معتبرسازي. Validating, establishing and maintaning a routine environmental monitoring program for clean rooms

Transcription

1 استقرار و حفظ يك برنامه معتبرسازي محيطي در اتاق هاي جاري مانيتورينگ تميز Validating, establishing and maintaning a routine environmental monitoring program for clean rooms ١

2 THE SAME IMPORTANCE!!!!! Cleanroom = ٢

3 What is a Cleanroom? According to Federal Standard 209E: A room in which the concentration of airborne particles is controlled and which contains one or more clean zones. ٣

4 What is a Cleanroom? According to BS 5295: A room with control of particulate contamination, constructed and used in such a way as to minimize the introduction, generation and retention of particles inside the room and in which the temperature, humidity and pressure shall be controlled as necessary. ٤

5 What is a Cleanroom? According to ISO : A room in which the concentration of airborne particles is controlled, and which is constructed and used in a manner to minimize the introduction, generation and retention of particles inside the room and in which other relevant parameters, e.g. temperature, humidity and pressure are controlled as necessary. ٥

6 Particle Particle is a very small speck of solid matter or liquid droplet. Particles are measured in micrometers which equals 1/1000 of a millimeter. ٦

7 Comparison of particle diameters ٧

8 Particles Classification Particles can be classified as : Non-Viable (Inert) particle: Federal Standard 209 E : a particle is defined as something solid or liquid (small droplets in the form of an aerosol) with a size ranging from 1/1000 µm to 1000 µm. Standard ISO : Solid or liquid object which, for purposes of classification of cleanliness, falls within a cumulative distribution that is based upon a threshold (lower limit) size in the range from 0.1 µm to 5 µm. Viable particle: Standard ISO : Particle that consist of, or supports, one or more live microorganisms ٨

9 What is Contaminant? A contaminant is something, either material (in solid, liquid or gaseous form) or a physical state, that is considered to be in the wrong place (and/or) at the wrong time. ٩

10 Sources of contamination Indoor environment People Skin scale, Microorganisms Tobacco smoke Hair Textile fibers Cleaning Maintenance Choice of material Choice of chemical Machinery Equipment Spray Painting Welding Grinding Construction material Fibrous insulation material Microorganisms in wet wood Outdoor environment Natural processes Wind Fire Natural cycle of plants in nature Manmade processes Motoring Combustion of fossil material Waste disposal ١٠

11 Particle Generation Sources inside the cleanrooms Personnel Production machinery and other equipment Production material Construction material Cleaning and disinfection material Textiles (garment, shoes, etc) ١١

12 The History of Cleanrooms It is clear that the first cleanroom were in hospitals. The work of Pasteur, Koch, Lister and other pioneer microbiologists and surgeon over a hundred years ago established that bacteria caused wound infections. It therefore followed that elimination of bacteria from the hospital and in particular, the operating room should prevent infection. ١٢

13 pioneer microbiologists ١٣

14 Cleanroom application Industry Products Electronics Computer, TV-Tubes, Flat Screens, Magnetic tape production Semiconductor Production of integrated circuits used in computer memory and control Micromechanics Gyroscopes, miniature bearings, compact disk player Optics Lenses, Photographic film, laser equipment Biotechnology Antibiotic production, Genetic engineering Pharmacy Sterile pharmaceuticals, Sterile disposable Medical Device Heart valves, Cardiac by-pass systems Hospital Immunodeficiency therapy, Isolation of contagious patients Food and Drink Disease-free food and drink, Brewery production ١٤

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16 Comparison Comaprison of International Standards Country and Standard US. 209D U.S. 209E United Kingdom BS 5295 Australia AS 1386 France ARNOR Germany VD ISO Standard Date of Current issue onwards M1.5 C M2.5 D M3.5 E or F 3.5 4, M4.5 G or H ,000 M5.5 J , ,000 M6.5 K 3,500 4,000, ١٦

