SCIENTIFICALLY BASED QUALITY BY DESIGN(QBD) and APPLICATION.pptx

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 COMPUTER AIDED DRUG DELIVERY SUBMITTED BY : SUBMITTED TO: PAWAN DHAMALA PROF. Mr. K MAHALINGAM 2 nd SEM , M.PHARMACY DEPARTMENT OF PHARMACEUTICS

2. CONTENTS INTRODUCTION SCIENTIFICALLY BASED QUALITY BY DESIGN APPLICATIONS OF SCIENTIFICALLY BASED QUALITY BY DESIGN 11-02-2023 © R R INSTITUTIONS , BANGALORE 2

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.  11-02-2023 © R R INSTITUTIONS , BANGALORE 3

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. 11-02-2023 © R R INSTITUTIONS , BANGALORE 4

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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. 11-02-2023 © R R INSTITUTIONS , BANGALORE 7

8. • The QbD approach was used to establish a relationship between the CPPs, CQAs, and clinical performance of the drug. 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. 11-02-2023 © R R INSTITUTIONS , BANGALORE 8

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. 11-02-2023 © R R INSTITUTIONS , BANGALORE 9

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. 11-02-2023 © R R INSTITUTIONS , BANGALORE 10

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. 11-02-2023 © R R INSTITUTIONS , BANGALORE 11

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. 11-02-2023 © R R INSTITUTIONS , BANGALORE 12

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. 11-02-2023 © R R INSTITUTIONS , BANGALORE 13

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. 11-02-2023 © R R INSTITUTIONS , BANGALORE 14

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. 11-02-2023 © R R INSTITUTIONS , BANGALORE 15

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: 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. 11-02-2023 © R R INSTITUTIONS , BANGALORE 16

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. 11-02-2023 © R R INSTITUTIONS , BANGALORE 17

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 11-02-2023 © R R INSTITUTIONS , BANGALORE 18

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 11-02-2023 © R R INSTITUTIONS , BANGALORE 19

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. 11-02-2023 © R R INSTITUTIONS , BANGALORE 20

21. REFERENCE 11-02-2023 © R R INSTITUTIONS , BANGALORE 21

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