Module 1

Regulatory Guidelines, Principles and Tools of QbD

Code: PHCO5316

Credits: 30

Aims

The module is designed to provide the fundamental concepts and tools applied to pharmaceutical product design, process design, process monitoring and continuous verification based on Quality by Design principles.

Characteristics

In this module the work-based learners are introduced to the core of the QbD framework, including quality target product profile (QTPP), product and process development (critical quality attributes – CQAs and critical process parameters – CPPs), API development, design space, control strategy and continuous improvement. These principles are underpinned by science, pharmaceutical quality systems, quality risk management and knowledge management. The tools that facilitate the implementation of the QbD approach, such as process analysers, design of experiments, and multivariate analysis will be introduced.

Outline Content

  • History, background, industry, regulators and industrial bodies;
  • International Conference on Harmonisation (ICH) & Q8R2, Q9, Q10 & Q11;
  • QbD principles – from QTPP to continuous improvement;
  • Case study examples;
  • Quantitative Risk Management (QRM) tools;
  • Risk Analysis (RA) in development process;
  • Design Space;
  • Role of Process Analytical Technology (PAT) in developing process understanding;
  • Introduction to analysers used as part of PAT;
  • Multivariate analysis;
  • Design of experiments using statistical packages
  • Development and manufacture of drug substances
  • Quality systems
  • QbD approach to project management

Learning outcomes

On successful completion of the module you should be able to:

  1. Discuss critically the principles of QbD, the origins of QbD, its current status of implementation within the international pharmaceutical industry and the regulatory context.
  2. Demonstrate a comprehensive understanding of the overall QbD ‘process flow’ from QTPP to continuous improvement;
  3. Analyse QbD issues by working through scenarios and real case studies.
  4. Discuss critically the fundamentals of Risk Analysis and QRM tools and how they are used in practice during pharmaceutical development;
  5. Apply and discuss critically the principles of design of experiments to gain knowledge and increase the understanding of pharmaceutical product development and manufacturing.
  6. Discuss critically the role of process analytical technology in enhancing the levels of process understanding and process control.
  7. Demonstrate critical and analytical thinking skills by evaluating relevant literature sources related to quality by design.

List of Lectures

  • Introduction to Quality by Design (Bruce Davis, Global Consulting).
  • ICH Q8, Q9 & Q10 & Q11 (Bruce Davis, Global Consulting).
  • ICH Q10 Pharmaceutical Quality System (Sean Hale, ex-AstraZenica).
  • From Quality Target Product Profile to Continuous Improvement (Bruce Davis, Global Consulting).
  • QbD and Active Pharmaceutical Ingredient (API) Manufacture (Q11) (Gerry Steele, PharmaCryst Consulting Ltd, ex-AstraZenica).
  • Quality Risk Management (QRM) Tools & Introduction of Risk Analysis for QbD (Bruce Davis, Global Consulting and Andrew Dennis, Bristol-Myers Squibb).
  • Manufacturing and Facilities – FDA Process Validation Guidance (Bruce Davis, Global Consulting).
  • Introduction to Design of Experiments (Claire Beckett and Eric Johansson, MKS Umetrics).
  • Exploration of Observational Data (Ian Cox, JMP Division of SAS).
  • Fundamentals of Experimental Design (Martin Owen, GlaxoSmithKline and Iain Grant, AffinisLbD).
  • Sequential Experimental Design (Kate Llewellyn & Gill Turner, GlaxoSmithKline).
  • Modelling & Mechanistic Understanding: Role in QbD (Andrew Dennis, Bristol-Myers Squibb).
  • Multivariate Analysis for Improved Process Understanding (Brad Swarbrick, CAMO Software AS).
  • Process Analysers (Line Lundsberg, Lundsberg Consulting).
  • Process Analytical Technology (Line Lundsberg, Lundsberg Consulting & Brad Swarbrick, CAMO Software AS).
  • The Regulatory aspects of QbD – Introduction (Mustafa Zaman, PAREXEL, ex-MHRA).
  • The Regulatory aspects of QbD – The QbD framework (Gustavo Marco, MHRA).
  • The Regulatory aspects of QbD – Inspection (Richard Funnell, MHRA).