The Analytical Quality by Design (AQbD) Process discuss about how should QbD be applied to Analytical Development.

Based on FDA and USP suggestions, the following AQbD approach can be taken:

1. Define the analytical target profile (ATP).

  • This is a predefined objective of the method that stipulates the performance requirements.

2. Determine what to measure and where/when to measure it based on critical quality attributes (CQAs).

3. Determine the method design.

  • These are the critical procedure attributes (CPAs) and analytical responses that you will be monitoring during the design.

4. Identify critical method parameters (CMPs).

  • These are the analytical conditions that significantly impact method performance.

5. How to analytical condition changes impact analytical responses.

6. Screen and optimize using design.

  • Here, you can use Design of Experiments (DoE), data acquisition, regression analysis or prediction model validation.
  • This leads to what is called the knowledg espace.
  • This is the space where we know how analytical responses will behave based on changes in analytical conditions.

7. Risk assessment and robust testing. 

  • Risk assessments (RA) are an integral part of the AQbD process. Their use facilitates identification and ranking of parameters that could impact method performance and conformance to the ATP.
  • AQbD risk assessments start with deconstructing the analytical method into Analytical Unit Operations.
  • Unit operation Inputs and the Analytical Actions related to the particular process steps are identified.

8. Method verification. Validation of the method in line with ICH Q2(R2) guidelines is typically carried out at a set point (normal operating condition - NOC) within the chromatographic spaces evaluated.

9. Define the method operable design region (MODR or control space)

  • MODR permits the flexibility in various input method parameters to provide the expected method performance criteria and method response without resubmission to FDA.
  • Once this is defined, appropriate method controls can be put in place and method validation can be carried out.

10. Control strategy. A meaningful method control strategy is established based on the wealth of data collected during the method development and verification stages.

  • The control strategy should include method parameters that influence method variability.

11. Continuous monitoring/lifecycle management. Periodically monitor the method’s performance to address gaps, and, as needed, update the process and analytical technology.

Contract development and manufacturing organizations (CDMOs) with QbD experience can effectively apply AQbD to method development and navigate the existing and recently updated guidelines. A CDMO will draw from its QbD experience to develop a robust method at the beginning, but always keeping the end in mind.

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