Cross contamination in Pharmaceuticals - by Jitendra J Jagtap

Presentation on cross contamination

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CROSS CONTAMINATION IN
PHARMACEUTICALS
Jitendra J. Jagtap (M.Pharm)

2. THE MANUFACTURING ENVIRONMENT
IS CRITICAL FOR PRODUCT QUALITY
1. Light
2. Temperature
3. Humidity
4. Air movement
5. Microbial contamination
6. Particulate contamination
7. Uncontrolled environment can lead to product degradation
product contamination
loss of product and profit
Jitendra J. Jagtap (M.Pharm)

3. CROSS-CONTAMINATION
What is Cross-Contamination ?
Definition of Cross-Contamination:
“Contamination of a starting material, intermediate
product, or finished product with another starting
material or product during production.”
(WHO)
Jitendra J. Jagtap (M.Pharm)

4. CROSS-CONTAMINATION
From where does Cross-Contamination originate?
1.Poorly designed air handling systems and dust extraction
systems
2.Poorly operated and maintained air handling systems and
dust extraction systems
3.Inadequate procedures for personnel and equipment
4.Insufficiently cleaned equipment
Jitendra J. Jagtap (M.Pharm)

5. Contamination
Contaminant
from
Environment
Operators
Contaminant
from
Equipment
Cross
Contamination
Product
from
Environment
Operators
Product
from
Equipment
CROSS-CONTAMINATION
Jitendra J. Jagtap (M.Pharm)

6. CROSS - CONTAMINATION
Jitendra J. Jagtap (M.Pharm)

7. CROSS - CONTAMINATION
Jitendra J. Jagtap (M.Pharm)

8. CROSS CONTAMINATION - RISK
Jitendra J. Jagtap (M.Pharm)

9. CROSS CONTAMINATION – CHEMICAL ANALYSIS
Jitendra J. Jagtap (M.Pharm)

10. CROSS- CONTAMINATION
Cross-contamination can be minimized by:
1.Personnel procedures (Skilled Manpower, Technical Awareness)
2.Adequate premises (Proper Lay out, Area Classification)
3.Use of closed production systems (Man & Material movement)
4.Adequate, validated cleaning procedures
5.Appropriate levels of protection of product
6.Correct air pressure cascade (HVAC design & Air Distribution)
Jitendra J. Jagtap (M.Pharm)

11. WHAT ARE CONTAMINANTS ?
Contaminants are,
1. Products or substances other than product manufactured
2. Foreign products
3. Particulate matter
4. Micro-organisms
5. Endotoxins (degraded micro-organisms)
“Cross-contamination is a particular case of
contamination”
Jitendra J. Jagtap (M.Pharm)

12. HOW ARE CONTAMINANTS REMOVED?
By efficient filtration of supply air
By dilution of contaminants or flushing contaminants by
supplying adequate air quantities to the room
Jitendra J. Jagtap (M.Pharm)

13. WHERE DO CONTAMINANTS COME FROM?
Outside air carries dust which is a contaminant
People generate contaminants:
 We completely shed our outer skin every 24 hrs
 Particles of 0,3 micron & greater are liberated at a rate varying

between of 100 000 to 10 million per minute
 A person walking will liberate 5000 bacteria/minute and a
single sneeze can produce up to 1 million bacteria
The manufacturing process itself can generate
contaminants
e.g. paint off equipment, dust from belt drives, etc
Jitendra J. Jagtap (M.Pharm)

14. WHY ALL THE CONCERN ABOUT DUST?
Typical size relationship between dust, bacteria and viruses
Virus
(0,006µm to 0,03µm)
Dust Particle
(0,5µm to 500µm)
Bacteria
(0,2µm to 2µm)
Dust Is a Bacteria Carrier
Jitendra J. Jagtap (M.Pharm)

15. Particle sizes
AIRBORNE CONTAMINANTS
Jitendra J. Jagtap (M.Pharm)

16. REMOVAL OF BACTERIA
As dust is a carrier, dust must be controlled
Ambient bacteria is removed by filtration
Internal bacterial distribution can be controlled by
directional air flow and air flushing or dilution
Surface bacteria is controlled by adherence to strict
cleaning sop’s
Jitendra J. Jagtap (M.Pharm)

