What is the good engineering practice (GEP)?
Good engineering practice (GEP) means to established engineering methods and standards that are applied throughout the project life-cycle to deliver appropriate, cost-effective solutions.
How can defined the Qualification?
A documented procedure which demonstrates that a piece of equipment
or process is designed, installed, and operated properly.
How can defined the validation?
The documented act of proving that any procedure, process, equipment, material, activity or system actually leads to the expected results.
What is the different between Validation and Qualification?
Qualification is demonstration of the specific system, premises or equipment that are able to achieve the predetermined acceptance criteria to confirm the attributes what it purports to do.
Validation is establishing a documented evidence to provide a high degree of assurance that a specific system, process or facility will consistently produce a product meeting its predetermined specifications and quality attributes.
What is the Definition of design Qualification?
The documented verification that the proposed design of the facilities, systems and equipment is suitable for the intended purpose.
What is the Definition of Installation Qualification?
The documented verification that the facilities, systems and equipment, as installed or modified, comply with the approved design and the manufacturer’s recommendations.
What is the Definition of Operational Qualification?
The documented verification that the facilities, systems and equipment, as installed or modified, perform as intended throughout the anticipated operating ranges.
What is the Definition of Performance Qualification?
The documented verification that the facilities, systems and equipment, as connected together, can perform effectively and reproducibly, based on the approved process method and product specification.
How can defined the commissioning in qualification of Equipment and Instruments?
Commissioning is the documented process of verifying that the equipment and systems are installed according to specifications, placing the equipment into active service and verifying its proper action. Commissioning takes place at the conclusion of project construction but prior to validation.
What is the selection criteria during clean area classification that should be addressed at the design and qualification stages?
The following criteria will be addressed during design and qualification stages of clean area classification in order to achieve an efficient clean area.
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building finishes and structure
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air filtration
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air change rate or flushing rate
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room pressure
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location of air terminals and directional airflow
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temperature
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humidity
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material flow
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personnel flow
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equipment movement process being carried out
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outside air conditions
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occupancy
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type of product.
What is the parameter should be consider to achieve targeted Air change rates in area?
The following parameter should be consider to achieve the required air changes per hour in a area that is-
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level of protection required
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the quality and filtration of the supply air
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particulates generated by the manufacturing process
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particulates generated by the operators
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configuration of the room and air supply and extract locations
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sufficient air to achieve containment effect
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sufficient air to cope with the room heat load
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Sufficient air to maintain the required room pressure.
What is the Cross-contamination ?
Contamination of a starting material, intermediate product or finished product with another starting material or material during production.
Examples of Cross-contamination
Where different products are manufactured at the same time, in different areas or cubicles, in a multi-product OSD manufacturing site, measures should be taken to ensure that dust cannot move from one cubicle to another.
How to manage the pressure cascade ?
The pressure cascade should be such that the direction of airflow is from the clean corridor into the cubicles,resulting in dust containment.
The corridor should be maintained at a higher pressure than the cubicles, and the cubicles at a higher pressure than atmospheric pressure.
What is the selection criteria of type of filters for required ambient quality air change rates and return air quality during design and qualification stages of clean area classification?
The type of filters required for different applications depends on Levels of Protection that is briefing in below table.
Table 1 -Levels of protection and recommended filtration
Level of protection |
Recommended filtration |
Level 1 |
Primary filters only (e.g. EN779 G4 filters) |
Level 2 and 3 |
Production facility operating on 100% outside air: primary plussecondary filters (e.g. EN779 G4 plus F8 filters) |
Level 2 and 3 |
Production facility operating on recirculated plus ambient air,where potential for cross-contamination exists: Primary plus secondaryplus tertiary filters (e.g. EN779 G4 plus F8 plusEN1822 H13 filters) |
Note: The filter classifications referred to above relate to the EN1822 and EN779 test standards (EN 779 relates to filter classes G1 to F9 and EN 1822 relates to filter classes H10 to U16).
Examples of levels of protection
Level 1 Area-General Area with normal housekeeping and maintenance, e.g. warehousing,secondary packing.
Level 2 Area-Protected Area in which steps are taken to protect the exposed pharmaceutical starting material or product from contamination or degradation, e.g. manufacturing, primary packing, dispensing.
Level 3 Area – Controlled Area in which specific environmental conditions are defined,controlled and monitored to prevent contamination or degradation of the pharmaceutical starting material or product
How to manage Pressure differential concept (high pressure differential, low airflow) ?
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The pressure differential between adjacent rooms should be considered a critical parameter, depending on the outcome of risk analysis.
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The limits for the pressure differential between adjacent areas should be such that there is no risk of overlap,
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For example-5 Pa to 15 Pa in one room and 15 Pa to 30 Pa in an adjacent room, resulting in no pressure cascade, if the first room is at the maximum tolerance and the second room is at the minimum tolerance.
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The high pressure differential between the clean and less clean zones should be generated by leakage through the gaps of the closed doors to the cubicle.
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The pressure differential should be of sufficient magnitude to ensure containment and prevention of flow reversal but should not be so high as to create turbulence problems.
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In considering room pressure differentials, transient variations, such as machine extract systems, should be taken into consideration.
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Pressure differential for achieving containment between two adjacent zones is 15 Pa, but pressure differentials of between 5 Pa and 20 Pa may be acceptable.
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Where the design pressure differential is too low and tolerances are at opposite extremities, a flow reversal can take place.
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For example,where a control tolerance of ± 3 Pa is specified, the implications of the upper and lower tolerances on containment should be evaluated.
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Low pressure differentials may be acceptable when airlocks (pressure sinks or pressure bubbles) are used.
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Note:The pressure differential concept may normally be used in zones where little or no dust is being generated. It may be used alone or in combination with other containment control techniques and concepts, such as a double door airlock.
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(Reference- TRS 937 Page No – 64,65 of 461)
Displacement concept (low pressure differential, high airflow)
The Displacement concept in which the air should be supplied to the corridor, flow through the doorway and be extracted from the back of the cubicle. Normally the cubicle door should be closed and the air should enter the cubicle through a door grille.
The velocity should be high enough to prevent turbulence within the doorway resulting in dust escaping.
This displacement airflow should be calculated as the product of the door area and the velocity, which results in large air quantities.
Note – This method of containment is not the preferred method, this concept should ideally be applied in production processes where large amounts of dust are generated.
(Reference:- TRS 937 – Page No – 64 of 461)
How to control the Cross-contamination in clean room?
Answer: Following measures assist in preventing cross-contamination that is-
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Correct directional air movement
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a pressure cascade system.
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The displacement concept (low pressure differential, high airflow),
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The pressure differential concept (high pressure differential, low airflow),
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The physical barrier concept.
Note:
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Contaminants may result from inappropriate premises (e.g. poor design,layout or finishing), poor cleaning procedures, contaminants brought in by personnel, and a poor HVAC system.
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Airborne contaminants should be controlled through effective ventilation.
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External contaminants should be removed by effective filtration of the supply air.
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Internal contaminants should be controlled by dilution and flushing of contaminants in the room, or by displacement airflow.