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    Contamination control is important for pharmaceutical manufacturing. Different cleanroom grades (A, B, C, D) have maximum permitted particle levels. Grade A is for high risk areas like filling zones. Monitoring in operation ensures product exposure is controlled. Verification during idle times thoroughly checks the environment. People and processes can contaminate products, so monitoring and standards like ISO and FDA are necessary for pharmaceutical cleanrooms. Particle counters use light scattering to detect and size airborne particles and ensure environments meet cleanroom standards.

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    Contamination control is important for pharmaceutical manufacturing. Different cleanroom grades (A, B, C, D) have maximum permitted particle levels. Grade A is for high risk areas like filling zones. Monitoring in operation ensures product exposure is controlled. Verification during idle times thoroughly checks the environment. People and processes can contaminate products, so monitoring and standards like ISO and FDA are necessary for pharmaceutical cleanrooms. Particle counters use light scattering to detect and size airborne particles and ensure environments meet cleanroom standards.

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    Contamination control is important for pharmaceutical manufacturing. Different cleanroom grades (A, B, C, D) have maximum permitted particle levels. Grade A is for high risk areas like filling zones. Monitoring in operation ensures product exposure is controlled. Verification during idle times thoroughly checks the environment. People and processes can contaminate products, so monitoring and standards like ISO and FDA are necessary for pharmaceutical cleanrooms. Particle counters use light scattering to detect and size airborne particles and ensure environments meet cleanroom standards.

    Copyright:

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    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    151 views28 pages

    Charn

    Uploaded by

    sksingh82
    Contamination control is important for pharmaceutical manufacturing. Different cleanroom grades (A, B, C, D) have maximum permitted particle levels. Grade A is for high risk areas like filling zones. Monitoring in operation ensures product exposure is controlled. Verification during idle times thoroughly checks the environment. People and processes can contaminate products, so monitoring and standards like ISO and FDA are necessary for pharmaceutical cleanrooms. Particle counters use light scattering to detect and size airborne particles and ensure environments meet cleanroom standards.

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    of 28

    Contamination Control for Pharmaceutical Industry

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    Manufacture of sterile medical product


    Grade A : The local zone for high risk operation e.g. filling zone, stopper bowls, open ampoules and vials, making aseptic connections Grade B : For aseptic preparation and filling Grade C : Clean areas for preparation of solutions when unusually at risk Grade D : Clean areas for preparation of solutions and components for subsequent filling
    2

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    Airborne Particulate Classification


    Max. permitted number of particles/m3 equal to or above ( EN/ISO 14644-1 ) Size (m) Grade A Grade B Grade C Grade D 0.5 at rest 5.0 at rest 3,500 3,500 350,000 3,500,000 1 1 2,000 20,000 0.5 in operation 5.0 in operation 3,500 350,000 3,500,000 not defined 1 2,000 20,000 not defined

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    Cleanroom Control
    ENVIRONMENT
    ISO 14644-1, -2 FS 209 E GMP, cGMP FDA Guidelines ISO 14644-3

    Verification

    Monitoring

    PROCESS
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    PEOPLE
    4

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    Monitoring Vs. Verification


    Monitoring (FDA or GMP) focus: parameters during operation
    Dynamic or in operation Potential effect on product is critical issue

    Verification is normally done during idle time


    Infrequent but thorough check of the environment as-built at rest
    5

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    Cleanroom Monitoring
    In Operation or Dynamic Only Relates to Process and Product Quality Data needed for Product Release Average only count data from same location
    each point must be below limit on the average but not necessarily each sample may be OK to delay ALERT or ACTION until 3rd or 5th consecutive high reading

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    Cleanroom monitoring
    Monitoring is intended to insure that the product exposure is controlled within limits because even with a good environment . . .

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    People as Contamination
    5 to 10 million cells per day 2300 micro-organisms per square cm Filter efficiency of clothing is highly variable

    . . . People and Process can contaminate the Product.


    8

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    Cleanroom Verification
    Initial and periodic certification
    Federal Standard 209E ISO 14644-1, -2

    Three states
    As-built At Rest Operational / Dynamic

    Averaging of Data from all positions


    9

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    Clean room Standards


    10

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    Particle counting regulations and specifications


    FDA
    The FDA stipulates that particle counts must be monitored in critical fill areas. Critical fill areas are where drugs are being dispensed into containers.

