Quality by design (QbD) is a systematic approach to product development that starts with predefined goals and focuses on product and process quality.

1. QUALITY BY DESIGN IN
PHARMACEUTICAL DEVELOPMENT
PHARMACEUTICALQUALITY ASSURANCE
DEPARTMENTOF PHARMACEUTICALSCIENCE AND TECHNOLOGY
BIRLA INSTITUTE OF TECHNOLOGY, MESRA

2. • Quality by design (QbD) is a systematicapproach to product development
that starts with predefined goals and focuses on product and process quality.
• understanding and controls founded on sound science, as well as quality risk
management (ICH Q8)
INTRODUCTION

3. • The emphasis of QbD began with the recognition that increased testing
does not essentially improve product quality; however, quality must be
built into the product.
• The regulatory agencies promote risk-based approaches and the
application of QbD principles in drug product development and
manufacturing.

4. QbD approach in product development, which is characterized
by following principles:
• Designing product and its manufacturing process to meet patient needs with
respect to safety and efficacy
• Designing manufacturing process to consistentlyproduce product meeting pre-
defined quality criteria
• Understanding impact of input parameters on product quality to adequately build
the control at the critical points in the process

5. • A CQA is a physical, chemical, biological, or microbiological property of an output
drug product that should be within an acceptable range to ensure the desired
product quality
• These characteristics can be critical or non-critical. The importance of an attribute is
determined primarily by its impact on the patient's safety and efficacy.
CRITICAL QUALITY ATTRIBUTES (CQA)

6. • Identity, assay, contentuniformity, degradation products, residual
solvents, drug release, moisture content,microbial limits, and
physical attributes such as color, shape, size, odor, score
configuration, and friability are examples of quality attributes of a
drug product

7. • A risk assessment would be beneficial in identifying critical material attributes
and process parameters. The evaluation should be based on the formulation
scientist'sscientific knowledge and expertise.
• A material or process attribute is considered critical when a change in that
attribute has a significant impact on the output material's quality (CQA).
RISK ASSESSMENT

8. Risk can be categorized depending upon likelihood and its impact on process or formula
(Figure 1). Considering 3 different levels (high, medium, and low)be considered.

9. • A CMA of a drug substance,excipient, or in-process material is a physical,
chemical, biological, or microbiological characteristic of an input material that
should be consistentlywithin an appropriate limit to ensure that drug
substance,excipient, or in-process material has the desired quality.
• The CMA is likely to have an impact on the drug product's CQA.
CRITICAL MATERIAL ATTRIBUTES (CMA)

10. • A manufacturing process CPP is a set of parameters that,
when changed, can potentially impact product CQA and
result in failure to meet the CQA limit.
CRITICAL PROCESS PARAMETERS (CPP)

11. • According to ICH Q8, this is the multidimensional combination and interaction
of input variables (e.g., material attributes) and process parameters that has
been shown to provide quality assurance.
• A design space can be created to support a single unit operation or the entire
process.
• The design space could be the direct result of DoE data analysis or other
validated models.
DESIGN SPACE

12. • Working in the design space is not considered a change.
• Moving out of the design space is considered a change and would normally
trigger a regulatory post-approval change process.
• The applicant proposes design space, which is subject to regulatory
assessmentand approval.

13. Pharmaceutical quality systems for quality by design

14. Quality by design system

16. • Figure 2 depicts a schematic representation of the QbD approach in product
development. It is based on the formulation scientist's scientific knowledge and
expertise.
• A material and process attribute is considered critical when a change in that
attribute has a significant impact on the quality (CQA) of the output material.
• The risk assessment is carried out by linking raw material attributes and process
parameters to CQAs in order to determine the severity of risk using tools such as
basic risk management methods (flowcharts, check sheets, etc.), Failure Mode
Effects Analysis (FMEA), risk ranking and filtering, and so on.

17. • This is a systemic approach to conducting experiments in order to maximize output. We
have the ability and experience to perform DoE in product development using software
such as Minitab and Statistica.
• Screening designs are used to screen a large number of factors in a small number of
experiments in order to identify the significant ones. The primary goal of these designs is
to identify main effects rather than interaction effects. Plackett-Burman and fractional
factorial designs are common in such studies.
DESIGN OF EXPERIMENT (DOE)

18. • Diagrams of Cause and Effect (fish bone/Ishikawa): This is a very simple
methodology for identifying multiple potential factors for a single effect .
• To identify the root cause, various causes associated with a single effect, such as
man, machine, material, method, system, and environment, must be considered.
RISK-ASSESSMENT METHODOLOGY

20. Prepared by:
Mr. Santosh Kumar
Mr. Navendu Roy
Mr. Aman kishor Mahto
PHARMACEUTICAL QUALITY ASSURANCE
DEPARTMENT OF PHARMACEUTICAL SCIENCE AND TECHNOLOGY
BIRLA INSTITUTE OF TECHNOLOGY, MESRA