SCIENTIFICALLY BASED QBD NAME:PAWAN DHAMALA SUB: CADD TOPIC:SCIENTIFICALLY BASED QUALITY BY DESIGN(QBD)

1. SEMINAR ON
SCIENTIFICALLY BASED
QUALITY BY DESIGN(QBD)
SUBJECT:- COMPUTER AIDED DRUG DEVELOPMENT
PRESENTED BY : PAWAN DHAMALA
YEAR : 2nd SEM M.PHARM
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2. CONTENTS
INTRODUCTION
SCIENTIFICALLY BASED QUALITY BY DESIGN
APPLICATIONS OF SCIENTIFICALLY BASED QUALITY BY
DESIGN
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3. INTRODUCTION
QbD comprises all elements of pharmaceutical development
mentioned in the ICH guideline Q8. Pharmaceutical Development
section is projected to provide a complete understanding of the product
and manufacturing process for reviewers and inspectors.
To design a quality product and its manufacturing process to
consistently deliver the intended performance of product is the aim of
pharmaceutical development. The information and knowledge gained
from pharmaceutical development studies and manufacturing
experience provide scientific understanding to support the
establishment of the specifications, and manufacturing controls.
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4. Different elements of pharmaceutical development include:
1. Defining Quality target product profile (QTPP)
2. Determination of critical quality attributes (CQA)
3. Risk assessment
4. Development of experimental design
5. Designing and implementing control strategy
6. Continuous improvement.
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7. • Some of the issues encountered by the regulatory agencies during the
assessment of a QbD based registration dossier are lack of relevant
explanations of the conclusions reached, insufficient graphical
presentations of the factor interactions, no information on statistical
validity of models, and not enough structure in the presented data
• Collaboration between scientists in industry, academia, and regulatory
bodies experts is necessary to overcome the above mentioned issues.
• Many scientific projects are devoted to design experimental space,
in-line process monitoring, and modeling of products and processes.
This knowledge should serve to provide a foundation for the
scientifically based QbD concept application.
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8. • The QbD approach was used to establish a relationship between the
CPPs, CQAs, and clinical performance of the drug.
1. Extended- release theophylline tablets were analyzed, showing that
some of the compendial tests are insufficient to communicate the
therapeutic consequences of product variability. Both critical and
noncritical attributes were used as inputs to the design space, which was
conditioned on quantitative estimates of efficacy and toxicity risk.
• A combined QbD and Discrete Element Model (DEM) simulation
approach was used to characterize a blending unit operation, by
evaluating the impact of formulation parameters and process variables
on the blending quality and blending end point.
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9. • QbD was used to establish content uniformity as CQA and
homogeneity, to identify potential critical factors that affect blending
operation quality.
• Results obtained were used to map a three dimensional knowledge
space, providing parameters to define a design space and set up an
appropriate control strategy.
• A quantitative approach was developed to simultaneously predict
particle and compact mechanical properties of a pharmaceutical blend,
based on the properties of the raw materials.
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10. 2. Experimental design was used to establish the design space, resulting in a
robust liposome preparation process.
• QbD principles were applied to an existing industrial fluidized bed
granulation process.
• Process analytical technology (PAT) monitoring tools were implemented at
the industrial scale process to increase the process knowledge.
• Scaled- down designed experiments were conducted at a pilot scale to
investigate the process under changes in CPPs. Finally, design space was
defined, linking CPPs to CQAs within which product quality is ensured by
design, and after scale- up, enabling its use at the industrial process scale.
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11. 3. The QbD approach was used in the formulation of dispersible tablets.
Critical material and process parameters were linked to CQAs of the product.
Variability was reduced by product and process understanding, which
translated into quality improvement, risk reduction, and productivity
enhancement.
• The risk management approach further led to a better understanding of the
risks, ways to mitigate them, and control strategy proposed commensurate
with the level of the risk.
• Using scientific knowledge derived from the literature and process
knowledge gathered during development studies and manufacturing to
support clinical trials, potential critical and key process parameters with a
possible impact on product quality and process performance, respectively,
were determined during a risk assessment exercise. The identified process
parameters were evaluated using a design of experiment approach.
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12. 4. QbD principles were used to investigate the spray drying process of
insulin intended for pulmonary administration. The effects of process
and formulation parameters on particle characteristics and insulin
integrity were investigated.
• Design of experiments and multivariate data analysis were used to
identify important process parameters and correlations between
particle characteristics. Principal component analysis was performed
to find correlations between dependent and independent variables.
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13. 5. A multiparticulate system, designed for colon- specific delivery of
celecoxib for both systemic and local therapy, was developed using
QbD principles.
• Statistical experimental design (Doehlert design) was employed to
investigate the combined effect of four formulation variables on drug
loading and release rate. Desirability function was used to
simultaneously optimize the two responses.
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14. 6. A QbD approach was also used to study the process of a
nanosuspension preparation, to establish appropriate specifications for
highly correlated active substance properties, to develop analytical
methods, and its usage in lead drug candidates optimization is proposed
to address productivity in drug discovery.
• The role of predictive biopharmaceutical modeling and simulation in
drug development, in the context of QbD was studied.
•The FDA has provided examples on implementation of QbD concepts
in abbreviated new drug applications (ANDA) for both immediate and
modified release dosage forms.
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15. SUMMARY
• QbD can facilitate innovation, increase manufacturing efficiency,
reduce cost/product rejects, minimize/eliminate potential compliance
actions, enhance opportunities for first cycle approval, streamline post
approval changes and regulatory processes, enable more focused
inspections, and provide opportunities for continual improvement.
• Many scientific projects are devoted to design space appointment,
in- line process monitoring, and modeling of products and processes.
This knowledge should serve to provide a foundation for the
scientifically based QbD concept application.
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