The International Society for Pharmaceutical Engineering (ISPE) has released the first two parts of the ISPE Guide Series:
Product Quality Lifecycle Implementation (PQLI) from Concept to Continual Improvement. These guides provide a practical approach
to implementation of International Conference on Harmonization (ICH) guidelines on pharmaceutical development, quality risk
management, and the pharmaceutical quality system, as well as FDA guidance produced under the Pharmaceutical CGMPs for the
21st Century Initiative, including guidance on process analytical technology (PAT) and quality systems (1–6). More recently,
FDA published guidance on process validation (7); the ISPE series also provides information and assistance to meet Stage 1
(Process Design) of this guidance.
The ISPE Guide series is intended to assist and be a reference for practitioners involved in development, implementation,
and application in manufacturing, including those involved in continual improvement. The suggestions, information, and examples
presented in Parts 1 and 2 of the series have been derived from input from a wide range of companies and individuals who have
hands-on experience of successfully applying enhanced, quality-by-design (QbD) approaches.
Part 1 of the ISPE Guide, Product Realization using QbD: Concepts and Principles, provides an overview of the series and a summary of enhanced, QbD approaches to development, including an introduction into
manufacture and continual improvement of products and processes. It also provides a practical discussion and examples of of
criticality, design space, and control strategy, which are addressed in ICH Q8 (R2) (1).
Part 2, Product Realization using QbD: Illustrative Example, offers a case study of the application of enhanced, QbD approaches to product realization. Part 2 addresses the development
and introduction into manufacturing of a small-molecule formulation and associated manufacturing process, as well as part
of the drug-substance synthetic route using enhanced, QbD approaches. Compared with other case studies in the public domain,
more detail is given about the application of systematic, iterative, and different approaches to product and process understanding
using quality risk management.
Parts 1 and 2 provide a range of how-to tools for practitioners developing products and their manufacturing processes using
the enhanced, QbD approach described in ICH Q8 (R2). These guides provide more insight than is given in the ICH guidelines,
and include more explanation and examples of individual topics, such as criticality as applied, for example, to critical quality
attributes and critical process parameters (CQAs and CPPs), design space, and control strategy.
The concepts in the ISPE Guide series apply to both new drug products and existing marketed products. The authors believe
that the principles also apply to drug-substance (small and large molecule) process development and continual improvement.