Structured Frameworks to Increase the Transparency of the Assessment of Benefits and Risks of Medicines: Current Status and Possible Future Directions.

Structured frameworks for benefit-risk analysis in drug licensing decisions are being implemented across a number of regulatory agencies worldwide. The aim of these frameworks is to aid the analysis and communication of the benefit-risk assessment throughout the development, evaluation, and supervision of medicines. In this review, authors from regulatory agencies, pharmaceutical companies, and academia share their views on the different frameworks and discuss future directions.

Regulatory review: How do agencies ensure the quality of decision making?

The Centre for Innovation in Regulatory Science (CIRS) Workshop on Regulatory Review brought together international regulators and multinational pharmaceutical company representatives to focus on best practices that underlie regulatory decision making, thereby facilitating the transparent, timely, procedurally predictable, and good-quality evaluation of new medicines. Participants investigated frameworks used by agencies, discussed challenges for regulatory agencies in making quality decisions, investigated the role of other stakeholders, and made recommendations of activities and processes that agencies and companies can consider to enable quality decision making.

Refining the benefit-risk framework for the assessment of medicines: valuing and weighting benefit and risk parameters.

A common framework is necessary for the transparent articulation of the benefits and risks of a therapeutic product across disparate stakeholders. The assignment of value and weighting to each component parameter presents challenges deriving from different stakeholder objectives, methods, and perspectives. Building on prior experiences with a validated framework approach, this forum focused on identifying challenges and approaches to the assignment of values and weightings using a case study applied to a hypothetical medicinal product.

Expediting patients' access to medicines by improving the predictability of drug development and the regulatory approval process.

Ideally, well-designed global pharmaceutical development programs that include simultaneous submissions to multiple regulatory agencies can result in predictable regulatory approvals and expedited access to medicines for all patients. The workshops described herein investigated current trends in development and submission strategies along with regulatory review performance data in order to consider whether barriers to predictable expedited approval outcomes can be overcome through innovative clinical development approaches and a better understanding of review processes and procedures, particularly as these relate to the assessment of a product's risk-benefit profile.

Measuring benefit and balancing risk: strategies for the benefit-risk assessment of new medicines in a risk-averse environment.

Measuring the benefits and risks of medicines is the underlying theme whenever the development, review, and regulation of new medicines are discussed. Workshop participants were asked to take the first steps toward defining a framework for benefit-risk (BR) assessment. The framework identifies the essential elements that both regulators and companies should consider throughout the development, review, and postmarketing experience of new medicines in order to apply a consistent approach toward the assessment of BR balance.

A new phosphate-selective sorbent for the Rem Nut process. Laboratory investigation and field experience at a medium size wastewater treatment plant.

P-control technologies for municipal wastewater are essentially based on "destructive" methods, that lead to formation of concentrated solid-phases (sludge), usually disposed-off in controlled landfills. Ion exchange, as a "non-destructive" technology, allows for selective removal and simultaneous recovery of pollutants, which can be recycled to the same and/or related productive lines. In this context, the REM NUT process removes nutrient species (HPO4 = , NH4+, K+) present in biologically oxidised municipal effluents and recovers them in the form of struvites (MgNH4PO4; MgKPO4), premium quality slow release fertilisers. The main limitation to the extensive application of this ion exchange based process is the non-availability of selective exchangers for specific removal of nutrient species. This paper illustrates laboratory investigation and pilot scale development of a so-called "P-driven" modified REM NUT scheme based on a new phosphate-selective sorbent developed at Lehigh University, PA, USA.

Rem nut ion exchange plus struvite precipitation process.

Nutrients control technologies from wastewater are based on destructive technologies which defer the problem fromthe diluted liquid-phase (effluent) to a more concentrated waste (sludge) in the case of phosphates, or to nitrogen gas and/or volatile compounds in the case of ammonia. The REM NUT process allows for simultaneous removal of phosphate and ammonium ions by selective ion exchange and recovery by chemical precipitation in the form of struvite (magnesium ammonium phosphate) from the spent exchangers regeneration eluates. In the paper revised versions of the REM NUT process, i.e., P-driven layouts, are presented and cost effectiveness is compared to chemical precipitation based on the use of ferric chloride.

Isolation and characterization of an adenovirus associated with inclusion body hepatitis in psittacine birds.

An outbreak is reported of inclusion body hepatitis in psittacines from a private aviary, in which several birds aged between 35 and 75 days had died without showing any clinical signs. Histological examination of the livers revealed severe hepatic damage with presence of large basophilic intranuclear inclusion bodies. Avian adenoviruses were isolated from the affected livers. Characterization of the isolates by means of restriction endonuclease analysis showed that they were similar to reference strain SR49 (serotype 3) which is associated with inclusion body hepatitis in chickens. This finding was confirmed by the virus neutralization test.

Evaluation of commercial ginseng products.

The variation in panaxoside content of roots and commercial products of Panax ginseng and P. quinquefolium was evaluated by a new spectrodensitometric TLC method. The method is rapid and applicable to all commercial products, and it has a relative standard deviation of 6.4%. Panaxoside patterns of slurry-filled capsules and root extracts most closely resembled those of whole roots. Tablets did not contain detectable panaxosides while teas and granules for infusion yielded only low concentrations. The wide variation among these products indicates the need for more rigid control.