17. DEFINING THE ENVIRONMENT
What is the manufacturing environment ?
How does the manufacturing environment effect
contamination and cross-contamination ?
Clean room concept
Jitendra J. Jagtap (M.Pharm)

18. WHAT IS A CLEANROOM ?
A clean room is an
environment where the
particulate
contamination &
bacterial contamination
are limited to prescribed
levels.
Jitendra J. Jagtap (M.Pharm)

19. HOW ARE CLEANROOMS CLASSIFIED ?
Jitendra J. Jagtap (M.Pharm)

20. CONTROLLED ENVIRONMENT STANDARDS
-
-
-
•= Uni-directional (Laminar Flow) ** = Maximum number of viable microorganisms permitted per m³
200
Jitendra J. Jagtap (M.Pharm)

21. FACILITY PARAMETERS THAT NEED TO BE
CONTROLLED
Temperature
Humidity
Air Cleanliness
Room Pressure
Air movement
Lighting
Jitendra J. Jagtap (M.Pharm)

22. HOW CLEAN SHOULD IT BE?
Level of Protection Concept
Defines environmental requirements
Working to defined environments helps prevent
contamination and cross-contamination
Allows production under optimal hygiene conditions
Takes into account
-product sensitivity to contamination
- therapeutic risk
Jitendra J. Jagtap (M.Pharm)

23. MANY DIFFERENT STANDARDS IN USE
Levels of Protection & Clean room Class
definitions currently in use.
EC, PIC/S, TGA, WHO, etc. : A, B, C, D.
US FDA : Critical and Controlled or
Class 100, 1000, etc.
ISPE : Level 1, 2 or 3 or
Cleanroom class (ISO 5, 6, etc.).
Companies : Various others such as White, Grey,
Black, Green, etc.
Jitendra J. Jagtap (M.Pharm)

24. Therapeutic risks
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CLEANROOM CLASS REQUIRED IS DEPENDANT ON
MANUFACTURING PROCESS BEING CARRIED OUT !
Jitendra J. Jagtap (M.Pharm)

25. LEVELS OF PROTECTION
PARAMETERS TO BE DEFINED:
Air cleanliness requirements (filter type and
position, air changes, air flow patterns,
pressure differentials, contamination levels by
particulate matter and micro-organisms)
Personnel and material transfer methods
Permitted operations
Building design & finishes
Jitendra J. Jagtap (M.Pharm)

26. Based on the Clean room Class Requirements, various
Levels of Protection have to be created, including:
1.Correlation between process operations and Cleanroom classes
2.Type of operation permitted in each Level of Protection zone
3.Definition of Clean room class (Contaminant parameters,
building materials, room requirements, air handling systems )
4.Requirements for personnel and material in the different
classes
(clothing, training, type of materials, etc. )
5.Requirements on entry conditions for personnel and material
(change & clean-down procedures )
LEVELS OF PROTECTION
Jitendra J. Jagtap (M.Pharm)

27. PARAMETERS INFLUENCING THE LEVEL OF
PROTECTION
Air Handling
System
Production Room
With
Defined
Requirements
Supply
Air
Outlet
Air
How does an Air Handling System influence the
Clean room Class or Level of Protection ?
Jitendra J. Jagtap (M.Pharm)

28. 1Number of particles in the air
2Number of micro-organisms in the air or on surfaces
3Number of air changes for each room
4Air velocity
5Air flow pattern
6Filters ( type, position )
7Air Pressure differentials between rooms
8Temperature, humidity
PARAMETERS INFLUENCING THE LEVEL OF
PROTECTION
Jitendra J. Jagtap (M.Pharm)

29. Cleanroom Class
defined by
Critical Parameters
Air Handling
System
Additional Measures
PARAMETERS INFLUENCING THE LEVEL OF
PROTECTION
Jitendra J. Jagtap (M.Pharm)

30. Air handling systems:
are the main tool for reaching required
parameters
but are not sufficient as such
Need for additional measures such as
Appropriate gowning (type of clothing, proper
changing rooms)
Validated sanitation
Adequate transfer procedures for materials and
personnel
PARAMETERS INFLUENCING THE LEVEL OF
PROTECTION
Jitendra J. Jagtap (M.Pharm)

31. Jitendra J. Jagtap (M.Pharm)