EN 12297-1998 en Biotechnology - Equipment - Guidance on Testing Procedures for Sterilizability《生物技术 设备 灭菌试验程序指南》.pdf

1、STD-BSI BS EN L2Z17-EN6L L77d LbZLiLb? 0720330 b2 = BRITISH STANDARD Biotechnology - Equipment - Guidance on testing procedures for s terilizability * in * The European Standard EN 122971998 has the status of a British Standard ICs 07.080 07.100.01 BS EN 12297: 1998 NO COPYING WITHOUT BSI PERMISSION

2、 EXCEPT AS PERMITTED BY COPYRIGH LAW STD-8SI BS EN L2277-ENGL 1778 m 1bZqbbS 0720311 7T7 m direction of the Sector Board for Amd. No. Date Materiais and Chemicals, was published under the authority of the Standards Board and comes into effect on 15 September 1998 BS EN 12297:1998 Text affected Natio

3、nal foreword This British Standard is the English language version of EN 122971998. The UK participation in its prepamtion was entrusted to Technical Committee CIy58, Biotechnology, which has the responsibility to: - aid enquirers to understand the text; - present to the responsible European committ

4、ee any enquiries on the - monitor related international and European developments and promulgate interpretation, or proposals for change, and keep the UK interests informed, them in the UK. A list of organizations represented on this committee can be obtained on request to its secretary. Cross-refer

5、ences The British Stanclads which implement intern b) select the analytical procedure to be used to determine the quantity of this indicator which is present in the equipment or plant. The appropriate biological indicator is preferably not hannful for the worker andor the environment; c) specify a s

6、terilization protocol including, as a minimum, the specification of the sterilizing agent and the mode of application; NOTE 1 Potential hazard to the operator during sterilization should be assessed. NOTE 2 Factors such as duration, temperature and dose should be included into the protocol. 3.3 Test

7、ing procedure Carry out the tesing procedures as foliows: a) load the equipment or plant with the indicator under conditions representative of conditions during processing; b) using the analytical procedure defined in 3.2, determine the quantity of indicator substance present at the time at which st

8、erihation procedures would be applied; c) apply the sterilization protocol specified in 3.2 to the piant or equipment bemg tested for stemi, d) using the analytical procedure selected in 3.2, determine the quantity of indicator present in the equipment or piant after application of the sterilization

9、 protocol; e) using the data obtained, express the strilimbiility of the equipment or plant; f) determine the approprbte steriiizability class to the equipment under test as described in the equipment standards with respect to the chosen indicator and sterihation protocol. 3.4 Choice of test methods

10、 if the results of the test method should be quickly available and with a limited amount of work involved in sterilizabiity demonstmtion runs, indirect test methods should be used. Indirect test methods may however only be applied if a validated correlation between the measured effect and the desire

11、d performance has been shown. When direct test methods are use4 they should be carried out using appropriate conlz-ols in order to eliminate false positive results as a consequence of incorrect handling of the samples. This means that parallel to the test sample preparation another culture tube is h

12、andled in the same way as the onguial sample but without inoculation as well as the inclusion of media samples which are sterilized by a validated sterihation. 3.6 Direct test methods The validation of a sterihation cycle can be done by analysis of an undiluted sample of the sterilized process mediu

13、m and by performing microbiological challenge tests. Microbiological challenge tests are usuaily carried out by filling the equipment or component to be investgated to a representative volume with a suitable medium and adjng indicator micro-organisms. This type of testing procedure is required if th

14、e indicator or process micro-organism(s) which is to be detected is present around or even below the detection limit of the test method of choice. A reliable reduction rate of indicator micro-organism can be determined whenever the number of colony forming units which can be detected is high enough

15、to allow the determination of Statistically reliable imcth - required sample volume: 20 mi to 50 ml; - test medim medium based on casein hydro-, - necessary incubation conditions: 2 days to - evaluation procedure: 20 ml sample + 200 ml test medium to be mixed and sealed with a sterile cap; - evaluat

16、ion result presence of spores (+/- 1) by detection of the absorbance of the sample. Similas test methods are also summarized in annex C B.2.3 Examples of application of test strips or spore bags Prior to routine testing the test areas should be exactly specified, especially for application of a chem

17、ical sterilization procedure. The specification of the test areas can be done with less effort if a combination of direct and indirect test methods is applied For evaluation of the sterilization effect the spore strips are immersed in culture tubes with a defined medium (e.g. soybean casein digest m

18、edium), incubation for 7 days at 37 OC. After this time the turbidity of the samples is measured. The result indicates whether micro-organisms have grown or not. The cell number after steniization can be determined by calculation and application of growth kinetics. B.3 Information on indirect tests

19、B.3.1 Measurement of the distribution of temperature or chemical sterilization agents Provided that a microbial test micro-organism is defined, the two physical parameters, either sterilization or exposure time and either temperature or dose, are the significant values for the efficiency of a siteri

20、kation process. While the overall sterilization time is the same for all components of a specific piece of equipment the effective sterilization temperature depends on heat transfer to and heat capacity of the various equipment components, or the dose of a chemical sterilant and its homogenous distr

