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

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

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

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

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

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

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

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

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

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

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

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

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

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

GMP Regulations 21 CFR Part 211 211.42 Design and construction features 211.56 Sanitation 211.63, 211.65, 211.68 Equipment design, construction & maintenance 211.84 Testing and approval or rejection of components, drug product containers, and closures 211.113 Control of microbiological contamination 211.146 Ventilation, air filtration, air heating and cooling 211.165 Testing and release for distribution Basics of Contamination Control

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

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

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

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

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

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

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

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

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

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

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

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

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

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