Summary of Changes to

Risk Classification of GMP Observations

Changes related to: Sterile Products C.02.029

Risk
1

Key Point
Added:
No environmental controls / No monitoring for viable microorganisms
during filling for aseptically filled products.
Revised:
Purified Water (PW) and Water for Injection (WFI) systems not validated
with evidence of problems such as high microbial / endotoxin counts.
replaced by
Water for Injection (WFI) systems not validated with evidence of
problems such as microbial / endotoxin counts not within specifications.
Revised (in italics):
Critical sterilization cycles based on Probability of Survival not validated.
(added)

Note: Observations followed by an arrow ( ) could be upgraded to Risk 1.

Added:
Medial fills do not simulate actual operations.
Capability of media to grow a wide spectrum of microorganisms not
demonstrated.
Misinterpretation of results for media-fills.
Each sterilizer load not considered as a separate lot for sterility testing.
PW is not used as the feed water for the WFI system and the clean steam
generator.
The WFI used in the preparation of parenterals is not tested for
endotoxins.
The WFI used for the final rinsing of containers and components used for
parenteral drugs is not tested for endotoxins when those containers and
components are not depyrogenated subsequently.
Added provision to upgrade ( ) to Risk 1:
Insufficient number of samples for room classification / inadequate
sampling methods ( ).
Removed provision for upgrade ( ) to Risk 1:
Inadequate maintenance of PW and WFI systems.
Inadequate re-validation of PW and WFI systems after maintenance,
upgrading, out-of-specs trends.
Inadequate practices / precautions to minimize contamination or prevent
mix-ups.
No consideration given to bioburden prior to sterilization.

Rev. Jul-03

Summary of Changes to
Risk Classification of GMP Observations
Changes related to: Sterile Products C.02.029

Risk

Key Point

2
cont

Revised:
No environmental controls / No monitoring for viable microorganisms
during filling. replaced by
Insufficient environmental controls / Insufficient monitoring for viable
microorganisms during filling for aseptically filled products.
Inadequate formation / training of personnel / clothing requirements.
replaced by
Inadequate training of personnel.
Inadequate gowning practices for clean and aseptic areas.
Sanitation / disinfection program incomplete. replaced by
Inadequate sanitation / disinfection program.
No SOPs for media-fills. replaced by
Inadequate procedures for media-fills.
Revised (in italics):
Aqueous-based products not subject to terminal steam sterilisation without
proper justification or approval through the marketing authorization.
(added)
Non-validated time limit between start of manufacturing and sterilization or
filtration. (replaces lapse)
Inadequate SOPs / practices / precautions to minimize contamination or
prevent mix-ups. (removed)
No consideration given to initial bioburden prior to sterilization and no
validated time limit between start of manufacturing and sterilization or
filtration. (removed)
Removed:
Inadequate inspection for particles and defects.

Rev. Jul-03

Added:
Steam used for sterilization not monitored to assure suitable quality and
absence of additives.
Inadequate control on the maximum number of personnel present in clean
and aseptic areas.
Gases used to purge solutions or blanket products not passed through a
sterilizing filter.
Inadequate inspection for particles and defects.