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…