Engineering Question & Answer
1.Question: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.
2.Question: 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.
3.Question: How can defined the Qualification ?
A documented procedure which demonstrates that a piece of equipment
or process is designed, installed, and operated properly.
4.Question: 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.
5.Question: 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.
6.Question: 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.
7.Question: 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.
8.Question: 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.
9.Question: 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.
10.Question: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.
- building finishes and structure
- air filtration
- air change rate or flushing rate
- room pressure
- location of air terminals and directional airflow
- material flow
- personnel flow
- equipment movement process being carried out
- outside air conditions
- type of product.
11.Question: What is the selection criteria of type of filters for required ambient quality air,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 plus
secondary 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 secondary
plus tertiary filters (e.g. EN779 G4 plus F8 plus
EN1822 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
12.Question:What is the parameter should be consider to achieve targeted Air change rates in area?
Answer: The following parameter should be consider to achive the required air changes per hour in a area that is-
- level of protection required
- the quality and filtration of the supply air
- particulates generated by the manufacturing process
- particulates generated by the operators
- configuration of the room and air supply and extract locations
- sufficient air to achieve containment effect
- sufficient air to cope with the room heat load
- sufficient air to maintain the required room pressure.
13.Question: 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
14.Question: How to control the Cross-contamination in clean room.
Answer: Following measures assist in preventing cross-contamination that is-
- Correct directional air movement
- a pressure cascade system.
- The displacement concept (low pressure differential, high airflow),
- The pressure differential concept (high pressure differential, low airflow),
- The physical barrier concept.
- 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.
- Airborne contaminants should be controlled through effective ventilation.
- External contaminants should be removed by effective filtration of the supply air.
- Internal contaminants should be controlled by dilution and flushing of contaminants in the room, or by displacement airflow.
15.Question: 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.
16.Question:How to manage Pressure differential concept (high pressure differential, low airflow) ?
- The pressure differential between adjacent rooms should be considered a critical parameter, depending on the outcome of risk analysis.
- The limits for the pressure differential between adjacent areas should be such that there is no risk of overlap,
- 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.
- 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.
- 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.
- In considering room pressure differentials, transient variations, such as machine extract systems, should be taken into consideration.
- 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.
- Where the design pressure differential is too low and tolerances are at opposite extremities, a flow reversal can take place.
- For example, where a control tolerance of ± 3 Pa is specified, the implications of the upper and lower tolerances on containment should be evaluated.
- Low pressure differentials may be acceptable when airlocks (pressure sinks or pressure bubbles) are used.
- 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.
- (Reference- TRS 937 Page No – 64,65 of 461)
17.Question: 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)
18.Question: Where we can used physical barrier concept?
The physical barrier concept used in manufacturing of Highly potent products should be manufactured under a pressure cascade regime that is negative relative to atmospheric pressure.Airtight ceilings and walls, close fitting doors and sealed light fittings should be in place.
19.Question: What is the relative humidity?
The ratio of the actual water vapour pressure of the air to the saturated water vapour pressure of the air at the same temperature expressed as a percentage.
it is the ratio of the mass of moisture in the air, relative to the mass at 100% moisture saturation, at a given temperature.
20.Question: What is the the “as-built” condition in Clean Room classification tests ?
Room classification tests in the “as-built” condition should be carried out on the bare room, in the absence of any equipment or personnel.
21.Question: What is the the “at-rest” condition in Clean Room classification tests ?
Room classification tests in the “at-rest” condition should be carried out with the equipment operating where relevant, but without any operators. Because of the amounts of dust usually generated in a solid dosage facility most clean area classifications are rated for the “at-rest” condition.
22.Question: What is the the “operational” condition in Clean Room classification tests ?
Room classification tests in the “operational” condition should be carried out during the normal production process with equipment operating and the normal number of personnel present in the room.
Generally a room that is tested for an “operational” condition should be able to be cleaned up to the “at-rest” clean area classification after a short clean-up time. The clean-up time should be determined through validation and is generally of the order of 20 minutes.
23.Question: What is the Unidirectional airflow (UDAF) and where can used?
Unidirectional airflow should be used to provide product protection by supplying a clean air supply over the product, minimizing the ingress of contaminants from surrounding areas and also provide protection to the operator from contamination by the product.
Sampling of materials such as starting materials,primary packaging materials and products, should be carried out in the Unidirectional airflow environmental conditions that are required for the further processing of the product In a weighing booth situation.
dispensary or weighing booth should be provided with unidirectional airflow for protection of the product and operator.
Reference: ( TRS 937 Page No – 59 of 461)
24.Question:What is Flow Direction of Pressure differential in Manufacturing facilities ?
Manufacturing facilities should be maintained at a positive pressure relative to the outside, to limit the ingress of contaminants.
Where facilities are to be maintained at negative pressures relative to the ambient pressure to prevent the escape of harmful products to the outside (such as penicillin and hormones), special precautions should be taken.
Negative pressure zones should, as far as possible, be encapsulated by surrounding areas with clean air supplies, so that only clean air can infiltrate into the controlled zone.
Mr. Shiv Kumar is the Author and founder of pharmaceutical guidance, he is a pharmaceutical Professional from India having more than 14 years of rich experience in pharmaceutical field.
During his career, he work in quality assurance department with multinational company’s i.e Zydus Cadila Ltd, Unichem Laboratories Ltd, Indoco remedies Ltd, Panacea Biotec Ltd, Nectar life Science Ltd. During his experience, he face may regulatory Audit i.e. USFDA, MHRA, ANVISA, MCC, TGA, EU –GMP, WHO –Geneva, ISO 9001-2008 and many ROW Regularities Audit i.e.Uganda,Kenya, Tanzania, Zimbabwe. He is currently leading a regulatory pharmaceutical company as a head Quality. You can join him by Email, Facebook, Google+, Twitter and YouTube