Licensing system

Producer responsibility obligations 1997 - guidance on evidence of compliance and accreditation of re-processors A new waste management licensing system - what it means - how it affects you... 

This section briefly summarizes the licensing system in each of the 10 countries, focusing on the power the dmg regulatory authorities in each country have over pharmaceutical facilities the sources of that power and the licensing process. 

Chong JP, Thommes P, Rowles A, Mahbubani HM, Blow JJ 1997 Characterization of the Xenopus replication licensing system. Methods Enzymol 283 549-564 Dasso M, Newport JW 1990 Completion of DNA replication is monitored by a feedback system that controls the initiation of mitosis in vitro-, studies in Xenopus. Cell 61 811-823... 

The EEC had already in place the Coim-cil Directive 65/65/EEC on the approximation of provisions laid down by law, regulation or administrative action relating to medicinal products. Many of the requirements under Coimcil Directive 65/65/EEC had already formed part of the Medicines Act. When Directives 75/318/EEC and 75/319/EEC were adopted by the Council of Ministers on 20 May 1975, they only supplemented and amended the original Directive 65/65/EEC. Therefore, when the United Kingdom joined the EEC in 1973, the provisions of these two new Directives did not substantially affect the licensing system that operated in the United... 

Table 3 Examples of in vitro and in vivo bioassays for which standard operating procedures have been developed (Schipper and Stronkhorst 1999) and studied for their applicability in the licensing system for disposal of dredged sediment (own results) or were evaluated in other studies (e.g. ER-CALUX).

Quality control when applying bioassays in a licensing system... 

The in vitro bioassay for dioxins with cleaned sediment extracts (DR-CALUX) proved to comply with the QA/QC criteria needed to guarantee the reliability of data in an inter- and intralaboratory study (Besselink et al., 2004). The chemical stability of dioxins makes it possible to apply destructive clean-up procedures which remove all matrix factors. Sample extraction and cleanup for other in vitro bioassays for specific mechanisms of toxicity require further development to make sure that the chemicals of interest are not lost or unwanted chemicals included in the sediment extract to be tested. Table 4 summarizes possible bioassays that could be performed in addition to chemical analyses with the dredged sediment in a licensing system. 

Dioxins are very persistent organic pollutants that are present in harbours as by-produets of ineomplete combustion and industrial processes (Besselink et al., 2004). Dioxins in sediments are not aeutely toxic, but are known to induce developmental, reproduetive and immune toxicity after ehronie exposure at low levels. In the licensing system for qualifying dredged material for... 

It is eoncluded that the determination of dioxin-like activity in cleaned sediment extracts using the DR-Luc bioassay has a consistent reproducibility, and can be used as a reliable and robust tool in the hazard assessment of dredged materials in a licensing system. Its advantage over ehemical analysis is that it also detects the effects of combined exposure as well as the effect of unidentified congeners or chemicals present in concentrations below the limit of detection of chemical analysis with a similar mode of action. In addition the use of cleaned sediment extracts circumvents the problem of disturbing sediment matrix effects. 

Chapter 6 addresses the issue of the applieability of in vitro and in vivo bioassays for hazard, risk and local impact assessment of dredged polluted sediments to be disposed of at sea. It discusses how and to what extent selected bioassays can fill in the gaps left open by chemical analysis and the way in which the bioassays may contribute to the present licensing system for disposal (Schipper et al., 2009b). 

Bioassays using cleaned sediment extracts are much more distinctive than bioassays with whole sediment for decision making in a licensing system. This is mainly due to the interference of matrix factors with the assessed endpoint when applying whole sediment instead of cleaned extracts. 

For hazard assessment in a licensing system chemical analysis on total sediment extracts or bioanalysis in order to quantify the bioavailability of the chemicals does not need to be included because the bioavailability will change greatly after disposal of the sediments. 

Local sediment impact assessment can direct the fine-tuning of the selection of chemical and bioassay analyses and the setting of safe levels in the licensing system. This could eventually lead to the decision to include some additional chemical analysis or bioassay in the routine screening. 

In November of 1997, President Clinton signed the Federal Food, Drug and Cosmetic Modernization Act of 1997. One section of this law required that all biologic products be licensed under the single licensing system. With his signature, President Clinton put an end to the CBER s dual licensing system. 

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