The merits of applying quality by design (QbD) to pharmaceutical products and processes is a topic of significant mutual interest
to both pharmaceutical manufacturers and regulatory agencies. The pharmaceutical industry is currently embracing QbD concepts
to help improve the robustness of manufacturing processes and to facilitate continuous improvement strategies to shape and
enhance product quality and manufacturing productivity. As such, both industry and regulators recognize the benefits of adopting
a QbD approach to drug-product development and manufacture, with key concepts described in International Conference on Harmonization
(ICH) guidelines Q8(R1) Pharmaceutical Development, Q9 Quality Risk Management, and Q10 Pharmaceutical Quality System.
This paper has been constructed to address the parallel opportunities of improving robustness and facilitation of continuous
improvement within the analytical-methods environment. The authors describe two concepts intended to stimulate further discussion
within the industry and regulatory arenas.
One concept is that the steps, tools, and approaches developed for application of QbD to manufacturing processes (and described
in ICH Q8, Q9, and Q10) have analogous application to the development and use of analytical methods. In other words, the approaches
that have been developed for defining critical quality attributes (CQAs) and process parameters for a drug product are transferable
and applicable to the design, development, implementation and life-cycle management of analytical methods.
Another concept presented in the paper is the use of an Analytical Target Profile (ATP). The incorporation of this concept
in the development cycle is viewed as having the potential to reduce the burdens of postapproval variations. This would be
accomplished by using the ATP as a new mechanism for describing analytical methods in regulatory submissions.
The potential benefits in adopting both concepts include:
- Facilitation of continuous improvement and technological innovation through more advanced regulatory approaches to change
- More effective use of industry and regulatory resources
- Enhanced method robustness and ruggedness through the product life cycle
- Fewer investigations related to analytical-method performance
- More robust method knowledge transfer as a result of enhanced analytical-method understanding as well as improved knowledge
Achieving these benefits will require significant changes by industry and regulatory agencies.
The authors provide an example of how to apply QbD concepts to analytical-method design, evaluation, control strategy definition,
and life-cycle management and discuss a proposal for the concept of a regulatory submission for an analytical method developed
through a QbD approach. Finally, the benefits of implementing these concepts, along with the implication of changing the paradigm,
will be discussed.
The ultimate goal of this position paper is to highlight that QbD concepts and terminology can be applied to analytical methods
and to suggest how adoption of a QbD approach might be used to develop more robust analytical methods and effective control
systems. At the same time, these efforts aim to support more advanced regulatory approaches to change management.
The ideas and concepts conveyed in this paper are the outcome of a joint effort of the Pharmaceutical Research and Manufacturers
of America (PhRMA) Analytical Technical Group (ATG) and the European Federation of Pharmaceutical Industries and Associations
(EFPIA) Analytical Design Space (ADS) topic team. Although these teams acknowledge that methods developed and validated through
traditional approaches are suitable for their intended use and produce reliable data, it is their strong belief that the approaches
described in this paper will lead to more robust methods. In addition, by implementing these approaches, there is the potential
to substantially reduce the postapproval variations burden. The content of this paper is intended to act as a stimulus for
further discussion and engagement with regulatory authorities and pharmacopeial bodies worldwide regarding the concept of
QbD as it applies to analytical methods.