PAT and Quality Improvement Library

    The PAT and Quality Improvement Library

    Quality by Design describes a system in which quality is designed into a product (in this case, a pharmaceutical) rather than being tested in after production. The concept of quality by design requires the use of statistic methods and analytics (including the tools collectively known as Process Analytical Technologies) to gain understanding of processes, which can be used to optimize and control them.

    Articles

    • Particle Analysis for the QbD Era
      ASPEX Corp. draws from its experience in other industries to provide an automated characterization solution for pharma.


    • Cracks in the Armor: Securing the Global Supply Chain
      Processes and systems must be well understood before technologies can be implemented.


    • New Patterns for Quality
      Quality by Design is breathing new life into quality systems and process analytical technology.


    • Building a Business Case for PAT
      Securing the support of upper management is essential to the successful implementation of Process Analytical Technology projects. Here, the authors provide a how-to guide.


    • Therapeutic Dose: Why Waste Time and Money on PAT? A Modest Proposal
      The globalization of business and the labor market provides a tempting trap for pharma companies.


    • Process Analytical Technology: Here to Stay
      Reducing waste, increasing production asset utilization and achieving real-time quality assurance and validation are just a few of the reasons that drug makers are increasingly turning to PAT.


    • Winning the Space Race (the Design Space Race)
      Complying with ICH Q8 requires knowledge of three key spaces: design, technology and regulatory. Here’s how one company used Design of Experiments to troubleshoot variability in the validation of a controlled-release pain reliever.


    • Determining the Manufacturability of Drug Layered Tablets
      Statistical methods can be used to explain and correlate assay variability and the capability of the drug-layering process, allowing process accuracy to be improved and controlled.


    • Quality by Design Takes Biopharma by Storm
      Quality by Design has lost its buzzword status as it becomes a reality for more biopharma companies. Contributing Editor Angelo De Palma examines how Wyeth, Schering and other firms are advancing the concept, and interviews FDA’s Moheb Nasr for his perspective.

    • Ranbaxy’s Designs on Quality
      In a remarkably short time, Ranbaxy Laboratories has become a force to reckon with in the pharmaceutical industry. Established in 1961, the company operated only in India until the early 1990s, when its founder, Dr. Parvinder Singh, set it on a path toward becoming a global company focused on research and development. Ranbaxy now operates 19 manufacturing facilities in seven countries, including four plants in the U.S.

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    White Papers

    • Kick Starting PAT to Achieve Quality by Design
      In 2002 the FDA announced a revolution in how they intended to regulate drug manufacturing with a continuous, process-centric approach to validation. Known as Quality by Design it incorporates Process Analytical Technology as a key tool for designing and optimizing manufacturing processes. The FDA encourages the timely adoption of new manufacturing technology, and this white paper explores and clarifies the practical implications of the directive, and identifies opportunities for immediate implementation of PAT in order to ensure a successful and profitable kick-start to QbD activities.


    • Combination Products: Navigating Two Quality Systems
      Interest in combination products is surging, but unique regulatory issues make them challenging.

    • More Whitepapers...

    Videos and Podcasts

    References

    Ask the Experts

    Process Analytical Technologies (PAT)

    FDA defines Process Analytical Technologies as systems for designing, analyzing, and controlling manufacturing through timely measurements (i.e., during processing) of critical quality and performance attributes of raw and in-process materials and processes with the goal of ensuring final product quality.  
    It is important to note that the term analytical in PAT is viewed broadly to include chemical, physical, microbiological, mathematical, and risk analysis conducted in an integrated manner.

