Regulatory concerns

Environmental laws and regulations including permits are reviewed in this chapter. Included are the Federal Clean Air Act Amendment (CAAA), the Federal Clean Water Act (CWA) regulations, the Resource Conservation and Recovery Act (RCRA) or, as it is also known, the Solid Waste Disposal Act. Also discussed along with the regulations under OSHAare the National Institute for Occupational Safety and Health (NIOSH) and the Hazardous Waste Operations and Emergency Response (HAZWOPER). 

The environmental regulations covered here are not intended to be all-inclusive but to provide a basic understanding of the impoitant environmental laws and regulations. 

The environmental technology section includes reviews of waste water treatment and air and waste minimization/pollution prevention. Waste water treatment procedures discussed include biological treatment, activated carbon adsorption, air and steam stripping, chemical precipitation, ion exchange, and membrane separation. 

Air pollution control technology includes thermal incineration, catalytic incineration, carbon adsorption, absorption, condensation, baghouse filtration, wet scrubbing, and electrostatic precipitation. 

The range of technology will provide the engineer with a sufficient background to understand the important air control measures. 

Polymorphs are different crystalline forms of the same pure substance or its salts. Hydrates, hemi- and semihydrates, mono- and dihydrates, anhydrous, solvates, and amorphous forms 

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Because of the special stabiHty of the hexafluoroarsenate ion, there are a number of appHcations of hexafluoroarsenates. For example, onium hexafluoroarsenates (33) have been described as photoinitiators in the hardening of epoxy resins (qv). Lithium hexafluoroarsenate [29935-35-1] has been used as an electrolyte in lithium batteries (qv). Hexafluoroarsenates, especially alkaH and alkaline-earth metal salts or substituted ammonium salts, have been reported (34) to be effective as herbicides (qv). Potassium hexafluoroarsenate [17029-22-0] has been reported (35) to be particularly effective against prickly pear. However, environmental and regulatory concerns have severely limited these appHcations. 

The concentration of the flavor in the dentifrice and the nature of substances added to bring out specific flavor notes and thereby make the flavor unique are significant concerns. The flavor must not be excessive it must not bum too strongly. Also, the flavor must not be a sensitizer. Synthetic sweeteners are usually added, although regulatory concerns limit their selection for example, cyclamate [100-88-9] is not used in the United States. 

Step f considers all of the background information discussed in Section 2.f. If the information requirement is based on a regulatory concern or a special purpose need, then Steps 2 through 5 are bypassed and a QRA should be performed. If the information is needed for decision making, you must determine whether the significance of the decision warrants the expense of a QRA. If not, you may be able to use less resource-intensive qualitative approaches to satisfy your information requirements. Table 8 contains examples of typical conclusions reached from qualitative risk analysis results. 

Hygiene and Regulation Almost unique to MF is the influence of regulatory concerns in selection and implementation of a suitable microfilter. Since MF is heavily involved with industries regulated by the Food and Drug Administration, concerns about process stability consistency of manufacture, virus reduction, pathogen control, and material safety loom far larger than is usually found in other membrane separations. 

Plant metabolism studies will provide information on the absorption, translocation, dissipation and degradation of the agrochemical. This information defines the residual analytes of regulatory concern that could include either the parent compound or metabolites in the field crops. Plant metabolism studies should be conducted with at least three crop representatives of three different crop groups listed in Table 1. One of the major objectives is to determine the comparative metabolism of the agrochemicals between animals and plants among different plant species. MAFF approves metabolism studies that are conducted in foreign countries, which should be operated under the certified GLP system. 

Diphenyl ethers in the soil are absorbed by roots with limited translocation generally to the foliage. Low levels of herbicide residues can be expected when the compound is used in accordance with good agricultural practice. The parent diphenyl ether compound is defined as the residue of analytical and regulatory concern. 

The definition of residue of regulatory concern is the parent, flumetralin, only... 

Environmental and regulatory concerns about the use of a chlorinated solvent (1,2-dichloroethane) in the final step. 

As gelatin is a common food additive with applications in the pharmaceutical industry, its introduction into foreign protein production systems may generate fewer regulatory concerns than other biopolymers. 

Information on current levels of endrin in the environment is limited however, the available data indicate that concentrations in all environmental media are generally negligible or below levels of concern. The FDA has concluded that endrin is no longer present in the environment to the extent that it may be contaminating food or feed at levels of regulatory concern (USDA 1995). No information could be found in the available literature on levels of endrin aldehyde or endrin ketone in the environment. 

In general, it is difficult to determine whether there is an effect on the mean QT/QTc interval that is so small as to be of no clinical consequence. However, drugs that prolong the mean QT/QTc interval by around 5 ms or less do not appear to cause TdP. On that basis, the threshold level of regulatory concern is 5 ms. 

The environmental burden of waterways with polychlorinated dibenzo-p-dioxins (PCDD) has been at the forefront of public and regulatory concern, because of the toxicity associated with particularly the 2,3,7,8-(laterally) substituted congeners, which have a tendency to bioaccumulate throughout the trophic food chain. Contamination of aquatic sediments by dioxins includes both non-point (e.g., atmospheric deposition) and point sources (e.g., industrial effluents, combined sewage overflows), and is generally characterized by a dominance of hepta- and octa-CDD, with minor contributions of hexa- to tetra-CDD [429]. Elevated concentrations of the 2,3,7,8-TCDD isomer tend to be associated with direct discharge from sources such as 2,4,5-trichlorophenol production [54,430]. 

Public and regulatory concern over the potential cancer risks posed by pesticide residues in the diet has been significant over the past two decades. While the consumption of foods containing residues of pesticides has not been correlated with the development of human cancers, pestieide exposure has been linked to some cancers in agricultural workers. In most cases, however,... 

The violation rate for antibiotics, as determined by USDA, also needs to be examined in order to discuss the regulatory concerns for antibiotic residues. Table 4 lists the violative residue rates for antibacterials in several species for the years 1979 through 1983. 

There are many examples of drugs which are successful in the marketplace but which have less than optimal pharmacokinetics. However, when a compound which has desirable pharmacokinetic characteristics is selected for clinical development, it can lead to a smoother clinical development programme, fewer regulatory concerns, a more straightforward datasheet and,... 

It is expected that different companies will develop different levels of process understanding and the level of understanding for a particular product can increase over time (life cycle). These differences will need to be accommodated in regulatory policies through a clear articulation of what is a minimum regulatory expectation (e.g., current requirements of CMC review information and process validation) and what is an optional opportunity for companies to improve efficiency while reducing risk to quality and regulatory concerns. 

After a change has been approved by all functional groups within the manufacturing setup and if it has no regulatory concerns, it can be implemented immediately. However, if the impact comes under any regulatory domain, the company may have to wait for regulatory approval. 

As the direct result of regulatory concerns, the objectives and orientation of R D activities are changing significantly, and the mix of researchers is also changing. 

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