EUROTHERM DANMARK by jolinmilioncherie

VIEWS: 4 PAGES: 20

									Introduction to PAT
                                                                2


                        Current State of Pharmaceutical
                        Manufacturing


     • Conventional pharmaceutical manufacturing is generally
       accomplished using batch processing with laboratory
       testing conducted on collected samples to evaluate
       quality.




Eurotherm Life Sciences Group
                                                                3



                        20th Century Process Validation




      • Establishing documented evidence that provides a high
        degree of assurance that a specific process will
        consistently perform as intended.




Eurotherm Life Sciences Group
                                                             4



                        Desired State

    • Product quality and performance achieved and assured
      by design of effective and efficient manufacturing
      processes.


    • Product specifications based on mechanistic
      understanding of how formulation and process factors
      impact product performance


    • Continuous "real time" assurance of quality




Eurotherm Life Sciences Group
                                                                          5

                       US drug products are of high
                       quality, BUT..
    • The introduction of new technologies has not been
      facilitated in
    • the US market slowing innovation, and modernisation of
      cGMP
    • resulting in:
    • An increasing burden on FDA resources:
          • Handling ~ 4,000 manufacturing supplements submitted yearly
          • FDA inspectors unable to meet statutory biannual GMP inspection
            requirement
          • Lower scrutiny of non-domestic industry
    • Cost implications for the industry from:
       • Low manufacturing and QA efficiency
Eurotherm Life Sciences Group
                                                                     6


                        Overall

       • The current approach to risk is probably delivering as
         much as is reasonably possible in respect of Safety,
         Efficacy
       • But at significant cost from a :
           • Regulatory perspective
           • Manufacturing perspective
       • Cost ultimately borne by the consumer
       • Regulatory uncertainty has had a negative impact on
         innovation
       • In an environment where customer awareness of
         different industry sector’s performance is changing their
         expectation of the industry’s deliverables


Eurotherm Life Sciences Group
                                                      7



                        PAT Guidance
    • Released September 29, 2004
    • Scientific principles and tools supporting
      innovation
        •PAT Tools
        •Process Understanding
        •Risk-Based Approach
        •Integrated Approach


    • Regulatory Strategy accommodating
       innovation
         •PAT Team approach to Review and
         Inspection
         •Joint training and certification of staff




Eurotherm Life Sciences Group
                                                                                        8



                        Process Analytical Technology -
                        Defined

• System for designing, analyzing, and controlling manufacturing
      • through timely measurements (during processing) of critical quality and
        performance attributes of raw and in-process materials and processes, with the
        goal of ensuring final product quality.


• The term analytical in PAT
      • includes chemical, physical, microbiological, mathematical, and risk analysis
        conducted in an integrated manner.




Eurotherm Life Sciences Group
                                                                         9



                        What PAT means

       • Understanding the process
            •A process is well understood when:
            •all critical sources of variability are identified and
            explained.
            •variability (e.g. raw materials) is managed by the
            process
            •product quality attributes can be accurately and reliably
            predicted.
       • Timely measurement (i.e. during processing).
       • Control of critical quality and performance
         attributes.



Eurotherm Life Sciences Group
                                                10



                        What PAT is

         • An enabling framework
         • Science based not procedure based.
         • Risk based
         • An integrated systems approach
         • Flexible
         • Voluntary




Eurotherm Life Sciences Group
                                                            11



                        What PAT is not.

      • It is NOT a regulation (CFR).
      • It is NOT mandatory.
      • It is not just adding a new sensor.
      • It is NOT a technique that must be applied
        throughout. It may be applied to part or all of a
        process




Eurotherm Life Sciences Group
                                                                12



                        Why PAT? What is wrong?

     • Most processes are fixed with variable materials,
       resulting in variable quality of product.
     • Most processes are not well understood.
     • Existing procedural approach has created a “climate of
       fear” stifling innovation.




Eurotherm Life Sciences Group
                                                                    13



                        The Potential Benefits

            • Reduced scrap
            • Improved quality of product (every time, by design)
            • Faster production
            • Quicker development, faster scale up
            • Encourages innovation
            • Reduced regulatory burden
            • Real-time release




Eurotherm Life Sciences Group
                                                                     14



                        Process Control System in a PAT
                        Context
      • Often requires new sensors (NIR, RAMAN, acoustics ...)
        for direct measurement of product attributes (e.g.
        moisture content, particle size, content uniformity, etc.)
      • New multi-variate data analysis performed “at-line” or
        “in-line”
      • Data records are “different”.
      • Feedback/feedforward within and between phases.




Eurotherm Life Sciences Group
                                                     15



                        Multivariate Data Analysis




Eurotherm Life Sciences Group
                                                                 16



                        How the process might change

      • More design of experiments during development to
        understand the process.
      • More data may be collected to continuously analyse it.
      • Process may be modified during its life, without
        revalidation.
      • Equipment may be added/removed/changed without
        validation.
      • Move from batch to continuous processing




Eurotherm Life Sciences Group
                                                                17



                        The FDA

        • The FDA have trained a few inspectors (4), more(50)
          are being trained.
        • The FDA are encouraging draft submissions.
        • The FDA wish to establish an open dialogue during
          development of a PAT process. (No more hiding data)
        • The Pat principle is very well supported by other
          regulatory agencies (e.e. EMEA)
        • One NDA has been Pat based (Aventis)




Eurotherm Life Sciences Group
                                                                        18


                        PAT, Process Control, MVDA and
                        Eurotherm ? Multi-variate data Analysis Tools


     Eurotherm




                                                   NIR etc. Sensor(s)




                                 Plant

Eurotherm Life Sciences Group
                                                                       19



                        And Finally…

            • The goal of PAT is to understand and control the
              manufacturing process
            • to ensure appropriate control of all relevant critical
              attributes of in-process materials (e.g., using process
              endpoints) to allow the process to manage the inherent
              variability of material attributes that can impact the
              quality of the output
            • Proactive science-based approach. Continuous
              validation (every lot is a validation lot) versus discrete 3-
              lot exercise.



Eurotherm Life Sciences Group
End Slide

								
To top