The potential for a structural break in the relationship can be tested by including a dummy variable that represents the sterilization period (December through January ). Figure . Gold stock, non-sterilized gold stock and monetary base Source: Monetary base: Friedman and Schwartz (, table B-, column ). Gold stock: Board of Governors of the Federal Reserve System (, table ). For sterilization, see Table A in the appendix below. Table I. Impact of changes in gold reserves on the monetary base dependent variable: change in monetary base Gold stock – not controlling for sterilization Gold stock – adjusted for sterilization Change in gold stock .* (.) .* (.) Change in gold stock X sterilization period dummy −.* (.) −. (.) R . . Note: time period: March – December (N = ). Robust standard errors in parentheses. The second regression includes a dummy variable for September , as it is unclear how the small remainder of the sterilized gold was desterilized. *indicates statistical significance at percent level. GOLD STERILIZATION AND THE RECESSION OF – The results in Table simply confirm the pattern in Figure . Changes in the gold stock explain changes in the monetary base very well, except during the period of sterilization. The coefficient on the interaction between the change in the gold stock and a dummy variable representing the sterilization period is nearly equal and opposite to the sign of the coefficient on the change in the gold stock, reflecting the sterilization offset. By contrast, the relationship between the monetary base and a measure of the monetized gold stock (adjust for sterilization) shows no structural break during this period. Furthermore, this equation can be estimated for the period through and then used to generate an out-of-sample forecast of the monetary base using actual gold flows.
This indicates how the monetary base would have behaved without sterilization, given the actual changes in the gold stock. This confirms the earlier conclusion that, by the fourth quarter of , the monetary base was percent smaller than it would have been had gold not been sterilized. Such a forecast raises the question of whether the observed inflows of gold in can be taken as given, or whether they were affected by the sterilization program. One argument is that the observed gold flows between December and August were unaffected by the sterilization program.
The absence, 79 removal or inactivation of viruses, mycoplasma and other adventitious agents, which could 80 contaminate a product, are not considered. 81 3. Legal basis 82 This guideline should be read in conjunction with Directive 2001/83/EC on the community code relating 83 to medicinal products for human use Directive 2001/82/EC on medicinal products for veterinary use as 84 amended and also the current Ph. Eur. 85 In addition, this guideline should be read in conjunction with all other relevant directives and 86 regulations, and all relevant Commission, (V)ICH and CXMP guidelines, Q&A documents and other 87 documents as linked to or published on the EMA website 88 4. General requirements 89 The guideline concerns only specific requirements relating to sterility and sterile products. For other 90 considerations on the manufacturing of the medicinal product, reference is made to other guidance 91 documents such as Guidelines on Manufacture of the Finished Dosage Form. 92 4.1. Manufacturing of sterile medicinal products 93 Documentation regarding sterilisation and aseptic processing to be included in the quality dossier, 94 Module 3, sections 3.2.P.2 Pharmaceutical development and 3.2.P.3 Manufacture for human products 95 or Part 2 A.4 Development pharmaceutics and Part 2 B Description of the manufacturing method for 96 veterinary products is presented below.
The documentation should be provided for all sites performing 97 sterilisation or aseptic processing related to the medicinal product, regardless of whether the processes 98 are performed in-house or outsourced. 99 The choice of method of sterilisation or aseptic processing should be justified, see section 4.3 Selection 100 of sterilisation method. 101 All sterilisation processes should be carried out according to the instructions of the Ph. Eur. unless 102 justified. 103 All sterilisation procedures for the active substance, the excipient(s) or the primary containers should 104 be described and the name and address of the site responsible should be stated. Validation data should 105 be provided as described below for each sterilisation process. The required validation data for terminal 106 microbial reduction processes is the same as for the sterilisation processes, except for the demonstration of a SAL of 10-6 107 or better. 108 When parametric release of sterility is proposed, the Guideline on real time release testing (formerly 109 Guideline on parametric release), EMA/CHMP/QWP/811210/2009-Rev1 (human products only), the 110 Guideline on Parametric release, EMEA/CVMP/QWP/339588/2005 (veterinary products only) and the 111 text of Ph. Eur. Chapter 5.1.1 should be taken into account. Guideline on sterilisation of the medicinal product, active substance, excipient and primary container EMA/CHMP/CVMP/QWP/BWP/850374/2015 Page 5/15 112 The levels of bioburden and bacterial endotoxins in the components (active substance, excipients and 113 primary package), as well as those introduced during manufacture and sterilisation can have an impact 114 on the level of bacterial endotoxins in the finished drug product.
See 5n for recommendations requiring cleaning and disinfecting blood-contaminated surfaces. Category II. 23, 47, 48, 51, 214, 378, 379, 382, 416, 1012 h. Detergent and water are adequate for cleaning surfaces in nonpatient-care areas (e.g., administrative offices). Category II. 23 i. Do not use high-level disinfectants/liquid chemical sterilants for disinfection of non-critical surfaces. Category IB. 23, 69, 318 j. Wet-dust horizontal surfaces regularly (e.g., daily, three times per week) using clean cloths moistened with an EPA-registered hospital disinfectant (or detergent). Prepare the disinfectant (or detergent) as recommended by the manufacturer. Category II. 68, 378, 380, 402, 403, 1008 k. Disinfect noncritical surfaces with an EPA-registered hospital disinfectant according to the label’s safety precautions and use directions. Most EPA-registered hospital disinfectants have a label contact time of 10 minutes. However, many scientific studies have demonstrated the efficacy of hospital disinfectants against pathogens with a contact time of at least 1 minute.
