The document discusses Quality by Design (QbD), a systematic approach to pharmaceutical development that emphasizes product and process understanding based on sound science. Some key points: - QbD aims to build quality into products from the design stage to reduce testing and variability. Critical quality attributes, materials, and process parameters are identified. - A design space defines the multidimensional operating conditions that maintain quality. Processes are in control if they stay within the design space. - QbD benefits include reduced development time, lower costs, improved troubleshooting and flexibility for changes compared to traditional quality testing approaches.

1. Quality by Design (Qbd)

2. Due to involvement of APIs, various non functional excipients, manufacturing process,
pharmaceutical products face a high degree of variability in their quality .

3. •
Dr. Joseph M. Juran believed that quality issues mostly arise due to the design.
• He emphasized that quality must be built into the products by design and the traditional
practice of quality by testing should be avoided
• Quality by Design (QbD) is a concept.
• By ‘Quality’ it means a product free from contamination and reliably delivering the
therapeutic benefit promised in the label to the consumer
• By ‘Design’ it means the planned step wise process of creating a drug product.
•
• .
 What it is
•A quality system for managing
product life cycle.
•A way of quantifying risk.
What isn’t
•New
•Design of Experiments [DoE]
•Design Space

5. • Before QbD era
• The suitability of either a drug substance or a drug product for its intended use. The term
includes such attributes such as the identity, strength and purity (ICH Q6A).
• In short product needs to be tested to ensure quality.
• ICH Q8 guideline was published in May 2006 for pharmaceutical product development, and
has been complemented by the ICH Q9 on Quality Risk Management and ICH Q10 for a
Pharmaceutical Quality System.
• These guidelines emphasize quality by design (QbD), a science-based approach for designing
formulations and manufacturing processes in order to ensure predefined product quality
objectives.
• The fundamental assumption underlying QbD is that the quality of the product can be
assured only if critical sources of variability is understood and is suitably mitigated or
controlled within a defined design space

7. Principle Qbd Concepts
• Risk and knowledge based decisions
• Systemic approaches process development
• Continuous improvement
• Leads to Capable processes

8. Qbd Goals
• To achieve meaningful product quality specifications that are based on clinical performance
[Objectivity in product specification design].
• To increase process capability and reduce product variability and defects by enhancing
product and process design, understanding, and control. [Objectivity in manufacturing].
• To increase product development and manufacturing efficiencies. [Objectivity in supply]
• To enhance root cause analysis and post-approval change management. [Objectivity in
regulatory processes]
QbD is defined in the ICH Q8 guideline as “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.”

9. Benefits of Qbd
• Reduces development time
• Minimizes product cost by multiple times
• Helps in effective trouble shooting
• Facilitates timely launch of products
• Increases consumer generic acceptance
• Monitors regulatory oversight with greater
flexibility
• Maintains product life cycle with greater
ease

11. C
Process validation Continually monitor
manufacturing process

12. Elements of QBd

13. Quality Target Product Profile (QTPP)
FDA defines QTPP as the quality attributes related to safety and efficacy of the product.
Includes, but not limited to:
• Desired Elements
• Dosage form
• Route of administration
• Device design
• Packaging design
•Necessary Elements
• Pharmacokinetic characteristics (e.g. BA/BE, Dissolution)
• Quality characteristics for intended use (e.g. potency, purity)
• Shelf life
• It may include route of administration, dosage form, delivery systems, dosage strength(s), container closure system, pharmacokinetic consideration and drug product quality criteria (e.g., sterility, purity, stability, and drug release).
• It is important to acknowledge that QTPP should only include patient relevant product performance elements. For example, tablet density or hardness may be included as a specification for process monitoring but may not be included in QTPP.

14. • Important to acknowledge that QTPP should only include patient relevant product
performance elements.
• For example, tablet density or hardness may be included as a specification for process
monitoring but may not be included in QTPP.
• If particle size is critical to the dissolution of a solid oral product, then the QTPP should
include dissolution but not particle size
• For an NDA, the QTPP is under development while for the ANDA product, the QTPP is well
established based on the properties of the drug substance (DS), characterization of the
reference listed drug products (RDL), RLD label and intended patient population.
• Therefore, a generic drug product is expected to have same QTPP as that of brand or
reference product.

16. Critical quality attributes (CQA)
• A physical, chemical, biological or microbial property or characteristic that
should be within an appropriate limit, range, or distribution to ensure the
desired product quality (Q8)
• Potential CQA are derived from the QTPP and guide product and process
development.

17. WHEN IS A QUALITY ATTRIBUTE A CQA?
When the attribute has an impact on:
• Efficacy: “What if patient gets the wrong dose” e.g.
potency
• Safety: “What if the product has degradants or
genotoxic impurity or heavy metals”
• Quality: “What if the product is damaged-will the
patient take it?”
CQA ensures that drug product remains within
safe and effective levels
•CQA is Quantifiable-Directly (e.g. Assay) or
indirectly (e.g. dissolution)
•The CQA list is dynamic and can be updated
based on product and process knowledge

19. • FDA defines Quality Risk Management (QRM) as a systematic process for the assessment,
control, communication and review of risks to the quality of the drug product across the
product lifecycle.
• The goal of QRM is therefore to identify risks within a process or event, analyzing the
significance of these risks, and take appropriate measures to mitigate such risks if deemed
unacceptable.
• ICH Q9
• QRM is integral part of QbD as it helps in identifying the extent of the impact of critical
material attributes (CMA) and critical process parameter (CPP) on CQAs, which can eventually
assist in prioritizing the CQAs . They are particularly important in complex processes, especially
that are involved in cases of biologics or bio-similar.

20. Critical Material Attributes (CMA)
• Material include Raw materials, reagents, solvents, processing aids, intermediate stage
materials, API (s), packaging and labelling materials [ICH Q7A]
• Material Attributes: A physical, chemical, biological or microbial characteristic of a material
that has direct impact on the CQA.
• Material quantity are typically fixed per batch.
• A Material Attribute (MA) can be quantified
• Example of MA: PSD, Impurity profile, Untapped and Tapped density, viscosity, sterility,
moisture level

22. Critical Process Parameters (CPP)
A process parameter whose variability has an
impact on a CQA and therefore should be
monitored or controlled to ensure the process
produces the desired quality [ICH Q8]
•A process parameter (PP) can be measured
and controlled (adjusted)
Examples of PP’s: Temperature, spray
rates, compression force, humidity,
machine speed, air flow rates, stirrer
rpm, rate of addition

23. • CQAs are a function of MAs and CPPs

24. • A design space is a multidimensional combination of input variables (e.g., material
attributes), their interactions and process parameters that have been demonstrated to
provide assurance of quality
• A design space may be constructed for a single unit operation, multiple unit operations, or for
the entire process.
• Though according to FDA guideline, defining design space is optional since the product and
process understanding can be established without a formal design space, nevertheless, such
approach can assist to better understanding and attain overall control of a system.
CPPs and MAs are not independent but correlates
•The design space is a mathematical expression or graphical representation of link between
CPPs, MAs and CQAs
A process running within the design space is said to be in control