QAS-032 - Quality Operations Procedures for Pharmaceutical, API, and Biotechnology - page 522

SOP No. QAS-032.00 Effective date: mm/dd/yyyy
Approved by:

51.7.2.6 incubation and inspection of media-filled units
• Leaking or damaged media-ill evaluation units shall be removed, and a record made of
such removal, following processing and prior to incubation of the media.
• Media-illed evaluation units shall be incubated for a minimum of 21 days.
• Incubation temperatures shall be appropriate for the speciic growth requirements of
microorganisms that are anticipated in the aseptic filling area.
• Media-illed units should be stored or manipulated to allow contact of the media to all
product contact surfaces in the unit.
• After completion of the incubation period, the media-illed containers shall be visually
inspected for the presence of microbial growth.
• Microorganisms present in contaminated units shall be identiied to help determine the
likely source of the contamination.

51.7.2.7 acceptance criteria
Acceptance criteria for initial performance qualification and requalification of an aseptic processing
line are shown in Table 51.3.

a. Successful USP growth promotion test results must be provided for the media utilized in
the media fill.

b. Any contaminated unit(s) (not just failures) will be investigated. This investigation should
include, but is not limited to, the following:

1. Any recovered microorganisms shall be investigated related to the reason and possible

origin of the recovered microorganism(s).

2. Examine contaminated unit(s) for a breach of its integrity.

3. Identify positive unit growth to at least the species level.

4. Examine the activities occurring during the filling of the unit in the tray where the

positive vial was found.

5. Review sanitization records.

6. Review environmental monitoring data including personnel monitoring data and train-

ing records. Alert and action level results will also be documented as per SOP,
QCS-000.

table 51.3
alert and action levels
number of units in single
media fill test

alert level (number of contaminated
units in a single media fill run) a

action level (number of
contaminated units in a single media
fill run) b

Nil 1*

≤5000

5000-10,000 1** 2***

1**** 2***

>10,000

a If a contaminated unit equals the alert limit: Investigate cause, conduct one additional run.
b If a contaminated unit is less than the action limit: Cease qualification media fill, investigate cause and repeat initial per-
formance qualification (three media fills).
*One contaminated unit is considered the cause for revalidation, following an investigation.
**One contaminated unit should result in an investigation, including consideration of a repeat media fill.
***Two contaminated units are considered the cause for revalidation, following an investigation.
****One contaminated unit should result in an investigation.