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    Media Fill

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    Kuruva Shiva
    The document discusses media fill, which is a process simulation used to validate aseptic processing and sterilization. It involves exposing a microbiological growth medium to product contact surfaces and process manipulations to simulate what the product will undergo. Key aspects of media fill that are reviewed include study design, frequency and size of runs, environmental conditions, media used, and interpretation of test results. Contamination found is evaluated against acceptance criteria to determine if the process passes qualification. Media fill is an important validation tool for sterile manufacturing facilities and processes.

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    Media Fill

    Uploaded by

    Kuruva Shiva
    642 views27 pages
    The document discusses media fill, which is a process simulation used to validate aseptic processing and sterilization. It involves exposing a microbiological growth medium to product contact surfaces and process manipulations to simulate what the product will undergo. Key aspects of media fill that are reviewed include study design, frequency and size of runs, environmental conditions, media used, and interpretation of test results. Contamination found is evaluated against acceptance criteria to determine if the process passes qualification. Media fill is an important validation tool for sterile manufacturing facilities and processes.

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    The document discusses media fill, which is a process simulation used to validate aseptic processing and sterilization. It involves exposing a microbiological growth medium to product contact surfaces and process manipulations to simulate what the product will undergo. Key aspects of media fill that are reviewed include study design, frequency and size of runs, environmental conditions, media used, and interpretation of test results. Contamination found is evaluated against acceptance criteria to determine if the process passes qualification. Media fill is an important validation tool for sterile manufacturing facilities and processes.

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    642 views27 pages

    Media Fill

    Uploaded by

    Kuruva Shiva
    The document discusses media fill, which is a process simulation used to validate aseptic processing and sterilization. It involves exposing a microbiological growth medium to product contact surfaces and process manipulations to simulate what the product will undergo. Key aspects of media fill that are reviewed include study design, frequency and size of runs, environmental conditions, media used, and interpretation of test results. Contamination found is evaluated against acceptance criteria to determine if the process passes qualification. Media fill is an important validation tool for sterile manufacturing facilities and processes.

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    of 27

    Media Fill

    A Process Simution
    Presented By
    Shikha Chauhan
    21 CFR 211.113
    Validation of Aseptic Processing and
    Sterilization

     Process Simulation / Media Fill


     Filtration Efficacy
     Sterilization of Equipment, containers and closures
    What is Media Fill?

    Includes exposing the microbiological growth


    medium to product contact surface of
    equipment, container closure systems, critical
    environments, and process manipulations to
    closely simulate the same exposure that the
    product itself will undergo.
    What should be considered for a
    media fill?

    1. Study design
    2. Frequency and number of runs
    3. Duration of runs
    4. Size of runs
    5. Line speed
    6. Environmental conditions
    7. Media
    8. Incubation and examination of media filled units
    9. Interpretation of test results
    1. STUDY DESIGN

    a. Factors associated with longest permitted runs


    b. Interventions
    i. Routine
    ii. Non routine
    c. Lyophilization, when applicable
    d. Aseptic assembly of equipment
    e. Number of personnel
    f. Aseptic additions/transfers
    j. Shift changes
    k. Gown changes
    l. Aseptic sample collection
    m. Line speed and configuration
    n. Weight checks
    o. Container closure system
    p. Written procedures
    2. FREQUENCY AND NUMBER OF RUNS
    a. Initial Qualification of line
    i. To be repeated enough times
    ii. Atleast three consecutive separate successful
    runs required
    b. Subsequent routine qualification
    i. Semi-annual for each line
    C. Additional qualification required in case
    of
    i. Facility and equipment modification
    ii. Line configuration changes
    iii. Significant changes in personnel
    iv. Anomalies in environmental testing results
    v. Container closure system changes
    vi. Extended shut downs
    vii.End point sterility failures
    d. Post failure media
    fill

    • Cause detected

    • Cause not detected


    Three consecutive
    successful runs
    required
    3. DURATION OF RUNS

    a. Full Batch size and duration is the ideal run

    b. Manual filling/closing

    c. Extensive Manual manipulation

    d. Fully automated procedure


    4. SIZE OF RUNS

    a. For a batch size of less than 5,000 units


    Atleast equal to the maximum batch
    size

    a. For a batch size of 5,000 units or more


    Generally acceptable starting point 5,000 to
    10,000 units
    Factors affecting run size

     Actual batch size

     Type of operation manual/mechanical

     Time consumed

     Type of facility open/isolated


    5. LINE SPEED

     Range of line speeds addressed

     One media fill one line speed


    6. ENVIRONMENTAL CONDITIONS

     Actual Conditions

     Stressful conditions inline with SOPs


    7. MEDIA
    Routine: Soybean caesin digest medium
    Exceptional: Fluid thioglycollate medium

    Growth promotion demonstration


    Bacteria
    Gram +ve
    Gram-ve
    Yeast and mold
    Size of innoculum
    Less than 100 CFU

    Failure of growth promotion and origin of


    contamination during simulation be
    investigated and media fill to be repeated
    8. INCUBATION AND EXAMINATION OF
    MEDIA-FILLED UNITS
    Temperature 20-35ºC
    Set temperature + 2.5ºC of target temperature

    Time
    Lower temperature 7 days
    Higher temperature 7 days
    Examination

    Pre-incubation
    Integral units to be incubated
    Units lacking integrity to be rejected

    After-Incubation is underway
    Selection/Rejection of damaged units to be justified

    Written procedure for aseptic intervention should be


    clear and specific
    9. INTERPRETATION OF TEST
    RESULTS

    Contaminated units to be considered


    objectionable
    Microorganism to be identified to species level.
    Contamination indicative of potential sterility
    assurance problem, regardless of run size
    Batch Size Number of Interpretation
    contaminated
    units
    Less than 5000 zero OK
    One Revalidation

    5000 to 10,000 zero OK


    One Investigate and consider
    repeat
    two Revalidation

    More than 10,000zero OK

    One Investigate and consider


    repeat
    two Revalidation
    Observed 0 1 2 3 4 5 6 7 8 9 10
    number of
    failures

    Upper 95% 3 4.74 6.3 7.75 9.15 10.51 11.84 13.15 14.43 15.71 16.96
    confidence
    limit
    Contamination rate =
    Upper confidence limit/Number of filled units
    X 100%

    Accepted contamination rate should be less


    than 0.1% with a 95% confidence level
    CONSIDERATIONS FOR EACH
    DOSAGE FORM

    Liquid products

    Injectable Powder products

    Suspension products

    Freeze Dried products


    Semi-Solid products

    Clinical trials material and small batch size products

    Biological and Biotechnology products

    Sterile Bulk Pharmaceuticals

    Blow Fill Seal Packed products


    SOURCES OF CONTAMINATION
    Aseptic practices
    Poor aseptic connections
    Poor sanitization
    Construction
    Poor gown design
    New line’s HVAC installation
    Velocity thru HEPA filters
    Mechanical failure
    References
    21 CFR 211.63
    21 CFR 211.65
    21 CFR 211.67

    21 CFR 211.84 (c)


    21 CFR 211.100(a)
    21 CFR 211.113(b)
    Thank You

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