1、INSTITUTE OF ENVIRONMENTAL SCIENCES AND TECHNOLOGY Contamination Control Division Reco ended Practice C023.2 IEST-RP-C023.2 Microrganisms in Cleanroms INSTITUTE OF ENVIRONMENTAL SCIENCES AND TECHNOLOGY Arlington Place One 2340 S. Arlington Heights Road, Suite 10 Arlington Heights, IL 6005-4516 Phone
2、: (847) 981-010 Fax: (847) 981-4130 E-mail: iestiest.org Web: ww.iest.org 2 Copyrighted material INSTITUTE OF ENVIRONMENTAL SCIENCES AND TECHNOLOGY IEST-RP-C023.2 IEST-RP-C023.2 INSTITUTE OF ENVIRONMENTAL SCIENCES AND TECHNOLOGY Copyrighted material 3 This Recomended Practice is published by the INS
3、TITUTE OF ENVIRONMENTAL SCIENCES AND TECHNOLOGY to advance the technical and enginering sciences. Its use is entirely voluntary, and determination of its aplicability and suitability for any particular use is solely the responsibility of the user. This Recomended Practice was prepared by and is unde
4、r the jurisdiction of Working Group 023 of the IEST Con-tamination Control Division. Copyright 206 by the INSTITUTE OF ENVIRONMENTAL SCIENCES AND TECHNOLOGY First printing, January 206 ISBN 978-0-9747313-6-0 PROPOSAL FOR IMPROVEMENT: The Working Groups of the INSTITUTE OF ENVIRONMENTAL SCIENCES AND
5、TECHNOLOGY are continualy working on improvements to their Recomended Practices and Reference Documents. Sugestions from those who use these documents are welcome. If you have a sugestion regarding this document, please use the online Proposal for Improvement form found on the IEST website at ww.ies
6、t.org/proposal/form.html. INSTITUTE OF ENVIRONMENTAL SCIENCES AND TECHNOLOGY Arlington Place One 2340 S. Arlington Heights Road, Suite 10 Arlington Heights, IL 6005-4516 Phone: (847) 981-010 Fax: (847) 981-4130 E-mail: iestiest.org Web: ww.iest.org 4 Copyrighted material INSTITUTE OF ENVIRONMENTAL S
7、CIENCES AND TECHNOLOGY IEST-RP-C023.2 IEST-RP-C023.2 INSTITUTE OF ENVIRONMENTAL SCIENCES AND TECHNOLOGY Copyrighted material 5 Microorganisms in Cleanrooms IEST-RP-C023.2 CONTENTS SECTION 1 SCOPE AND LIMITATIONS.7 2 REFERENCES7 3 TERMS AND EFINITIONS.8 4 BACKGROUND AND PURPOSE10 5 MICROBIAL CONTROL
8、STRATEGY1 6 ENVIRONMENTAL CONTAMINATION CONTROL.13 7 DESIGN/IMPLEMENTATION OF PERSONEL CONTAMINATION CONTROL PROCEDURES14 8 ESTABLISHING AN EFECTIVE CLEANROM CLEANING PROGRAM17 9 DESIGN/IMPLEMENTATION OF AN ENVIRONMENTAL MONITORING PROGRAM.21 FIGURE 1 PROCES FOR DETERMINING REQUIRED CONTROL STRATEGI
9、ES.12 TABLE 1 GOWNING CONFIGURATIONS.14 2 TYPICAL ASEPTIC GOWNING PROCEDURE15 3 DISINFECTANT GUIDE18 4 CHARACTERISTICS OF VARIOUS TYPES OF MICROBIOLOGICAL AIR SAMPLING EQUIPMENT.26 5 APROPRIATE RECOVERY MEDIA, INCUBATION CONDITIONS, AND INCUBATION TIMES FOR COMON ENVIRONENTAL ORGANISM TYPES29 APPEND
10、IX A BIBLIOGRAPHY30 6 Copyrighted material INSTITUTE OF ENVIRONMENTAL SCIENCES AND TECHNOLOGY IEST-RP-C023.2 IEST-RP-C023.2 INSTITUTE OF ENVIRONMENTAL SCIENCES AND TECHNOLOGY Copyrighted material 7 INSTITUTE OF ENVIRONMENTAL SCIENCES AND TECHNOLOGY Contamination Control Division Recommended Practice
11、 023.2 Microorganisms in Cleanrooms IEST-RP-C023.2 1 SCOPE AND LIMITATIONS 1.1 Scope This Recomended Practice (RP) provides guidelines for the control and quantitative measurement of viable contamination in the air and on surfaces in environ-ments that require control of such contamination. This inc
12、ludes areas designated as aseptic and those consid-ered nonsterile. The procedures and techniques em-ployed to achieve the desired level of microbial control are dependent on the level of bioburden that can be tolerated. This RP presents an introduction to the cur-rently acepted methods for bioburde
