1. Basics of Contamination Control
Basics of Contamination Control Workbook
Basics of Contamination Control
This product was funded by a grant awarded under the President’s High Growth Job Training Initiative as implemented by the U.S. Department of Labor’s Employment & Training Administration.  The information contained in this product was created by a grantee organization and does not necessarily reflect the official position of the U.S. Department of Labor. All references to non-governmental companies or organizations, their services, products, or resources are offered for informational purposes and should not be construed as an endorsement by the Department of Labor. This product is copyrighted by the institution that created it and is intended for individual organizational, non-commercial use only
Basics of Contamination Control
© 2006 QCM Inc - Basics of Contamination Control

2. Basics of Contamination Control
Audience
Manufacturing
Quality Control
Quality Assurance/Regulatory
Facilities/Engineering
Materials Management/Warehouse
Basics of Contamination Control

3. Basics of Contamination Control
Agenda
Define Contamination Control
Sources of Contamination
Review Regulations Relating to Contamination Control
21 CFR Part 211
Components of a Contamination Control Program
Best Practices in Developing & Maintaining a Contamination Control Program
Review Citations
Basics of Contamination Control

4. Basics of Contamination Control
Training Goals
To provide participants the information that will aid in establishing and maintaining a Contamination
Control Program.
Gain a better understanding of the aspects of product manufacturing that have the potential to contribute to product contamination.
Make employees aware of areas they can assist in reducing the potential
of product contamination
Basics of Contamination Control

5. What is Contamination Control?
Definition
Proactive prevention of contamination
Contamination is considered any foreign
environmental, chemical and biological matter.
To ensure:
Product free of foreign matter
Appropriate control measures exist to prevent product contamination.
Environments & product contact areas do not contribute to product contamination
Gowning practices
Materials/containers/closures do not contribute to product contamination
Appropriate documentation system of such practices
Basics of Contamination Control

6. Sources of Contamination
Raw Materials
PEOPLE
PRODUCT
Equipment
Water
Air &
Surfaces
Basics of Contamination Control

7. Cleanroom Contamination Classification
Substance
Energy
Physical
Chemical
Biologic
Dust
Organic Compounds
Bacteria
Thermal
Dirt
Inorganic Salts
Fungus
Light
Grit
Vapor
Spore
Electromagnetic (EMI)
Fiber
Mist
Pollen
Electrostatic(ESD)
Lint
Fume
Virus
Radiation
Jewelry
Smoke
Human Skin
Electrical
Cells/Hair
Living creatures
Basics of Contamination Control

8. Basics of Contamination Control
Size of Particulates
Courtesy of C. Bolotin Contamination Control Winter ‘06
Basics of Contamination Control

9. ISO 14644-1 Cleanroom Standards
Particle Size
Class
0.1 µm
0.2 µm
0.3 µm
0.5 µm
1 µm
5 µm
ISO 1 10 2
ISO 2
100 24 4
ISO 3
1,000
237
102 35 8
ISO 4
10,000
2,370
1,020
352 83
ISO 5
100,000
23,700
10,200
3,520[100]
832 29
ISO 6
1,000,000
237,000
102,000
35,200 [1000]
8,320
293
ISO 7
352,000 [10,000]
83,200
2,930
ISO 8
3,520,000 [100,000]
832,000
29,300
ISO 9
35,200,000
8,320,000
293,000
Notes: Number of particles per cubic meter (m3) or ft3
Basics of Contamination Control

10. Sources of Contamination
People - Greatest Factor
General hygiene, microbiology, poor clean/ controlled room practices, unhealthy, untrained, not following procedures etc.
Basics of Contamination Control

11. Sources of Contamination
People
Shedding cells, skins, oils
Inappropriate gowning
Exposed skin, hair, clothing etc
Ex. Incorrectly wearing cleanroom attire
Bringing additional items into clean areas
Jewelry, shoes, clothing, purses, keys, cell phones
Basics of Contamination Control

12. Sources of Contamination
Equipment
Improper design, improper and ineffective cleaning (cross contamination), inadequate maintenance
Facilities
Inappropriate design
Pest Control
Materials/Containers/Closures
Contaminated, mishandled, improper
storage
Environment
Air, surfaces, temperature, humidity, water, insufficient cleaning
Cardboard, wood pallets, etc
Basics of Contamination Control

13. Sources of Contamination
Goal: Prevent or minimize
external particulates from entering the clean/controlled areas.
Monitor & Control
Basics of Contamination Control

14. Basics of Contamination Control
Why Monitor?
Regulatory Requirement
We must!
Safe Product
Ensure product safety
Data to support satisfactory operation of facility, equipment quality systems
Validation, Statistical Process Control (SPC) & Proof that we do it
Confirm absence of objectionable organisms
Basics of Contamination Control

15. GMP Regulations 21 CFR Part 211
Design and construction features
Sanitation
211.63, ,
Equipment design, construction & maintenance
Testing and approval or rejection of components, drug product containers, and closures
Control of microbiological contamination
Ventilation, air filtration,
air heating and cooling
Testing and release for distribution
Basics of Contamination Control

