This document discusses sources of contamination in sterile manufacturing facilities. It identifies potential sources as facilities, flows, equipment, cleaning, personnel, utilities, and processes. Specific microorganisms found in air, water, equipment, and humans are outlined. Proper facility design, including layout, materials of construction, HVAC, and utilities are described. Human behavior and proper training are important to avoid contamination issues. Effective cleaning requires the right tools, temperature, time, concentration and antimicrobial agents. Molds can grow where there is moisture, nutrients and suitable temperature. Proper decontamination of classified environments and clean room design are also covered.

1. Regulatory Science of Sterile Manufacturing Process
RSSMP- Week – Two
(2/4)
Roohi B. Obaid & Obaid Ali
29 July 2018 at Karachi

2. Tutorials
Move on ..

3. Sources of
Contamination
Facilities

4. Sources of
Contamination
Facilities Flows

5. Sources of
Contamination
Facilities Flows
Equipment

6. Sources of
Contamination
Facilities Flows
Equipment Cleaning

7. Sources of
Contamination
Facilities Flows
Equipment Cleaning
Personnel

8. Sources of
Contamination
Facilities Flows
Equipment Cleaning
Personnel Utilities

9. Sources of
Contamination
Facilities Flows
Equipment Cleaning
Personnel Utilities
Process

10. Sources of
Contamination
Facilities Flows
Equipment Cleaning
Personnel Utilities
Process Materials

11. Air
500 to 700 viable microbes /m3
of typical indoor office air

12. Water
up to 100 viable microbes/ ml in
incoming city water

13. Equipment
Varying level of microbes

14. Raw
Material
Microbial Burden

15. Human

16. Trillion in normal flora100
Per sq.
cm
100, 000 on skin
Billion on face10

17. Gut carries 1 kg weight of bacteria

18. Microbial
Growth
Spores Atmosphere Temperature Food

19. Facilities
Material of Construction
Layout Work Areas

20. Materials of
Construction
Resist chipping, flacking, oxidizing,
compatible with disinfectant, durable &
easy to maintain such as stainless steel
work surfaces, epoxy floors & plastic
laminates

21. Layout
Work Areas
Single passage airflow …
… define ingress & egress
Personnel
In-process
Components
Materials & Waste

22. HVAC
Controlled temperature
Appropriate pressure differential
Controlled humidity

23. Water &
Compressed
Gas System
Appropriate construction material
Use of filters
Controls to prevent contamination

24. Utilities
Chemical, microbial & Particulate
Monitoring performed to verify
quality of

25. Minimum human intervention
Human
Behavior

26. Slow Movement
Human
Behavior

27. Human
Behavior
Limited Communication

28. No disruption of Laminar
Human
Behavior

29. Restricted entry & exit during
processing
Human
Behavior

30. Sanitization of Gloves
Human
Behavior

31. Cleaning is the most important
step to successful disinfection
Efficient tool for cleaning

32. Access to microbes
Sometimes surfactant is required

33. Temperature
Time
Application
Concentration

34. Potential
Troubles
Process effectiveness & diligence of workers
Rushing the process, not giving importance
Activity is often delegated to most recent hires

35. Workers may not be fluent in English
SOPs only in English … workers
language may be different
Mostly outsourced contract activity
High turnover in contractorsPotential
Troubles

36. Untrained Workers in microbial awareness
Activity often performed during night shift
Minimal supervisionPotential
Troubles

37. All staff should be trained on proper
use of disinfectants
Educational material should be available
for all employees
Esp. new hires
Potential
Troubles

38. Follow up with routine surveillance programs
For documents, users, equipment,
water quality etc.
Continually analyze
generated data
Potential
Troubles

40. Antimicrobial
Agent

41. Antimicrobial
Agent
Fast acting

42. Antimicrobial
Agent
Fast acting
Act against many microbes w/o harming surface
or person

43. Antimicrobial
Agent
Fast acting
Act against many microbes w/o harming surface
or person
Good penetrating power, compatible with
detergent

44. Antimicrobial
Agent
Fast acting
Act against many microbes w/o harming surface
or person
Good penetrating power, compatible with
detergent
Chemically stable, environment friendly

45. Haolgens, Phenolics,
Heavy Metals, Alcohols,
Quaternary Ammonium
Compounds, Aldehydes,
Per oxygen Compounds
Antimicrobial
Agent

46. Antimicrobial
Agent
They do not prevent mold
Oxidizer damages equipment
Oxidizer oxidize themself

47. Molds
Moisture
Nutrient
Temperature
Light
/ dark

48. Molds
Growth in water saturated air
64 – 97% RH … type of surface
Surface wetting (< 97% RH)
100%
RH

49. Microbes
are
everywhere
Microbes cannot be
seen by naked eye, so
to clean it you need to
have good tools, skill
& approach

50. How it
should
be?

51. Decontamination of Classified Environment

52. Unclassified
Controlled
Classified
Aseptic

53. Poorly designed & poorly
maintained facilities are more
difficult to maintain the
desired conditions
Clean Room
Reality

54. Supplied amount of clean air
to the environment is
everything
Clean Room
Reality

55. More air changes in the
higher classified area
Clean Room
Reality

56. HEPA filter in different
environments must have same
efficiency
Clean Room
Reality

57. Clean room construction
differences in different
classes but walls & floors are
often identical
Clean Room
Reality

58. They are supposed to be clean
Every surface & every item of
room
Clean Room
Reality

59. There is excess water
somewhere, if you found
molds
Take Home
Messages

60. Increased frequency of
sporicidal use, if you find
spores frequently
Take Home
Messages

61. … focus on gown rooms, air
locks & pass through, if
spores persist
Take Home
Messages

62. Logical Process
will give sound
data
Cultivate data and
make body visible to
keep wheel moving
on continuous
improvement

64. Manual operations are difficult to validate
If it is done, it might be inappropriate
If it is not written, it is not done
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