Transcript A Seminar on REGULATORY ASPECTS OF PHARMACEUTICAL …

A
Seminar on
VALIDATION OF
COMPRESSED AIR
CONTENT
 Introduction
 How Compressed Air System(CAS) works?
 Test functions and Acceptance criteria
 Validation protocol :
 Installation Qualification (IQ)
 Operational Qualification (OQ)
 Performance Qualification (PQ)
 Applications
 How to gain efficiencies and power savings?
 References
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Introduction
 What is compressed air?
 Commonly called Industry's Fourth Utility
 Air that is condensed and contained at a
pressure that is greater than the atmosphere
 The process takes a given mass of air, which
occupies a given volume of space, and
reduces it into a smaller space. In that space,
greater air mass produces greater pressure.
The pressure comes from this air trying to
return to its original volume
 It is used in many different manufacturing
operations. A typical compressed air system
operating at 100 psig (7 bar) will compress
the air down to 1/8 of its original volume.
(figure CA1-1)
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• Compressed air is an important component of pharmaceutical
manufacturing facilities
•
It provides many of the air types necessary for a manufacturing
facility to function, including: breathing air , motive air for
machines , process air , analytical air and Product Direct Impact , or
"cGMP" air
• The application for which the compressed air will be used will
dictate the level of air quality that is appropriate for use
•
There are two main categories of applications: Direct Impact
Systems and Indirect Impact System
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Direct Impact Systems :
• The systems will have direct contact with the product
• The system will provide an excipient, or produce an ingredient or
solvent
• The system will be used in cleaning or sterilizing
• The system will preserve product status
• The system will produce data which is used to accept or reject the
product
• The system will be a process control system that can affect product
quality and there will be no system for independent verification of
control system performance
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Indirect Impact or No Impact Systems :
• The system will not contact the product or materials that
ultimately become part of the product
• The systems are generally site or building systems and
are not tailored specifically to aseptic manufacturing
facilities
• The systems will deal with a side activity of the
manufacturing process (such as waste disposal)
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How the Compressed Air System(CAS) works?
• Each component in a typical system helps to deliver clean, dry,
compressed air that’s free of pressure fluctuations at its point of
use
• If any component is working inefficiently, the system’s
performance suffers and operating costs rise
• Like any high-pressure system, they are prone to leaks or other
failures that can result in lower performance
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Typical Compressed Air System Layout :
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Components of the CAS system
• Inlet filter:
Removes particles from the air entering the compressor
• Compressor :
Compresses air to a small volume, increasing the pressure
(Reciprocating compressors are frequently used)
• Motor : Drives the compressor
• Compressor Controller :
Directs the compressor’s output and it may be microprocessor,
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electromechanical or pneumatically based
• Aftercooler :
Compression leaves the air hot and wet. The aftercooler lowers
the temperature of the air leaving the compressor and removes
water that condenses as the air cools
• Separator : Removes liquids from the compressed air
• Receiver : Stores a large reserve of compressed air to maintain
a smooth flow to the plant
• Air line Filter :
Removes solids and liquids from the compressed air stream.
Can be placed throughout the system
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• Dryer :
- Helps to eliminate any remaining moisture in
the compressed air by using either a refrigerated
condenser or a desiccant
- Refrigerated condensers cool the air to condense water vapours
into a liquid that is then drained from the system. Desiccants are
powders or gels that remove water by absorbing it
• Condensate Trap :
- Collects and discharges liquid that condenses out of the air
stream
- Integral part of aftercoolers, dryers and separators
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• Distribution Piping :
Links the components. It distributes the air from a main header to
branch lines and sub headers to drop points connected to individual
tools
• Pressure regulator :
Controls air pressure and flow at individual points of use
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Test Functions :
1. Perform Installation Qualification
2. Perform general operational controls verification testing
3. Operate system throughout the range of operating design
specifications or range of intended use
4. Verify that the compressed air system is capable of supplying
pressurized compressed air to all use points. Perform an
operational test of the distribution system and pressure
regulators by monitoring the pressure output at the
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respective use points
5. Perform a capacity test to verify that the system is capable of
supplying the required gas, pressure, and flow rate at each
use point
6. Verify that in-line filters are integrity tested. Confirm that all
documentation clearly indicates acceptable test results
7.
Perform dew point measurement
8.
Perform hydrocarbon content measurement
9.
Perform viable particulate count, microbiological at critical use
points after sterile filters (refer to Federal Standard 209E)
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10. Identification of oxygen content
11. Record the range of all process or equipment parameters (set
points, flow rates, timing sequences, concentrations, etc.)
verified during Operational and Performance Qualifications
testing
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Acceptance Criteria :
1. The system is installed in accordance with design specifications,
manufacturer recommendations and cGMPs. Instruments are
calibrated, identified, and entered into the calibration program
2. General controls, alarms, and interlocks operate in accordance
with design specifications
3. The system operates in accordance with design specifications
throughout the operating range or range of intended use
4. The compressed air distribution system must consistently deliver
pressurized compressed air to the use points at the design
pressure as specified
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5.
