The Analytical Target Profile
Table I*: Comparison of traditional and quality-by-design (QbD) approaches to a pharmaceutical process.
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QbD, as defined in ICH Q8(R1), is a systematic approach to pharmaceutical development beginning with predefined objectives
that emphasize product and process understanding as well as product and process control. Arguably, to date, industry has
focused on product-development activities with little emphasis on defining tools for the analytical chemist. The development
of appropriate analytical methods is, however, fundamental to establishing product and process control (in a traditional-
or a QbD-development approach) and the overall control strategy (see Table I).
In many ways, the development and documentation of method requirements has not changed in decades. The EFPIA/PhRMA working
group is now introducing an approach that describes a way to capture the predefined performance requirements of analytical
methods—that is the ATP.
The ATP is a tool that can be used in the establishment of any analytical methodology, whether intended as a component of
a QbD approach or in the development approaches that have been used historically. In either case, the ATP can be used to describe
the method requirements needed to adequately measure the defined CQAs of the drug product. An ATP would be developed for each
method used in the overall product control strategy; it would define what the method has to measure and to what level the
measurement is required (i.e., performance level characteristics—such as precision, accuracy, working range, sensitivity—and
the associated performance criteria). It is this ATP that would drive the design and development of appropriate analytical
methods and it is proposed that the ATP could also form the basis of a regulatory submission.
An ATP would be defined in the same way that the process control strategy is defined and in the same manner CQAs requiring
measurement are identified. It is important that the analytical-method's performance characteristics and criteria are clearly
defined in conjunction with the ATP. Currently, the method-performance characteristics requiring validation would be followed
according to the guidelines described in ICH Q2(R1) Validation of Analytical Procedures: Text and Methodology. In the future, these guidelines would be considered in conjunction with the specific nature and requirements of the method
as defined in the ATP. These criteria can be derived from a knowledge of how the method will be used—over what range of analyte
concentrations it will be used, what precision is required to ensure the analyst can confidently determine whether a material
meets specification, and so forth. It is clear that some methods (e.g., continuous on-line quantitative spectroscopic methods)
will not be amenable to validation approaches strictly adhering to the current ICH Q2(R1) guideline. As such approaches evolve,
the methodology to assess suitability for intended use will need to be developed.
Applying QbD to analytical methods
Having defined the ATP, the principles of QbD can be used during method development and evaluation to ensure that an appropriate
analytical-measurement technology is selected and that the analytical method is designed to meet its intended performance
requirements. In addition, the assessment of the methodology will need to evolve as the program develops.
There are, of course, different approaches companies may wish to adopt in ensuring the analytical method is developed to meet
its intended performance requirements (defined by the ATP), including the traditional approach followed by the industry today.
An alternative approach might be more structured and fully embrace the concepts of QbD. For example, ICH Q8(R), Step 2, defines
"a systematic approach to development that begins with predefined objectives [in this case the ATP] and emphasizes product
and process understanding and process control, based on sound science and quality risk management."
Figure 1: Components of application of quality by design (QbD) to analytical methods (Courtesy of Authors).
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The establishment of an ATP is in complete alignment with ICH Q10, that is, the application of a holistic quality-management
system. Although additional information is gained when using an ATP combined with a QbD approach, the ATP can also facilitate
the establishment of some of the recommendations of ICH Q10 when used with a traditional approach. The application of the
ATP provides confidence that future method changes and improvements may be introduced with the full knowledge of their likely
effect on the product (see Figure 1).
The following case study illustrates how the ATP concept affords the opportunity for continuous improvements in analytical
methods and technologies without the need for prior regulatory approval. In addition, the case study demonstrates the potential
impact on different testing sites and how they can benefit from a QbD approach by being flexible enough to accommodate site-specific
business and operational preferences with respect to adopted measurement technology.
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