmaceutical cGMPs for the 21st Century: A Risk-
Based Approach” has made it imperative to use QBD approach
in pharmaceuticals. To understand QBD well, we have to
understand main guidelines prescribed by ICH-
 ICH-Q8: (Pharmaceutical Development) and
 ICH-Q9: (Quality Risk Management)
 ICH-Q10: (Pharmaceutical Quality System)

7. ICH Q8
This guideline describes the suggested contents for the 3.2.P.2
(Pharmaceutical Development) section of a regulatory
submission in the Common Technical Document (CTD) format.
Objectives:
• To design a quality product and its manufacturing process to
consistently deliver the intended performance of the
product.
• Provide scientific understanding to support the
establishment of the design space, specifications, and
manufacturing controls.
Quality
by
testing

8. QBD approach, combining design space development and risk management tools

9. Comparison between
the traditional and QBD
Approach
(ICH Q8 guideline)

10. Elements of Pharmaceutical development
QBD comprises all elements of pharmaceutical development
mentioned in the ICH guideline Q8. To design a quality product and
its manufacturing process to consistently deliver the intended
performance of product is the aim of pharmaceutical
development.
Different elements of pharmaceutical development include-
 Defining an objective
 Determination of critical quality attributes (CQA)
 Risk assessment and design space
 Development of experimental design
 Designing and implementing control strategy
 Continuous improvement.

11. Advantages of QBD
 Better understanding of the process.
 Less batch failure.
 More efficient and effective control of change.
 Return on investment / cost savings.
 Reduction of post-approval submissions.
 Less intense regulatory oversight and less post-approval
submissions.
 More drug availability and less recall and improved yields,
lower cost, less investigations, reduced testing, etc.
 Continuous improvement over the total product life cycle.
 Contributes substantially to realize the better, cheaper and
safer mandate.

12. Disadvantages of QBD
 Internal unwillingness in company
 Lack of belief in a business case. It is assumed that QBD
would require more time to file generic products or that the
amount of clinical trials necessary to implement QBD for
drug substance production
 Lack of technology to implement.
 Alignment with third parties.
 Inconsistent treatment of QBD across FDA. It is believed
that FDA may not review filings in a consistent manner.
 Lack of concrete guidance for industry.

13. Conclusion
QBD has gain importance in the area of pharmaceutical
processes like drug development, formulations, analytical
method and biopharmaceuticals. The main reason behind
adoption of QBD is the regulatory requirements.
Pharmaceutical industry needs a regulatory compliance so as
to get their product approved for marketing. Nevertheless QBD
approach gives quality product with cost effective procedures
and that is the basic need. Moving within design space would
not require post approval changes thereby reducing the cost
involved.

14. References
1. M. N. Nasr. Implementation of quality by design (QbD): status, challenges, and next steps. FDA
Advisory Committee for Pharmaceutical Science. Available
at:http://www.fda.gov/ohrms/dockets/ac/06/slides/2006-4241s1_6.ppt (accessed 11/21/2007).
2. L. X. Yu. Implementation of quality-by-design: OGD initiatives. FDA Advisory Committee for
Pharmaceutical Science. Available at: http://www.fda.gov/ohrms /dockets/ac/06/slides/2006-
4241s1_8.ppt(accessed 11/21/2007).
3. W. P. Ganzer, J. A. Materna, M. B. Mitchell, and L. K. Wall. Current thoughts on critical process
parameters and API synthesis. Pharm. Technology.46–66 (2005), July.
4. Lawrence X. Pharmaceutical Research 2007; vol 25: No 4.
5. Kozlowski S. Protein therapeutics and the regulation of quality: a brief history from an OBP
perspective: as the biotechnology industry has matured through various stages of growth,
regulatory agencies have evolved in response to the need to define quality standards. Biopharm.
International.20(10),37–40 (2007).
6. Abboud L, Hensley S. Drug manufacturing, out of date for years, gets a shot in the arm – US’s FDA
prods industry to adopt innovations, raise quality standards. The Wall Street Journal Europe, 03
September 2003.
7. USFDA. Innovation and continuous improvement in pharmaceutical manufacturing
pharmaceutical cGMPs for the 21st Century(2004). www.fda.gov/ ohrms/dockets /ac/04/briefing/
2004 4080b1_01_manufSciWP.pdf
8. Food and Drug Administration CDER. Draft guidance for industry, ANDAs: Impurities in drug
products; 2005.
9. ICH.Quality Risk Management Q9(2005) . www.ich.org /fileadmin/ Public_Web_Site/ ICH_Products/
Guidelines/Quality/Q9/Step4/Q9_Guideline.pdf
10. ICH. Pharmaceutical Quality System Q10 (2008). www.ich.org /fileadmin /Public _Web_Site
/ICH_Products/Guidelines/Quality/Q10/Step4/Q10_Guideline.pdf

15. Thank You