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![Slide 32 May 2008
Definition of Design Space
The material attributes and process parameters that
assure quality.
The multidimensional combination
and interaction of input variables
(e.g. material attributes) and
process parameters that have been
demonstrated to provide assurance
of quality.
Roll pressure
Gap width
Screen Size
300
200
100
0
-100
Dataset - Run1-10a.M3
Observed vs. Predicted $Time [Last comp.] (Aligned)
0 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200 210 220 230 240 250 260
$Time (normalized)
SIMCA-P+ 11.5 - 05/02/2007 23:17:07](https://image.slidesharecdn.com/qualitydesign-140920223401-phpapp01/85/Quality-design-32-320.jpg)
Uploaded byabubacker siddiq
Quality design
This document summarizes the steps in a Quality by Design (QbD) approach for pharmaceutical development: 1. Define the Target Product Profile to outline the desired quality characteristics. 2. Determine the Critical Quality Attributes that ensure the product's safety, efficacy and quality. 3. Link the material attributes, process parameters and Critical Quality Attributes through experimental studies and risk assessment. 4. Define the Design Space as the multidimensional combination of input variables and process parameters that provide quality assurance. 5. Establish a control strategy for inputs, processes and outputs to maintain final product quality within the design space.
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- 1. QUALITY BY DESIGN Slide 1 May 2008 Training Workshop on Pharmaceutical Development with focus on Paediatric Formulations Mumbai, India Date: May 2008
- 2. Dr Tom Sam President Industrial Pharmacy Section International Pharmaceutical Federation (FIP) Slide 2 May 2008 QUALITY BY DESIGN
- 3. Slide 3 May2008 QUALITY BY DESIGN processes products
- 4. Slide 4 May2008 What is Quality? Quality Patient (or surrogate) Target Product Quality Profile Requirements = need or expectations “Good pharmaceutical quality represents an acceptably low risk of failing to achieve the desired clinical attributes.”
- 5. Slide 5 May2008 Which quality do we want for our medicines ? 6σ DPMO (defectsper million opportunities) Restaurant bills Airlines baggagecheck in Best-in-class Egypt Air (5,8s) Air India(5,8) Lufthansa (6,6s) Quantas, SAS 2σ 3σ 4σ 5σ 6σ 7σ Source: Motorola, Air Safety Online Quelle: Motorola, Air Safety Online
- 6. With which qualitydo we manufacture our medicines: 6σ, 5σ, 4σ, 3σ, 2σ ? DPMO (defectsper million opportunities) Slide 6 May 2008 Restaurant bills Airlines baggagecheck in Best-in-class Egypt Air (5,8s) Air India(5,8) Lufthansa (6,6s) Quantas, SAS 2σ 3σ 4σ 5σ 6σ 7σ Source: Motorola, Air Safety Online Quelle: Motorola, Air Safety Online Current Mfg Quality provided to patients
- 7. How do wefill this quality gap in the pharmaceutical industry? Slide 7 May 2008 SSiiggmmaa ppppmm DDeeffeeccttss YYiieelldd 22s 330088,,553377 33s 6666,,880077 44s 66,,221100 55s 223333 66s 33..44 6699..22%% 9933..33%% 9999..44%% 9999..9988%% 9999..9999996666%% CCoosstt ooff QQuuaalliittyy 2255--3355%% 2200--2255%% 1122--1188%% 44--88%% 11--33%% Current Mfg Quality provided to patients DDaattaa ffrroomm:: DDrr.. DDoouugg DDeeaann & FFrraanncceess BBrruuttttiinn PPrriicceeWWaatteerrhhoouusseeCCooooppeerrss …………bbyy tteessttiinngg !!!!!!!!
