Additives risk/benefit balance

Under Article 26, the grounds for refusing a marketing authorisation have been amended under the review. The new provision allows a refusal if the risk-benefit balance of the product is not favourable, if the therapeutic efficacy is insufficiently substantiated, or if its qualitative and quantitative composition is not as declared. The application may also be refused if the documents are not submitted in accordance with the requirements set out in the Directive. The MA holder/applicant is responsible for the accuracy of the data and documentation submitted. The rmfavourable risk-benefit balance is the additional ground for refusal, although in practice this has previously been applied. 

Approval Approval process for biological medicinal products is the same as other chemically synthesized small molecules. The legal test is firmly based upon an assessment of risk-benefit balance. However, in assessing risk-benefit balance of a biological medicinal product, EU law requires the applicant to provide certain additional information. If the medicinal product contains a new biological active substance, the applicant must comply with the requirements set out in article 8(3) of Directive 2001/83/EC by providing results of the pharmaceutical and nonclinical testing, and clinical trials. 

Aside from consideration of drug toxicity, some antimicrobial use requires more in tensive risk-benefit analysis. An example of this is the decision to use isoniazid prophylactically to prevent tuberculosis. Because the hepatotoxicity of isoniazid increases in frequency with age, older persons (>45 years) who are candidates for isoniazid prophylaxis (positive skin test) must have additional risk factors for tuberculosis to balance the potential toxic effects. These include evidence of recent skin-test conversion, immunosuppression, or previous gastrectomy. Older patients without additional risk factors are more likely to suffer toxicity from isoniazid than derive benefit from its use. ... 

As noted above, the Committee of Enquiry into the use of CS in Northern Ireland recommended that chemical agents intended for use in the control of a civil disturbance should be assessed from the viewpoint more of a medicinal drug than that of a military weapon (HMSO, 1969,1971). However, in reaching this conclusion the Committee did make the distinction that with new drugs there is a need for a balanced risk-benefit analysis and these are purely professional medical considerations. However, with a chemical intended for use against humans for peacekeeping purposes, while many of the hazard and risk assessments are of a medical nature, additional other questions may arise which are concerned with social policy and there may also be... 

The book does not focus on occupational safety and health issues, although improved process safety can benefit each area. Detailed engineering designs are outside the scope of the book. This book intends to identify issues and concerns in batch reaction systems and provides potential solutions to address these concerns. This should be of value to process design engineers, operators, maintenance personnel, as well as members of process hazards analysis teams. While the book offers potential solutions to specific issues/concerns, ultimately the user needs to make the case for the solutions that best satisfy their company s requirements for a balance between risk reduction and cost. In many instances the book provides one or more sources of additional information on the subject which could be of value to the reader. 

In the Preface to the First Edition we emphasised some key factors that led us to produce another text book in the general area of pharmacology and phar-macotlierapy. For those who make decisions on the general availability of medicines, as well as those who provide treatment for individual patients, the essential need to be aware of and to balance the benefits and risks of medicines is paramount. Errors in these judgements will prove costly both financially and in terms of additional morbidity and mortality. 

The regulators are not only interested in statistical significance but also in clinical importance. This allows them, and others, to appropriately balance benefit and risk. It is good practice therefore to present both p-values and confidence intervals and indeed this is a requirement within a submission. Most journals nowadays also require results to be presented in the form of confidence intervals in addition to p-values. 

The UK Committee of Safety of Medicines has previously warned that paroxetine appeared to be no more effective than placebo in the treatment of depression in adolescents and might be associated with a greater risk of self harm (SEDA-28, 16). In a meta-analysis of both published and unpublished placebo-controlled trials of SSRIs in childhood and adolescent depression, only fluoxetine seemed clearly to be associated with a positive benefit-harm balance (26). The evidence of efficacy for sertraline and citalopram was doubtful, while the risk of serious adverse events was significantly increased. Additionally, for both drugs the risk of suicidal behavior was numerically increased. In regard to venlafaxine, the risk of suicidal behavior was significantly greater than placebo. 

The use of sodium nitrite as a preservative is a classic example of the often delicate balance between risk and benefit. On the one hand, there is an enormous benefit in reducing the prevalence of fatal toxins in meats by the addition of sodium nitrite. On the other, there is the added risk that sodium nitrite may inerease the level of nitrosamines in eertain foods. Nitrites are still ased as food additives, but the allowable level of nitrites in eured meats has been reduced. 

Low doses can reduce activity of the thyroid gland, lowering hormone production in the gland. Doctors must maintain the fine balance between the risks and benefits of using radioactive iodine. On one hand, this small, additional exposure may tip the balance in favor of cancer formation. On the other, this small additional exposure can restore health by slowing an overactive thyroid and improve health conditions. 

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