    Federal Standard 209E


    Fed Std 209E defines clean room classifications Clean Room classes are based on the numbers of 0.5 and larger, particles per cubic foot. The classifications are as follows:

    Class 1 to Class 100,000


    Class 1 and 10 are typically used in semiconductor manufacturers clean rooms. Class 100 and 1000 are typically used in pharmaceutical applications. Critical fill areas are class 100. Class 10,000 and class 100,000 are used in manufacturing environments.
    11

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    ISO Regulations
    ISO 14644-1 Cleanroom Design (new 209E)

    will eventually replace FS209E, even in USA (3 - 5 years)

    EU GMP Annex I - Sterile Products


    requires monitoring of 5 um particles as well as 0.5 um

    ISO 13408

    Aseptic Guidelines
    12

    very similar to FDA version for liquid filling

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    Recent ISO Documents related to cleanrooms


    ISO Document ISO-14644-1 ISO-14644-2 ISO-14644-3 ISO-14644-4 ISO-14644-5 ISO-14644-6 ISO-14644-7 ISO-14644-8 ISO-14698-1 ISO-14698-2 ISO-14698-3 Title Classification of Air Cleanliness Cleanroom Testing for Compliance Methods for Evaluating & Measuring Cleanrooms & Associated Controlled Environments Cleanroom Design & Construction Cleanroom Operations Terms, Definitions & Units Enhanced Clean Devices Molecular Contamination Biocontamination: Control General Principles Biocontamination: Evaluation & Interpretation of Data Biocontamination: Methodology for Measuring Efficiency of Cleaning Inert Surfaces Status Active Active Draft Active Draft Draft Draft Draft Active Active Active
    13

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    Verification: ISO 14644-1


    ISO 14644-1
    ISO Class

    FED STD 209E


    English Metric

    ISO 14644-1 adds


    2 ultra-clean classes
    ISO Class 1 ISO Class 2

    1 2 3 4 5 6 7 8 9 1 10 100 1,000 10,000 100,000 M1.5 M2.5 M3.5 M4.5 M5.5 M6.5

    1 very dirty class


    ISO Class 9

    Total of 9 classes Counts / cubic meter Must specify room status


    as-built / at rest / in operation
    14

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    Verification: ISO 14644-1 versus FS 209E


    Parameter Minimum sample volume FS 209E ISO 14644-1

    2.83 liter 2.0 liter (0.1 cubic foot) (0.07 cubic foot) not specified 1 minute

    Minimum sample time Minimum number of samples at each location

    Note: Typical sample volume may be larger than minimum listed above especially for smaller size particles in very clean areas (better than ISO Class 5 or FS 209E Class 100)
    15

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    Particle Counter and Theory of Operation

    16

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    Theory of Particle Counter

    17

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    Theory of Particle Counter


    There are three basic elements in all particle counting systems: 1) The sensor
    The sensor is the device that detects particles using a light scattering method of detection.

    2) The sample delivery system


    The sample is delivered to the sensor by the use of a vacuum pump.

    3) The counting electronics


    The particle counts are processed and displayed by on board circuitry or in software.
    18

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    Sensor

    Counting Electronics

    Sample Delivery System (pump)

    19

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    The Sensor
    Columnating lens Laser diode

    Reflector

    Light trap

    Quiet State, no particles present.

    Photo detector

    Particle in the view volume.


    20

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    Sample Delivery
    A vacuum pump is used to pull the sample air through the sensor. The flow is measured in cubic feet per minute (cfm). 1.0cfm pump 0.1cfm pump

    21

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    Counting Electronics
    +V Threshold Circuit
    This circuitry is duplicated from one channel up to six channels depending on the model counter

    CH3

    +V

    CH2

    Digital signals to counting circuitry

    Analog Signal in +V

    CH. 3 CH. 2 CH. 1


    CH1

    22

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    Particle Sizing
    The larger the particle , the larger the corresponding output pulse from the sensor.

    23

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    Counting Modes
    Cumulative Differential

    Size 3 Size 2 Size 1


    24

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    Block Diagram for Airborne Particle Counter

    25

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    Airborne Particle Counter


    Sensitivities 0.1 to 25 micron

    26

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    Particle Counter Calibration Methods


    Count Correlation
    Compare to a standard reference instrument Compare to a standard count standard media

    Size Calibration
    Calibrate to a NIST traceable particle (mono-dispersed) Requires volumetric full stream or known view volume sensors

    Count Correlation Calibration


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    Size Size Calibration


    27

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    THANK YOU FOR YOUR ATTENTION

    28

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