- 8. Slide 8 May2008 The quality mantra “Quality can not be tested into products; it has to be built in by design”
- 9. How can wemodernize our industry? More knowledge of our products and processes, allowing better design and more control Better management: - introduction of quality risk management - expansion of GMP to more extensive pharmaceutical quality system Slide 9 May 2008
- 10. Slide 10 May2008 Dr Ajaz Hussain ‘‘PPhhaarrmmaacceeuuttiiccaall GGMMPPss ffoorr tthhee 2211sstt CCeennttuurryy’’
- 11. Slide 11 May2008 The knowledge pyramid MECHANISTIC KNOWLEDGE How? “CAUSAL" KNOWLEDGE What “Causes” What? CORRELATIVE KNOWLEDGE What Is Correlated to What? DESCRIPTIVE KNOWLEDGE: What? Need for regulatory oversight Knowledge based decisions Desired State Current State First Principles Why?
- 12. The New QualityParadigm – The Evolving Regulatory Framework ICH Q8/Q8(R) - Pharmaceutical Development Slide 12 May 2008 PAT Guidance ICH Q9 – Quality Risk Management ICH Q10 – Pharmaceutical Quality Systems Product Design Process Design Scale-up & Transfer Commercial Manufacture Product Life Cycle Product
- 13. Slide 13 May2008
- 14. Definition: Quality byDesign Quality by Design is 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. Slide 14 May 2008 EMEA/CHMP/ICH/518819/2007
- 15. Quality by Designapproach Slide 15 May 2008 can be used for Active pharmaceutical ingredients Materials incl excipients Analytics Simple dosage forms Advanced drug delivery systems Devices Combination products (e.g. theranostics)
- 16. Slide 16 May2008 Impact of QbD Companies re-organize their science Universities change their curriculum Health authorities change their assessment and inspection
- 17. Step 1. Agreeon the Target Product Profile Step 2. Determine the Critical Quality Attributes (CQAs) Step 3. Link the drug and excipient attributes and the process parameters to the CQAs Step 4. Define the Design Space Step 5. Define the Control Strategy Step 6. Prepare QbD registration file Step 7. Product lifecycle management and Slide 17 May 2008 continual improvement EMEA/CHMP/ICH/518819/2007 QUALITY BY DESIGN
- 18. Slide 18 May2008 What are the steps in a Quality by Design approach? 1. TARGET PRODUCT PROFILE 2. CRITICAL QUALITY ATTRIBUTES 6. PRODUCT LIFECYCLE MNGMNT 3. LINK MAs AND PPs TO CQAS 5. ESTABLISH CONTROL STRATEGY 4. ESTABLISH DESIGN SPACE
- 19. Slide 19 May2008 Step 1. Agree on the Target Product Profile Target Product Profile: - a prospective and dynamic summary of the quality characteristics of a drug product - that ideally will be achieved to ensure that the desired quality, and hence the safety and efficacy, of a drug product is realised. The TPP forms the basis of design of the product. Consider: dosage form route of administration strength release / delivery of the drug pharmacokinetic characteristics (e.g., dissolution; aerodynamic performance) drug product quality criteria (e.g., sterility, purity).
- 20. TPP for paediatricdosage form TPP adult TPP paediatric (may Slide 20 May 2008 depend upon age group)
- 21. Slide 21 May2008 What are the steps in a Quality by Design approach? 1. TARGET PRODUCT PROFILE 2. CRITICAL QUALITY ATTRIBUTES 6. PRODUCT LIFECYCLE MNGMNT 3. LINK MAs AND PPs TO CQAS 5. ESTABLISH CONTROL STRATEGY 4. ESTABLISH DESIGN SPACE
- 22. CRITICAL QUALITY ATTRIBUTES Slide 22 May 2008 - definition A critical quality attribute (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. EMEA/CHMP/ICH/518819/2007
- 23. Step 2. Determinethe Critical Quality Drug product CQAs are used to guide the product and process development. Slide 23 May 2008 Attributes (CQAs) solid oral dosage forms: typically those aspects affecting - product purity - product potency - product stability - drug release. other delivery systems: can additionally include more product specific aspects, such as - aerodynamic properties for inhaled products - sterility for parenterals, - adhesive force for transdermal patches.