17 General Standards Federal Standard 209 (A to D) The first Federal Standard 209 was published in 1963 in the USA and titled Cleanroom and Work station Requirements, Controlled Environments. It was revised in 1966 (209A), 1973 (B), 1987 (C), 1988 (D) and 1992 (E). The cleanroom class limits, given in the earlier 209 A to D versions, are shown in table below. Class Particle / ft µm 0.2 µm 0.3 µm 0.5 µm 5.0 µm NA NA 100 NA NA 1000 NA NA NA NA NA NA NA NA NA ١٧

18 General Standards Class Name SI English M 1 M M 2 M M 3 M M 4 M M 5 M M 6 M M 7 Federal Standard 209 E Class Limits 0.1 µm 0.3 µm 0.3 µm 0.5 µm Volume Units Volume Units Volume Units Volume Units (m 3 ) (ft 3 ) (m 3 ) (ft 3 ) (m 3 ) (ft 3 ) (m 3 ) (ft 3 ) µm Volume Units (m 3 ) (ft 3 ) ١٨

19 General Standards British Standards BS 5295: This standard which is entitled Environmental cleanliness in enclosed space was first published in 1976 and revised and published in it is divided into five sections: Part 0: general introduction, terms and definitions for cleanrooms and clean air devices Part 1: specifications for cleanrooms and clean air devices Part 2: Methods for specifying the design, construction and commissioning of cleanrooms and clean air devices. Part 3: Guide to operational procedures and disciplines applicable to cleanrooms and clean air devices Part 4: Specification for monitoring cleanrooms and clean air devices ١٩

20 BS 5295; Environmental Cleanliness Classes Class of environmental cleanliness C D E F G H J K L M 0.3 µm NS NS NS NS NS NS NS: No specified limit Maximum permitted number of particles per m µm 5 µm 10 µm 25 µm 35 0 NS NS NS NS NS NS NS NS NS NS NS NS NS ٢٠

21 General Standards ISO Standards: Technical Committee 209 of the International Organization for Standardization (ISO) is close to completing its work on new international cleanroom standards which will more than likely displace the current U.S. Federal Standard 209E. ISO/TC209 has proposed ten (10) documents which will make up the cleanroom standards. Many of these documents are at the final voting stage and can be legally used in trade. ٢١

22 General Standards ISO : Classification of air cleanliness ISO : Specification for testing and monitoring ISO : Metrology and Test Method ISO : Design Construction and Start-up ISO : Cleanroom Operations ISO : Terms and Definitions ISO : Enhanced Clean Devices ISO : Molecular Contaminations ٢٢

23 Selected ISO airborne particulate cleanliness classes for cleanrooms and clean zones Maximum concentration limits (particles per m 3 ) Class 0.1 µm 0.2 µm 0.3 µm 0.5 µm 1 µm 5 µm ISO Class ISO Class ISO Class ISO Class ISO Class ISO Class ISO Class ISO Class ISO Class ٢٣

24 Grade A B (a) C (a) D (a) Selected ISO airborne particulate cleanliness classes for cleanrooms and clean zones Maximum permitted number of particles/m 3 equal to or above at rest (b) 0.5 µm µm 1(d) 1(d) in operation 0.5 µm not defined (c) not defined (c) (a) In order to reach the B,C and D grades, the number of air changes should be related to the size of the room and the equipment and personnel present in the room. The air system should be provided with appropriate filters such as HEPA for grades A,B and C. (b) At rest should be received in the unmanned state after the min clean up period. (c) Appropriate alert and action limits should be set for the results of particulate and microbiological monitoring. If these limits are exceeded, operating procedure should prescribe corrective action. (d) These areas are expected to be completely free from particles of size greater than or equal to 5 µm as it is impossible to demonstrate the absence of particles with any statistical significance the limits are set to 1 particle/m 3. during the cleanroom qualification it should be shown that the areas can be maintained within the defined limits. ٢٤ µm 1(d) 2000

25 Hazard, Control & Monitoring ٢٥

26 WHY VALIDATION? In biologicals few grams = millions $ Mandatory for cgmp Makes good economic sense Higher productivity Fewer rejects Lower Utility cost More efficient Use of equipments More effective use of monpower ٢٦

27 Step by step approach Design Qualification Validation Master Plan Commissioning and Start-up Installation Qualification Cleanroom Certification Operation Qualificatioin Performance Qualification Routine Environmental Monitoring Program ٢٧

