Cross-contamination control

Verification of materials and product dispersal around manufacturing facility in buildings A, B, and C. 

Verification of spread of materials and products during maintenance and cleaning of environmental and process air handling plant and equipment. 

Verification of containment of materials and products during processing. 

Verification of movement of personnel, gowning, and laundry as per design. 

Verification of utilities design, mix-up, identification, check valves, and back-flow prevention. 

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Cross-Contamination Control Two parameters particularly useful in controlling the cross-contamination are the air-handling systems and dust collection. 

Facilities validation is a critical process in a pharmaceutical industry and the types of pharmaceutical forms produced must be considered. Facilities that produce different pharmaceutical forms have different specific requirements and different critical parameters based on risk assessment. All facilities must have an adequate flow of people, raw materials, bulk products, and finished products. These flows must be created in order to avoid cross-contamination. Additionally, pressurized rooms and adequate SOPs should be supplied to minimize the risk of cross-contamination. Controlled air temperature and humidity are also required and should be validated to ensure adequate stability of the product. 

HVAC system design influences architectural layouts with regard to items such as airlock positions, doorways and lobbies. The architectural components have an effect on room pressure differential cascades and cross-contamination control. The prevention of contamination and cross-contamination is an essential design consideration of the HVAC system. In view of these critical aspects, the design of the HVAC system should be considered at the concept design stage of a pharmaceutical manufacturing plant. 

Materials and products should be protected from contamination and cross-contamination during all stages of manufacture (see also section 5.5 for cross-contamination control). 

Aseptic filling validation (media fill studies) Cross-contamination control Computerized pharmaceutical system Quality assurance/control laboratory validation... 

Contaminant concentrations Dispersal of airborne contaminants such as odors, fumes, smoke, VOCs, etc. transported by these airflows and transformed by a variety of processes including chemical and radiochemical transformation, adsorption, desorption to building materials, filtration, and deposition to surfaces evolution of contaminant concentrations in the individual zones air quality checks in terms of CO2 levels cross-contamination evaluation of zones air quality evaluations in relation to perception as well as health. Methods ate also applicable to smoke control design. 

Negative controls demonstrate the absence of laboratory contamination or sample cross-contamination. DNA extracts from nontransgenic plants, clean buffer and mastermix with no template DNA added are common negative controls that are run concurrently with the test samples in the PCR. 

To avoid cross-contamination of control samples, untreated controls are collected before the treated samples. Preferably, personnel who handle the upper cores should be different from those handling the lower depth cores. This further reduces potential cross-contamination of lower depth cores. Sampler handlers should change their gloves each time a new subplot is sampled. The use of disposable shoe covers also lessens the possibility of cross-contamination. 

The field laboratory set up by the field research group is a key element to completing successful worker exposure/re-entry research. The field laboratory may be set up in close proximity to the treated field, but should be located at a reasonable distance from the treated area to avoid cross-contamination of field samples and field controls. 

Field fortification (commonly referred to as field spiking) is the procedure used to prepare study sample matrices to which have been added a known amount of the active ingredient of the test product. The purpose for having field fortification samples available in a worker exposure study is to provide some idea of what happens to the test chemical under the exact environmental field conditions which the worker experiences and to determine the field storage stability of the test substance on or in the field matrix materials. Field fortifications do not serve the purpose of making precise decisions about the chemical, which can better be tested in a controlled laboratory environment. The researcher should not assume that a field fortification sample by its nature provides 100% recovery of the active ingredient at all times. For example, a field fortification sample by its very nature may be prone to cross-contamination of the sample from environmental contaminants expected or not expected to be present at the field site. 

Delineation of these three zones should be based on sampling and monitoring results and on an evaluation of the potential routes and amount of contaminant dispersion in the event of a release. Movement of personnel and equipment among these zones should be minimized and restricted to specific access control points to prevent cross-contamination from contaminated areas to clean areas. A decision for evaluating health and safety aspects of decontamination methods is presented in Figure 16.22.105... 

Contamination of peroxides has been a major source of accidents by runaway decompositions, particularly during handling and use. Therefore all equipment that is in contact with peroxides must be thoroughly cleaned. When a diluent is used, it should be properly selected and its purity must be strictly controlled. The use of dedicated loading/unloading equipment and avoidance of the use of shared or manifold equipment are methods to reduce the possibility of cross-contamination. 

The space between inner and outer cylinders forms the annulus. The column bottom plate is made of stainless steel and typically contains 90 exit holes below the annulus. The holes are covered by a filter plate to keep the stationary phase in place. Three different column sizes are available for the laboratory P-CAC unit the physical characteristics of the different annular columns are summarized in Table 1. The collection of the different fractions at the lower end of the annular column is regulated by a fixed glide ring system. Each chamber in the fixed glidering corresponds to an exit holes in the bottom plate of the column. The number of exit holes equals the number of chambers. The fixed glide ring system allows the continuous and controlled recovery of the separated fractions at the end of the column. Thus cross contamination is avoided and precise fraction collection is ensured. The whole process of collecting the fractions is conducted in a closed system. Unused eluent can be easily recycled. 

There must be an effective separation of rooms to prevent cross-contamination, about which measures shall be taken. Particular care shall be taken when sampling and tests and/or calibrations are undertaken at sites other than a permanent laboratory facility. The technical requirements for accommodation and environmental conditions that can affect the results of tests and calibrations shall be documented. The access to the laboratory shall be restricted to authorised persormel only. If customers or other people visit the laboratories they must be accompanied. The extent of control is based on the parlictrlar circrrmstances. 

Only authorized personnel should be allowed to handle the material and this handling should be done under the supervision of a responsible person. Access to stored material should be controlled. Different seed lots or cell banks should be stored in such a way to avoid confusion or cross-contamination. It is desirable to split the seed lots and cell banks and to store the parts at different locations so as to minimize the risks of total loss. 

The control group(s) should be housed and handled in an identical manner to the treated groups. Precautions may be necessary to prevent cross-contamination of the control animals with the test substance. This problem is particularly troublesome when a powdered diet formulation is used, which tends to spread contaminated dust all around the animal room. 

Operations with high cross-contamination potential (e.g., mixtures of test or control articles with animal diets) are often conducted in small, dedicated, individual cubicles equipped with special and separate air-handling systems or are conducted under a fume hood. Special mixing equipment (e.g., enclosed twin-shell blenders) can be used to reduce the chance of cross-contamination. 

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