13、n control and environmental monitoring as wel as the devices avail-able for the quantification of airborne and surface vi-able contamination. This document also describes disinfectants, their le-thality spectrum, and techniques for their aplication. 1.2 Limitations Any controled area designated for
14、the manufacture or storage of a medical device, pharmaceutical product, or fod product is subject to regulations imposed by agencies that govern each industry. This document is not intended to supersede or substitute for these regula-tions. It is intended to provide a framework for met-ing the regul
15、atory requirements and to achieve the highest level of bioburden control required for other types of environments. In selecting a disinfectant, it is the responsibility of the user to consider al factors related to but not necesar-ily limited to personel safety, aplication devices, methods, surface
16、compatibility, residues, and bacteri-cidal or bacteriostatic eficiency. The selection of testing and disinfection methods var-ies with the desired level of airborne and surface bioburden. 2 REFERENCES The cited editions of the folowing documents are in-corporated into this RP to the extent specified
17、 herein. Users are encouraged to investigate the posibility of aplying the most recent editions of the references. 2.1 Documents ANSI/AMI/ISO 1137194 Sterilization of health care productsRequirements for validation and rou-tine controlRadiation sterilization ANSI/AMI/ISO 1737-1195 Sterilization of m
18、edi-cal devicesMicrobiological methodsPart 1: Esti-mation of population of microrganisms on products Asociation of Oficial Analytical Chemists. The Ofi-cial Methods of Analysis of AOAC International 18th Ed., Chapter 6, p. 4, 7, 8. Guidance for Industry Sterile Drug Products Produced by Aseptic Proc
19、esingCurent God Manufacturing Practice. September 204. US Fod and Drug Ad-ministration. IEST-RP-C03: Garment System Considerations For Cleanroms and Other Controled Environments IEST-RP-C018: Cleanrom Housekeping: Operat-ing and Monitoring Procedures IEST-RP-C034: HEPA and ULPA Filter Leak Tests ISO
20、 1464-1 Cleanroms and asociated controled environmentsPart 1: Clasification of air cleanlines ISO 1464-4 Cleanroms and asociated controled environmentsPart 4: Design, construction and start-up ISO 14698-1 Cleanroms and asociated controled environmentsBiocontamination controlPart 1: General principle
21、s and methods ISO/DTR 14698-3 Cleanroms and asociated con-troled environmentsBiocontamination controlPart 3: Measurement of the eficiency of proceses of 8 Copyrighted material INSTITUTE OF ENVIRONMENTAL SCIENCES AND TECHNOLOGY IEST-RP-C023.2 cleaning and/or disinfection of inert surfaces bearing bio
22、contaminated wet soiling or biofilms Parenteral Drug Asociation Task Force on Decon-taminating Agents. 1986. Decontaminated Agents. Journal of Parenteral Science and Technology 40 (3): 104-109 Parenteral Drug Asociation. Technical Report #13Fundamentals of an Environmental Monitoring Program US Air
23、Force. December 1, 1972. Technical Order 0-25-203 Contamination Control of Aerospace Facilities, (ww.robins.af.mil/logistics/LGEDA/Documents/ 0series.htm) USP 29NF 24 United States PharmacopeiaNational Formulary January 1, 206 2.2 Sources and Addresses ANSI American National Standards Institute 25 W
24、est 43rd Stret New York, NY 1036, USA Phone: 212-642-490 Fax: 212-398-023 ww.ansi.org AMI Asociation for the Advancement of Medical Instrumentation 110 North Glebe Road, Suite 20 Arlington, VA 2201-4795 Phone: 703-525-4890 Fax: 703-276-0793 ww.ami.org AOAC Asociation of Oficial Analytical Chemists 4
25、81 North Frederick Avenue Suite 50 Gaithersburg, MD 2087-2417, USA Phone: 301-924-707 Fax: 301-924-7089 ww.aoac.org FDA US Fod and Drug Administration Division of Manufacturing and Product Quality Ofice of Compliance 560 Fishers Lane Rockvile, MD 20857, USA Phone: 88-463-632 ww.fda.gov IEST Institut