- 24. Excipient Quality Attributes Slide 24 May 2008 Product-centric Quality by Design API Purity Chemical purity Physical form Raw Material quality Formulation Process Related Particle size Mechanical Properties Excipient Compatibility DRUG PRODUCT API Quality Attributes Formulation Parameters
- 25. Slide 25 May2008 What are the steps in a Quality by Design approach? 1. TARGET PRODUCT PROFILE 2. CRITICAL QUALITY ATTRIBUTES 6. PRODUCT LIFECYCLE MNGMNT 3. LINK MAs AND PPs TO CQAS 5. ESTABLISH CONTROL STRATEGY 4. ESTABLISH DESIGN SPACE
- 26. Step 3. Linkthe drug and excipient attributes and the process parameters to the CQAs Slide 26 May 2008 Observat ion People Observat ion UCL=111.55 UCL=112.65 Equipment Observat ion UCL=112.65 Measurement Process UCL=116.68 UCL=111.55 Materials UCL=111.17 Environment INPUTS (X) Quality Attributes y = ƒ(x) Inputs to the process control variability OUTPUT y of the Output Observat ion Individual Value 20 22 24 26 28 30 32 34 36 38 40 120 115 110 105 100 95 90 _ X=102.37 LCL=88.05 I Chart Individual Value 40 42 44 46 48 50 52 54 56 58 60 115 110 105 100 95 90 85 80 _ X=97.94 LCL=83.23 I Chart Observat ion Individual Value 60 62 64 66 68 70 72 74 76 78 80 115 110 105 100 95 90 _ X=99.63 LCL=87.71 I Chart Observat ion Individual Value 80 82 84 86 88 90 92 94 96 98 100 110 105 100 95 90 85 _ X=98.76 LCL=86.35 I Chart Individual Value 40 42 44 46 48 50 52 54 56 58 60 115 110 105 100 95 90 85 80 _ X=97.94 LCL=83.23 I Chart Individual Value 60 62 64 66 68 70 72 74 76 78 80 115 110 105 100 95 90 _ X=99.63 LCL=87.71 I Chart Process Parameters Observat ion Indiv idual Value 1 11 21 31 41 51 61 71 81 91 115 110 105 100 95 90 85 UCL=114.17 _ X=99.95 LCL=85.72 I Char t Source: Moheb Nasr, FDA
- 27. M1 Material Attributes Slide 27 May 2008 Mapping the Linkage Inputs: Outputs: M2 P1 P2 P3 CQA1 CQA2 CQA3 Relationships: CQA1 = function (M1) CQA2 = function (P1, P3) CQA3 = function (M1, M2, P1) P2 might not be needed in the establishment of design space Process Parameters Critical Quality Attributes Source: Moheb Nasr, FDA
- 28. Experimental Approach forIdentifying Design of Experiments (DOE) is an efficient method to determine relevant parameters and interactions Slide 28 May 2008 Parameters 1. Choose experimental design (e.g., full factorial, d-optimal) 2. Conduct randomized experiments Experiment Factor A Factor B Factor C 1 + - - 2 - + - 3 + + + 4 + - + 3. Analyze Data Determine significant factors
- 29. ICH Q9 QualityRisk Management Slide 29 May 2008 Initiate Quality Risk Management Process 1. Risk language Assessment The new 2. Risk Control Output / Result of the Quality Risk Management Process 4. Risk Review Formal Risk Management Process
- 30. Slide 30 May2008 What are the steps in a Quality by Design approach? 1. TARGET PRODUCT PROFILE 2. CRITICAL QUALITY ATTRIBUTES 6. PRODUCT LIFECYCLE MNGMNT 3. LINK MAs AND PPs TO CQAS 5. ESTABLISH CONTROL STRATEGY 4. ESTABLISH DESIGN SPACE
- 31. Step 4. Definethe Design Space The linkage between - the process inputs (input variables and process parameters) and - the critical quality attributes can be described in the design space. Slide 31 May 2008
