Pharmacy PAT Implementation
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Questions and Answers

Which of the following are critical attributes that affect blend uniformity? (Select all that apply)

  • API Concentration (correct)
  • Blender Capacity (correct)
  • Rotation Speed (correct)
  • Tablet Size

    • PAT stands for Process Analytical Technology.

    True

    What is the main technology used in PAT?

    Near Infrared (NIR) spectroscopy

    PAT allows investigation into a process to find the causes of __________.

    <p>variability</p> Signup and view all the answers

    Match the following PAT solutions with their correct descriptions:

    <p>Near Infrared Spectrometer = In-line, On-line, At-line Raman Spectrometer = In-Line Viscometer = At-line, In-line Particle Size Analyzer = At-line, In-line</p> Signup and view all the answers

    What does PAT require in terms of mindset?

    <p>A mindset shift and new analytical tools</p> Signup and view all the answers

    What does Process Analytical Technology (PAT) aim to ensure during the manufacturing process?

    <p>Final product quality</p> Signup and view all the answers

    Which of the following are advantages of implementing PAT? (Select all that apply)

    <p>Lower production costs</p> Signup and view all the answers

    PAT is primarily a product-centric approach.

    <p>False</p> Signup and view all the answers

    What are Critical Process Parameters (CPP)?

    <p>Process parameters whose variability impacts critical quality attributes.</p> Signup and view all the answers

    PAT is often associated with in-process control testing during __________.

    <p>commercial manufacturing</p> Signup and view all the answers

    What is the role of near-infrared (NIR) spectroscopy in PAT?

    <p>To monitor and control processes for quality assurance.</p> Signup and view all the answers

    When implementing PAT, sufficient knowledge of the process needs to be gathered only in the late stages of development.

    <p>False</p> Signup and view all the answers

    Which of the following is NOT a benefit of using PAT?

    <p>Increasing product variability</p> Signup and view all the answers

    What is the typical integration time for the Linear Variable Filter System?

    <p>10 ms typical, minimum 10 µsec</p> Signup and view all the answers

    NIR and Raman spectroscopy both require sample preparation.

    <p>False</p> Signup and view all the answers

    What kind of housing does the Real-time process monitoring NIR solution have?

    <p>Rugged, IP65 housing</p> Signup and view all the answers

    The _____ should be constructed from materials deemed acceptable according to registered or compendia testing regimes.

    <p>spectral reference library</p> Signup and view all the answers

    Which of the following attributes are critical for production processes?

    <p>All of the above</p> Signup and view all the answers

    Thief sampling is considered representative for sampling powders.

    <p>False</p> Signup and view all the answers

    What does the Spectral Match Value (SMV) method correlate to?

    <p>Mean spectrum</p> Signup and view all the answers

    _____ is when the same chemical structure but different physical characteristics may lead to production issues.

    <p>Raw material qualification</p> Signup and view all the answers

    What type of NIR spectrometer uses a 10 ms typical integration time?

    <p>Linear Variable Filter System</p> Signup and view all the answers

    What is a key requirement for raw material qualification using NIR?

    <p>Establishing a spectral reference library</p> Signup and view all the answers

    Raman spectroscopy is known to be sensitive to moisture levels in samples.

    <p>False</p> Signup and view all the answers

    Which technique can detect color without issues?

    <p>NIR Spectroscopy</p> Signup and view all the answers

    Study Notes

    Process Analytical Technology (PAT)

    • PAT is a system for designing, analyzing, and controlling manufacturing through timely measurements of critical quality and performance attributes of raw and in-process materials and processes.
    • The goal of PAT is to ensure final product quality, and quality cannot be tested into products; it should be built-in or designed.

    PAT: A Paradigm Shift in Pharma Industry

    • PAT is process-centric, not product-centric.
    • PAT aims to design and develop well-understood processes that consistently ensure pre-defined quality at the end of the manufacturing process.

    Traditional Approach vs PAT Approach

    • Traditional approach: process is developed, frozen, and validated using 3 commercial batches, with subsequent quality control via off-line investigation in the laboratory.
    • PAT approach: at-line, on-line, and in-line analysis for identifying critical sources of variability and establishing process understanding, enabling continuous process verification.

