August 14, 2021: Pharmaceutical Interview Questions and Answers

#DiffrentialPressureGradeA #AirChangesISO8 #HEPALeaakTest #AirVelocityLocation

1. Explain design consideration in sterile manufacturing area for contamination prevention and clean area separation

  • Airflow direction shall be from areas of higher cleanliness to adjacent less clean areas.
  • Higher air cleanliness shall have a substantial positive pressure differential relative to adjacent rooms of lower air cleanliness.
  • Positive pressure differential of at least 10-15 Pascals (Pa) should be maintained between adjacent rooms of differing classification (with doors closed).
  • 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.
  • When 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.
  • Continuous monitoring of pressure differentials between cleanrooms with frequently recorded.

2. What is the air changes requirement for Class 100,000 (ISO 8)?

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.

3. What is difference between filter leak testing and efficiency testing?

An efficiency test is a general test used to determine the rating of the filter. An intact HEPA filter should be capable of retaining at least 99.97 percent of particulates greater than 0.3 μm in diameter.

The purpose of leak test is to detect leaks from the filter media, filter frame, or seal.

4. What is the limit of HEPA filter leak test?

While performing leak test, a single probe reading equivalent to 0.01 percent of the upstream challenge would be considered as indicative of a significant leak.

5. Why measurement of velocity is important in the aseptic area? What should be measurement location and distance from filter face?

HEPA filter leak testing alone is insufficient to monitor filter performance. It is important to conduct periodic monitoring of filter attributes such as uniformity of velocity across the filter (and relative to adjacent filters). Variations in velocity can cause turbulence that increases the possibility of contamination. Velocities of unidirectional air should be measured 6 inches from the filter face and at a defined distance proximal to the work surface for HEPA filters in the critical area. Velocity monitoring at suitable intervals can provide useful data on the critical area in which aseptic processing is performed. The measurements should correlate to the velocity range established at the time of in situ air pattern analysis studies.

Reference: FDA Guidance for Industry: Sterile Drug Products Produced by Aseptic Processing – Current Good Manufacturing Practice – September 2004

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