UNIT II BP606T.pptx
- 1. UTILITIES AND MAINTENANCE IN STERILE AREAS Presented By Ms. Kiran R. Divekar Assistant Professor Sanjivani College of Pharmaceutical Education & Research, Kopargaon
- 2. Sterile products are very critical and sensitive in nature hence it requires very high degree of precaution and prevention is required in its preparation and there shall be strict compliance with standards prescribed by regulatory authorities.
- 3. 1. Air handling units for sterile product manufacturing shall be different from those of other areas. 2. Critical areas such as aseptic filling areas, sterilised components, unloading areas and changing room should conform to grades B, C and D respectively and shall have separate "Air handling units".The filter configuration in the Air handling unit shall be suitably designed to achieve the grade of air as given inTable below: Grade At rest (b) In operation (a) Maximum number permitted particles per cubic meter 0.5µm 5µm 0.5µm 5µm A (a) 3520 29 3500 29 B (a) 35200 293 352000 2930 C (a) 352000 2930 3520000 29300 D (a) 3520000 29300 Not Defined Not Defined
- 4. 3. For products which are filled aseptically, the filling room shall meet Grade B condition at rest. 4.The Filling operation shall take place under Grade A condition which shall be demonstrated under working of simulated conditions which shall be achieved by providing Laminar air flow work station with suitable HEPA Filters. 5. For products which are terminally sterilized, the filling room shall meet Grade C conditions.
- 5. 6. Manufacturing and component preparation areas shall meet Grade C conditions. 7. After Completion of preparation, Washed components and vessels shall be protectedWith Grade C background. 8. For GradeA Laminar air Flow work stations, the air flow rates shall be 0.3 meter per second (ForVertical air flow) and 0.45 meter per second (For Horizontal ail flow).
- 6. 9. Differential pressure between areas of different environmental shall be at 15 Pascal. 10. Unless there are product specific requirements, temperature and humidity in the aseptic areas shall not exceed 27◦C and 55% Relative Humidity respectively. 11. All the parameters listed above shall be verified and monitored at regular periodic intervals.
- 7. 12. Recommended frequencies for Periodic monitoring shall be as follows: • Particulate monitoring in Air : 6 monthly • HEPA Filter integrity testing :Yearly • Air Change Rates : 6 Monthly • Air Pressure differential : Daily •Temperature and Humidity : Daily • Microbial monitoring : Daily
- 8. 13.There shall be written environmental monitoring programs and Microbiological shall be recorded. 14. Recommended limits for microbiological monitoring of in operation clean areas is give in belowTable : Grade Air sample cfu / m3 Settle Plates (dia.90mm) cfu / 2 hrs Contact Plates (dia.55mm) cfu per plate Glove points (five fingers) cfu per layer A <1 <1 <1 <1 B 10 5 5 5 C 100 50 25 - D 500 100 50 - (Cfu: Colony forming units)
- 9. Appropriate action shall be taken immediately if the result of the results of particulate and microbial count exceeds limit.
- 11. • Sterile areas/ aseptic processing areas should have: 1.Smooth and easily cleanable Floors, 'Walls and Ceilings. 2.Temperature and humidity controls. 3.Air supply with HEPA filters (less than 100 particles of 0.5 Micron with Not more than I Cfu/cm3) under positive pressure (air flow rate 90 feet/ minute). 4.Environmental conditions monitoring system. 5.A system for Cleaning and disinfecting to produce aseptic/ sterile conditions. 6.Cleaning and disinfection of sterile areas (periodically)
- 12. CONTROL OF CONTAMINATION IN STERILE AREAS •There are two main Sources of Contamination: A. Area/Facilities B. People.
- 13. i. In the areas/ Facilities where sterile products are manufactured air should be supplied under positive differential pressure with HEPA filters designed to keep Microorganisms and other particles at low level. ii. In sterile areas all the surfaces of floors, walls, ceilings etc should be hard and free from cracks to avoid dust and microorganism accumulation and should permit easy cleaning. iii. Access to sterile areas must be Controlled/ Restricted to people and entry and exit to sterile areas should be only permitted through change areas. A. Areas/Facilities
- 14. B. People i. Keep Body, hair, face, hands and nails clean. ii. Report illness, injury, respiratory and skin problems. iii. Follow the written changing and wash-up procedures. iv. Do not use cosmetic and wear jewellery and wrist watches. v. Do not take papers and documents in sterile area. vi. Avoid eating, chewing, drinking and smoking in sterile areas. vii.Avoid coughing and sneezing (If it is unavoidable, please leave the sterile area). viii.Use gloves and disinfect them regularly. ix. Follow the written changing and wash-up procedures. x. Always check on worn and damaged garments. xi. Unless there is a special hazard, do not pick anything from floor. xii.Keep talking to the minimum while working in sterile areas. xiii.Do not move vigorously, always move gently and steadily.
- 15. Control of contamination by cleaning and disinfection The written procedures regarding Cleaning and disinfection should be followed exactly and strictly. Before disinfection, it is necessary to clean the area completely. All the cleaning and disinfecting agents and materials themselves should be clean. Avoid cleaning by mops use equipments.
- 16. Use vacuum cleaners for sucking dust. Always start cleaning walls and ceiling from top to avoid recontamination. Special care should be taken for selecting right Cleaning and disinfecting agents in right dilution. All the equipments and accessories must be cleaned after used and stored in clean dry place.