Post on 17-Aug-2015
transcript
Surang Judistprasert
Bio-innova & Synchron co.,ltd.
Quality by Design Vs Control Strategy
Turning QbD into a Practical Reality
”A systematic approach to development thatbegins with predefined objectives andemphasizes product and process understandingand process control, based on sound science andquality 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
• 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
“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 acombination 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 providethe 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
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
Guideline / Instructions Part 2
Example Materials
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
How to set product target profile
How to set process scheme?
• 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 granulationDry granulationDirect compressionFunctional coatedPackaging closure design
• Recommend one or more of the strategies.
• Summarize the results if things go as proposed.
• What to do next.
• Identify action items.
Control strategy
Risk Assessment to Identify Variables Potentially Impacting Product Quality
Potential impact of Excipients on Drug Product CQAs
DOE and overall risk assessment in line with process understanding developed
Example design space Example Control Strategy for CQAs
This slide will be provided only attendee in the seminar room
Tools for R&D
Thank you…