License studies

Phase IV. post-licensing studies in the target population, with widening of entry criteria to broaden experience in clinical practice study objectives are typically surveillance for safety or further comparisons with other therapies. The results of such trials are more likely to be used for marketing purposes than in support of applications to regulatory authorities. 

A previous rotavirus vaccine, RotaShield, was approved by the FDA in 1998, but was removed from the market only a little more than a year later, after post-licensing studies had shown a risk of intussusception of 1 in 10000 recipients. 

Observational studies An adsorbed human diploid cell rabies vaccine (Rabivax) has been tested in a post-licensing study in 150 cases of suspect rabid animal bites [42 ]. Adverse events included pain at the injection site (3.4%), swelling with induration (2.8%), and fever and headache (1.4%) there were no serious adverse events. 

Application for at least one Product License supported by an outline of production, information on master seeds/master cells and bio-containment if applicable, and protocols for studies of host animal safety and efficacy... 

Tricyclic antidepressants are not licensed for use in the anxiety disorders, so in theory the SSRIs should not be compared with them in cost-effectiveness terms. The SSRIs and venlafaxine are supplanting benzodiazepines as the latter s long-term problems become more appreciated. The SSRIs will take an increasing proportion of the market. However, in comparison with the overall costs of the anxiety disorders, this drug expenditure can be justified. Further cost-offset and cost-effectiveness studies will help hammer this point home. 

The studies revealed that problems in licensing pharmaceutical establishments can be grouped into those relating to legal stmctures and those relating to implementation. 

The study has shown that most of the countries have licensed their drug establishments in accordance with legislation. There are exceptions in Cuba, where only approximately 50% of the manufacturers are licensed (although all the unlicensed manufacturers are legal), and in Estonia, where only 4% of wholesalers are licensed. 

Nearly all the clinical data comes from the use of atosiban (see Peptide Antagonists), a peptide oxytocin antagonist that is licensed in Europe for acute (48 h) treatment of preterm labour. Early clinical studies demonstrated the ability of atosiban to inhibit uterine contractions associated with labour [14]. Following these successful phase II trials, full phase III trials were... 

To determine maximum individual risk, generic frequency data are required for explosion events for Process Units 1 and 2. For Process Unit 1, incident data were available from the unit licenser identifying three explosions in approximately 15,000 operating years, for an explosion frequency of 2.0 x 10-4 per year. For Process Unit 2, a fault tree analysis of the nitrogen vessel brittle fracture event had been conducted as part of an unrelated project. That study concluded that the frequency of brittle fracture failure of the nitrogen vapor storage vessel was 5x10"4 per year. 

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