26、e of Environmental Services and Technology 2340 S. Arlington Heights Road, Suite 10 Arlington Heights, IL 6005-4516, USA Phone: 847-981-010 Fax: 847-981-4130 ww.iest.org ISO In the US: Documents available from IEST 2340 S. Arlington Heights Road, Suite 10 Arlington Heights, IL 6005-4516, USA Phone:
27、847-981-010 Fax: 847-981-4130 ww.iest.org Outside the US: Documents available from represen-tative ISO member body organization PDA Parenteral Drug Asociation 3 Bethesda Metro Center, Suite 150 Bethesda, D 20814 USA Phone: 301-656-590 Fax: 301-986-0296 ww.pda.org USAF Robins Air Force Base WR-ALC/LK
28、CB Robins AFB, GA 31098, USA Phone: 478-926-110 ww.robins.af.mil USP US Pharmacopeia 12601 Twinbrok Parkway Rockvile, MD 20852-1790, USA Phone: 80-27-872 ww.usp.org 3 TERMS AND EFINITIONS anion A negatively charged atom or group of atoms. antimicrobial A compound or formulation used to retard the gr
29、owth of or to kil microrganisms. antiseptic A substance that prevents or inhibits the growth of microrganisms without necesarily kiling them. The term antiseptic is usualy asociated with sub-stances used on humans or animals. antistatic compound A chemical substance that is capable of neutralizing a
30、 surface charge. NOTE: Most antistatic compounds function via one of the folowing two properties: a) Electrostatic charge neutralization, in which the surface charge of one polarity is disi-pated by aplying charged materials of the oposite polarity to the surface. The most ef-fective antistatic comp
31、ounds in this category are quaternary amonium chlorides. IEST-RP-C023.2 INSTITUTE OF ENVIRONMENTAL SCIENCES AND TECHNOLOGY Copyrighted material 9 b) Film formation, in which moisture from the air absorbs onto a film of (nonionic) antistatic compound, thereby disipating the buildup of charge. In the
32、microelectronics industry, and wherever else there is concern regarding the presence of ion species, reduction of static through the use of nonionic formulations is prefered. aseptic The state of having eliminated al detectable viable microrganisms. bacteria One-celed, microscopic organisms lacking
33、chloro-phyl that multiply by fision. Bacteria typicaly meas-ure from 0.2 to 50 m in diameter. bacterial spore A resistant body produced by a vegetative bacterial cel. These spores may be resistant to heat, ultraviolet light, and desication, and may remain dormant for extended periods of time. bacter
34、icide A substance or formulation capable of destroying bacteria. bacteriostat A compound or formulation that retards or prevents the growth of bacteria. Bacteriostats act reversibly; when they are removed, cels resume their normal growth paterns. bioburden A measure of the number of microrganisms re
35、sident on or within products and inanimate objects. A com-mon synonym is microcount. cation A positively charged atom or group of atoms. CFU (colony-forming unit) Either one or an agregate of microbial cels which, when cultivated on solid media, wil develop into a single visual colony. cleanrom A ro
36、m in which the concentration of airborne parti-cles is controled and which contains one or more clean zones. controled A term used to describe a proces or environment in which parameters such as temperature, presure, hu-midity, contaminate level and so forth are maintained within specified limits. c
37、ritical A term used to describe a parameter whose impact on a product or proces renders that product or proces useles if the parameter is out of the controled limits. decontamination The removal of microrganisms, chemical residue, or particulate from liquids, surfaces, air, or other gases. dedicated