16. Components of a Contamination Control Program
Compliance Assessment
Product Testing
Environmental Monitoring
Viable/Non-Viable Monitoring
Utility Monitoring – Gases, Water, Compressed Air
Materials/Components/Containers/ Closures
Equipment Qualification & Cleaning Validation
Facility Design
Disinfectant Practices
Training
Basics of Contamination Control

17. Compliance Assessment
Consult with Guidelines & Regulations
US & Foreign Agencies
Evaluation of Processes
Oral Solid Dose vs Liquid
Toxic Compounds
Generation of particles (Dusty Operations)
Open vs Closed Operations
Evaluation of Facilities & Equipment
Site location
Facility & Equipment Design
Multi-use vs Dedicated Operations
Room Classifications, Clean Rooms, Barriers or Isolators
Disinfectants
Basics of Contamination Control

18. Basics of Contamination Control
Product Testing
Assess chemical and microbiological purity
Compendial methods (USP, EP, JP Testing)
Method Development
Use validated methods of analysis
Methods are appropriate for evaluating product over relevant ranges.
Development of appropriate specifications
Adherence to SOPs/Batch Records
Operations & Equipment Maintenance/Calibration
Incubation times
Sample Handling & Storage
Basics of Contamination Control

19. Environmental Monitoring
Viable Monitoring – TSA & SDA Media
Air
Active Air Sampling
Passive Air Sampling
Settling Plates
Surfaces
Contact Plates
Swab
Static (no activity) vs Dynamic (with activity)
Temperature & Relative Humidity (R/H)
Pressures
Procedure to detail what can and can not be brought into manufacturing areas.
No cardboard, wood products/pallets, packing materials
Basics of Contamination Control

20. Environmental Monitoring
Water – Purified Water &WFI
Viable Counts - Bioburden
Filtration
Pour Plates
Chemistry Analysis pH
Conductivity
TOC
Basics of Contamination Control

21. Environmental Monitoring
Evaluation of incoming goods
Raw materials
Meet COA and internal specifications
Vendor selection
Quality
Bioburden (microbial limits)
Identity
Containers, closures etc.
Certificate of Analysis (COA)
Cleanliness
Storage & Handling
Basics of Contamination Control

22. Equipment Qualification & Cleaning Validation
Documented studies to support
Equipment is of appropriate design
Materials of construction, suitable for
environment
Meets intended need
Effective equipment cleaning & maintenance procedures
Cleaning history
Maintenance history
Compatibility of cleaning agents
Confirm removal of cleaning agent
Basics of Contamination Control

23. Facilities Design & Control
Segregation of process areas from mechanical/utility areas
Orderly operational flows for
personnel, materials and processes
Group similar type operations
Sanitary design
Pest control
Baits, traps
Clean & orderly
Basics of Contamination Control

24. Cleaning & Disinfectant Practices
Understand the environment
Cleanliness required
Type and amount of organic matter/microorganisms present
Surface type
Potential for deterioration or corrosion
Type of water available
Contact time
Basics of Contamination Control

25. Cleaning & Disinfecting Definitions
Antiseptic
Inhibits or destroys microorganism.
No sporicidal activity
Biocide
Kills all living microorganisms including spores
Decontamination
Removal of microorganisms; not quantifiable
Disinfection
Process to remove or eliminate all pathogenic organisms except spores.
Sanitation
Process of bringing contamination to a safe level typically applies to cleaning of inanimate objects
Basics of Contamination Control

26. Decontamination Practices
Expectation that companies
Document/data to support effectiveness of cleaning practices
Document/data to support satisfactory changeover and
line clearance activities
Basics of Contamination Control

27. Basics of Contamination Control
Training Program
Training, Training, Training
Operators, lab personnel, engineers, support groups
Periodic training
General GMP
Contamination Control & What Impacts the Environment
Gowning practices
Clean room Behavior
What not to do in manufacturing areas
What not to bring in manufacturing area
How to transport materials in manufacturing areas
SOPs to support all the above and GMP related activities
Basics of Contamination Control

28. Basics of Contamination Control
Controls
Method Validation
Equipment Validation
Cleaning Validation
Disinfectant Validation
Environmental Monitoring
People
Facility Design & Process Flow
Materials Management
Well written Policies & Standard Operating Procedures (Controlled Documents)
Training
Basics of Contamination Control

29. Basics of Contamination Control Summary
FDA expects systems to support proactive
contamination control
Standard operating procedures (SOPs) & data to support the systems designed to monitor and control the environment;
Sanitation practices
Cleaning & disinfecting of facility & equipment surfaces
Facility Design and Process Flow
Good hygiene, gowning practices & clean room behavior
Evaluation of incoming materials, containers & closures
Controlled processes for movement of materials to
and from clean rooms
Product evaluation and testing of in-process and release samples
Environmental monitoring
HVAC - Viable/Non-Viable Particulate, Temperature, R/H, Pressures
Training
Basics of Contamination Control