Sterilizing equipment

It is necessary to determine the bioburden and make cycle verification studies when ethylene oxide sterilization is used, as it is for other sterilization methods. The manufacturer of hospital sterilization equipment provides cycle recommendations based on the expected bioburden and the consideration of an appropriate safety factor. In ethylene oxide sterilization, it is necessary to determine if residues of the stefilant are absorbed by the sterilized article, and to examine the possible formation of other potentially toxic materials as a result of reaction with ethylene oxide. 

Horizontal laminar flow clean air benches are not BSCs (Section 10.3.4). They discharge HEPA-filtered air across the work surface and toward the user. These devices only provide product protection. They can be used for certain dean activirie.s, such as the dust-free assembly of sterile equipment or electronic devices. These benches should never be used when handling potentially infectious materials. The worker can be exposed to materials on the clean bench. Horizontal clean air benches should never be used as a substitute for, i biological safety cabinet. 

The threshold odor concentration of amines in air is typically 10 to 40 ppb. These levels are considerable less than any regulatory limit but offer potential for triggering complaints in laundries, kitchens, and sterilizing equipment rooms. 

Sterile equipment and aseptic sampling techniques shall be used when necessary. 

In Chapter 5.4, optical ultraviolet radiation sensors are described, including UV-enhanced silicon-based pn diodes, detectors made from other wide band gap materials in crystalline or polycrystalline form, the latter being a new, less costly alternative. Other domestic applications are personal UV exposure dosimetry, surveillance of sun beds, flame scanning in gas and oil burners, fire alarm monitors and water sterilization equipment surveillance. 

Three vacuum systems are commonly used in modern aseptic manufacturing facilities (1) house vacuum systems, (2) vacuum systems dedicated to lyophilization equipment, and (3) vacuum systems dedicated to autoclaves or other sterilization equipment. 

Where possible, each alarm and safeguard feature should be challenged by simulation of actual alarm conditions within the sterilizer equipment system. Where simulation of physical alarm conditions would be impractical, alarm circuitry may be challenged by use of electrical input signals. 

Brief sterilizer equipment or process description shall be included for initial certification. 

Component sterilizers steam sterilization process. A steam autoclave is used at ABC Pharmaceutical Industries to sterilize equipment and components used in aseptic processing. The following system description... 

ABC Pharmaceutical Industries information. The equipment preparation pages of the master batch record specify the validated sterilization processes to be employed in the preparation of the equipment for (product name) USP. Cycle sterilization parameters are defined along with attributes such as loading patterns and the mechanics of operating the sterilizing equipment. The following lists the sterilization cycles utilized for the equipment required in the processing of (provide product name) USP ... 

In the second edition, 64 new validation SOPs are added to describe documentation required for sterility assurance, qualification and requalification template reports of major sterile equipments, critical applicable procedures, templates for certification guidelines, media fill procedures, environmental control guidelines, training, and critical environmental performance evaluation procedures. 

If it is assumed that the radiation sterilizer equipment and facilities have been qualified and microbiological studies have been conducted as previously outlined, the next step in the validation process is the complete evaluation of the radiation sterilization cycle. Tests are conducted to determine the effect of minimum and maximum product density on the ability of the minimum or nominal radiation dose—determined during the microbiological studies to produce a given log reduction in the biological indicator population—to sterilize the load. For example, it was found that a 0.2-Mrad dose of cobalt-60 will produce a 1-log reduction in the population of B. pumilus. The microbial load of a one-package polyvinyl chloride (PVC) device (intravenous administration site) was estimated to be approximately 1000. A probability of a nonsterility level of 10 6 is desired, therefore theoretically, the minimum dose necessary to produce a 9-log reduction in the microbial population is 1.8 Mrad. 

Alkylating agents Disrupt structures of proteins and nucleic acid Formaldehyde is used to inactivate viruses without destroying antigenic properties, glutaraldehyde is used to sterilize equipment, betapropiolactone is used to destroy hepatitis viruses, and ethylene oxide to sterilize objects that would be harmed by elevated temperatures... 

Dogs are anaesthetized with a combination of Rompun (xylazine hydrochloride, 1 ml/10 kg, i.v.) and Ketavet (ketamine hydrochloride, 0.7 ml/10 kg, i.v.) after premedication with Temgesic (Buprenorphin, 0.2mg/kg i.m.) and ventilated with 66% N2O and 33 % O2 and 1 % Isofluorane. All procedures are performed under aseptic conditions using sterilized equipment. 

Some sterile powder formulations (these are predominantly, but not exclusively, antibiotics) may require sampling, mixing, milling, and subdivision activities similar to those found in oral powder manufacturing. The facilities and equipment utilized for these products is substantially different from that used for liquids, and the production area bears little resemblance to that utilized for liquids. These materials are received sterile and must be processed through sterilized equipment specifically intended for powder handling in a fully aseptic environment with ISO 5 protection over all open container activities. 

Aseptic compounding areas typically require a means to introduce sterile equipment, tubing, and other items, so access to a sterilizer is desirable. The aseptic compounding area may be contiguous to the aseptic filling suites. If it is not, separate gowning areas must be provided for personnel as well as separate air locks/pass-throughs (see below). 

Aseptic processing in the pharmaceutical industry is almost entirely dependent upon the proficiency of the personnel assigned to this most critical of all activities. The operators must be able to consistently aseptically transfer sterile equipment and materials in a manner that avoids contamination of those materials [1]. This is no mean feat given the contamination continuously released by personnel and the prevailing need for personnel for execution of the process activities. 

The U.S. market in hospital sterilizing equipment is ca 70 x 10 . Manufacturers of various types of equipment are given in Table 1. 

Non-routine operations during aseptic process Assembly of sterile equipment prior to use Mechanical failure Inadequate or improper sanitization Transfer of materials within APA Routine operations during aseptic process Airborne contaminants Surface contaminants Failure of sterilizing filter Failure of HEPA filter Inadequate or improper sterilization From most to least likely. (From Ref. I)... 

All equipment used in controlled manufacturing or compounding processes should be designed, staged, and sanitized in a manner that facilitates unvarying routine operation, with minimal human intervention. This reduces the potential for random crosscontamination by operative personnel. Improperly sanitized or sterilized equipment or components are also a possible source of contamination. Monitoring of representative surfaces of process equipment should be carried out and documented. 

The sterilization process for any equipment or supplies that are sterilized prior to introduction into the controlled environment must be validated, with sterilization records and verifications included in all product batch histories. Validation of sterilization equipment, alone, is not sufficient to assure sterility. Because the types of materials being sterilized, and the arrangement of articles within the sterilizer can effect results, standardized load configurations must be developed and validated. 

Dry-heat sterilization is generally a less complicated process than steam sterilization it is, however, relatively slow and requires higher temperatures and/or longer exposure times. This is because of the fact that microbial lethality is lower with dry heat than that for steam at the same temperature. There are various temperatures and periods of treatment for dry heat depending on the pharmacopeia. The U.S. Pharmacopeia (USP) states that the dry-heat sterilization process for containers for sterile pharmaceutical products should be at a temperature of 160-170°C for a period of 2-4 hr. The British Pharmacopeia states that items sterilized by dry heat should be kept at a temperature not less than 160°C for at least 1 hr. For the Pharmacopeia Nordica, the recommendation is 30 min at 180°C. Different materials and sterilization equipment used account for the discrepancies between these pharmacopeias, but there is also a lack of sufficient information concerning dry-heat sterilization. ... 

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