Cleanroom

Optical counters have been widely used to monitor cleanroom technology and particles in oil. Instmments manufactured by Royco Inc. (Menlo Park, California) are available for studying aerosols and particles in Hquids. The HIAC counter (HIAC Instmments, Monte Claire, California) is a widely used stream counter for particles in fluid. One of the more recently developed optical counters is available from Particle Sizing Systems (Santa Barbara, California). The configuration of one of the widely used counters, the Climet counter, is shown in Figure 16. A general review of photozone counters is available (3). 

Artifacts may be introduced from the environment or through preparative techniques. When assessing individual tiny particles of material, the risk of loss or contamination is high, so that samples of this nature are handled and prepared for examination in a clean bench or a cleanroom (class 100 or better). 

The purpose of open unidirectional airflow benches is to protect products from particulate contaminants by creating a controlled environment. These benches are used, for example, in electronic, biological, pharmaceutical, and food industries. It should be mentioned that within pharmaceutical production, aseptic sterile processes must be carried out in a Class 100 environment (U.S. Federal Standard 209 E, Airborne Particulate Cleanliness Classes in Cleanrooms and Clean Zones). To avoid particle contamination in the bench, horizontal or vertical airflow with high-efficiency particulate air (HEPA)-filtered air is used. The air velocity is normally 0.4-0.5 ra s". Some examples of typical arrangements of open unidirectional airflow benches are shown in Fig. 10.51. 

I he configuration B1 uses the same flow distribution inside the room as is common in horizontal flow cleanrooms. 

IEC continues to have numerous applications to the detection and quantification of various inorganic ions.1 1 This is particularly true in water analysis.5-14 Inorganic ions in a variety of other sample types, such as food and beverages,1518 rocks,19-23 biological fluids, (blood, urine, etc.),24-31 pharmaceutical substances,32 33 concentrated acids,34 alcohols,35 and cleanroom air36 have also been analyzed by IEC. IEC has also been employed in isotopic separation of ions,37 including the production of radioisotopes for therapeutic purposes.3839 Typical IEC sample matrices are complex, and may contain substances that interfere with measurement of the ion(s) of interest. The low detection limits required for many IEC separations demand simple extraction procedures and small volumes to avoid over-dilution. Careful choice and manipulation of the eluent(s) may be needed to achieve the desired specificity, especially when multiple ions are to be determined in a single sample. 

Additional guidelines on pharmaceutical cleanroom classifications (which became effective on January 1, 1997, for Europe) are contained in Ref. 263. 

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

Ramstorp, M. 2000. Contamination Control and Cleanroom Technology. Wiley. 

Table 10.1 summarizes the parameters of the final four-channel YI structure. The IO chips are fabricated using Silicon-oxynitride (cleanroom) technology. Details of the fabrication process have been described extensively elsewhere41. 

IQAir HealthPro and Cleanroom Series H13 (IQAir North America, Inc., Santa Fe Springs, CA, 1-800-500-4AIR, http //www.iqair.us/products.cfm)... 

Cleanrooms are pressurized to prevent contaminant from entering. The FDA specifies a minimum of 0.05 inch water (12.5 Pa) difference in pressure between cleanrooms of different classifications, with the more critical, cleaner rooms having higher pressures. A schematic diagram showing the pressure gradient through air locks is shown in Fig. 9.1. 

Other systems and areas that require cleaning are chromatographic columns and surfaces in the facilities, especially cleanrooms. A rigorous cleaning program has to be implemented to minimize potential product contamination. This includes a limit being set for the maximum carryover of contaminants and validated by the validation process (Exhibit 9.7). 

An environment should have appropriate controls for temperature, pressure, and relative humidity. For aseptic production, cleanroom conditions monitored for particles and bioburden contamination are necessary. Equipment must be validated and maintained with current calibration. Processes must be developed and validated to ensure the production of pure and consistent product. 

Manufacturing is performed in cleanroom conditions. Sterilization processes in the form of heat, steam, gas, or radiation are applied to ensure microorganisms are destroyed in the drug product. For protein-based drugs that can be damaged by the normal sterilization processes, the product is manufactured under aseptic conditions. Both sterility and pyrogen tests are performed to ensure parenteral drug products are safe to be injected. 

Current state-of-the-art manufacturing processes are realized in non-cleanroom classified areas. Automation has been introduced in most manufacturing lines, but substantial progress is needed in view of the further decrease in wafer thickness. 

Walsh, G. (2002). Proteins Biochemistry and Biotechnology. Wiley, Chichester. Whyte, W. (2001). Cleanroom Technology. Wiley, Chichester. 

Depending on the nature of the products, the unloading of dryers might have to take place in a segregated area (e.g., cleanrooms for cGMP products). 

These test procedures are performed to determine average air flow velocity and uniformity of velocity within a cleanroom, clean zone, or unidirectional flow work zone, as well as to determine air supply volume uniformity. 

Observe and report any deviation from the proper aseptic techniques in cleanroom. See attachment no. 1700.80(L). 

Testing associated with the sterility test but requiring the use of live microorganisms (e.g., validation, stasis testing) should be carried out in laboratory facilities completely separate from the cleanroom. 

If the product produces a suspension, flocculation, or deposit in the media, after 14 days, suitable portions (e.g., 2 to 5%) of the contents of the containers should be transferred to fresh media under cleanroom conditions and reincubated for a further 7 days. 

This type of testing generally involves inoculation of a coupon (chosen to simulate cleanroom surfaces, e.g., stainless steel, polycarbonate, etc.) with the challenging organism. 

Efficacy Test on Ceiling (Cleanroom Design) (Coupons)... 

New hires must participate in the next scheduled media fill after receiving pertinent cleanroom training per appropriate SOPs. 

Personnel monitoring was performed three times a day which personnel worked in processing rooms and cleanrooms has been monitored according to SOP. The results of personnel monitoring were reviewed for the hnger-prints and garments and found satisfactory during run 1, run 2, and run 3. 

Behavior in the cleanroom Initial, then once/year... 

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