38、 shoes Fotwear or shoes compatible with an environment or proces that are maintained solely within that envi-ronment. Typicaly these wil only leave the envi-ronment for cleaning or replacement. degowning or dofing The act of removing cleanrom garments in a con-troled maner to prevent damage and unec
39、esary contamination of the garments. deodorant A compound or formulation with the ability to coun-teract undesirable odors. The ability of a formulation to counteract odor is directly related to its antimicro-bial function, provided that the odor arises from the waste products of the microrganisms c
40、el metabo-lism. Odors vary acording to the fod source utilized by the microrganism. disinfectant An agent or chemical that destroys vegetative forms of harmful microrganisms, especialy on inanimate objects. NOTE: A disinfectant may be les efective in destroying bacterial spores. Disinfection does no
41、t necesarily sterilize a surface. flora The types of microbiological organisms found in an environment. foging A proces of decontamination in which the decon-taminant is administered by means of its conversion to an aerosol. fumigation A proces of decontamination in which the decon-taminant is admin
42、istered in gaseous form at ambient presure. fungi Any of a major group of saprophytic and parasitic lower plants that lack chlorophyl and include molds, rusts, MutS, mushroms and yeasts. fungicide A substance or formulation that is capable of destroy-ing fungi. fungistat A compound or formulation th
43、at retards or prevents the growth of fungi. Fungistats act reversibly; when the fungistats are removed, the cels resume their normal growth paterns. Gram-negative bacteria Bacteria that do not retain the purple color of the crystal violet dye when treated with Grams staining 10 Copyrighted material
44、INSTITUTE OF ENVIRONMENTAL SCIENCES AND TECHNOLOGY IEST-RP-C023.2 technique. Therefore, the safranin is visible, giving a red or pink color. Gram-positive bacteria Bacteria that retain the purple color of the crystal violet dye when treated with Grams staining technique. Grams staining technique A m
45、ethod for staining and clasifying bacteria, de-veloped by Dr. Hans C.J. Gram. HEPA (high-eficiency particulate air) filter An extended-medium, dry-type filter in a rigid frame when tested at rated airflow having a minimum parti-cle colection eficiency of 9.97% for 0.3-m mas median diameter particles
46、 of DOP when tested in acordance with MIL-STD-282. ionic contamination Contamination in the form of atoms having electrical charge. Comon examples include singly charged atoms (ions) from Group IA (such as sodium and potasium) and Group VIA (such as fluorine and chlorine) of the periodic table. isok
47、inetic sampling The condition of isoaxial sampling in which the mean velocity of the air entering the sampling probe inlet is the same as the mean velocity of the unidirectional airflow at that location. kGy (kilogray) 100 grays; a standard unit used to measure the ab-sorbed dose of radiation. micro
48、biological clean area A defined space with a filtered air suply that is de-signed to acomodate the performance of activities for which the control of viable particles is esential. morphology The characteristic shape, color and consistency of a mi-crobial colony when cultivated on various solid media
49、. noncorosive, nonstaining Terms aplied to formulations to indicate that they should have a minimal efect on the integrity or ap-pearance of surfaces with which they come in contact. nonionic A term used to describe compounds and formulations that do not poses charged materials. pathogen A microrganism capable of causing disease. pyrogen A substance capable of producing fevers. The most comon pyrogens are endotoxins, a clas of lipo-polysacharides that comprise the outer wal of Gram-negative bacteria and are themselves byproducts of cel metabol
