Clean room design

Figure 3.2. Generalized clean room design. Entry of personnel occurs via changing rooms, where the operators first remove their outer garments and subsequently put on suitable clean room clothing (see e.g. Figure 3.3). All raw materials, portable equipment, etc. enters the clean room via a transfer lock. After being placed in the transfer lock, such items are sanitized (where possible) by, for example, being rubbed down with a disinfectant solution. They are then transferred into the clean room proper, by clean room personnel. Processed product usually exits the clean room via an exit transfer lock and personnel often exit the room via a changing room separate from the one they entered (in some cases, the same changing room is used as an entry and exit route). Note that, in practice, product may be processed in a number of different (adjacent) clean rooms...

Considering the number of permutations of container, closure system, and other product attributes that must be encompassed in a process simulation program, it should be evident that only in the simplest of situations would a single set of media fills be adequate to provide coverage of all aseptic processes performed. Where multiple lines are present in the facility, each should be considered independently. Process simulation results of one line are not predictive of results on another because the contamination rate is primarily dependent upon human performance. Even identical equipment in two clean rooms designed to the same standard will not give uniform results unless the aseptic technique of the operators is at the same level of performance. 

During and after the processing, the samples need to be inspected and characterized requiring equipment for characterization including optical microscopes, surface profilers, SEM, and elUpsometers. For more detailed information on clean room design and functionality as well as the equipment, we refer to text books such as Chang and Sze (1996) and Madou (1997). 

Nonwoven wipe categories include products for babies and adults, the food service and electronics industries, medical and clean room appHcations, industrial cleaning, computer diskettes, and household products such as dusters, tea towels, shoe cleaning cloths, towelettes, and hand towels. Nonwoven fabrics are used to filter air, water, petroleum (qv), food, and beverages. Nonwovens loaded with abrasives, cleansers, or finishes can be found in a variety of products used by many industries and in many homes to scour or poHsh. Also, a majority of garments designed to protect industrial workers and consumers from hazardous environments are made from nonwoven fabrics. 

P. R. Austin and S. W. Timmerman, Design and Operation of Clean Rooms, Business News Publishers, Detroit, MI, 1965. 

The clean laboratory for trace metals was divided into three areas entrance laboratory (with clothes changing annex), instrument laboratory, and ultraclean sample preparation laboratory, all under positive pressure with active charcoal filtered air. Personnel using the clean rooms were required to wear hair caps, polyethylene gloves, laboratory coats, and designated shoes. These items are worn only in the clean rooms. 

Note that, with the exception of the PECVD reactors, all of the processing units are commercially available. Furthermore, PECVD reactors similar to the optimal designs determined by Brass and Lee [5] are commercially available, as well. In Table 10.5-1, price quotations from vendors are provided, together with estimates of the clean room area required. 

A survey of the environmental control and monitoring technology used in several experimental studies indicated significant limitations in experimental control capability. There are seven controlled-environment chambers or clean-room facilities in the United States for human exposure (community air pollution inhalation) from which studies have been reported. Another is under construction at the University of North Carolina in association with the epa at Chapel Hill. There are three chambers in Canada of similar design. 

Table 9-1 lists design features of the exposure chambers in the United States that have air-cleaning equipment. The facility at the University of Maryland Hospital, Baltimore, has a chamber with activated-charcoal and high-efficiency particle filters and controlled temperature and humidity. St. Vincent s Hospital and New York University, New York City, each have a clean-room facility. The University of Pennsylvania Hospital, Philadelphia, has a self-contained, reinforced-concrete... 

Clean rooms are environmentally controlled areas within the pharmaceutical facility in which critical manufacturing steps for injectable/sterile (bio)pharmaceuticals must be undertaken. The rooms are specifically designed to protect the product from contamination. Common potential contaminants include microorganisms and particulate matter. These contaminants can be airborne, or derived from process equipment, personnel, etc. 

Clean rooms are designed in a manner that allows tight control of entry of all substances (e.g. equipment, personnel, in-process product, and even air Figures 3.1 and 3.2). In this way, once a clean environment is generated in the room, it can easily be maintained. 

Design qualification auditing the design of a facility (or element of a facility, such as a clean room) to ensure that it is compliant with the specifications laid down and that it is therefore capable of meeting GMP requirements. 

All ductwork should be sealed in accordance with SMACNA Class A rating, which requires all seams, joints, fasteners, penetrations, and connections to be sealed. Sealant should be FDA acceptable for the application, and nonhydrocarbon based. Leakage rates as low as 1% total airflow are not uncommon. All ducts passing through a clean room wall or floor should be provided with stainless steel sheet metal collars and sealed at the opening. Details of sealing methods should be provided on the design documents. 

All facilities in a pharmaceutical industry must be designed and validated in order to assure the minimum risk of cross-contamination. Facilities validation must include the products and personnel flow, rooms design and cleaning, air and humidity systems, and water pipelines. 

The importance of maintaining air pressure differentials in the enclosures of the aseptic suite within the ranges specified in the design plans cannot be overemphasized. Reversal of airflow, which can occur if the relative room pressures are upset, can allow contaminated air from a noncontrolled region into the clean room, thus defeating the purpose of the HEPA-filtered air supply. 

Clean rooms are maintained under a state of operational control on the basis of dynamic (operational) data. Class limits are given for each class name. The limits designate specific concentrations (particles per unit volume) of airborne particles with sizes equal to and larger than the particle sizes shown in Table 2 [7,10-12,14],... 

The American CPAC initiative NeSSI [23] developed a micro reactor sampling and calibration system intended for analytical applications in the oil industry. Industrial partners such as Swagelok and Parker/Hannifin developed the system originally designed for the gas supply in clean room facilities. This approach is well advanced with respect to valves, gauges, analytical sensors and pipe fittings. 

Finally, clean room floor space is expensive, so this system has been designed so that the entire reactor can be outside the clean room, with one face occupying wall space only. 

Other features of this system are comparable to the Applied Materials Epi 7010, in that robotic wafer loading is included, and the system is fully computerized as well as designed for through-the-clean-room wall operation. 

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