28 Design Qualification Determine the facility design task force Determine the process environment requirements Determine of operational requirements, Material, waste and personnel flow Develop a conceptual lay out Develop a detailed system engineering Prepare design and specification Determine construction start date ٢٨

29 Validation Master Plan An all-inclusive plan that lists your company s philosophical approach to validation efforts : Introduction Manufacturing facility and Process description General layout Facility Materials and personnel flow Facility Environmental Classifications Facility pressurization and differential Air flow Project Scope Validation Program Overview Validation cycle and Document Flow Diagrams Design review IQ, OQ, PQ protocols Process qualifications Protocols Protocol final report Validation Test methods Project time lines SOPs Responsibilities Maintenance Of Validation and Revalidation Definitions References ٢٩

30 Commissioning and Start-up Encompass all aspects of the completion phase of any facility built Organizing and Planning FAT SAT Static Testing Operator Training Start-up reports Full Functional Testing System and Equipment Mannuals Spare parts management IQ and OQ documentation ٣٠

31 Installation Qualification IQ will describe what the system is intended to do, or what its function is, and also summarizes all the major components of the systems. Two major systems : Architectural Finishes ( material construction) Room, windows, paint, lights, Counters, Horizontal surfaces, Fixtures, Supply and Return Fixtures HVAC systems Utility connections, Air Handling units, Ductwork, Ventilation and pressure, Systems Design Codes, Insulation materials, Damper and Air volume, Hepa and Pre-Filters, Fire Detection system, Direct digital Control ٣١

32 Cleanroom Certification After HVAC system has been balanced Its now time to certify your cleanrooms HEPA filters certification using standard Particle size challenge like DOP Noise level Light level Air patterns: parallelism + unidirectional( aseptic fill area) Humidity / temp. Room non viable particulate counts Recovery time Room Air change rates Differential Pressures Air Flow Direction ٣٢

33 Operation Qualificatioin Sop review Calibration review Test of alarms Test of controls Start up/ Shut down Sequence Verification Normal Run Mode Verification Security Checks Batch Sequencing Product reporting Historical Data Logging Real time Trends Product Tracking Verification of Normal Operations Verificaions of Abnormal Operations ٣٣

34 Bio-contamination standards ISO Bio-contamination control; General principles ISO Evaluation and interpretation of bio-contamination data ISO Bio-contamination control of surfaces IEST RP CC.023 Microorganisms in Cleanrooms ٣٤

35 Biocontamination Control Iso A formal system of biocontamination control ( Formal system) shall be established, implemented, and maintained within cleanrooms and associated environments. The formal system will assess and control factors that can affect the microbiological quality of the process and product. ٣٥

36 Routine Environmental Monitoring Program Biocontamination control of Surfaces in Cleanrooms and associated controlled environments Protocol Airborn Biocontamination control of Cleanrooms and associated controlled environments Protocol Biocontamination control of Textiles in clean rooms and associated controlled environments Protocol ٣٦

37 Biocontamination Control ٣٧

38 Biocontamination Control ٣٨

39 Biocontamination Control ٣٩

40 Biocontamination Control ٤٠

41 The EU GMP guide (1997) values for microbiological monitoring in the operational state, for the manufacture of sterile products. Recommended limits for microbial contamination (a) Grade Air sample Settle plates (diam.90 mm) contact plates (diam.55 mm) Glove print,5 fingers cfu/m 3 cfu/4 hours (b) cfu/plate cfu/glove A <1 < 1 < 1 < 1 B (a) C (a) D (a) a These are average values. b Individual settle plates may be exposed for less than 4 hours. ٤١

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44 سخنراني هاي دو هفته ا ينده معاونت تضمين كيفيت بيوتروريسم و راههاي پيشگيري ازا ن Bioterrorism & Preventive ways سخنران : ا قاي دكتر مهدي پروين ا شتياني زمان: چهارشنبه 1387/6/6 ٤٤ بهداشت دهان و دندان Mouth and tooth hygiene سخنران : ا قاي دكتر قاسم نيكزاد زمان: چهارشنبه 1387/6/13