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| Figure: Aseptic filling operation |
Assessment made based on the FDA 2004 Aseptic guidance:
1. Initial clean room qualification includes, in part, an assessment of air quality under as-built, static conditions.
A. True B. False
2. Air in the immediate proximity of exposed sterilized containers/closures and filling/closing operations would be of appropriate particle quality when it has a per-cubic-meter particle count Contains Nonbinding Recommendations of no more than 3520 in a size range of 0.5 μm and larger when counted at representative locations normally not more than 1 foot away from the work site, within the airflow, and during filling/closing operations. This level of air cleanliness is also known as Class 100 (ISO 5).
A. True B. False
3. Videotape or other recording mechanisms have been found to be useful aides in assessing airflow initially as well as facilitating evaluation of subsequent equipment configuration changes. It is important to note that even successfully qualified systems can be compromised by poor operational, maintenance, or personnel practices.
A. True B. False
4. Air monitoring samples of critical areas should normally yield no microbiological contaminants. Agency recommend affording appropriate investigative attention to contamination occurrences in this environment
A. True B. False
5. A velocity of 0.45 meters/second (90 feet per minute) has generally been established, with a range of plus or minus 20 percent around the setpoint. Higher velocities may be appropriate in operations generating high levels of particulates.
A. True B. False
6. It is vital for rooms of higher air cleanliness to have a substantial positive pressure differential relative to adjacent rooms of lower air cleanliness. For example,
(a) A positive pressure differential of at least 10-15 Pascals (Pa) should be maintained between adjacent rooms of differing classification (with doors closed).
(b) When doors are open, outward airflow should be sufficient to minimize ingress of contamination, and it is critical that the time a door can remain ajar be strictly controlled
A. (a: True; b-: False), B. (a: True; b-: True), C. (a: False; b-: True), D. (a: False; b-: False)
7. The aseptic processing room and adjacent cleanrooms have the same classification.
(a) Maintaining a pressure differential (with doors closed) between the aseptic processing room and these adjacent rooms can provide beneficial separation.
(b) In any facility designed with an unclassified room adjacent to the aseptic processing room, a substantial overpressure (e.g., at least 12.5 Pa) from the aseptic processing room should be maintained at all times to prevent contamination.
(c) If this pressure differential drops below the minimum limit, it is important that the environmental quality of the aseptic processing room be restored and confirmed.
i. a & b is true
ii. b & c is true
iii. c & a is true
iv. a, b & c true
8. Air change rate is another important cleanroom design parameter. For Class 100,000 (ISO 8) supporting rooms, airflow sufficient to achieve at least 20 air changes per hour is typically acceptable. Significantly higher air change rates are normally needed for Class 10,000 and Class 100 areas.
A. True B. False
9. A compressed gas should be of appropriate purity (e.g., free from oil) and it’s microbiological and particle quality after filtration should be equal to or better than that of the air in the environment into which the gas is introduced.
A. True B. False
10. That sterile membrane filters be used for autoclave air lines, Lyophilizer vacuum breaks, and tanks containing sterilized materials.
A. True B. False
11. Sterilized holding tanks and any contained liquids should be held under positive pressure or appropriately sealed to prevent microbial contamination.
A. True B. False
12. HEPA filter integrity should be maintained to ensure aseptic conditions. Leak testing should be performed at installation to detect integrity breaches around the sealing gaskets, through the frames, or through various points on the filter media. Thereafter, leak tests should be performed at suitable time intervals for HEPA filters in the aseptic processing facility.
A. True B. False
13. Any aerosol used for challenging a HEPA filter should meet specifications for critical physicochemical attributes such as viscosity.
A. True B. False
14. Dioctylphthalate (DOP) and poly-alpha-olefin (PAO) are examples of appropriate leak testing aerosols.
A. True B. False
15. A single probe reading equivalent to 0.01 percent of the upstream challenge would be considered as indicative of a significant leak and calls for replacement of the HEPA filter or, when appropriate, repair in a limited area
A. True B. False
16. Any intervention or stoppage during an aseptic process can increase the risk of contamination. The design of equipment used in aseptic processing should limit the number and complexity of aseptic interventions by personnel.
For example,
(a) Personnel intervention can be reduced by integrating an on-line weight check device, thus eliminating a repeated manual activity within the critical area.
(b) Rather than performing an aseptic connection, sterilizing the preassembled connection using sterilize-in-place (SIP) technology also can eliminate a significant aseptic manipulation.
(c) Automation of other process steps, including the use of technologies such as robotics, can further reduce risk to the product.
i. a & b is true
ii. b & c is true
iii. c & a is true
iv. a, b & c true
17. Products should be transferred under appropriate cleanroom conditions. For example, lyophilization processes include transfer of aseptically filled product in partially sealed containers. To prevent contamination, a partially closed sterile product sho
uld be transferred only in critical areas.
uld be transferred only in critical areas.
A. True B. False
18. Facility design should ensure that the area between a filling line and the lyophilizer provide for Class 100 (ISO 5) protection. Transport and loading procedures should afford the same protection.
A. True B. False
19. If stoppered vials exit an aseptic processing zone or room prior to capping, appropriate assurances should be in place to safeguard the product, such as local protection until completion of the crimping step. Use of devices for on-line detection of improperly seated stoppers can provide additional assurance.
A. True B. False
20. Drains are considered inappropriate for classified areas of the aseptic processing facility other than Class 100,000 (ISO 8) areas.
A. True B. False
21. Deviation or change control systems should address atypical conditions posed by shutdown of air handling systems or other utilities, and the impact of construction activities on facility control. Written procedures should address returning a facility to operating conditions following a shutdown.
A. True B. False
22. In media fill for Lyophilization operations, FDA recommends that,
(a) Unsealed containers be exposed to partial evacuation of the chamber in a manner that simulates the process.
(b) Vials should not be frozen, and precautions should be taken that ensure that the medium remains in an aerobic state to avoid potentially inhibiting the growth of microorganisms.
A. (a: True; b-: False), B. (a: True; b-: True), C. (a: False; b-: True), D. (a: False; b-: False)
23. The media fill simulation run sizes should be adequate to mimic commercial production conditions and accurately assess the potential for commercial batch contamination.
A. True B. False
24. Growth promotion units should be inoculated with a <100 CFU challenge. If the growth promotion testing fails, the origin of any contamination found during the simulation should nonetheless be investigated and the media fill promptly repeated.
A. True B. False
25. During media fill each unit should be filled with an appropriate quantity and type of microbial growth medium to contact the inner container closure surfaces (when the unit is inverted or thoroughly swirled) and permit visual detection of microbial growth.
A. True B. False
26. The interior of the isolator should meet Class 100 (ISO 5) standards.
A. True B. False
27. Air balance between the isolator and other direct interfaces (e.g., dry heat tunnel) should also be qualified.
A. True B. False
Ans Key
| Sr. No. | Ans. | Sr. No. | Ans. | Sr. No. | Ans. |
| 1 | TRUE | 11 | TRUE | 21 | TRUE |
| 2 | TRUE | 12 | TRUE | 22 | B |
| 3 | TRUE | 13 | TRUE | 23 | TRUE |
| 4 | TRUE | 14 | TRUE | 24 | TRUE |
| 5 | TRUE | 15 | TRUE | 25 | TRUE |
| 6 | B | 16 | iv | 26 | TRUE |
| 7 | iv | 17 | TRUE | 27 | TRUE |
| 8 | TRUE | 18 | TRUE | ||
| 9 | TRUE | 19 | TRUE | ||
| 10 | TRUE | 20 | TRUE |
