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MCC PRESENTATION - GMP MANUFACTURING ENVIRONMENTS

MCC PRESENTATION - GMP MANUFACTURING ENVIRONMENTS. Module 1. Presented by : Deryck Smith Consulting Engineers. GMP MANUFACTURING ENVIRONMENTS. Presentation Outline Module 1: Introduction to GMP Environments Module 2: Air Conditioning System Components

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MCC PRESENTATION - GMP MANUFACTURING ENVIRONMENTS

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  1. MCC PRESENTATION - GMP MANUFACTURING ENVIRONMENTS Module 1 Presented by : Deryck Smith Consulting Engineers

  2. GMP MANUFACTURING ENVIRONMENTS Presentation Outline Module 1: Introduction to GMP Environments Module 2: Air Conditioning System Components Module 3: Types & Configurations of AC Systems Module 4: Pressure Cascades & building Layouts Module 5: Validation, Qualification & Maintenance

  3. GMP MANUFACTURING ENVIRONMENTS Topics for this Module • What makes up the manufacturing environment (not just Environmental Control System) • Contamination & cross-contamination • How cleanrooms are defined • Levels of Protection 

  4. Module 1: Introduction to GMP Manufacturing Environments • The primary objective of manufacturing in an ideal GMP environment is that this should lead to a high quality product being produced. • Manufacturing in an ideal environment not only leads to better quality products but should also result in : * Improved production rates. * Operator comfort, satisfaction and safety. 

  5. Personnel Validated processes Procedures Raw Materials Equipment PackingMaterials Premises Environment Factors Contributing to Quality Products Validated processes The most important! Equipment Premises Environment

  6. GMP MANUFACTURING ENVIRONMENT PERSONNEL PRODUCT ENVIRONMENT PROTECTION PROTECTION PROTECTION Prevent Protect from Avoid contact product dust with dust cross-contamination discharge Prevent Protect from Avoid contact ambient fume with fumes contamination discharge Acceptable Prevent Avoid comfort contamination effluent conditions of staff discharge Correct temperature and humidity Design considerations for a manufacturing facility • Three primary considerations to be addressed to ensure a safe and productive manufacturing facility

  7. The manufacturing environment is critical for product quality • The environment comprises aspects such as: • Light • Temperature • Humidity • Air movement • Microbial contamination • Particulate contamination Uncontrolled environments can lead to: • Product degradation & contamination • Loss of Product & Profit PIC/S PH 1/97 (Rev.3) #3.3 & 3.12

  8. What are Contaminants ? Contaminants are : • Products or substances other than product manufactured • Foreign products • Particulate matter • Micro-organisms • Endotoxins (degraded micro-organisms) Cross-contamination is a particular case of contamination

  9. Cross – Contamination (1) What is Cross-Contamination ? Definition of Cross-Contamination “Contamination of a starting material, or of a product with another starting material or product.” PIC/S PH 1/97 (Rev.3) Pg. 134

  10. Cross – Contamination (2) From where does Cross-Contamination originate? • Poorly designed air handling systems and dust extraction systems • Poorly operated and maintained air handling systems and dust extraction systems • Inadequate procedures for personnel and equipment • Insufficiently cleaned equipment PIC/S PH 1/97 (Rev.3) # 3.14

  11. Contamination Contaminants from Environment & Operators Contaminants from Equipment Cross Contamination Product from Environment & Operators Product from Equipment Cross-contamination (3) PIC/S PH 1/97 # 5.10

  12. Cross-Contamination (4) Cross-contamination can be minimized by • Personnel procedures • Adequate premises • Use of closed production systems • Adequate, validated cleaning procedures • Appropriate Levels of Protection of product • Correct air pressure cascade 

  13. 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.  More about this later!

  14. 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 eg paint off equipment, dust from belt drives, etc 

  15. Why All the Concern About Dust? Dust Is a Bacteria Carrier Virus (0,006µm to 0,03µm) Dust Particle (0,5µm to 500µm) Bacteria (0,2µm to 2µm) Typical size relationship between dust, bacteria and viruses

  16. Airborne Contaminants Particle sizes

  17. 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. 

  18. Defining the Environment • What is the manufacturing environment ? • How does the manufacturing environment effect contamination and cross-contamination ? • Cleanroom concept 

  19. What Is a Cleanroom ? A cleanroom is an environment where the particulate contamination & bacterial contamination are limited to prescribed levels.

  20. How Are Cleanrooms Classified ?

  21. Controlled Environment Standards - - 200 - • = Uni-directional (Laminar Flow) ** = Maximum number of viable microorganisms permitted per m³. Annex 1 # 3 CONTROLLED ENVIRONMENT STANDARDS BS EN ISO 1 4644-1: 1999, Federal Standard and Approximate Equivalents.

  22. Facility Parameters That Need To Be Controlled • Temperature • Humidity • Air Cleanliness • Room Pressure • Air movement • Lighting

  23. 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

  24. Many Different Standards In Use Levels of Protection & Cleanroom 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.

  25. Cleanroom Class Required Is Dependant on Manufacturing Process Being Carried Out ! Manufacturing Environment requirements Cleanroom Class A / B Cleanroom Class C Cleanrm. Class D Others Therapeutic risks

  26. 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 

  27. ISO 14644-1 ISO5U ISO 5T ISO 7 ISO 8 Washing of Containers X Preparation of solution for terminal sterilization X Preparation of solutions for aseptic filling X X X Depyrogenisation of containers X Filling for terminal sterilization X Filling for aseptic process X Etc. Levels of Protection All operations within a pharmaceutical facilility must be correlated to well-defined Cleanroom classes. Example: U = Uni-directional T = Turbulent Annex 1, # 3, Pg 41

  28. Levels of Protection Based on the Cleanroom Class Requirements, various Levels of Protection have to be created, including: • Correlation between process operations and Cleanroom classes • Type of operation permitted in each Level of Protection zone • Definition of Cleanroom class (Contaminant parameters, building materials, room requirements, air handling systems ) • Requirements for personnel and material in the different classes (clothing, training, type of materials, etc. ) • Requirements on entry conditions for personnel and material (change & clean-down procedures )

  29. Air Handling System Production Room With Defined Requirements Supply Air Outlet Air Parameters Influencing the Level of Protection (1) How does an Air Handling System influence the Cleanroom Class or Level of Protection ?

  30. Parameters Influencing the Level of Protection (2) • Number of particles in the air • Number of micro-organisms in the air or on surfaces • Number of air changes for each room • Air velocity • Air flow pattern • Filters ( type, position ) • Air Pressure differentials between rooms • Temperature, humidity

  31. Parameters Influencing the Level of Protection (3) Cleanroom Class defined by Critical Parameters Additional Measures Air Handling System

  32. Parameters Influencing the Level of Protection (4) 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 changingrooms) • Validated sanitation • Adequate transfer procedures for materials and personnel Questions & Answers

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