SCIENTIFICALLY BASED QUALITY BY DESIGN(QBD) and APPLICATION PAWAN DHAMALA

1. 11-02-2023 © R R INSTITUTIONS , BANGALORE 1
SEMINAR ON
SCIENTIFICALLY BASED QUALITY BY DESIGN(QBD) and APPLICATION
RR COLLEGE OF PHARMACY
SUBMITTED BY: SUBMITTED TO:
PAWAN DHAMALA PROF. Mr. K MAHALINGAM
2nd SEM , M.PHARMACY
DEPARTMENT OF PHARMACEUTICS

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. APPLICATION OF QBD
• 1. Implementation of QbD for the development of a vaccine candidate:
• Quality by Design (QbD) principles were applied to accelerate process
development to manufacture a vaccine candidate at commercial scale.
• By leveraging an existing manufacturing platform process, a risk
assessment was used to differentiate process parameters that could be
defined using a combination of scientific and historical manufacturing
knowledge from those that merited additional process characterization by
experimentation. Select parameters, and their inter-actions, were evaluated
by a Design of Experiment (DoE) series.
• This systematic approach required less time and fewer resources and
resulted in the definition of a reliable and robust manufacturing process that
meets regulatory requirements.
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16. • 2. Quality by design(QbD) based process development for biotherapeutic
purification:
• QbD was introduced to biotech manufacturing in 2004 with the publication
of the PAT Guideline. Over the past decade, the biotech industry and its
regulatory agencies have worked together effectively to elucidate the
roadmap for QbD implementation.
• While the underlying concepts have been widely accepted and most major
manufacturers are in the advanced stages of integrating QbD into the
various work processes, smaller and midsized manufacturers struggle with
successfully implementing QbD.
• 3) QbD to analytical method:
A) For chromatographic technique:
Eg: a) In determination of impurity.
b) In screening of column used for chromatography.
c) In development of HPLC method for drug products/ substances.
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17. d) In capillary electrophoresis.
e) In stability studies.
f) In UHPLC.
B) For hyphenated technique:
Eg: a) In LC–MS method development.
C) In bio-analytical method development.
D) In dissolution studies.
E) For spectroscopic measurements:
Eg: a) In handling complex spectroscopic data.
b) In mass spectroscopy.
c) In near infrared.
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18. • 4) Other applications of QbD or elements of QbD
a) Pharmaceuticals
• In modified release products.
• In sterile manufacturing
• In solid oral dosage form
• Contribution of (SEM/EDX) to QbD by investigation of pharmaceutical
materials
• In gel manufacturing
• QbD for ANDAs
• In tableting process
• Impact of genotoxic impurities on process development
• In co-precipitation process
• Nano-suspension preparation
• In analysis of excipients and API
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19. b) Biopharmaceuticals.
• In manufacturing of protein
• In production and characterization of monoclonal antibody
• For chromatographic technique used for purification
• PAT and QbD for biopharmaceutical
• In nano-medicine
• Challenges and solution for application of QbD to biopharmaceutical
c) Clinicals.
d) Genetics
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20. 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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21. REFERENCE
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