Regulatory Requirements, Conclusions

Currently, HPLC/fiuorescence is still the most common technique for the determination of residues of oxime carbamates. With the introduction of ESI and APCI MS interfaces, HPLC/MS analysis for oxime carbamates in various sample matrices has become widespread. However, for a rapid, sensitive, and specific analysis of biological and environmental samples, HPLC/MS/MS is preferred to HPLC/MS and HPLC/fiuorescence. With time, improved and affordable triple-quadrupole mass spectrometers will be available in more analytical laboratories. With stricter regulatory requirements, e.g., highly specific and conclusive methods with lower LOQ, HPLC/MS/MS will be a method of choice for oxime carbamates and their metabolites. 

The worst case scenario for a food chemist who produces a dangerous food product or fails to detect the dangers in an existing food product is to be fired or even go to jail for violating regulatory requirements. If you are an independent food chemist consultant, and you come to wrong conclusions, and your client loses a lawsuit, that same client may turn around and sue you for negligence. 

Given this level of expectation and the known levels of citations, the case for ensuring that validation is a key objective of any pharmaceutical ERP project would seem conclusive. The various areas covered by regulatory requirements for computerized systems can be summarized in Table 8.1. 

As we described earlier in this chapter, there is a wide range of external and internal sources which affect the semiconductor facility s compliance status or its ability to implement its environmental management program. The ability for early identification or detection of environmental problems or issues is one of the most important skills and tools that facility compliance personnel can have. This conclusion is based on the collective experience of industry compliance personnel over the last 10-15 years as they have coped with the sharp increase in the number of environmental regulatory requirements. 

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. 

Another theme which we constantly reiterated in all of our communications with EPA on TSCA, and indeed in all other advocacy matters, was the need for regulatory action to be based upon adequate scientific data and defensible conclusions. Historically, the Agency had been too quick to impose requirements on the basis of incomplete, controversial or ambiguous scientific evidence. 

One concern with equivalence and non-inferiority trials is that a positive conclusion of equivalence/non-inferiority could result from an insensitive trial by default. If, for example, equivalence is established then this could mean either that the two treatments are equally effective, or indeed equally ineffective. If chosen endpoints are insensitive, dosages of the drugs too low, patients recruited who are not really ill and the trial conducted in a sloppy fashion with lots of protocol deviators and dropouts, then the treatments will inevitably look very similar Clearly we must ensure that a conclusion of equivalence/non-inferiority from a trial is a reflection of the true properties of the treatments. The regulatory guidelines (ICH ElO) talk in terms of assay sensitivity as a requirement of a clinical trial that ensures this. 

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