    Key Advantages of PAT

    • Better process understanding, leading to faster product development/scale-up, robust and reliable processes, and product quality assurance at lower costs.
    • Generating cost savings through reduced production cycle times, energy consumption, and reagent consumption.
    • Improving safety through process automation.
    • Enabling continuous processing and real-time release to shorten production cycle time and achieve process efficiency.
    • Facilitating continuous improvement and being eco-friendly by reducing waste and energy consumption.

    PAT Implementation in Product Life Cycle

    • PAT implementation spans the entire product life cycle, from early development to commercial manufacture.
    • PAT is often associated with in-process control testing in commercial manufacturing, but it's essential to gain sufficient knowledge of the process/product in early development stages.

    PAT Application in Solid Dosage Manufacturing Line

    • PAT is used to monitor and control powder flow, particle size, and moisture levels to ensure consistent tablet compression.
    • NIR and in-line Particle Size Analyzer (PSA) are used to monitor and control the process.
    • PAT ensures that powder blends are not segregating during compression and potency is consistent over the entire process.

    PAT Application in Liquid Dosage Manufacturing Line

    • PAT is used to monitor and control process parameters such as purity, identity, and conformity to predict how to process material in a QbD environment.
    • NIR is used to monitor and control the filling process to ensure content uniformity/assay is consistent over the entire process.
    • In-line Viscometer and Headspace Gas Analyzer are used to monitor and control process parameters.

    Critical Process Parameter (CPP)

    • CPP is a process parameter whose variability has an impact on a critical quality attribute.
    • PAT is used to monitor and control CPPs to ensure the process produces the desired quality.
    • Risk assessment and experimentation are used to establish the linkage between potential CPPs and CQAs.### PAT: Major Techniques
    • Near-Infrared (NIR) Spectroscopy and Raman Spectroscopy are two major techniques in Process Analytical Technology (PAT)

    NIR Spectroscopy

    • Uses short wave region (700-1100nm) for transmission measurements and long wave region (1100-2500nm) for diffuse reflectance measurements
    • Components: light source, slit, mirror, diffraction grating (prism), order sorter, detector
    • Setup and calibration: slit opening, mirror distance, grating position
    • Fourier Transform IR (FTIR) and Linear Variable Filter (LVF) are two types of NIR spectrometers

    Overtones and Combinations in NIR Spectra

    • Each overtone describes the information of the previous one, but one order of magnitude less in intensity
    • Spectrum of biscuit dough with main areas of absorption identified

    NIRS Applications

    • Identification, qualification, and assay of starting materials, intermediates, and finished products
    • Verification of physicochemical properties
    • Gaining process understanding
    • Monitoring and controlling processes (off-line, at-line, on-line, in-line)
    • Continuous improvement and life cycle management
    • Enables enhanced assessment of quality of materials and processes by extensive and more representative sampling

    NIRS in PAT Analysis

    • Not all NIR spectrometers are suitable for PAT analysis
    • Requirements for PAT analysis: capturing critical material and process information within a very short time frame
    • Considerations: stability, reliability, robustness, ruggedness, mobility, ease of installation and operation

    LVF NIR PAT Solutions

    • Real-time process monitoring
    • Field, at-line, in-line analysis
    • Rugged, IP65 housing, internal rechargeable battery
    • USB powered, Bluetooth or USB connection
    • Weight: 318g (portable device), 250g (handheld device)

    MicroNIR Cloud-Based and On-Device Analysis

    • Cloud-based and on-device analysis capabilities
    • Real-time process monitoring and analysis

    PAT for Raw Material Quality Monitoring

    • Raw material quality test: current facts
    • Physical and mechanical attributes are critical for production process
    • Minor differences in physical attributes can affect process robustness
    • PAT principles and tools can provide relevant information relating to physical, chemical, and biological attributes

    NIR and Raman Spectroscopy in Raw Material Application

    • Similarities: non-destructive, handheld devices, no sample preparation, user-friendly, work through plastic

    • Differences: required multiple standards for defining statistical threshold### NIR and Raman Spectroscopy in Raw Material Application

    • Dipole moment variation is active in all kinds of pharma ingredients in NIR spectroscopy, while polarizability variation is active in limited pharma ingredients in Raman spectroscopy.

    • Measurement principle: NIR spectroscopy measures the absorbed, reflected, or transmitted radiation, whereas Raman spectroscopy measures the inelastically scattered radiation.

    • Duration per analysis: NIR spectroscopy takes a maximum of 2 seconds, while Raman spectroscopy takes 5 seconds to minutes.

    • Signal output: NIR spectroscopy produces a fingerprint signal, while Raman spectroscopy produces sharp peaks.

