Quality by design vs control strategy
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This document discusses Quality by Design (QbD) and how to implement it in a practical way. It defines QbD and outlines the key steps, which include establishing a target product profile, identifying critical quality attributes, defining a design space, control strategy, validation, and lifecycle management. Design spaces can be defined using design of experiments or multivariate analysis of historical data. Tools like DOE and MVA are useful for establishing and monitoring the design space. The document provides an example target product profile and discusses how to set the profile and manufacturing process scheme based on the active pharmaceutical ingredient's properties. It also discusses using risk assessment to identify critical variables and control strategies. The overall goal is developing a robust process understanding and control
Quality by design vs control strategy
- 1. Surang Judistprasert Bio-innova & Synchron co.,ltd. Quality by Design Vs Control Strategy Turning QbD into a Practical Reality
- 2. ”A systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management” • ICH Harmonized Tripartite Guideline, Pharmaceutical Development Q8(R1), November 2008 •FDA Guidance for Industry, Q8(R1) Pharmaceutical Development, June 2009 Definition of Quality by Design (QbD) ICH and FDA
- 3. • Establish Target Product Profile (TPP) • Identify Critical Quality Attributes (CQA) • Define Product Design Space • Define Process Design Space • Establish Control Strategy • Validate and File • Monitor and Lifecycle Management Key steps in QbD
- 4. “A design space can be defined in terms of ranges of input variables or parameters (DOE), or through more complex mathematical relationships. It is possible to define a design space as a time dependent function (e.g., temperature and pressure cycle of a lyophilisation cycle), or as a combination of variables such as principal components of a multivariate model (MVA). Factors can also be included if the design space is intended to span multiple operational scales. Analysis of historical data can provide the basis for establishing a design space (MVA). Regardless of how a design space is developed, it is expected that operation within the design space will result in a product meeting the defined quality attributes.” Formal definition of the Design Space concept
- 5. DOE and MVA DOE in QbD - Knowledge tool - Identify critical Interactions MVA to manage resulting data amount - Additional knowledge - Batch evolution models - Batch summary models DOE to establish and confirm Design space MVA to monitor process relation to design space
- 6. Guideline / Instructions Part 2
- 8. Quality attribute Target Criticality Dosage form Tablet, max. wt 200 mg Not applicable Potency 20 mg Not applicable Pharmacokinetics Immediate release enabling Tmax in 2 hr or less Relate to Dissolution Appearance Tablet conforming to description shape and size Not applicable Identity Positive for API Critical Assay 95-105% LA of API Critical Impurities API123 NMT 0.5% , other imp. NMT 0.2% , total imp. NMT 1% Critical Water NMT 1% Not critical, API not sensitive for hydrolysis Content Uniformity Meet USP Critical Resistance to crushing (hardness) 5-12 kp Not critical since relate to dissolution Friability NMT 1% Not critical Dissolution Consistent with immediate release, e.g. NLT 75% at 30 mins Critical Disintegration Not more than 15 mins Not critical, precursor to dissolution Microbiology If test required, meets USP criteria Critical only with drug product support microbial growth Target product profile
- 9. How to set product target profile
- 10. How to set process scheme?
- 11. • Prior knowledge about Nature and Stability of API • Hydrolysis • Oxidation • Acid hydrolysis • Basis hydrolysis • Photo sensitive • Hygroscopic • Polymorph change • Nature of agglomerate • Particle size distribution • Solubility • Moisture content • Residual solvent First priority Wet granulation Dry granulation Direct compression Functional coated Packaging closure design
- 12. • Recommend one or more of the strategies. • Summarize the results if things go as proposed. • What to do next. • Identify action items. Control strategy
- 13. Risk Assessment to Identify Variables Potentially Impacting Product Quality
- 14. Potential impact of Excipients on Drug Product CQAs
- 15. DOE and overall risk assessment in line with process understanding developed
- 16. Example design space Example Control Strategy for CQAs
- 17. This slide will be provided only attendee in the seminar room Tools for R&D
- 18. Thank you…