Process Analytical Technology

Process Analytical Technology (PAT) has been defined by the United States Food and Drug Administration (FDA) as a mechanism to design, analyze, and control pharmaceutical manufacturing processes through the measurement of critical process parameters and quality attributes.

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The FDA has outlined a regulatory framework^[1] for PAT implementation. With this framework - according to Hinz^[2] - the FDA tries to motivate the pharmaceutical industry to improve the production process. Because of the tight regulatory requirements and the long development time for a new drug, the production technology is "frozen" at the time of conducting phase-2 clinical trials.

Generally, the PAT initiative from FDA is only one topic within the broader initiative of "Pharmaceutical cGMPs for the 21st century - A risk based appraoch".^[3]

PAT implementation

The challenge to date with PAT for pharmaceutical manufacturers is knowing how to start. A common problem is picking a complex process and getting mired in the challenge of collecting and analyzing the data.

The following criteria serve as a basic framework for successful PAT roll-outs: (From A PAT Primer)

• Picking a simple process. (Think Water for Injection (WFI) or Building Monitoring System (BMS)
• All details and nuances are well understood and explained for that process.
• Determine what information is easily collected and accessible through current instrumentation.
• Understanding the appropriate intervals for collecting that data.
• Evaluating the tools available for reading and synchronizing the data.

Long-term goals

The long term goals of PAT are to:

• reduce production cycling time
• prevent rejection of batches
• enable real time release
• increase automation
• improve energy and material use
• facilitate continuous processing

Currently near-infrared (NIR) spectroscopy applications dominate the PAT projects. A possible next-generation solution is Energy Dispersive X-Ray Diffraction (EDXRD) ^[4]. For a detailed review of PAT tools see Scott ^[5], or Roggo ^[6].

References

• FDA: PAT Initiative
• EMEA: Inspections - Process Analytical Technology
• ASTM PAT Committee