9. Why disinfection for Grade A & B
Decontamination Based on Risk Assessment
Effectiveness to reach 2 log reduction for spores
10. Why disinfection for Grade A & B
Decontamination Based on Risk Assessment
Effectiveness to reach 2 log reduction for spores
3 log reduction for vegetative/fungi on sample surface
11. Why disinfection for Grade A & B
Decontamination Based on Risk Assessment
Compatibility of disinfectant with the surface
12. Why disinfection for Grade A & B
Decontamination Based on Risk Assessment
Compatibility of disinfectant with the surface
Suitability & Safety of handling
13. Why disinfection for Grade A & B
Decontamination Based on Risk Assessment
Efficacy & Reproducibility of the application procedure
Potential residue of disinfectant
14. Why disinfection for Grade A & B
Decontamination Based on Risk Assessment
Be careful while studying surface characteristics & exposure time
Do not rely: Prove via study on actual surface with actual process
15. Disinfection effectiveness is a continuous process
Maximum
time between
disinfection
More
intensive EM
sampling
Pre-requisite
of Initial
Qualification
22. Sterilization of Disinfectant/Cleaning Agent is nothing
Need to be filtered with 0.2 u
In a Sterilized Container
Filtration should be in a
Controlled Environment
23. Sterilization of Disinfectant/Cleaning Agent is nothing
Need to be filtered with 0.2 u
In a Sterilized Container Integrity of the Filter should be tested after use
Filtration should be in a
Controlled Environment
24. Sterilization of Disinfectant/Cleaning Agent is nothing
Need to be filtered with 0.2 u
In a Sterilized Container Integrity of the Filter should be tested after use
After filtration maintain Environmental Conditions of storage during studied life
Filtration should be in a
Controlled Environment
31. If EM results cross Action Level do you think risk of
product safety is under question
32. If EM results cross Action Level do you think risk of
product safety is under question
Yes No
33. If EM results cross Action Level do you think risk of
product safety is under question
Yes No
34. Do you think product qualified for Sterility Test &
manufactured in this area needs to be assessed for safety
35. Do you think product qualified for Sterility Test &
manufactured in this area needs to be assessed for safety
Yes No
36. Do you think product qualified for Sterility Test &
manufactured in this area needs to be assessed for safety
Yes No
37. Do you think other products manufactured in these
suspected dates need to be assessed for safety
38. Do you think other products manufactured in these
suspected dates need to be assessed for safety
Yes No
39. Do you think other products manufactured in these
suspected dates need to be assessed for safety
Yes No
40. How would you quantify the effectiveness of any CAPA
Program. Please make a list
41. How would you quantify the effectiveness of any CAPA
Program. Please make a list
Just review with
great care
previous CAPA on
the same issue
42. What would be the procedure for media fill of terminal
sterilized product?
43. Media Fill for Terminal Sterilization Process
Media fills are NOT
required for terminally
sterilized process.
If it will be performed
it will fail
Absolutely
unreasonable to
perform media fill
44. Does any situation exist where aseptic manufacturing facility is
allowed for manufacturing operations without qualification of air
flow pattern neither in static nor in dynamic conditions?
45. Does any situation exist where aseptic manufacturing facility is
allowed for manufacturing operations without qualification of air
flow pattern neither in static nor in dynamic conditions?
NO
without evaluating
smoke study pattern
in your critical area
If it is, it’s a big
question on safety
46. Lets fight with Logic and Balance it
Inspector’s Observation
Zero Microbiological Testing of IPA
used as Disinfectant
Lets share your
thoughts
47. Lets fight with Logic and Balance it
Ideal paradigm
is where there
is no
contamination
Will it ever be
possible ???
What’s the difference between viable and non-recoverable
organisms?
48. Lets fight with Logic and Balance it
Can someone be sure that things
are in control?
49. Lets fight with Logic and Balance it
Testing of IPA for
bioburden certainly
provides more
information about
control
54. cGMP Issue
Finished dosage form site compliant for cGMP
Design of process … adequate protection from microbial contamination
Major GMP issue at API site
Manual Opera
Media Fill: Used very high pH medium Growth Promotion Capability not evaluated
Media dried at 85 to 95℃ Representative temp was 20 to 25 ℃ ?
55. Quality System
Production system
most deficient
Process simulation
inadequate
Process simulation
insensitive
Loss of media fill
basic benefit of
prompt detection
Sound scientific
foundation support
was absent
Reliability of daily
decisions under
question
56. Quality System
Product development
& process validation
intended to yield
Important
information about
product & process
Poorly conceived
study and conclusion
based on assumption
may lead to
Erroneous process
design decision &
consequent risk to
product quality
Rational experiment
design is required
Continuous learning
throughout the life
cycle
57. Intensive aseptic activity by personnel considered to be the
root of contamination
Ultimately ended up with modification in process to
include semi-closed process concept as well as automation
Case StudyOutcome
61. cGMP Issue
Container closure integrity problem identified
Cleaning of floor with uncontrolled shower of tap water done
Finished product dropped
Sealed vials exposed to tap water ? ? ?
62. Quality System
Packaging &
labeling system
deficient
Poor handling
sealed glass
Rough
handling
Sub-visible
hairline cracks
Contamination
confirmed
Same organism
found in water
tank
63. Quality System
Critical GMP
concept required
to be reinforced
Every production
phase through
packaging must be
robust
Assure proper
design of
manufacturing
operations
Assure proper
control of
manufacturing
operations
Assure proper
maintenance of
manufacturing
operations
Continuous
learning
throughout the life
cycle
64. Poor & rough handling
Caused septicemia to several patients
Case StudyOutcome
67. Background
Meda fill-60% units
found contaminated
Minor correction to
satisfaction
3 media fill runs
2nd media fill with
high level of
contamination
Isolate of both
failures was common
skin borne microbes
(Staph. Cocco)
Sterility failure also
occurred in last 6
months
68. cGMP Issue
Multiple skilled manual interventions in process
These steps posed significant risk to the product
Significant manual interventions
Inadequate aseptic gowning by personnel ? ? ?
69. Quality System
Initial minor
corrections
3 consecutive
media fill
Personnel
performance of
aseptic
connections
Personnel
performance of
aseptic
manipulations
Personnel
performance at
bulk stage …..
Design flaw in
gowning
70. Knowledge, Ability & Skills
……equipment connection changed to Sterilized in
Place (SIP)
Case StudyOutcome