Quality by design

Quality by design

1. Quality by Design Siddu K M 1 st M P harm D epartment of Pharmaceutics Al Ameen College of Pharmacy, Bengaluru

2. CONTENTS INTRODUCTION ICH Q8 GUIDELINES PHARMACEUTICAL DEVELOPMENT ANNEX TO PHARMACEUTICAL DEVELOPMENT REGULATORY AND INDUSTRY VIEWS ON QBD APPLICATIONS OF QbD IN PHARMACEUTICAL UNIT OPERATIONS 25-02-2019 2 Al Ameen College Of Pharmacy, Bengaluru

3. Introduction Quality is suitability of either a drug substance or a drug product, which includes identity, strength, and purity. QbD : The pharmaceutical quality by design is a systematic approach to development that begins with predefined objectives and emphasizes product and process control, based on sound science and quality risk. 25-02-2019 3 Al Ameen College Of Pharmacy, Bengaluru

4. ICH Q8 GUIDELINES In the ICH guidelines , Q8 guidelines mainly discuss about Pharmaceutical development. There are two parts of ICH Q8 guidelines PART 1 : P harmaceutical Development PART 2 : Annex to Pharmaceutical Development 25-02-2019 4 Al Ameen College Of Pharmacy, Bengaluru

5. PART 1 : PHARMACEUTICAL DEVELOPMENT Components of the drug product Drug substance Excipients Drug product Formulation development Overages Physicochemical & biological properties Manufacturing process development Container closure system Compatibility 25-02-2019 5 Al Ameen College Of Pharmacy, Bengaluru

6. PART 2 : ANNEX TO P’CEUTICAL DEVELOPMENT Quality Target Product Profile (QTPP) Critical Quality Attributes(CQA) Risk Assessment Design space Control strategy Product lifecycle management & continual improvement 25-02-2019 6 Al Ameen College Of Pharmacy, Bengaluru

7. Components of drug product Drug substance The physicochemical and biological properties of the drug substance that can influence the performance of the drug product and its manufacturability. Solubility Water content Particle size Crystal properties Biological activity permeability 25-02-2019 7 Al Ameen College Of Pharmacy, Bengaluru

8. Excipients The excipients chosen, their concentration, and the characteristics that can influence the drug product performance or manufacturability should be discussed relative to the respective function of each excipients. The compatibility of the drug substance with excipients should be evaluated. For products that contain more than one drug substance, the compatibility of the drug substances with each other should also be evaluated. 25-02-2019 8 Al Ameen College Of Pharmacy, Bengaluru

9. Drug product Formulation development Intended usage and route of administration Information from formal experimental designs the manufacturing process Overages In general, use of an overage of a drug substance to compensate for degradation during manufacture or a product’s shelf life, or to extend shelf life, is discouraged. Any overages in the manufacture of the drug product, whether they appear in the final formulated product or not, should be justified considering the safety and efficacy of the product 25-02-2019 9 Al Ameen College Of Pharmacy, Bengaluru

10. Physicochemical and Biological Properties The physicochemical and biological properties relevant to the safety, performance or manufacturability of the drug product should be identified and discussed . 25-02-2019 10 Al Ameen College Of Pharmacy, Bengaluru

11. Manufacturing process development The manufacturing process development programme should identify any critical process parameters that should be monitored or controlled (e.g., granulation end point) to ensure that the product is of the desired quality. An assessment of the ability of the process to reliably produce a product of the intended quality (e.g., the performance of the manufacturing process under different operating conditions, at different scales, or with different equipment) can be provided. 25-02-2019 11 Al Ameen College Of Pharmacy, Bengaluru

12. Container Closure System Consideration should be given to the intended use of the drug product and the suitability of the container closure system for storage and transportation (shipping ). The choice of primary packaging materials should consider, e.g., choice of materials, protection from moisture and light, compatibility of the materials of construction with the dosage form (including sorption to container and leaching), and safety of materials of construction. Justification for secondary packaging materials should be included, when relevant. 25-02-2019 12 Al Ameen College Of Pharmacy, Bengaluru

13. Compatibility The compatibility of the drug product with reconstitution diluents (e.g., precipitation, stability) should be addressed to provide appropriate and supportive information for the labelling . This information should cover the recommended in-use shelf life, at the recommended storage temperature and at the likely extremes of concentration. 25-02-2019 13 Al Ameen College Of Pharmacy, Bengaluru

14. 25-02-2019 14 Al Ameen College Of Pharmacy, Bengaluru

15. Quality Target Product Profile The quality target product profile forms the basis of design for the development of the product. Considerations for the quality target product profile could include: Intended use in clinical setting, route of administration, dosage form, delivery systems . Dosage strength(s) Container closure system ; 25-02-2019 15 Al Ameen College Of Pharmacy, Bengaluru

