The first fruits of that programme, published in the June edition of the Journal of Pharmaceutical Innovation, represent a preliminary stage in attempting to provide practical guidance on how to implement these concepts into pharmaceutical processes. Dubbed the Product Quality Lifecycle Implementation (PQLI), it was designed by ISPE as an initiative to help pharmaceutical manufacturers meet the requirements of ICH Q8, Q9 and Q10 in a way that would be acceptable to regulatory authorities. Early indications are that the PQLI's efforts have been well-received. Jacques Morenas of the Agence française de sécurité sanitaire des produits de santé (AFSSAPS) said: "EU regulators are ready to work with ISPE on this topic taking into account it is a critical point. Work is already on progress as we can see with work made into PAT team at the EMEA level and we will be happy to continue." ICH Q8, Q9 and Q10 together encompass the principles of Quality by Design (QbD), in which the quality aspects of a production process and the resulting product are designed to be built-in from the start, based on a clear understanding of the process and using a well-defined risk-management strategy. QbD has been pushed by the US Food and Drug Administration (FDA) since its publication of their report on Pharmaceutical cGMPs for the 21st Century back in 2002. Back in 2004 Janet Woodcock, recently appointed director of the Center for Drug Evaluation and Research (CDER) at the FDA for the second time, said QbD means that "product and process performance characteristics are scientifically designed to meet specific objectives, not merely empirically derived from performance of test batches." Those initial concepts have since been refined in the FDA's Critical Path Initiative , and essentially lay down a challenge to the pharmaceutical industry: understand your processes, and control those processes to the extend that any variations - which currently might lead to a batch being discarded after lab testing - can be responded to in real-time. Gulf between theory and practice... While this is all very laudable in theory, there is still a long way to go before practical implementation of this concept can be achieved. And that is what the ISPE has set out to achieve - a 'how-to' guide, based on best practices, that will allow QbD to be applied to both drug substances and finished pharmaceuticals. The task is made doubly hard, given that the Q8 and Q10 documents are already in the process of being revised by ICH. That aside, PQLI's first efforts have been published a series of articles detailing progress in recent months in three key areas of QbD: criticality, design space and control strategy. A way to establish criticality - in other words the features of a process or product that are of fundamental importance to its quality - is the main thrust of the first article in the series. It describes a mechanism for categorising and delineating criticality for quality attributes, variables, material attributes and process parameters in accordance with a risk based approach reflective of QbD principles articulated in ICH Q8. The article introduces the adoption of a Criticality Analysis Decision Tree to categorise criticality relative to a variable's impact to quality and delineate levels of criticality with respect to relative risk. Design Space - a concept introduced in ICH Q8 in 2005 - in essence means defining the boundaries of a process or product. It is essentially a 'snapshot' in time that represents current knowledge of a process. A change that moved out of the design space, for example, might require post-approval changes to a drug dossier. The second article in the PQLI series looks at the link between patient experience and product quality, and asks how risk assessment methodologies integrate with process design principles. It also provides some perspective on selection of mechanistic versus empirical approaches, and clarifies how they may be applied to legacy products, and biotech products. The authors also discuss a number of methods for depicting design space. Finally, the control strategy article proposes a model process to enable a clear logic to be used on how such a strategy differentiates between patient and business requirements. It also describes a linkage from critical quality attributes, e.g. via critical process parameters, to individual controls such as analytical, PAT (process analytical technologies), engineering, procedural or other controls. The model illustrates how the control strategy embraces ICH requirements (product and systems), and aims to provide a discussion bridge between disciplines such as development scientists and controls engineers. Other publications from the PQLI are due later this year, according to ISPE. For example the legacy team aims to publish a paper in JPI on how similar approaches could be applied to existing products that have not had QbD built in from the outset.
Commenting on the publications, Moheb Nasr, Director of the Office of New Drug Quality Assessment at the FDA, said: "These papers, and the PQLI initiative, are important 'next steps' to facilitate the implementation of QbD and to answer the tangible challenges."