Risk of contamination

By rolling on a two-roll mill the molecular weight of the polymer can be greatly reduced by mechanical scission, analogous to that involved in the mastication of natural rubber, and so mouldable materials may be obtained. However, bulk polymerisation is expensive and the additional milling and grinding processes necessary make this process uneconomic in addition to increasing the risk of contamination. 

An alternate method involved pre-machining the core detail to contour while it was stabilized in a frozen block of water or other medium. This entailed the expense and time to freeze the block and keep it frozen during machining as well as the risk of contaminating the core bond surfaces. In addition it was difficult to maintain the dimensional tolerances necessary to match the spar dimensions to the core adequately. Both spar and core details had machining tolerances and significant hand sanding of the core was often required to match the details. 

Systems in which it is easy to make an error should be avoided. To reduce the risk of contaminated product and reworked batches, it is generally better to avoid bringing several chemicals together in a manifold. However, manifolding can be done safely and it may be the best design when all factors are considered. 

The bench should be supplied with HEPA-filtered unidirectional airflow, having a velocity sufficient to sweep particulate matter away from the working area. Normally a velocity of 0.45 m s plus or minus 20% is adequate. It is important to monitor the air velocity at suitable intervals because significant reduction in velocity or uniformity in velocity can increase the risk of contamination. 

No matter how well installed, insulation is always at risk of contamination from outside sources. Overfilling of vessels, leaking valves and flanges, oil thrown off from rotating transmission shafts and motors can all penetrate protective cladding or lining systems. Consideration of any insulation s compatibility with possible contaminants should be considered in these situations. 

A vent pipe must be fitted at the highest point of every storage tank. Wherever possible, it should be visible from the filling point and terminate in the open air, in a position where any oil vapor will not be objectionable and, in the event of an overflow, there will be no damage to property, fire risk of contamination of drains. 

Most oxygen trim systems interpose an additional link in the air/gas ratio controller. Others use an additional valve. Most types are based on the zirconia cell installed in the flue, while others use paramagnetic or electrolytic cell methods. The zirconia type has the advantage that there is no time lag in sampling, nor is there a risk of contamination of the sample. 

Cooling towers and evaporative condensers release into the atmosphere fine droplets of water, which may carry sources of contamination such as algae and bacteria. Many of these thrive at the temperatures to be expected in water cooling systems and one of them, Legionella pneumophila, has been identified as a particular hazard to health. Cooling apparatus should be cleaned and disinfected frequently to reduce these risks of contamination and should not be located where water droplets can be drawn into ventilation air intakes. 

The submerged culture process continues to increase in terms of the percentage of dtric acid produced compared to that produced by the surface culture method. Tower bioreactors are preferred over stirred reactors because they cost less, there is less risk of contamination and they are less limited by size. 

Optimisation of biomass production would require a large inoculum, comprising 10% of each inoculum stage. However, this involves many transfers which increases the risk of contamination. 

The correct answer is seven. In practice, the number of inoculum steps does not usually exceed four to reduce the risk of contamination. This also reduces capital investment and production costs since fewer transfers require fewer vessels for development of the inoculum. 

Contamination of the production vessel leads to serious financial penalties and each step in the inoculum train is monitored for contamination. To reduce the risk of contamination during sampling it is usual to take a sample from the residue left in each vessel after its contents have been transferred to the next reactor. Since these contamination checks are retrospective, a heavy reliance is placed on the growth characteristics of the production organism. Kinetic variables such as growth rate and oxygen consumption rate are also used to assess the quality of the inoculum. 

Liquid polymers can support biological growths. Maintain good housekeeping practice to reduce the risk of contamination. 

Appendices This section is most likely to contain additional data associated with biological-based products. It should contain information as regards the facilities and equipment used for the manufacture of biotech products. Assessment of the risk of contamination from adventitious agents such as transmissible spongiform encephalopathy agents (TSEs), bacteria, mycoplasma, fungi or viruses should also be provided. Additional information on novel excipients that have not been used before should also be included in this section. 

The most direct method is the separation of the enantiomers by HPLC using chiral columns. It has the advantage that there is no risk of contamination from chiral resolving agents. The formation of diastereoisomers... 

Another common practice in hospitals is the repackaging of products purchased in bulk into smaller containers. Increased handling ofthe product inevitably increases the risk of contamination, as shown by one survey when hospital-repacked items were found to be contaminated twice as often as those in the original pack (Public Health Laboratory Service Report 1971). 

Filtrahon followed by aseptic sealing (plastic containers). Since the product is not sterilized in its final container, a bactericide m be included to reduce the risks of contamination. 

The greatest risk of contamination of a pharmaceutical product comes from its immediate environment. Additional protection from particulate and microbial contamination is therefore essential in both the filling area of the clean room and in the aseptic unit. This can be provided by a protective work station supplied with a unidirectional flow of filtered sterile air. Such a facility is known as a laminar airflow unit in which the displacement of air is either horizontal (i.e. from back to front) or vertical (i.e. from top to bottom) with a minimum homogenous airflow rate of 0.45 ms" at the working position. Thus, airborne contamination is not added to the work space and any generated by manipulations within that area is swept away by the laminar air currents. 

Today it has become clear that the effect of trace elements in living systems, in food, and in the environment depends on the chemical form in which the element enters the system and the final form in which it is present. The form, or species, clearly governs its biochemical and geochemical behaviour. lUPAC (the International Union for Pure and Applied Chemistry) has recently set guidelines for terms related to chemical speciation of trace elements (Templeton et al. 2000). Speciation, or the analytical activity of measuring the chemical species, is a relatively new scientific field. The procedures usually consist of two consecutive steps (i) the separation of the species, and (2) their measurement An evident handicap in speciation analysis is that the concentration of the individual species is far lower than the total elemental concentration so that an enrichment step is indispensable in many cases. Such a proliferation of steps in analytical procedure not only increases the danger of losses due to incomplete recovery, chemical instability of the species and adsorption to laboratory ware, but may also enhance the risk of contamination from reagents and equipment. 

There are a number of other elements appearing from time to time in the laboratory. From these, chromium and nickel are most common. Both appear in enhanced concentrations in workers exposed to welding fumes, in galvanization processes, and in processing of ores. Prolonged exposure to Cr and/or Ni causes cancer and affects the kidney. Preferred methods of determination of Ni and Cr in urine are GF-AAS. Because of the risk of contamination of the very low concentrations in urine, extreme precautions in sample handling and analysis must be carried out. 

Advantages Simplified regimen for patient Increased patient compliance at home Decreased labor Decreased costs Decreased risk of contamination (due to less manipulation) Minimize infusion-related reactions from intravenous lipid emulsions Decreased vein irritation (especially with PPN) Improved stability compared to TNA Increased number of compatible medications Decreased bacterial growth compared to TNA Easier visual inspection Can use 0.22-micron bacterial retention filter Cost savings if unused (i.e. not spiked) intravenous lipid emulsion can be reused... 

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