Quality by design (QbD)

the main target is to build the quality into the product, prior the actual testing procedure.

1. Quality : The suitability of a drug substance or a drug product for its intended use; customer satisfaction. The concept of Quality by design was summarized by a well known quality expert Joseph Moses Juran ; he believed that quality could be planned and that most quality associated problems have their origin in the way which quality was planned in the first place. Adapted from: QbD concept as presented by U.S.F.D.A

2. The principles of QbD have been used to advance the product and process quality in every industry. Because of need of potent drug with safety profile, pharmaceutical industries are investing billions of money in the drug discovery and development process with endeavour to design quality product and that to with consistency in manufacturing process to deliver the intended performance of product.

3. The Juran Trilogy defines the word " quality " as having two meanings: first , the presence of features that create customer satisfaction; second , the reliability of those features. Failures in features create dissatisfactions, so removing failures is the purpose of quality improvement, while creating features is the purpose of quality by design.

4. During the drug development process , the aspects like drug substances, excipients, container closure systems, manufacturing processes and quality control tests are critical to product quality . QbD involves thorough understanding of process; a goal or objective is defined before actual start of process.

5. FDA’s view of QbD is ‘‘ QbD is a systematic approach to product and process design and development’’. This concept was accepted by FDA in 2004 and detailed description was given in ‘pharmaceutical cGMPs for 21st century – a risk based approach’. ‘‘ QbD does not necessarily mean less analytical testing’’ rather, it means the right analysis at the right time, and is based on science and risk assessment.

6. Regulatory Control Guidelines Emphasising QbD :  The QbD approach which is based on scientific and methodical product development was included in the quality guidelines of ICH from 2005 onwards. This approach includes, ICH Q8 : Pharmaceutical Development, Q9 : Quality Risk Management, and Q10 : Pharmaceutical Quality System guidelines . The pharmaceutical products quality was also emphasised in Process Analytical Technology [PAT] guidelines for new pharmaceutical product development and quality .

7. Adapted from: PME

8. Factors affecting properties of products and processes: Mixing speed Pressure Temperature Moisture level Raw material Sterility Dissolution ………so on

9. ICH Q8: Pharmaceutical Development: It discusses the various element of Quality by Design . Define the Quality Target Product Profile Identify the Quality Attributes Perform a Risk [Assessment] Analysis Determine the Critical Quality Attributes and Critical Process Parameter Determine the Design Space Identify a Control Strategy

10. Quality Target Product Profile [QTPP]: QTPP is “Prospective summary of the quality characteristics of a drug product that ideally will be achieved to ensure the desired quality, taking into account safety and efficacy of the drug product”. It is the quality characteristics that the drug product should possess in order to reproducibly deliver the therapeutic benefit promised in the label. 2. Quality Attributes: Once QTPP has identified, the next step is to identify the relevant CQAs. A critical quality attribute as defined by ICH is a physical, chemical, biological, or microbiological characteristic that should be within an appropriate limit, range, or distribution to ensure the desired product quality.

11. For Drug Substance [Chemical] For Drug Product [Tablet] Appearance Particle size Morphic forms Water content Residual solvents Organic impurities Inorganic impurities Heavy metals Residue on ignition Assay Appearance Identification Hardness Uniformity of dosage Physical form Dissolution Degradation products Water content Assay

12. ICH Q9: Quality Risk Management [QRM]

13. ICH Q10: Quality System A control strategy normally include input material controls, process controls and monitoring, design space around individual or multiple unit operations, and/or final product specifications used to ensure consistent quality . The finished drug products are tested for quality by assessing if they meet specifications.

14. Advantages of QbD Benefits for Industry : Better understanding of the process. Less batch failure. More efficient and effective control of change. Return on investment / cost savings . Advantages of QbD : Patient safety and product efficacy are focused. Scientific understanding of pharmaceutical process and methods is done. It involves product design and process development. Science based risk assessment is carried. Critical quality attributes are identified and their effect on final quality of product is analysed . It offers robust method or process. Business benefits are also driving force to adopt QbD .

15. C onclusion Quality activities must try to detect quality problems early enough to permit actions without requiring compromise in cost, schedule or quality. The emphasis must be on precaution rather than on just correction of quality problems. Hence the quality has to be built in the product as well as services through proper planning, so that the forth coming failure can be avoided. Quality cannot be tested into products but should be built-in or should be by design.

16. References “Quality by design approach: Regulatory need”, AJC (2017) 10, S3412–S3425 “APPLICATION OF QUALITY BY DESIGN TO DIFFERENT ASPECTS OF PHARMACEUTICAL TECHNOLOGIES”, IJPSR, 2017; Vol. 8(9): 3649-3662.