Process analytical technology (PAT) is a system for designing, analyzing and controlling manufacturing processes based on an understanding of the scientific and engineering principles involved and identification of the variables that affect product quality. The primary goal of PAT is to provide processes that consistently generate products of predetermined quality.

Our PAT approach is consistent with the FDA perspective that quality cannot be tested into products, but should be built in. We achieve improved quality and efficiency through:

  • Reduction of cycle times using on-, in- or at-line measurements and controls
  • Prevention of reject product and waste
  • Real-time product release
  • Increased use of automation
  • Facilitation of continuous processing using small-scale equipment, resulting in improved energy and material use and increased capacity

Building Quality Into Products

We have extensive experience solving solid state problems in drug products and bring exceptional skill to the analysis and control of complex attributes such as solid form, particle size and particle shape. Given a compound of interest, we have the capabilities to:

  • Determine the solid forms attainable and their relevance to manufacture and use
  • Select the optimum solid form
  • Develop analytical methods to verify the presence of and quantify the concentration of the selected form in API
  • Investigate the physical properties of the solid such as particle size, particle shape, stability, ease of drying, filterability, solubility and dissolution rate
  • Develop a manufacturing process that consistently provides the desired form of the API having the desired physical characteristics
  • Aid in setting API specifications
  • Determine excipient compatibility
  • Aid in formulation design
  • Develop drug product manufacturing strategies that are consistent with the solid properties of the API
  • Develop analytical methods to verify the presence of and quantify the concentration of the selected form in drug product
  • Aid in setting drug product specifications

Process Control

Once we understand the properties of the drug product components, we identify the processing variables that control the relevant properties. Identification of these variables requires a multivariate approach. First, PAT implementation involves the design of manufacturing processes based on the solid state properties and stability of the components at critical points throughout manufacturing. Then, measurement and control of the critical parameters integrates a spectrum of analytical technologies interfaced to production plant control networks and incorporated into standard procedures.

Our experts partner with you to establish process understanding and design process analytical control strategies. Building on our meticulous cGMP pharmaceutical research and analysis, we can assist you in all aspects of PAT implementation, including:

  • Process understanding through advanced solid state research
  • Identification of critical control variables using multivariate techniques
  • Development and validation of appropriate analytical methods for measuring critical control variables
  • Transfer of analytical methods to on-, in-, or at-line use
  • Consultation and assistance in method validation and use after transfer

Potential Regulatory Impact

Our extensive experience in cGMP solid state research and analysis will help you meet PAT challenges today and in the future. Documentation of quality by design during the pre-IND meeting, the end of Phase II meeting and in regulatory submissions will enable early FDA review of the CMC section of an NDA. Addressing issues and further quality by design activities can result in classification of the drug substance and drug process manufacturing process as low risk. In some cases, this approach results in a less comprehensive or eliminated preapproval inspection. These procedural changes present opportunities for more rapid regulatory approval and reduced time to market.