Clarifying Design Space, Process Analytical Technology and Quality by Design

For pharmaceutical and biopharmaceutical manufacturers, there are a lot confusion around the concepts of design space (DS), Process Analytical Technology (PAT), and Quality by Design (QbD).

Emerson's Zuwei Jin

Zuwei Jin
Senior Life Sciences Consultant

Emerson’s Zuwei Jin believes that this confusion has largely limited the opportunities where PAT may be implemented, since many of these decisions need to be made early, such as in the process design stage.

In the Life Sciences industry, QbD is:

…outlined in its [U.S. Food and Drug Administration] report “Pharmaceutical Quality for the 21st Century: A Risk-Based Approach.”[5] In the past few years, the agency has implemented the concepts of QbD into its pre-market processes. The focus of this concept is that quality should be built into a product with an understanding of the product and process by which it is developed and manufactured along with a knowledge of the risks involved in manufacturing the product and how best to mitigate those risks.

Zuwei explains that QbD is the overall science/risk based approach for developing validatable processes.

In an American Association of Pharmaceutical Scientists (AAPS) presentation, Design Space Considerations, DS is defined:

  • Scientific concept for ensuring quality

    • Multidimensional parametric space within which acceptable quality product is obtained

      • Includes input material attribute and process parameter ranges
    • Is proposed by the applicant
  • Regulatory concept
    • Defines allowable operational flexibility
    • Specific to a product and process

Zuwei notes that DS and PAT are two groups of control strategies possibly to be used in QbD. DS focuses on critical process parameters (CPP) and is based on the philosophy that all process parameters (input) can be controlled to the extent that the product quality (output) will stay within the specification.

PAT focuses on critical quality attributes (CQA) and is based on the assumption that an in-line quality monitoring instrument is technologically available and that there is a realistic decision-making platform that can control multiple process parameters (inputs) to steer the quality (output) within the specification limits.

Both approaches require development of extensive process and product understanding. DS would require extensive offline tests to validate the design space and need to provide evidence that all the control loops can independently control the process parameters within the specified range.

PAT would require extensive validation of the instruments’ ability to measure the quality attributes (through offline testing) and the control platform’s capability for dealing with complicated interactions and response dynamics among multiple process inputs.

For example, does a spectrophotometer have to be in PAT? While it is true in many PAT implementations, spectrophotometers are not the only inline monitoring instrument that can provide quality readings.

Zuwei highlights that one important implication is that the decisions made on control strategies need to be done early. At the same time, when process understandings are being developed—usually before the end of stage 1—then process design for successful and effective implementations of design space and PAT are required.

Process Validation Lifecycle

Process Validation Lifecycle

The decisions made on control strategies would also be greatly facilitated by early access to advanced control technology provided by the automation companies and equipment vendors.

You can connect and interact with other pharmaceutical and biotech experts in the Life Sciences group in the Emerson Exchange 365 community.

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