By law, the user must follow all applicable label instructions on EPA-registered products. If the user selects exposure conditions that differ from those on the EPA-registered product label, the user assumes liability for any injuries resulting from off-label use and is potentially subject to enforcement action under FIFRA. Category II, IC. 17, 47, 48, 50, 51, 53-57, 59, 60, 62-64, 355, 378, 382 l. Do not use disinfectants to clean infant bassinets and incubators while these items are occupied. If disinfectants (e.g., phenolics) are used for the terminal cleaning of infant bassinets and incubators, thoroughly rinse the surfaces of these items with water and dry them before these items are reused. Category IB. 17, 739, 740 m.
if not more resistant than, B. anthracis spores (>6 log10 reduction of B. anthracis spores in 5 minutes with acidified bleach [5,250 ppm chlorine])313. Thus, one can extrapolate from the larger database available on the susceptibility of genetically similar organisms314. Second, many of the potential bioterrorist agents are stable enough in the environment that contaminated environmental surfaces or fomites could lead to transmission of agents such as B. anthracis, F. tularensis, variola major, C. botulinum toxin, and C. burnetti 315. Third, data suggest that current disinfection and sterilization practices are appropriate for managing patient-care equipment and environmental surfaces when potentially contaminated patients are evaluated and/or admitted in a health-care facility after exposure to a bioterrorist agent. For example, 25 Guideline for Disinfection and Sterilization in Healthcare Facilities, 2008 sodium hypochlorite can be used for surface disinfection
. In instances where the healthcare facility is the site of a bioterrorist attack, environmental decontamination might require special decontamination procedures (e.g., chlorine dioxide gas for B. anthracis spores). Because no antimicrobial products are registered for decontamination of biologic agents after a bioterrorist attack, EPA has granted a crises exemption for each product Of only theoretical concern is the possibility that a bioterrorist agent could be engineered to be less susceptible to disinfection and sterilization processes 309. Toxicological, Environmental and Occupational Concerns Health hazards associated with the use of germicides in healthcare vary from mucous membrane irritation to death, with the latter involving accidental injection by mentally disturbed patients316.
The particle size was of great influence as may be seen from the table. Sand was found most efficient when the grain size was between sieve numbers 40 and 60, while glass beads destroyed bacteria most rapidly when they passed sieve No. 60, but not 80. An increase in size resulted in a lower death rate, and a decrease had the same effect. Vegetative cells were more sensitive than spores, but the difference was not great. With the spores of Bacillus cohaeren8, when shaken with glas beads in distilled water, the death rate constant was K = 0.8. Escherichia coli under identical conditions had the constant 1.8. The same E. coli aken with the same glass beads in broth showed a death rate constant of only 0.8, the protection being probably due to the foaming. The spores of different species differ considerably in their sensitivity to mechanical destruction, as table I shows, and this difference is not correlated with the difference in heat resistance.
4 on February 25, 2017 by guest http://mmbr.asm.org/ Downloaded from STERILIZATION OF MICROORGANlSMS According to Campbell-Renton (1942b), bacteriophage is sensitive to shaking, but a great variation of sensitivity was observed with different phages. The shaking was carried out without addition of solid particles. With Salmonella schottmuelleri, the phage was inactivated to a much greater extent than the bacteria. It is possible to obtain apparently phage-free cultures of bacteria by shaking, provided that the culture is not too heavily infected with phage. 2. Death by pressure. It is not very probable, reasoning a priori, that pressure can affect bacteria suspended in a liquid.
On the first day, the vegetative bacteria would die and those spores that germinate by next day are then killed the following day. The process depends on germination of spores in between inspissation. If the spores fail to germinate then this technique cannot be considered sterilization. At temperature 100o C: ƒ Boiling: Boiling water (100o C) kills most vegetative bacteria and viruses immediately. Certain bacterial toxins such as Staphylococcal enterotoxin are also heat resistant. Some bacterial spores are resistant to boiling and survive; hence this is not a substitute for sterilization. The killing activity can be enhanced by addition of 2% sodium bicarbonate. When absolute sterility is not required, certain metal articles and glasswares can be disinfected by placing them in boiling water for 10-20 minutes. The lid of the boiler must not be opened during the period. ƒ Steam at 100o C: Instead of keeping the articles in boiling water, they are subjected to free steam at 100o C. Traditionally Arnold’s and Koch’s steamers were used.
An autoclave (with discharge tap open) can also serve the same purpose. A steamer is a metal cabinet with perforated trays to hold the articles and a conical lid. The bottom of steamer is filled with water and heated. The steam that is generated sterilizes the articles when exposed for a period of 90 minutes. Media such as TCBS, DCA and selenite broth are sterilized by steaming. Sugar and gelatin in medium may get decomposed on autoclaving, hence they are exposed to free steaming for 20 minutes for three successive days. This process is known as tyndallisation (after John Tyndall) or fractional sterilization or intermittent sterilization. The vegetative bacteria are killed in the first exposure and the spores that germinate by next day are killed in subsequent days.