Safety database

The first approach is based on the boiling point under reduced pressure data, which can easily be found in the technical literatureTS. The manufacturers catalogues for substances also give these values. The tables that appear in Part Three systematically mention this data whenever available. They do not appear in any of the safety databases in the safety shee produced by the chemical industry for users. 

Currently, gene therapy is restricted to life-threatening and severely disabling diseases, but when a larger safety database has been accumulated there should be expanded opportunities for therapy. It is not possible or desirable to identify a uniform recipe for the safety studies that should be conducted with gene therapy... 

Process Safety Database American Petroleum Institute (API) Reviewed only... 

The European Health and Safety Database (HASTE) European Foundation for the Improvement of Living and Working Conditions Reviewed only... 

The hazard to the population therefore increases throughout the trial process as more people are given greater cumulative amounts of the drug in a less-controlled and monitored manner. However, with each additional patient treated, the clinical experience with the drug also increases, providing a greater safety database in the most relevant species, that is, man. The risk... 

Ilb- larger scale trials in patients (several hundreds) to formally assess the dose-response relationship and continue to expand the efficacy and safety databases. 

To enlarge the formal safety database and thereby act as an insurance policy to address problems occurring at a later stage in a drug s evolution. 

Sample sizes for clinical trials are discussed more fully elsewhere in this book and should be established in discussion with a statistician. Sample sizes should, however, be sufficient to be 90% certain of detecting a statistically significant difference between treatments, based on a set of predetermined primary variables. This means that trials utilising an active control will generally be considerably larger than placebo-controlled studies, in order to exclude a Type II statistical error (i.e. the failure to demonstrate a difference where one exists). Thus, in areas where a substantial safety database is required, for example, hypertension, it may be appropriate to have in the programme a preponderance of studies using a positive control. 

Healthy volunteers Efficacy studies Safety database... 

Myocarditis Analyses of postmarketing safety databases suggest clozapine is associated with an increased risk of fatal myocarditis, especially during, but not limited to, the first month of therapy. In patients in whom myocarditis is suspected, discontinue clozapine treatment promptly. 

A preliminary report by the Lilly Worldwide Phar-macoviligance Safety Database found no major or minor malformations in 20 of 23 prospectively identified pregnancies in which olanzapine exposure occurred (Goldstein et ah, 2000). There were three (13%) spon-... 

Review or resolution of edits and queries Medical management Adverse event management and reporting Development and maintenance of study-specific safety database Serious adverse event (SAE) reporting to regulatory authorities Project management... 

Where the test product generates plasma levels that are substantially above those of the reference product, the regulatory concern is not therapeutic failure but the adequacy of the safety database from the test product. Where the test product has levels that are substantially below those of the reference product, the regulatory concern becomes therapeutic efficacy. When the variability of the test product rises, the regulatory concern relates to both safety and efficacy because it may suggest that the test product does not perform as well as the reference product, and the test product may be too variable to be clinically useful. 

Ensuring that all of these data are in the database correctly is an enormous task, and one that is covered in this chapter only briefly. Section 10.14 provides a brief discussion of safety databases. For more detailed discussions, see Prokscha (2007). 

The biotechnology information for food safety database—http //www.iit. edu/ sgendel/fa.htm... 

Other types of replication-deficient viral vectors that have been used in the gene therapy field include Herpes simplex viral (HSV) vectors that (1) are able to transduce nondividing cells and (2) are highly infective for neurologic tissue and vaccinia vectors. Vaccinia vectors in turn (1) are able to transduce nondividing cells and (2) have the ability to efficiently infect many types of cells. The primary safety concerns for HSV vectors are the potential for tropism to the CNS and the potential for latency and reactivation. Vaccinia vectors contain the same backbone as the smallpox vaccine, thus the available safety databases for vaccinia administration in humans consist primarily of preventive vaccination in a healthy population. Principal safety concerns with the use of vaccinia vectors include (1) their ability to replicate in humans and possibly... 

At the time of approval for marketing, the safety database for a new drug will often include 3,000 to 4,000 exposed individuals, an insufficient number to detect rare adverse events. For example, in order to have a 95% chance of detecting an adverse event with an incidence of 1 per 10,000 patients, an exposed population of 30,000 patients would be required. 

The design and the execution of safety pharmacology studies are focused upon the safety of human volunteers and patients in clinical trials. ICH S7A and may be soon S7B strive for effective integration of safety pharmacology results with those of the non-clinical (toxicology) and clinical safety databases. 

---