21、ibution, respectively Therefore, the temperature distribution and the time needed in order to achieve a homogenous temperature distribution are key issues for this type of investigation. 3 days; 55 OC; 121, 31, 51. O BSI 1998 STD-BSI BS EN 12277-ENGL 1778 D Lb24bb7 0720321 b48 W Page 10 EN 122971998

22、 Dunng development of equipment or components, acceptance testing and/or validation runs critical areas inside the specific equipment with respect to steriiizabiiity should be determined. For thermal sterilization the temperature distribution inside the investigated equipment gives basic information

23、 on the sterilizability under specific conditions. A set of temperature measurements wiU be used for determining the place with the lowest temperature during a test sterilization cycle or with the longest heat penetration time until a specified temperature is reached The required temperature distrib

24、ution data can be obtained either by the multiple installaton of identical probes and only a few test runs or by measurements employing only a few probes and an increased number of test runs. It is possible to install temperature probes for single use, such as colour change strips, or to use electri

25、cal measurement principles for multiple use which may or may not penetrate the equipment to be tested. Thermwouples or thermocouples combined with integrated dah acquisition represent these two situations. Exploratory runs are required to determine the appropriate sterilization time interval for giv

26、en caloric values of the energy source. Correlations on sterilization time and a homogenous temperature distribution should be established for every piece of equipment or component which is validated Additionally, temperature probes at every condensate drain can be instailed in order to detennine fk

27、om the temperature concitions in the condensate drain for the specified temperatures inside of a specific piece of equipment. For chemicals or in Steriltests, in: Standardisierungs-und Aum2tstungsempfehungen fr Bioreaktoren und periphme Einrichtungen, p. 97-105, DECHEMA, Frankfurt/Main, 1991. EA Maj

28、oor and H.LM Leiieveld. hposal of a test pnxedure: Standardization of methods for tating of the hygienic chmteristics of food prixessing equipment. 1 October 1984 CEN TC2WG4Doc. N60. ICH. Waihuser. Praxis der Sterilisation-Desinfektion-Konservierung- Keimidentakrung-Betriebshyg.ie. 4. berarbeitete u

29、nd Erweiterte Awe. Thieme, Stuttgart, New York, 1988. Principles and Pmctice of Disinfection, Preseruatwn and Sterilization. AD. Russell (ed.). Blackwell Scientific hblidons. Mord NF X42-101 Biotechnology - Frocedure for testing the capability fw a fernLentation phnt operating under Ster Progress Re

30、port 3: Containment Validation of a Continuous Centsifuge. “NO-Report 898376, Apeldoom/NL, 1989. A method for the assessment of in-line steam stmizability of processing equipment. A W Trmperley et al. ilends in Food Science & Technology, 4 (1993) 3,80-82. EG-Leitfaden einer Guten HmteUungspr-axis fu

31、r Ammimittel. Pharm. Ind. 52 (1990), 853. Die Vdidkrung milcrobiologischer Untersuchungmthoden. Pharm. Ind. 54 (1992), 58. Komittee fr mikrobiologische Reinheit der international Pharmaceutical Federation (PI?). Validhng und Kontr0.e nicht standardisierter SterilisatZonsvahm. Phann Ind. 55 (1993), 1

32、62. Europische Pharmabpe (PH.EUR.2), Part 1-11,1980-1988, maison Saint Ruffine. United States Pharmacopeia, (USP zw), US Pharmacopeial Convention, Maryhd, 1990. Methods of testing of sterility, p. 11-48. A eloian. In S.S. Block (ed.), Disinfection, sterilization and preservation, 2nd Edition, Lea &

33、Febiger, Philadelphia, 1977. Man& of Meulods for geneml Bacteriolog% chapter 23. Ph. Gerhardt (ed.). American Society for Microbioloa, Washington D.C., 1981. clea.ning Validation and Resiu? Limits: a contribution to current discussions. AO. Zeller. Phar Techn. Eur. p.1827. November 1993. Sm techniqu

34、es involved in study of adsorption of micrO-organis?ns to surfafies. J.W. Costerton. In: Attachment of Micro-qan.iSms to living and detrital surjaces (p. 403-423). John Wdey & Sons, Inc. USA. Microcalorimem as a tool in microbiology and microbial ecologg Gustafsson L, In: Mimobes in the Sea, Sleigh

35、(ed.), Ellis Horwood La., Chichester, Enghd, 1987. Gene Probes for Bactema. AJ.L Macario, E.C. de Macario, Academic Press inc. San Diego, 1990. Council Directive 9/219/EEC of 23 April 1990 on the contained use of geneticay modified micro-organisms. OJEC 08.05.1990, no L 117 p 1. Council Directive 90

36、/679/EEC of 26 November 1990 on the protection of workers from risks related to exposure to biological agents at work (seventh individual Directive within the meaning of Article 16 (1) of Directive 899ilEEC). OJEC 31.12.1990, no L 374, p 1. EN 285 EN 554 Sterilization - Steam sterilizers - Large ste

37、rizers. Serizatwn of medical devices - Validation and mutine control of sterilization by moist heat. Biotechnology - Large-scale process and production - Geneml requirements for management and organization for strain conservatwn pmcedures. EN 1619 O BSI 1998 STDDBSI BS EN L2277-ENGL 1778 Lb24bb7 072

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