Quality by Design for Analytical Methods: Implications for Method Validation and Transfer - Pharmaceutical Technology

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Quality by Design for Analytical Methods: Implications for Method Validation and Transfer
The authors describe how traditional approaches to analytical method and validation may benefit from alignment with quality-by-design concepts.

Pharmaceutical Technology
Volume 36, Issue 10, pp. 74-79


The switch to a QbD approach to method development is already beginning to bring improvements to the performance of analytical methods. Opportunities also exist to modernize and standardize industry's approach to method validation and transfer. By aligning method validation concepts and terminology with those used for process validation as well as equipment qualification, there is an opportunity to ensure that efforts invested in method validation are truly value adding, rather than simply being a check-box exercise, and to reduce confusion and complexity for analytical scientists.


Analytical Target Profile (ATP). The combination of all performance criteria required for the intended analytical application that direct the method development process. An ATP would be developed for each of the attributes defined in the control strategy. The ATP defines what the method has to measure (i.e., acceptance criteria) and to what level the measurement is required (i.e., performance level characteristics, such as precision, accuracy, working range, sensitivity, and the associated performance criterion). The ATP requirements are general ones and linked primarily to the intended purpose, not to a specific method. Any method conforming to the ATP is considered suitable. The ATP can be regarded as the focal point for all stages of the analytical life cycle.

Method Design. The collection of activities performed to define the intended purpose of the method, select the appropriate technology, and identify the critical method variables that need to be controlled to assure the method is robust and rugged.

Method Development. The collection of activities performed to select an appropriate technique and method conditions that should have the capability to meet the ATP requirements.

Method Design Space (MDS). The multidimensional combination and interaction of input variables (e.g., material attributes) and method parameters that have been demonstrated to provide assurance of data quality. In contrast to the ATP, the MDS is related to a specific method. Method Design Space is also known as Method Operable Design Region (MODR)

Method Understanding. The knowledge gained from the collection of activities performed to understand the relationship between variation in method parameters and the method performance characteristics.

Method Installation. The collection of activities necessary to ensure that a method is properly installed in its selected environment. This will include the knowledge transfer activities, such that the laboratory understands the critical control requirements of the method and the activities required to ensure that the laboratory can meet these requirements (e.g., purchasing of appropriate consumables, such as columns and reagents, and ensuring that reference standards are available, appropriate equipment is available, and appropriate training is given to personnel. Method Installation will only be a separate activity in cases where the method is not designed and developed in the routine laboratory.

Method Qualification (MQ). The collection of activities and/or results necessary to demonstrate that a method can meet its ATP. Experiments that are performed as part of the MQ exercise must be appropriate for the specific intended use as defined in the ATP. This determination may involve demonstrating the method has adequate precision and accuracy over the intended range of analyte concentrations for which it will be used.

Continued Method Verification (CMV). The activities that are performed to continually ensure that the method remains in a state of control during routine use. This includes both continuous method performance monitoring of the routine application of the method as well as a method performance verification following any changes.

Continuous Method Performance Monitoring (CMPM). The activities that demonstrate that a method continues to perform as intended when used with the actual samples, facilities, equipment, and personnel that will routinely operate the method.

Method Performance Verification (MPV). The activities that demonstrate that a method performs as intended following a change in the method operating conditions or operating environment. The need and extent of method performance verification is determined through risk assessment.


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