16. Critical Quality Attributes A CQA is a physical, chemical, biological, or microbiological property or characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality. CQAs are generally associated with the drug substance, excipients, intermediates (in-process materials) and drug product . CQAs of solid oral dosage forms are typically those aspects affecting product purity, strength, drug release and stability . CQAs for other delivery systems can additionally include more product specific aspects, such as aerodynamic properties for inhaled products, sterility for parenterals , and adhesion properties for transdermal patches. 25-02-2019 16 Al Ameen College Of Pharmacy, Bengaluru

17. Risk Assessment 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 tools can be used to identify and rank parameters (e.g., process, equipment, input materials) with potential to have an impact on product quality, based on prior knowledge and initial experimental data. 25-02-2019 17 Al Ameen College Of Pharmacy, Bengaluru

18. Risk assessment tools Failure Mode Effects Analysis [FMEA] Failure Mode, Effects and Criticality Analysis [FMECA] Fault Tree Analysis [FTA] Hazard Analysis and Critical Control Points [HACCP] Hazard Operability Analysis [HAZOP] Preliminary Hazard Analysis [PHA] 25-02-2019 18 Al Ameen College Of Pharmacy, Bengaluru

19. Design Space The multidimensional combination and interaction of input variables and process parameters that have been demonstrated to provide assurance of quality. Working within the design space is not considered as a change. Movement out of the design space is considered to be a change and would normally initiate a regulatory post approval change process.  25-02-2019 19 Al Ameen College Of Pharmacy, Bengaluru

20. 25-02-2019 20 Al Ameen College Of Pharmacy, Bengaluru

21. Control strategy A control strategy is designed to ensure that a product of required quality will be produced consistently. It should justify how in-process controls and the controls of input materials (drug substance and excipients), intermediates (in-process materials), container closure system, and drug products contribute to the final product quality. It can be possible to design an adaptive process step (a step that is responsive to the input materials) with appropriate process control to ensure consistent product quality. 25-02-2019 21 Al Ameen College Of Pharmacy, Bengaluru

22. A control strategy can include, Control of input material attributes (e.g., drug substance, excipients, primary packaging materials) based on an understanding of their impact on process ability or product quality; Product specification(s ); Controls for unit operations that have an impact on downstream processing or product quality (e.g., the impact of drying on degradation, particle size distribution of the granulate on dissolution ); In-process or real-time release testing in lieu of end-product testing (e.g. measurement and control of CQAs during processing ); A monitoring program (e.g., full product testing at regular intervals) for verifying multivariate prediction models. 25-02-2019 22 Al Ameen College Of Pharmacy, Bengaluru

23. Product Lifecycle Management and Continual Improvement Throughout the product lifecycle, companies have opportunities to evaluate innovative approaches to improve product quality Process performance can be monitored to ensure that it is working as anticipated to deliver product quality attributes as predicted by the design space . For certain design spaces using mathematical models, periodic maintenance could be useful to ensure the model’s performance . 25-02-2019 23 Al Ameen College Of Pharmacy, Bengaluru

24. REGULATORY AND INDUSTRY VIEWS ON QBD FDA initiated the adoption of new technologies and risk based approaches in pharma product development and are encouraged in 21 st century . As defined by an FDA official, the QbD concept represents product and process performance characteristics scientifically designed to meet specific objectives, not merely empirically derived from performance of test batches. QbD can facilitate innovation, increase manufacturing efficacy, cost reduction, minimize potential compliance actions, streamline post approval changes etc., 25-02-2019 24 Al Ameen College Of Pharmacy, Bengaluru

25. 25-02-2019 25 Al Ameen College Of Pharmacy, Bengaluru

26. 25-02-2019 26 Al Ameen College Of Pharmacy, Bengaluru

27. Once the product understanding is obtained, it is possible to identify and manage critical sources of variability and design effective manufacturing process that allow assurance of quality in real time. EMA , FDA, and ICH have appointed ICH quality implementation working group, which prepared a document which provides an overview on different modelling techniques in QbD . In QbD context, the model is defined as a simplified representation of a system using mathematical forms . Models are expected to predict the behavior of system and enhance scientific understanding under a set of conditions. 25-02-2019 27 Al Ameen College Of Pharmacy, Bengaluru

28. 25-02-2019 28 Al Ameen College Of Pharmacy, Bengaluru

29. 25-02-2019 29 Al Ameen College Of Pharmacy, Bengaluru

30. Thank You 25-02-2019 30 Al Ameen College Of Pharmacy, Bengaluru