MedDRA Labeling Groupings to Improve Safety Communication in Product Labels.

The granularity and structure of the International Council for Harmonisation's (ICH) Medical Dictionary for Regulatory Activities (MedDRA) are useful for precise coding of adverse events (AEs) for data analysis. In product labeling for healthcare practitioners, however, the granularity of MedDRA Preferred Terms (PTs) can obscure the communication of adverse reactions (ARs). Driven by a focus on patient safety, business needs, and regulatory guidance, many sponsors and regulators have begun to develop institution-specific approaches to clustering similar AR terms in medical product prescribing information on a product-by-product basis. However, there are no agreed upon conventions that describe which AR terms may be appropriate to group together. In order to improve safety communication to patients and healthcare providers, there is an urgent need for a harmonized international approach to the creation and use of groups of MedDRA PTs which we refer to as "MedDRA Labeling Groupings (MLGs)" in medical product prescribing information. Given its long-standing contributions towards the design of Standardised MedDRA Queries (SMQs), the Council for International Organizations of Medical Sciences (CIOMS) convened an Expert Working Group (EWG) with involvement of multiple major stakeholders to produce a consensus document on principles and points to consider in the development of MLGs. The CIOMS MLG EWG identified variations in grouping of MedDRA PTs in product labels, and in the current document, proposes a strategy for improving the communication of drug safety labeling. It is envisaged that the use of these consensus recommendations would be voluntary and applied to product labels in a manner that is consistent with existing regulatory frameworks.

High precision isotope ratio measurements on by thermal ionization mass spectrometry using ion.

Studies were carried out to determine the 10B/11B isotope ratio by positive thermal ionization mass spectrometry (P-TIMS) analyzing boron as rubidium borate ions. Of the 36 different ionic species formed, the boron and rubidium isotope ratios were obtained from the ion intensity ratios of the most suitable ion pairs corresponding to masses 212, 213 and 215, 213 respectively. The investigations were carried out to explore the possibility of correcting the observed isotope ratio of boron by using a modified internal normalization technique based on the observed Rb isotope ratio. The method is based on the relation of isotopic fractionation of boron as a function of the rubidium (natural isotopic composition) isotopes fractionation obtained during TIMS analysis from the same filament loading. The application of the methodology to improve the precision of the observed 10B/11B isotope ratio during analysis of irradiated boron alloy samples is demonstrated. Improvement in precision from 0.25% to better than 0.05% was demonstrated using this approach.

Determination of boron at sub-ppm levels in uranium oxide and aluminum by hyphenated system of complex formation reaction and high-performance liquid chromatography (HPLC).

Boron, at sub-ppm levels, in U3O8 powder and aluminum metal, was determined using complex formation and dynamically modified reversed-phase high-performance liquid chromatography (RP-HPLC). Curcumin was used for complexing boron extracted with 2-ethyl-1,3-hexane diol (EHD). Separation of complex from excess reagent and thereafter its determination using the online diode array detector (DAD) was carried out by HPLC. Calibration curve was found to be linear for boron amounts in the sample ranging from 0.02 microg to 0.5 microg. Precision of about 10% was achieved for B determination in samples containing less than 1 ppmw of boron. The values obtained by HPLC were in good agreement with the data available from other analytical techniques. The precision in the data obtained by HPLC was much better compared to that reported by other techniques. The present hyphenated methodology of HPLC and complex formation reaction is interesting because of cost performance, simplicity, versatility and availability when compared to other spectroscopic techniques like ICP-MS and ICP-AES.