• Course objectives
• QbD in the context of the ICH guidelines for pharmaceutical manufacturing industry in the 21st century
• Overview and definitions; how new is the QbD concept?
• Current status of QbD implementation

ICH Guidelines

• Risk-based, modern pharmaceutical manufacturing
• Brief review of ICH Q8, ICH Q9, ICH Q10 and ICH Q11
• ICH guidance covering questions and answers on Q8, Q9 and Q10 (2011)

QbD Methodology

• The evolution of process understanding
• Target Quality Profile, Critical Quality Attributes
• Process parameters ranking methods

Screening the Experimental Space

• Advantages of design of experiments (DoE) vs. one factor at a time approaches
• The importance of pre-DoE experimentation and planning
• Factors, ranges, number of le vels, responses
• Design quality: resolution and efficiency
• Commercial DoE software (sometimes a second opinion can be useful)

Robust Process Design

• Key and Critical Process Parameters
• Response surface methodology, process optimization (at small or intermediate scale) to define a design space
• Strategies in defining a design space
• Process validation in the QbD paradigm
• Control strategy

• Semi-quantitative risk estimates
• Process risk quantification using Monte Carlo simulations

Pharmaceutical Process Scale-Up

• Design space and scale-up factors
• Scale-up theory; scaling-up by scaling-down
• Mixing and scale-up calculations in turbulent regime, mixing times calculations (micromixing, mesomixing, and macromixing)
• Effective scale-up of heterogeneous solid-liquid processes (catalytic, API crystallization process scale-up)
• Process understanding for effective technology transfer
• Advantages and challenges of continuous chemical processing

Process Analytical Technology

• PAT principles, levels of PAT implementation
• Control strategies
• Real time release

Regulatory Advantages

• QbD submissions
• FDA and EMEA QbD pilot programs
• Learning from QbD “pioneers”
• QbD Elements

Hands-on Workshops

• Crystallization process, screening the experimental space
• Successful scale-up of a fast reaction system
• ICH Q11 example 10.1
• QbD HPLC method development