    Process Analytical Technology Tools

    There are many current and new tools available that enable scientific, risk-managed pharmaceutical development, manufacture, and quality assurance. These tools, when used within a system can provide effective and efficient means for acquiring information to facilitate process understanding, develop risk-mitigation strategies, achieve continuous improvement, and share information and knowledge. In the PAT framework, these tools can be categorized as:

    • Multivariate data acquisition and analysis tools.
    • Modern process analyzers or process analytical chemistry tools.
    • Process and endpoint monitoring and control tools.
    • Continuous improvement and knowledge management tools. An appropriate combination of some, or all, of these tools may be applicable to a single-unit operation, or to an entire manufacturing process and its quality assurance. Controls may be in-line, on-line or at-line
    • In-line sensors or probes are in direct contact with process materials inside the reactor and transmit signals outside.
    • On-line analysis diverts process material to a connected analysis loop, analyzes it, and returns it to the vessel.
    • At-line measurements employ laboratory-type analyzers, but require sampling and sometimes human intervention.

    A variety of imaging systems and spectroscopic techniques (NIR, IR, Raman among them) can be used, but sensors and other analyzers and measuring devices can also be applied. PAT comprise a toolkit that can be used to achieve quality by design in pharmaceutical development, and that can allow for continuous improvement in pharmaceutical manufacturing.

    Articles

    Rick Cooley on PAT

    Emil Ciurczak on PAT

    Gawayne Mahboubian-Jones on PAT

    Justin Neway on PAT

    Case Histories

        
    Abiogen Pharma
    Astra-Zeneca
    Aspen Pharmacare
    BMS
    Johnson & Johnson
    Novartis
    Pfizer
    Talecris
    Wyeth

     

    White Papers

    • Online Reaction Monitoring of Inprocess Manufacturing Samples by UPLC
      Process Analytical Technology (PAT) is a critical component in manufacturing, relied upon to ensure product quality and improve process yields. Here we discuss the use of novel Waters technology for online reaction monitoring of inprocess manufacturing samples, which allows for simultaneous quantification of APIs and process impurities.


    • Pharmaceutical Manufacturing: Is It the Antithesis of Creative Destruction?
      PAT and QbD can only move forward if the industry sheds its habit of QbA (i.e., quality by analysis)


    • Multivariate Calibration: A Science-Based Method
      A new method for multivariate calibration is less costly to implement than standard PLS or PCR methods, and eliminates the need to introduce additional variability into an otherwise stable process. It also allows specific responses to be proven from first principles.


    • The Business Case for PAT
      Having trouble justifying PAT projects to top management? The business drivers for PAT are compelling, both on the regulatory and on the financial side. This Rockwell Automation white paper discusses how to conduct a “productivity improvement appraisal” and how to handle discovery and analysis phases of any PAT project.


    • PAT Needs and Applications in the Bioprocess Industries
      In this comprehensive report, the authors examine what PAT means in practice for the biotechnological manufacture of pharmaceuticals. They analyze regulatory issues, monitoring methods and available technologies, and compare their findings against the needs for monitoring in bioprocess-based pharmaceutical production.


    • Chemometrics Basics
      Using chemometric algorithms, modern computer technologies and rapid spectroscopic analysis, provides the basis for the modern-day development of methods of chemical analysis with the best rewards.


    • Demystifying Multivariate Analysis of Umetrics
      In order to identify sources of process variability, you need to be able to integrate information ranging from raw material and intermediate measurements to processing and environmental data. Multivariate analysis techniques such as principle component analysis (PCA) and partial least squares (PLS) can be highly effective. Chris McCready, an engineering specialist with the software firm UMetrics, shows how MVA methods can be applied to improve your process IQ.


    • More Whitepapers...


    PAT Talks

    Videos and Podcasts

    References

    Ask the Experts

    		     

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    Submit Information on PAT and Quality Improvement

    Have you developed expertise in PAT, Quality by Design or any facet of quality improvement as it pertains to pharmaceutical scaleup and manufacturing?  Would you like to share best practices and lessons learned with your colleagues around the world?  If so, please let us know and send us a draft of the article, or a 250-word abstract summarizing what you'd like to write about.  We'll use that to develop the article for publication and/or add it to this online library.  Please send your abstracts or articles to ashanley@putman.net.