for seminar PharmaTalk 19 June 2015 @Bangkok

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

7. Example Materials

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…