This document discusses an environmental contaminant that emerged and caused multiple media fill failures on a specific manufacturing line. The same fungal isolates were found in each failure, though in varying proportions and frequencies. An investigation identified inadequate cleaning and sanitization as the major cause, with an area inside a machine panel that had never been cleaned or sampled considered the primary source. The incident exposed deficiencies in the facilities and equipment system, environmental monitoring system, and laboratory system, as the early warning needed to prevent product contamination failed to detect the issue until the media fill. Bringing the environment back under control after an airborne contaminant is allowed to proliferate unchecked was noted as not being a simple task.

1. Regulatory Science of
Sterile Manufacturing Process
Obaid Ali
August 2018
Case Study - 05

2. Emergence of a persistent & problematic
Environmental Contaminant
Ref: Richard. L. Friedman,
US-FDAApril 2005 (PDA)

3. Difficult
Experienced multiple media fill
failures on a specific line
Same recurring fungal isolates
common to each of them

4. Difficult
Proportion was
not same
Frequency was
not same
Some additional microorganisms
also isolated

5. Difficult
There was no history of particular
organism
?

6. Difficult
New locations
?

7. Remember
Environmental Monitoring system
never recovered this organism
before media fill
There was no alert limit
in history

8. Remember
Extensive EM sampling under
investigation
Multiple locations
identified upon …

9. Inadequate cleaning &
sanitization was found
the major cause

10. An area inside a
machine panel located
in the critical zone that
has never been cleaned
or sampled was
considered a primary
source of this
incidence

11. Facilities & Equipment system was
clearly
Laboratory system was
deficient
Environmental Monitoring was
Substandard
Deficient
Inadequate

12. Early warning need to
prevent product
contamination was
failed & caught upon
media fill

13. All parts of the line &
room that were
sterilized but prone to
have contamination
risk ……

14. One such contaminant
became air borne & is
allowed to proliferate
unchecked, it is not a
simple task to bring the
environment back
under control
Tough Lesson