All in-line filters are integrity tested and qualify per
manufacturer’s operating specifications
6. Dew point must be <0° or lower
7. Hydrocarbon content must be ≤ 1 ppm
8. Viable particulate must be ≤ 1.0 cfu/10 ft3
9. Nonviable particulate counts must be ≤ 100/ft3 of 0.5μ or larger
at all critical use points
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Method for Dew point and Oil content
• As per Air Quality Standards ISO 8573 and Filter Standard ISO 12500 for
compressed air there are nine part to it as follows :
Part 1 - Contaminants and Purity classes
Part 2 - Test methods for aerosol oil content
Part 3 - Test methods for the measurement of humidity
Part 4 - Test methods for solid particle content
Part 5 - Determination of oil vapor and organic solvent
content
Part 6 - Test methods for gaseous contaminant content
Part 7 - Test method for viable microbiological contaminant
content
Part 8 - Test methods for solid particle content by mass
concentration
Part 9 - Test methods for liquid water content
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Validation Protocol :
• It includes :




Installation Qualification
Operational Qualification
Performance Qualification
Final Report
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Installation Qualification (IQ)
•
This section establishes documented verification that key
aspects of equipment adhere to approve design intentions and
recommendation of manufacturer have been suitably consider
• In addition to the common requirements outlined in the
"General" section, the following are required for Distribution
systems
• The piping should be supported, labeled, and sloped to drain
completely
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Contd…
• Materials of construction will vary with gas type, and must
agree with specification
• Verify that in-line filters can be integrity tested
• Verify that the systems have been thoroughly cleaned and dried
before operation
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Operational Qualification
• This section Establishes that there is a documented verification
that the installed system functions as a specified and that there is
a sufficient documentary evidence to demonstrate this
• The OQ protocol will outline tests to study capacity and pressure
during estimated minimum and maximum use
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Contd…
• All use points supply the specified pressure prior to any
pressure reducing valves or equipment
• All use point supply the volume of gas as specified
• Each peak load use point as specified by use or equipment
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Performance Qualification
• This section gives documented verification that the equipment
performance in its normal operating environment is
consistently exactly as specified in User Requirement
Specification (URS)
• Testing will include viable and total particulate counts, dew
point, hydrocarbon analysis, and purity analysis
• Each point of use will be tested at least three times over 10
working days. Every use point of the system must be tested
several times over the course of the study.
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Contd…
• Hydrocarbon Monitoring should show less than 0.2 mg/m3 (25
mg/125 liters) detected. (the lower limit of a Dragger tube)
• The highest total particulate count from the five one-minute
runs must meet class 100 or EC Class A criteria
• Viable Monitoring (not needed of integrity tested final filter is
in place) less than 0.03 CFU/ft3 or less than 1 CFU/m3
• Since the gas is field sampled under non-sterile conditions, a
few sporadic, individual, tests may fail. Persistent test failures
with any individual test, or group of tests, will indicate a
system failure
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Contd…
• The dew point of compressed air less than or equal to -10°C, or
less than the lowest temperature to which the system is exposed
• Identity and Purity (Nitrogen) Not less than 99.0% nitrogen by
volume. Not more than 0.001% Carbon Monoxide. No
appreciable odor
• Identity and Purity (Oxygen) Not less than 99.0% Oxygen by
volume. No appreciable odor
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Final Report
•
Depending on IQ , OQ and PQ data final report is made and
that will indicate whether your system is validated or not
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Applications :
Level of application
Function
• Shop air
(Filtered centrifugal
separator)
• Removes solids 3 microns
& larger, 99% of water
droplets, & 40% of oil
aerosol
• Air Tools, Sand Blasting,
Pneumatic Control
Systems
(Dryer and Air line filter)
• Removes moisture
producing a 35° to 50°F (1.67° to 10°C) pressure
dew point, removes 70%
of oil
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Contd…
Level of Application
Function
• Instrument Air, Paint
Spraying, Powder
Coating, Packing
Machines
(Dryer, Oil remover
filter)
• Removes moisture &
produces a 35° to 50°F (1.67° to 10°C) pressure
dew point, removes
99.999% of oil aerosols,
and all particles .025
microns and larger
• Indoor Applications, Food
Industry, Dairy Industry,
Laboratories
(Dryer , Filter and Oil
vapour absorber)
• Removes moisture &
produces a 35° to 50°F (1.67° to 10°C) pressure
dew point, removes
99.999% of oil aerosols,
all particles .025 microns
and larger, oily vapor, oily
smell, & oily taste
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Contd…
Level of Application
Function
• Breathing Air
(continuous or
portable)
• Removes harmful
compressed air
contaminants and will
produce Grade D
breathing air
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How to get efficiency and power savings?
•
Establish regular maintenance programme
• Hunt for air leaks
• Educate your plant staff and emphasizing the importance of
monitoring the line
• Check system operating pressure
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References
 Agalloco James, Carleton J. Fredric “Validation of
Pharmaceutical Processes”; Third edition
 Syed Imitiaz Haider, Pharmaceutical Master Validation Plan,
The ultimate guide to FDA , GMP and GLP compliance
 Syed Imtiaz Haider, “Validation Standard Operating
Procedure”,2nd Edition
 www.usvalidation.com
 http://www.validationwhat.com/compressed-air-quality.html
 http://validationworld.com
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THANK YOU
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