- 32. Slide 32 May2008 Definition of Design Space The material attributes and process parameters that assure quality. The multidimensional combination and interaction of input variables (e.g. material attributes) and process parameters that have been demonstrated to provide assurance of quality. Roll pressure Gap width Screen Size 300 200 100 0 -100 Dataset - Run1-10a.M3 Observed vs. Predicted $Time [Last comp.] (Aligned) 0 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 170 180 190 200 210 220 230 240 250 260 $Time (normalized) SIMCA-P+ 11.5 - 05/02/2007 23:17:07
- 33. Slide 33 May2008 What are the steps in a Quality by Design approach? 1. TARGET PRODUCT PROFILE 2. CRITICAL QUALITY ATTRIBUTES 6. PRODUCT LIFECYCLE MNGMNT 3. LINK MAs AND PPs TO CQAS 5. ESTABLISH CONTROL STRATEGY 4. ESTABLISH DESIGN SPACE
- 34. Slide 34 May2008 Design Space 1a EMEA/CHMP/ICH/518819/2007 RReessppoonnssee ssuurrffaaccee pplloott ooff iinn--vviittrroo rreelleeaassee aass aa ffuunnccttiioonn ooff ttwwoo ccrriittiiccaall ppaarraammeetteerrss ooff tthhee mmiixxiinngg aanndd llaammiinnaattiioonn pprroocceessss.. CCoonnttoouurr pplloott ooff iinn--vviittrroo rreelleeaassee
- 35. Knowledge Space Slide35 May 2008 Design Space Control Space Design Space
- 36. Step 5. Definethe Control Strategy The control strategy should describe and justify how in-process controls and the controls of - input materials (drug substance and excipients), - container closure system, - intermediates and the controls of end products contribute to the final product quality Slide 36 May 2008
- 37. Slide 37 May2008 5. CONTROL STRATEGY Elements of a control strategy can include, but are not limited to, the following: • Control of input material attributes (e.g., drug substance, adhesive polymer, primary packaging materials) based on an understanding of their impact on processability or product quality • Product specification(s) • Controls for unit operations that have an impact on downstream processing or end-product quality (e.g., the impact of solvent on degradation) • In-process or real-time release in lieu of end-product testing • A monitoring program (e.g., full product testing at regular intervals) for verifying multivariate prediction models.
- 38. Slide 38 May2008 What are the steps in a Quality by Design approach? 1. TARGET PRODUCT PROFILE 2. CRITICAL QUALITY ATTRIBUTES 6. PRODUCT LIFECYCLE MNGMNT 3. LINK MAs AND PPs TO CQAS 5. ESTABLISH CONTROL STRATEGY 4. ESTABLISH DESIGN SPACE
- 39. Step 7. Productlifecycle management Slide 39 May 2008 continual improvement Minimal Approach QbD Approach • Reactive (i.e., problem solving and corrective action) • Preventive action • Continual improvement facilitated
- 40. Better processes willlead to products Slide 40 May 2008 with less variability NNooww ((GGMMPP)) DDrruugg PPrroodduucctt VVaarriiaabbllee IInnppuutt FFiixxeedd PPrroocceessss VVaarriiaabbllee OOuuttppuutt VVaarriiaabbllee IInnppuutt AAddaapptteedd PPrroocceessss CCoonnssiisstteenntt OOuuttppuutt PPAATT//QQbbDD
- 41. The Revolution inQuality Thinking Slide 41 May 2008 Quality by Testing and Inspection Enhanced • product knowledge • process understanding Quality by Design quality assured by well designed product & process
Editor's Notes
- #3 <number> सितंबर 21, 2014