    • Fluorescence issue: There is no issue with fluorescence in NIR spectroscopy, but fluorescence interference may occur in Raman spectroscopy.

    • Analysis of color samples: NIR spectroscopy has no issue, while Raman spectroscopy may damage or burn the sample.

    • Parameters that can be detected:

      • Moisture level: Yes in NIR spectroscopy, not sensitive in Raman spectroscopy.
      • Particle size difference: Yes in NIR spectroscopy, not sensitive in Raman spectroscopy, and affects processability.
      • Crystallinity: Yes in NIR spectroscopy, not sensitive in Raman spectroscopy.

    • Liquid analysis: NIR spectroscopy requires sampling, while Raman spectroscopy does not.

    • Safety for operators: NIR spectroscopy is eye-safe, while Raman spectroscopy poses an eye injury risk and requires safety goggles.

    • PAT suitability: NIR spectroscopy is suitable, while Raman spectroscopy is not.

    Handheld NIR and Raman Spectroscopy: Performance Comparison

    • Raman spectroscopy is active for 99.5% of API and excipients, while NIR spectroscopy is active for 100% of chemicals.
    • Total performance: Raman spectroscopy performs well for 53% of samples, moderately for 34%, and poorly for 13%, while NIR spectroscopy performs well for all samples.
    • Fluorescence interference occurs in Raman spectroscopy, leading to weak signals and longer analysis times.

    Raw Material Identification is Not PAT

    • Raw material identification confirms the chemical structure of a molecule, while PAT (Process Analytical Technology) confirms physical characteristics.
    • Different physical characteristics of the same substance may have different processability and/or efficacy, leading to production and/or bioavailability issues.
    • Raman and NIR spectroscopy are used in raw material identification.

    NIRS in Incoming Raw Material Identification and Qualification

    • NIRS (Near-Infrared Spectroscopy) is based on the comparison of spectral data with a spectral reference library.
    • Qualification is often performed after sample identification, with the qualification spectral library derived from samples representing different grades of the same substance.
    • If identification and/or qualification are based on more than one analytical method, it should be clear which reference method(s) will be replaced by the proposed NIR procedures.
    • NIRS may be supplemented by other analytical procedures to ensure specificity.

    NIR Library Development Recommendation

    • The spectral reference library should be established from several batches of different substances.
    • The library should be constructed from materials deemed acceptable according to registered or compendia testing regimes.
    • Samples from all relevant suppliers should be incorporated into the library.
    • Samples should exhibit the variation typical for the substance to be analyzed (e.g., variation in solid-state form, particle size, crystallinity, synthesis route, storage time).

    Spectral Match Value (SMV)

    • SMV is a simple, flexible, and powerful RM qualification method based on correlation to a mean spectrum.
    • SMV performs a pairwise wavelength correlation across a defined spectral region.

    Raw Material Qualification: Source Difference

    • NIR spectroscopy can differentiate between two different sources of riboflavin sodium phosphate, despite both meeting compendial specifications.
    • Source difference is detected using SMV method.

    Raw Material Qualification: Particle Size Difference

    • SMV model can differentiate between Cefixime powder and Cefixime micronized based on particle size difference.
    • Spectra shift is observed due to different particle size.

    Raw Material Qualification: Batch Consistency

    • NIR spectroscopy can evaluate different batches of Citicoline, a highly hygroscopic powder.
    • Batches meeting compendial specifications may still have differences in solubility and moisture content, affecting production.

    PAT For Process Monitoring

    • PAT is used for process monitoring and control in pharmaceutical manufacturing.

    Drying Monitoring

    • NIR spectroscopy is used for in-line process monitoring of fluid bed drying.
    • Quantitative calibration model: PLS for LOD determination.

    Blending Monitoring

    • Thief sampling is considered non-representative due to disturbance of local composition and non-homogenous sampling.
    • PAT instruments lead to 'grab' samples, but are a better approach than thief sampling.
    • The latest US FDA process validation guidance of 2011 states that all sources of variability should be understood.

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    Related Documents

    PAT Implementation-Pharmanexa-NR PDF 2024

    Description

    This quiz is about the implementation of Process Analytical Technology (PAT) in the pharmaceutical industry, focusing on quality assurance and production efficiency. It is based on a seminar presentation by Noviani Rustanto at the Seminar Farmasi Nasional Pharmanexa 2024.

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