Quality By Design In pharmaceutical Development

1. QUALITY BY DESIGN IN PHARMACEUTICAL DEVELOPMENT
PRESENTED BY GUIDE
MR. SHUBHAM GAJANAN WAGH PROF. S.C.ATRAM
M.pharm (pharmaceutics) 1st year
VIDYA BHARATI COLLEGE OF PHARMACY, AMRAVATI-444602
2021-22

2. INDEX
Sr. No. Contents Page No.
1 Introduction 3
2 Benefits of quality by design 4
3 Approaches to pharmaceutical development 5
4 Flow of quality by design 6
5 Product profile 7
6 Critical Quality Attributes (CQAs) 8-9
7 Risk assessment 10
8 Design space 11
9 Control strategy 12
10 Life cycle management and continuous improvement 13
11 References 14
2

3. INTRODUCTION
Definition of quality by design
 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
 Quality by Design is a concept first outlined by Joseph M. Juran in various publications.
 He supposed that quality could be planned. The concept of QBD was mention in ICH Q8 guidelines,
which states that, “To identify quality can not be tested in products, i.e. Quality should be built in to
product by design.”
Objective of QbD
 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.
3

4. BENEFITS OF QUALITY BY DESIGN
Benefits of QBD for Industry
 Eliminate batch failures.
 Minimize deviations and costly investigations.
 Empowerment of technical staff.
 Increase manufacturing efficiency, reduce costs and project rejections and waste.
 Better understanding of the process.
 Continuous improvement.
 Ensure better design of product with less problem.
Benefits of QBD for FDA
 Provide better consistency.
 More flexibility in decision making.
 Ensure scientific base of analysis.
 Ensures decisions made on science and not on empirical information.
 Improves quality of review.
4

5. APPROACHES TO PHARMACEUTICAL DEVELOPMENT
5
Aspects Traditional Quality by design
Pharmaceutical development Empirical
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 feedback
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

6. FLOW OF QUALITY BY DESIGN
6
Product profile
Identify critical quality attributes (CQA)
Carry out risk assessment
Establish the design space
Describe control strategy
Life cycle management and continuous improvement

7. PRODUCT PROFILE
Target Product Profile (TPP)
 “A prospective summary of the quality characteristics of drug product that ideally will be achieved to
ensure the desired quality, taking in to account safety & efficacy of drug product.”(ICH Q8)
 Target product profile should includes- Dosage form, Route of administration, Dosage strength,
Pharmacokinetics, Stability
 The TPP is a patient & labeling centered concepts, because it identifies the desired performance
characteristics of the product, related to the patient’s need & it is organized according to the key section in
the drug labeling.
Quality Target Product Profile (QTPP)
 QTPP is a quantitative substitute for aspects of scientific safety & efficacy that can be used to design and
optimize a formulation and mfg. 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.
7

8. CRITICAL QUALITY ATTRIBUTES (CQAS)
Definition
 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.
 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, score configuration, and friability. These attributes can be
critical or not critical.
Critical Material Attributes (CMA)
 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 within an appropriate limit to
ensure the desired quality of that drug substance, excipient, or in-process material.
 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.
8

9. Critical Process Parameter (CPPs)
 Critical process parameters (CPPs) are defined as “parameters whose variability have an impact on
a CQA and therefore should be monitored or controlled to ensure the process produces the desired
quality”
 Process robustness is defined as the ability of a process to demonstrate acceptable quality and
performance and tolerate variability in inputs at the same time.
 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
9
CRITICAL QUALITY ATTRIBUTES (CQAS)

10. RISK ASSESSMENT
 Quality risk management is a systematic process for the assessment, control, communication and
review of risks to the quality of the drug (medicinal) product across the product lifecycle.
 Risk assessment is a valuable science-based process used in quality risk management that can aid in
identifying which material attributes and process parameters potentially have an effect on product
CQAs.
 Risk assessment is typically performed early in the pharmaceutical development process and is
repeated as more information becomes available and greater knowledge is obtained.
 Risk assessment is the linkages between material attributes & process parameters.
 It is performed during the lifecycle of the product to identify the critical material attributes (CMA)
& critical process parameters (CPP).
10

11. DESIGN SPACE
As per ICH Q8-
Design Space 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.
 The relationship between the process inputs (material attributes and process parameters) and the critical
quality attributes can be described as the design space
 A design space may be built for a single unit operation or for the ensure process.
 Design space is proposed by the applicant and is subject to regulatory assessment and approval (ICH Q8).
 A design space can be described in terms of ranges of material attributes and process parameters.
 It can also be described through more complex mathematical relationships.
 It is possible to describe a design space as a time dependent function (e.g., temperature and pressure
cycle of a lyophilisation cycle), or
 As a combination of variables such as components of a multivariate model.
11

12. CONTROL STRATEGY
 Control strategy is defined as “a planned set of controls, derived from current product and process understanding
that assures process performance and product quality”.
 The ability to evaluate and ensure the quality of in- process and/or final product based on process data which
typically include a valid combination of measured material attributes and process controls. ICH Q8(R2).
 The control strategy can include the following elements: procedural controls, in process controls, lot release testing,
process monitoring, characterization testing, comparability testing and stability testing .
 Control strategy Based on process and product understanding, during product development sources of variability are
identified.
 Understanding the sources of variability and their impact on processes, in-process materials, and drug product
quality can enable appropriate controls to ensure consistent quality of the drug product during the product life cycle.
Elements of a Control Strategy
 Procedural controls
 In-process controls
 batch release testing
 Process monitoring
 Characterization testing
 Comparability testing
 Consistency testing 12

13. LIFE CYCLE MANAGEMENT AND CONTINUOUS IMPROVEMENT
13
 In the QbD paradigm, process changes within the design space will not require review or approval. Therefore,
process improvements during the product life cycle with regard to process consistency and throughput could
take place with fewer post approval submissions.
 In addition to regulatory flexibility, the enhanced understanding of the manufacturing process would allow more
informed risk assessment as per ICH Q9 regarding the affects of process changes and manufacturing deviations
on product quality.
 Manufacturing, the experience grows and opportunities for process improvement identified are operating space
could be revised within the design space without the need for post-approval submission.
 Over the lifetime of a product, process changes may be required to be made and may require process
characterization, validation and filing of the changes to the approved process design space.
 The quality system needs to provide adequate oversight during QbD implementation of changes that will not go
through regulatory approval.
 Robustness of the quality system would need to be demonstrated with respect to the following four elements:
 process performance/product quality monitoring
 preventative/corrective action,
 change management and
 management review of process performance and product quality

14. REFERENCE
 https://www.slideshare.net/ManishRajput58/quality-by-design-in-pharmaceutical-development-141388093
 https://learnaboutgmp.com/good-validation-practices/pharmaceutical-quality-by-design-qbd-an-introduction-
process-development-and-applications/
 https://www.google.com/amp/s/www.pharmatutor.org/articles/quality-by-design%3Famp
14